QUESTION:Why Christensenella minuta is important? Christensenella minuta: A bacterium which is the most heritable member of the gut microbiota and which also influences host weight. There has been considerable interest in a particular member of the gut microbiota, a bacterial species named Christensenella minuta, which is a member of the Firmicutes phylum. Three recent findings have generated this interest. First, the Christensenella genus appears to be found so far only in human hosts. Second, C. minuta was found to be the most heritable species in the human gut microbiome, meaning that it is the species whose presence or absence in our gut is mostly determined by the genes of its human host. Third, evidence suggests that the presence of C. minuta can directly affect the weight of its host by as yet unknown mechanisms. C. minuta is more likely to be present in leaner people, and adding C. minuta to the gut tracts of mice resulted in leaner mice. These findings suggest a potential use of C. minuta as a probiotic for weight control.
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Q:- Gut-Brain axis? A:- Gut brain axis shows the link between the gut microbiota and brain behaviour. It linked in the form of the regulation of eachother.It means whenever changes occur in gutmicrobiota that leads to change in the behavior of brain. In last two decades it was studied that stress leads to change in the gutmicrobial flora and that leads to change of host behaviour . However the effects of the microbiota or the absence there of on behaviour remained unclear. It also alter in different composition of gut microflora. With altered or absent gut flora shows various molecular differences. It includes changes in levels of brain derived neurotrophic factors, expression of various neurotransmitter receptors and alterations in the turnover of certain neurotransmitter including serotonin.
QUE):Role of Microbes in Human Health and Diseases? >>Microbes are ubiquitous and have ecological interactions with almost all life forms. Likewise, humans invariably engage in host-microbial interactions that could induce short-term or long-term effects. Some of these longterm crossover interactions have allowed successful colonization of microbes within or on the human body, collectively known as the human microbiome or human microbiota. The human microbiome is identified as playing a key role in various physiological processes like digestion, immunity, defense, growth, and development. Any dysbiosis in the human microbiome structure could induce the onset of various metabolic or physiological disorders. Cumulatively the human microbiome is considered as a virtual human organ that is essential for host survival. Additionally short-term biological interactions of the host and microbes have exposed microbes to the human cellular system. This exposure could have allowed the microbes to invade human cells for their growth and reproduction induced onset of various infectious diseases.
What are Probiotics? Probiotics are live microorganisms that are intended to have health benefits when consumed or applied to the body. Many of the microorganisms in probiotic products are the same as or similar to microorganisms that naturally live in our bodies.
What are Prebiotics ? Probiotics are nondigestible food components that selectively stimulate the growth or activity of desirable microorganisms.
What are Synbiotics ? Synbiotics are products that combine probiotics and prebiotics.
What are Psychobiotics? Psychobiotics are beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that influence bacteria–brain relationships. They exert anxiolytic and antidepressant effects characterised by changes in emotional, cognitive, systemic, and neural indices. Bacteria–brain communication channels through which psychobiotics exert effects include the enteric nervous system and the immune system.
QUESTION: How much percent of the human body mass is covered by microorganisms? ANSWER: The human body contains trillions of microorganisms Because of their small size; however, microorganisms make up only about 1 to 3 percent of the body's mass (in a 200-pound adult, that’s 2 to 6 pounds of bacteria), but play a vital role in human health.
1. Probiotics = Probiotics are live bacteria and yeasts that are good for body, especially for the digestive system.
2. Prebiotics = Prebiotics are compounds in food that induce the growth or activity of beneficial microorganisms such as bacteria and yeast.
3. Psychobiotics = Psychobiotics is a term used in preliminary research to refer to live bacteria that, when ingested in appropriate amounts, might confer a mental health benefit by affecting microbiota of the host organism.
4. Synbiotics = When Gibson introduced the concept of prebiotics he speculated as to the additional benefits if prebiotics were combined with probiotics to form what he termed as Synbiotics. A synbiotic product beneficially affects the host in improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract by selectively stimulating the growth and/or activating the metabolism of one or a limited number of health-promoting bacteria.
5. Gut – Brain Axis = The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions.
[The Role Of Gut Microbial Metabolites] >The gut microbiome seems to play a key role in the metabolism and degradation of several metabolic compounds.Almost 10% of all circulating metabolites (small molecules of less than 1–1.5 kDa molecular weight) in the human organism are derived from bacteria and participate in human metabolic pathways. Indeed, proteins and carbohydrates constitute the main fuels for microbial fermentation in the gut. Interestingly, in the proximal colon, the carbohydrate fermentation which leads to the production of succinate, short-chain fatty acids (SCFAs), and gazes takes place. Based on a plethora of animal studies and a handful human studies, the SCFAs are beneficial microbial metabolites in the prevention and therapy of obesity and associated metabolic disorders.On the contrary, in the distal colon, the proteolytic fermentation resulting in the production of several deleterious metabolites such as branched-chain fatty acids (BCFAs), phenols,and ammonia takes place.
Q)What is Functional Redundancy? Ans: A characteristic of species within an ecosystem where certain species contribute in equivalent ways to an ecosystem function such that one species may substitute for another.
Q)Pyrosequencing? Ans: Pyrosequencing is a method of DNA sequencing that differs from Sanger sequencing, in that it relies on the detection of pyrophosphate release and the generation of light on nucleotide incorporation, rather than chain termination with dideoxynucleotides.
QUESTION:What is Molecular Chronometers? Nucleic acids or proteins used as “clocks” to measure amount of evolutionary change over time. It's use based on several assumptions like, sequences gradually change over time, changes are selectively neutral and relatively random amount of change increases linearly with time.
QUESTION:What is cause-effect relationship? A cause-effect relationship is a relationship in which one event (the cause) makes another event happen (the effect). One cause can have several effects.
For example, let's say you were conducting an experiment using regular high school students with no athletic ability. The purpose of our experiment is to see if becoming an all-star athlete would increase their attractiveness and popularity ratings among other high school students. Suppose that your results showed that not only did the students view the all-star athletes as more attractive and popular, but the self-confidence of the athletes also improved. Here we see that one cause (having the status of an all-star athlete) has two effects (increased self-confidence and higher attractiveness ratings among other students).
QUESTION:What is functional redundancy? Functioning can be evaluated in the short-term, in which case the magnitude of the process is of interest, or in the long-term, measured as the probability that this is maintained in the face of environmental change. In both cases, functioning is an emergent property of ecosystems: interactions between the system’s members and coevolution result in functioning which deviates from that expected from a system in which functioning was simply additive. In the case of environmental change, redundancy—the phenomenon in which a function is carried out by multiple species in an ecosystem—buffers functioning, as for any given environmental state there will be multiple organisms within a functional group which can perform optimally at a range of environmental conditions. Reference: DOI: 10.5772/58981
QUESTION:What is pyrosequencing? DNA sequencing is critical to identifying many human genetic disorders caused by DNA mutations, including cancer. Pyrosequencing is less complex, involves fewer steps, and has a superior limit of detection compared with Sanger sequencing. The fundamental basis of pyrosequencing is that pyrophosphate is released when a deoxyribonucleotide triphosphate is added to the end of a nascent strand of DNA. Because deoxyribonucleotide triphosphates are sequentially added to the reaction and because the pyrophosphate concentration is continuously monitored, the DNA sequence can be determined.
Pyrosequencing is designated as a sequence-by-synthesis technique because DNA synthesis is monitored in real time. It is based on the pioneering and elegant, basic science work of Pål Nyrén, PhD, who first demonstrated in 1987 that DNA polymerization can be monitored by measuring pyrophosphate production, which can be detected by light. Edward Hyman, PhD, capitalized on Dr Nyrén's work to invent pyrosequencing 1 year later, although it took several more years to be fully commercialized and more widely implemented. Reference: https://doi.org/10.5858/arpa.2012-0463-RA
1.Method of delivery at birth. According to the CDC, as of 2014, 32.2% of all deliveries in the United States are performed by cesarean section. The composition of the gut bacterial community is different in infants delivered by cesarean section from that of infants born by vaginal delivery. Infants born by vaginal delivery are exposed to the mother's bacteria at birth, which influences the infant's gut bacteria and stimulates white blood cells and other components of the immune system. Studies have suggested that infants born by cesarean section are at greater risk of developing obesity and/or diabetes than those born vaginally.
2.Infant feeding. Infant feeding is another important factor for establishing the bacterial community in the gut, because the mother's milk is not sterile. Human breast milk has been recognized as a source of commensal and potential probiotic bacteria that influence the development of infant gut bacteria. Human breast milk contains >700 species of bacteria. Although human milk bacterial communities are generally complex and vary individually, the median bacterial load is ∼106 bacterial cells/mL through time. Thus, it has been estimated that a lactating infant consuming 800 mL breast milk/d could ingest up to 8 × 108 bacterial cells daily, which is ∼100 times higher than previous estimates, and the composition changes over the course of lactation. It appears that Streptococci and Staphylococci are predominant bacterial genera in human milk both of these are also predominant in the skin microbiota. Therefore, human milk may also contain some skin bacteria.
3.Genetics. The number of specific bacteria found in the gut microbiota is influenced in part by the genetic makeup of the host in ways that affect host metabolism and ultimately can affect health. Family members have been found to have more similar microbiota communities than unrelated individuals, and the gut microbiota is more similar in monozygotic than in dizygotic twins. However, there are currently no genome-wide studies that have characterized specific genes and pathways that determine the composition of the gut microbiome, although certain genes in the immune system are associated with inflammatory bowel disease.
4.Infections. A human study of Clostridium difficile patients and asymptomatic carriers with the use of 16S ribosomal RNA gene pyrosequencing found that both had reduced microbial richness and diversity compared with healthy subjects. C. difficile infection is a typical result of severe dysbiosis in the gut microbiota. Interestingly, transplantation of the gut microbiome from healthy donors to infected patients increased microbial richness and diversity, and it is currently applied clinically.
5.Diet. The role that food-ingested bacteria play in the gut microbiome had been underestimated in the past, possibly because of methodologic limitations that have been overcome in recent years. Numerous studies, both in research mice and in humans, have shown that high-calorie diets contribute to obesity and T2D. However, increasing evidence suggests that the link between diet and obesity lies in the gut microbiota. Understanding that diet is an important contributing factor to the composition of the gut microbiome makes it the most logical target to manipulate. Interventional studies show that dietary changes result in substantial and rapid changes in the make-up of the gut microbiome. Studies in mice have demonstrated that a high-fat diet (60% fat) decreases the number of bacterial species (α diversity) in the gut microbiome, and the composition of the gut microbiome between mice given a high-fat diet (unpurified) and those given a regular unpurified diet is very different (β diversity).
Few definitions of things those were discussed during lecture:-
CORE MICROBIOME:- A core microbiome is defined as the group of microbes commonly found within a host's microbiome, using persistence of the association as the criterion to select microbes potentially providing critical function within the habitat in which they are found.
DYSBIOSIS:-Dysbiosis (also called dysbacteriosis) is a term for a microbial imbalance or maladaptation on or inside the body.
CAUSE - EFFECT RELATION :- A cause-effect relationship is a relationship in which one event causes another to happen. Whenever the cause occurs, the effect must also occur.
RARE BIOSPHERE:- Rare biosphere refers to a large number of rare species of microbial life, i.e. bacteria, archaea and fungi, that can be found in very low concentrations in an environment.
FUNCTIONAL REDUNDANCY:- A characteristic of species within an ecosystem where certain species contribute in equivalent ways to an ecosystem function such that one species may substitute for another.
PYROSEQUENCING:- Pyrosequencing is a method of DNA sequencing based on the "sequencing by synthesis" principle, in which the sequencing is performed by detecting the nucleotide incorporated by a DNA polymerase. Pyrosequencing relies on light detection based on a chain reaction when pyrophosphate is released.
A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.
To understand the range of human genetic and physiological diversity, the microbiome and the factors that influence the distribution and evolution of the constituent microorganisms must be characterized. This is one of the main goals of the Human Microbiome Project (HMP). The outcome might also provide perspective on contemporary human evolution: that is, on whether and how rapidly advancing technology, and the resultant transformation of human lifestyles and the biosphere, influences the 'micro-evolution' of humans and thereby health and predisposition to various diseases.
Definitions which were discussed in the lecture earlier:-
1. Probiotics :- Probiotics are the live microorganisms which confer health benefit when they are administered in adequate amount according to the WHO. For example, the organisms from genus Lactobacillus and Bifidobacteria are widely used for gaining health benefits. This bacteria are example of probiotics.
2. Prebiotics - Prebiotics are compounds or substrates which are not digested by humans but these compounds are able to stimulate the growth of selective microorganisms living in colon. It is believed that they stimulate the growth of good bacteria and thus confer benefit to the host. Human breast milk which contains oligosaccharides helps to formulate gut microflora of newborn so they can be a good example of prebiotics.
3. Psychobiotics :- Psychobiotics are probiotics which confer mental health benefits when they are taken in an adequate amount. It is estimated that they might be used in cure of mental health issues like anxiety and depression.
4. Synbiotics :- Synbiotics is a combination of prebiotics and probiotics. It is believed that it benefits the host by improving the survival and activity of microorganisms.
5. Gut-brain axis :- The gut-brain axis is a bidirectional communication system between the GI tract and Central Nervous System.The gut–brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, including the hypothalamic–pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, including the enteric nervous system and the vagus nerve, and the gut microbiota. It is thus believed that gut microbiota plays an important role in changing the CNS system and thus affects mood of a person.
# Human genetics and immune interactions in early development. The composition of the human microbiome is unique in each individual, and the differenceamong individuals are large compared to the typical biochemical differences within a person over time. Identical twins are barely more similar to one another in microbial composition and structure than are non-identical twins, at least over the range of environmental factors captured in studies to date, suggesting that the effect of the human genome is limited, and that most of microbial community assembly may be determined by environmental factors.
# Body site When the microbiomes of large cohorts of people at a given body site are compared, individuals fit on a continuum of microbial diversity within a human population, rather than clustering into discrete groups. During human development, the human microbiome follows body site-specific trajectories, so that each body site develops a specific biogeography. The skin, for example, shows dramatic variation in microbiome composition and structure across different sites. The physical and topographical characteristics of skin play a significant role in shaping the microbial community similarity between sites. These factors also play a role in shaping the individuality of the microbiome, so that each person develops a unique microbial signature on their skin, irrespective of the differences between skin sites.
# Diet Diet has been studied extensively in relation to the gut microbiome, but less so with respect to other microbiomes at other sites across the body. Modulating diet is an ideal opportunity for low-risk, culturally and psychologically acceptable intervention to change the microbiome. Therefore, this avenue of research could yield noveltherapeutic strategies through targeted dietary interventions should gut microbiota be shown to be causative for certain diseases. Evidence to date suggests that long-term diet has very large effects on gut microbiome composition although a sufficiently extreme short-term dietary change can cause people to resemble one another within days.
#Antibiotics The effect of antibiotics on all microbiomes is expected to be large compared to other factors, and preliminary studies have been performed to determine the impact. The gut microbiome in adults appears not to be resilient to repeated antibiotic administration. The same antibiotic appears to affect particular microbes differently depending on the rest of the microbiome, perhaps due to different growth phases, metabolic states, or contextual microbial network in which the microorganisms find themselves. An especially interesting area of research is the increasing evidence that antibiotics in early life have a profound effect of the gut microbiome that can result in the later development of obesity, asthma, inflammatory bowel disease and other disorders.
# Lifestyle Lifestyle is also thought to have a strong influence on microbiome composition. Cohabitation with pets, such as dogs, has a statistically significant association with the microbiome. In one study, the skin microbiome of couples living together has a closer resemblance if the couple has a dog, but, intriguingly, a small child did not provide the same trend, so couples with a child but no dog were not significantly more similar to one another than couples without a child. Pet ownership and exposure to livestock have been associated with decreased risk of asthma. Interrupting this exposure in infants from human populations with a known ancestral history of interaction with animals has been shown to lead to a substantial increase in atopy,especially asthma. If these results turn out to be caused by the microbiome, rather than simply correlative, they suggest potential new therapeutic strategies for disease intervention could come from microbial exposure focused on immune activation.
Gnotobiotic mice: Gnotobiotic Mice refers to mice in which every microorganism present is defined and the study of organisms whose every germ is carefully controlled. Germ-free mice are one class of gnotobiotic animals, but mice associated with defined bacterial communities (e.g. Altered Schaedler's Flora) are also considered gnotobiotic. Gnotobiotic animals are kept in isolators for long-term maintenance of their microbiological status.Work on germ-free mice began in 1940's to understand how microorganisms contribute to physiology and disease.
List of important gut microbiome, whose activities protect human health and digestive wellbeing.
1. Christensenella minuta: A highly heritable bacterial species which has been found to be strongly associated with obesity through an unknown biological mechanism. This novel genome provides a valuable resource for future obesity therapeutic study, which is beneficial for weight management.
2. Akkermansia muciniphila: Akkermansia muciniphila is a mucin-degrading bacterium commonly found in human gut. A. muciniphila has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders. Due to its highly promising probiotic activities against obesity and diabetes.
3. Barnesiella: This species has the ability to prevent pathogenic species of antibiotic-resistant bacteria from colonising the gut. Ex: Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization.
4. Adlercreutzia equolifasciens: These bacteria turn compounds found in soy into a special antioxidant that may help prevent cancers and heart disease.
5. Oxalobacter formigenes: Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones.
QUESTION:What is Gnotobiology, Gnotobiosis and Gnotobiotic animals? Gnotobiology is the science of study of animals or other organisms raised in environments free of germs or those which contain only specifically known germs. Scientists compare gnotobiotic animals with ordinary animals whose bodies carry many germs, like bacteria, viruses and parasites.
Gnotobiosis is a condition in which all the forms of life present within an organism can be accounted for. Typically gnotobiotic organisms are germ-free or gnotophoric (having only one contaminant).
A gnotobiotic animal is an animal in which only certain known strains of bacteria and other microorganisms are present. Technically, the term also includes germ-free animals, as the status of their microbial communities is also known. However, the term gnotobiotic is often incorrectly contrasted with germ-free.
QUESTION:What is tissue tropism and how it can be used? Tissue tropism is the cells and tissues of a host that support growth of a particular virus or bacterium. Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues. Other viruses may infect primarily a single tissue. This concept is central to the radiological evaluation of infectious disease.
Pathology As infections that display tissue tropism will thrive in certain tissue locations, this characteristic can be helpful in making a diagnosis from radiological imaging. Findings of infection on imaging that are localized in a pattern typical for a particular microbial organism allow for. This is particularly useful when serological confirmation can take days or weeks, as in the cases for many of the viral encephalitides.
Radiographic features Radiological diagnosis of the underlying microbial pathogen responsible for presenting infection allows for the use of specific antimicrobial therapy much before the causative organism is eventually confirmed. This is particularly true for viruses which are confirmed through the use of PCR, which can take days to weeks. The degree to which microbes display tissue tropism varies and indeed not all of them do.
Examples of tissue tropism include: Bilateral thalamic involvement in Japanese encephalitis Medial temporal and limbic involvement in herpes simplex encephalitis Terminal ileum for gastrointestinal tuberculosis
QUESTION:What is law of minimum? In the 19th century, the German scientist Justus von Liebig formulated the “Law of the Minimum,” which states that if one of the essential nutrients is deficient, organism will be poor even when all other essential nutrients are abundant. It states that growth is dictated not by total resources available, but by the scarcest resource (limiting factor). The law has also been applied to biological populations and ecosystem models for factors such as sunlight or mineral nutrients.
QUESTION:What is law of tolerance? It states that an organism's success is based on a complex set of conditions and that each organism has a certain minimum, maximum, and optimum environmental factor or combination of factors that determine success.
It was develop by American zoologist Victor Ernest Shelford in 1911.
The absence of an organism can be limited by the qualitative or quantitative insufficiency from the various environmental factors which may come up to the limits of tolerance for that organism. Environmental factors involved climatic change, topographic location and biological necessities of both plants and animals.
This law is possibly the more precise indication of natural complexity. Each individual or a population is subject to an ecological change that crop up the minimum and maximum capacity to any complex environmental factors. The range wherein it carried out from the minimum to maximum signify the limit of tolerance of an organisms, if all known factors are actually within the particular range of a certain organisms yet it still fails, it is important to consider extra factors of interrelationships with other organisms.
It is been studied that an organisms may have an extensive tolerance for one factor yet a slight array for another. When an organism has a wide range on all factors it indicates that a certain organisms are most widely distributed and are contribute to augment diversity in the community.
QUESTION:What is Phylogenetic inertia? The concept of ‘phylogenetic inertia’ is routinely deployed in evolutionary biology as an alternative to natural selection for explaining the persistence of characteristics that appear sub-optimal from an adaptationist perspective.
Phylogenetic inertia or phylogenetic constraint refers to the limitations on the future evolutionary pathways that have been imposed by previous adaptations. Charles Darwin first recognized this phenomenon, though the term was later coined by Huber in 1939.
Darwin explained the idea of phylogenetic inertia based on his observations; he spoke about it when explaining the "Law of Conditions of Existence". Darwin also suggested that, after speciation, the organisms do not start over from scratch, but have characteristics that are built upon already existing ones that were inherited from their ancestors; and these characteristics likely limit the amount of evolution seen in that new taxa. This is the main concept of phylogenetic inertia.
Richard Dawkins also explained these constraints by likening natural selection to a river in his 1982 book The Extended Phenotype.
There have been several studies that have been able to effectively test for phylogenetic inertia when looking into shared traits; predominantly with a comparative methods approach. Some have used comparative methods and found evidence for certain traits attributed to adaptation, and some to phylogeny; there were also numerous traits that could be attributed to both. Another study developed a new method of comparative examination that showed to be a powerful predictor of phylogenetic inertia in a variety of situations. It was called Phylogenetic Eigenvector Regression (PVR), which runs principal component analyses between species on a pairwise phylogenetic distance matrix. In another, different study, the authors described methods for measuring phylogenetic inertia, looked at effectiveness of various comparative methods, and found that different methods can reveal different aspects of drivers. Autoregression and PVR showed good results with morphological traits.
About tissue trophism #Tissue trophism Tropism refers to the ability of a given pathogen to infect a specific location. Organ or tissue tropism reflects the ability of a given pathogen to infect a specific organ or sets of organs. Some pathogens are broadly tropic, infecting all or most organs, while others are restricted to a given tissue or even to certain tissue niches.
# Variations in Tropism S. aureus resides as a commensal in the nose and upper respiratory tract of 30% of individuals . However, it also has the ability to cause a range of diseases, from localized skin abscesses to endocarditis, pneumonia, osteomyelitis, or disseminated infection. The seasonal influenza viruses mainly infect the upper respiratory tract, while pandemic influenza as well as some highly pathogenic avian influenza viruses (e.g., H5N1) have increased ability to infect the lower respiratory tract. Influenza viruses can also infect extrapulmonary tissues, leading, for example, to conjunctivitis.
# Impact of Tropism on Disease Severity. As long as S. aureus resides as a commensal in the upper respiratory tract, it does not cause any symptoms . In contrast, S. aureus bacteremia has a 15%–50% case fatality rate. Likewise, mortality from S. aureus infective endocarditis is 22%–66% .
#Impact of Tropism on Disease Transmission
Pathogen location also strongly influences transmission to new hosts. Transmission of S. aureus from bacteremia appears to involve passage through the gastrointestinal tract followed by fecal spread. In contrast, bacterial colonization on the skin and in the nose may facilitate person-to-person transmission.
#Impact of Tropism on Treatment Drug tissue penetration varies depending on chemical structure, formulation, and delivery. Treatment choices will therefore be influenced by the sites of infection. For example, S. aureus abscesses may be treated by incision and drainage alone, or with topical antibiotics. In contrast, bacteremia will require systemic antibiotics, and endocarditis may require surgery.
The placental microbiome is the nonpathogenic, commensal bacteria claimed to be present in a healthy human placenta and is distinct from bacteria that cause infection and preterm birth in chorioamnionitis.Until recently, the healthy placenta was considered to be a sterile organ but now genera and species have been identified that reside in the basal layer. It should be stressed that the evidence for a placental microbiome is controversial.Most studies supporting the existence of a placental microbiome lack the appropriate experimental controls, and it has been found that contamination is most likely responsible for reports of a placental microbiome. The placental microbiome more closely resembles that of the oral microbiome than either the vaginal or rectal microbiome. In a healthy placental microbiome, the diversity of the species and genera is extensive. A change in the composition of the microbiota in the placenta is associated with excess gestational weight gain, and pre-term birth.The placental microbiota varies between low birth weight infants and those infants with normal birth weights. While bacteria are often found in the amniotic fluid of failed pregnancies, they are also found in particulate matter that is found in about 1% of healthy pregnancies. In non-human animals, part of the microbiome is passed onto offspring even before the offspring are born. Bacteriologists assume that the same probably holds true for humans.
- Autism Spectrum Disorder (ASD) and role of prevotella species.
- Autism spectrum disorder (ASD) is a complex developmental condition that involves persistent challenges in social interaction, speech and nonverbal communication, and restricted/repetitive behaviors. One potentially important environmental factor of ASD is abnormal intestinal flora. A large fraction of autistic children suffer from gastrointestinal (GI) problems. Prevotella is a key genus in determining gut microbiome profile. Prevotella plays a key role in digesting carbohydrate-rich food, but also that diet patterns can affect the abundance of Prevotella in human gut. Prevotella species also have essential genes for biosynthesis of vitamin B1, which was reported to mitigate ASD symptoms. A significantly lower abundance of the Prevotella cluster in autistic children could be linked to a low carbohydrate diet, however, autistic and neurotypical children generally consume comparable amounts of carbohydrate and fiber.
QUESTION:What is Asian diet, Mediterranean diet and Western diet? Asian diet Oldways introduced the Asian Heritage Diet Pyramid in 1995 at the International Conference on the Diets of Asia in San Francisco, developed in conjunction with the Cornell-China-Oxford Project on Nutrition, Health and Environment, and the Harvard School of Public Health. The traditional diet in many Asian countries is often closely tied to both religious practices and long-standing customs, and the record of these eating habits is an excellent source of information and culinary inspiration: Vegetables and more vegetables, strong spices, rice and noodles, seafood, and soy products.
Mediterranean diet The Mediterranean diet is a diet inspired by the eating habits of Italy and Greece in the 1960s. The principal aspects of this diet include proportionally high consumption of olive oil, legumes, unrefined cereals, fruits, and vegetables, moderate to high consumption of fish, moderate consumption of dairy products (mostly as cheese and yogurt), moderate wine consumption, and low consumption of non-fish meat products. Olive oil has been studied as a potential health factor for reducing all-cause mortality and the risk of chronic diseases.
Western diet The Western diet or standard American diet (SAD) is a modern dietary pattern that is generally characterized by high intakes of red meat, processed meat, pre-packaged foods, butter, candy and sweets, fried foods, conventionally-raised animal products, high-fat dairy products, eggs, refined grains, potatoes, corn (and high-fructose corn syrup) and high-sugar drinks, and low intakes of fruits, vegetables, whole grains, grass-fed animal products, fish, nuts, and seeds. The modern standard American diet was brought about by fundamental lifestyle changes following the Neolithic Revolution, and, later, the Industrial Revolution.
SHOCKING FACT!!!!!!!! Question: Does Gut bacteria really affect human mood?????? Answer: The human gut is lined with more than 100 million nerve cells, more than in the spinal cord or in the peripheral nervous system. Yes, humans have brain cells in large intestines! This explains why antibiotics which disturb the gut microbial ecosystem might cause neuropsychiatric effects, interact with psychotropic medications, and/or influence person’s mood. Chemicals implicated in depression and happiness such as serotonin are also found in the gut; 90% of serotonin is manufactured in the digestive tract and not the brain. Many antidepressants work by increasing serotonin. According to Scientists gut bacteria produce many other neurotransmitters such as dopamine, norepinephrine, acetylcholine, and GABA (Gamma aminobutyric acid), which are critical for mood, anxiety, concentration, reward, and motivation. The gut microbiome can cause changes in how our brains react. So, Yes, gut bacteria really affect human mood.
Dysbiosis is often defined as an “imbalance” in the gut microbial community that is associated with disease. This imbalance could be due to the gain or loss of community members or changes in relative abundance of microbes. Dysbiosis is a disequilibrium of commensal flora with respect to the endobiogenic needs of the individual organism. This disequilibrium may be due to three basis reasons: (1) insufficiency of commensal flora, (2) loss of diversity: a relative imbalance in the normal commensal flora, and (3) pathogenic flora competing with the commensal microbiome. Alterations in the microbiota can result from exposure to various environmental factors, including diet, toxins, drugs, and pathogens. There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity.
QUESTION:What is association vs causation? When considering the relationship between exposures and health outcomes, it is important to distinguish between association and causation.
Association: Is a specified outcome more likely in people with a particular exposure. Is there a link? Association is a statistical relationship between two variables. Two variables may be associated without a causal relationship. Association or correlation can be observed between many variable, but causation can only be determined from data collected from a controlled experiments.
Causation: Causation occur when a change in one variation produces a change in another variable. Causation means that the exposure produces the effect. It can be the presence of an adverse exposure, e.g., increased risks from working in a coal mine, using illicit drugs, or breathing in second hand smoke. Causative factors can also be the absence of a preventive exposure, such as not wearing a seatbelt or not exercising. A cause must be associated with the outcome, but simply demonstrating an association is not enough. To conclude that lack of exercise is a cause of heart disease, one needs to review the body of evidence suggesting a causal relationship and also consider other criteria.
For example, Does exposure to tobacco smoke and air pollution precede the occurrence of lung cancer? Is there a strong association between smoking and subsequent occurrence of lung cancer? Is it possible that having lung cancer causes one to smoke? It is interesting to note that when lifelong smokers are told they have lung cancer or emphysema, many of them quit smoking. This makes it seem as if ex-smokers are more likely to die of emphysema or lung cancer than current smokers.
QUESTION:What is Interactome and Interactomics? The interactome is the whole set of molecular interactions that occur within a particular cell. The term interactome was originally coined in 1999 by a group of French scientists headed by Bernard Jacq, and is often described in terms of biological networks.
Interactomics is a discipline at the intersection of bioinformatics and biology that deals with studying both the interactions and the consequences of those interactions between and among proteins and other molecules within a cell.
Molecular interactions can occur between molecules belonging to different biochemical families or within a given family, such as proteins, nucleic acids, lipids, and carbohydrates. Interactomes may be described as biological networks, and most commonly, interactome refers to protein-protein interaction (PPI) network and protein-DNA interaction networks (also called gene regulatory networks), or subsets thereof.
Therefore, a typical interactome includes transcription factors, chromatin regulatory proteins, and their target genes. Interactomics aims to compare such networks of interactions between and within species in order to discover patterns of network preservation and/or variation. Interactomic methods are currently being used to predict the function of proteins with no known function, especially in the field of drug discovery.
QUESTION: What are Postbiotics? ANSWER: Postbiotics are by-products of the fermentation process carried out by probiotics in the intestine. In other words, as probiotics feed on prebiotics, postbiotics are produced. They are basically the “waste” of probiotics. Waste products don’t sound like they would be of much use to us. they are responsible for multiple important health-boosting functions in our gut. Some examples of postbiotics include organic acids, bacteriocins, carbonic substances and enzymes. They result naturally from the existence and survival of microorganisms living in our gut, though they can also be added directly through therapeutic processes.
The Gut Brain Connection: How Gut Health Affects Mental Health
Your microbiome—the diverse population of microbes (bacteria) that live in your gastrointestinal (GI) tract—plays an important role in the health of your gut, and in other aspects of your physical health, from inflammatory skin disorders to obesity. Researchers now say that this role of promoting good health may extend to include the health of your brain and neurological systems.
What’s the Connection? The thousands of different types of both “good” and “bad” bacteria that populate the microbiome normally exist in a balance in favor of beneficial bacteria that help prevent overgrowth of bad bacteria that can harm your heath. Studies have shown there is potential harm associated with an imbalance in the microbiome due to inflammation, intestinal permeability or lack of bacterial diversity, any of which may be associated with an overgrowth of unhealthy bacteria. In some cases, researchers are confronted with the classic “chicken or egg” question with respect to the association between gut bacteria and poor health, in terms of which comes first. Does an overgrowth cause the disorder or does the disorder cause an overgrowth of bad bacteria?
Bacteria on the Brain Current thinking in the field of neuropsychology and the study of mental health problems includes strong speculation that bipolar disorder, schizophrenia, and other psychological or neurological problems may also be associated with alternations in the microbiome. Researchers speculate that any disruption to the normal, healthful balance of bacteria in the microbiome can cause the immune system to overreact and contribute to inflammation of the GI tract, in turn leading to the development of symptoms of disease that occur not only throughout your body, but also in your brain. This system of connections and communication between the gastrointestinal tract and the brain is referred to as the “gut-brain axis.” Some researchers speculate that infections occurring in early life could negatively affect the mucosal membrane in the GI tract, disrupting the gut-brain axis, and interfering with normal brain development. The mucosal membrane can also be altered in other ways, such as through poor diet choices, radiation treatment, antibiotic use, and chemotherapy.
What You Can Do? To maintain or restore the health of your microbiome and support good overall health, it is important to maintain a strong balance in favor of beneficial bacteria in your digestive tract. The first step is to eat a well-balanced diet that includes foods with probiotic or prebiotic ingredients that support microbial health by helping to restore balance to the gut microbiome. These are foods that contain live beneficial (probiotic) bacteria and, in the case of prebiotics, contain substances like specific types of fiber that nurture the growth of probiotic bacteria.
Probiotic Foods Until more is known, look to a variety of readily available probiotic foods that supply varying amounts beneficial live bacteria that grow during carefully controlled fermentation processes. Some of these are common foods you may already be including in diet, while others may seem a bit more exotic, though they are readily available in supermarkets. Probiotic foods and beverages include plain yogurt, kefir, cottage cheese, fresh sauerkraut, kimchi, kombucha, apple cider vinegar, and miso. Keep in mind that the probiotic effects of these foods are destroyed by cooking, processing, or preserving at high temperatures.
Prebiotic Foods. Unlike probiotic foods, prebiotic foods do not contain living organisms. They contribute to the health of the microbiome because they contain indigestible fibers that ferment in the GI tract, where they are consumed by probiotic bacteria and converted into other healthful substances. Prebiotic foods include artichokes, leeks, onions, garlic, chicory, cabbage, asparagus, legumes, and oats.
The Impact of Postbiotics on Host-Microbiota Interactions
Probiotics are viable by definition and their stability and viability were considered to be an essential prerequisite for their health benefits. For postbiotics, however, viability is no longer the most important criterion. Postbiotic efficacy is based on the microbial metabolites, proteins, lipids, carbohydrates, vitamins, organic acids, cell wall components or other complex molecules that are generated in the matrix that is fermented. In some cases the postbiotic composition can be influenced by food processing methods such as heat, sonication, irradiation and high pressure. The microorganisms involved in the fermentation process might respond differently to these methods. For example, some proteins originating from bacteria that are inactivated by heat might denature, while irradiation might cause mutations in nucleic acids. Therefore, the composition of the postbiotic product and thus the host response to the postbiotic products depends on the complete food production process.
The molecular mechanisms underlying the effects of postbiotics seem to be mediated through an interaction between the host and microbial products. This in turn can trigger the host immune system, and thereby trigger e.g., anti-inflammatory responses. Studies describing these molecular mechanisms are often performed in vitro, mechanisms of action leading to these benefits in humans have not been fully elucidated. An example of a possible mechanism immunomodulation by postbiotics in humans could be derived from an in vitro experiment showing the innate response of macrophages to non viable Lactobacillus casei cells. A suspension with heat-killed bacterial cells resulted in an increase in the expression of pro-inflammatory cytokines and enhanced the transcription of Toll-like receptors (TLR-2, TLR-3, TLR-4 and TLR-9). Moreover, several in vitro studies have shown that heat treated Bifidobacterium cells induce cellular immune and anti-inflammatory responses by inhibiting IL-8 secretion in intestinal epithelial cells obtained from patients with UC. It was suggested that these effects in UC patient derived cells are induced by released microbial soluble anti-inflammatory factors that inhibit IL-8 secretion in intestinal epithelial cells. This was not caused by one single factor. Furthermore, it is hypothesized that postbiotic compounds from Lactobacilli spp. can exert immunomodulation activity by increasing levels of Th1-associated cytokines and reducing Th2-associated cytokines.
IMP.. STUDY!!!!!!!! QUESTION: What is the Relationship Between Prebiotics, Probiotics, and Postbiotics??? ANSWER: According to recent research that most of the positive effects of the probiotics are actually due to postbiotics. They may also provide the bases for the proper processing of prebiotics, promoting a healthy prebiotic population in yet another manner. Simply, Prebiotics proceed probiotics, which proceed postbiotics. Postbiotics, in turn, promote the use of prebiotics. Prebiotics are like the “food”, probiotics are the microorganisms themselves, and postbiotics are the results of probiotics consuming that “food”. Postbiotics, while being a sort of probiotic waste, are what may be exerting many of the health effects on humans. This relationship is helps us to understand the symbiotic relationship between gut microorganisms and humans on an even deeper level.
1. Microbial consortia = A microbial consortium is two or more microbial groups living symbiotically. Consortiums can be endosymbiotic or ectosymbiotic. The concept of consortium was first introduced by Johannes Reinke in 1872.
2. Interactome = The sum of these host and microbe metabolite interactions is referred to as the human interactome. Human and microbial metabolites interact so often that the interactome is almost impossible to quantify. Eg :- Consider that the genome of the pathogen HIV codes for nine genes, which generate 19 proteins. According to Fu and team, there are 1,443 direct interactions (3,300 total interactions) between just these 19 proteins and metabolites in the human body.
Post biotics = Postbiotics are byproducts of probiotic bacterial fermentation. When probiotics feed on certain types of fiber molecules in order to thrive, they leave behind “waste products” that are collectively called postbiotics. The microbiota therefore naturally releases postbiotics, which in turn help regulate the composition of the microbiome. Post biotics are immobilised probiotics which when ingested, may have the ability to exert positive biological responses and restore intestinal homeostasis in a similar manner to probiotics. Postbiotics are currently being referred to as modified, inactivated, non-viable, para- or ghost probiotics.
1. Microbial consortia = A microbial consortium is two or more microbial groups living symbiotically. Consortiums can be endosymbiotic or ectosymbiotic. The concept of consortium was first introduced by Johannes Reinke in 1872.
2. Interactome = The sum of these host and microbe metabolite interactions is referred to as the human interactome. Human and microbial metabolites interact so often that the interactome is almost impossible to quantify. Eg :- Consider that the genome of the pathogen HIV codes for nine genes, which generate 19 proteins. According to Fu and team, there are 1,443 direct interactions (3,300 total interactions) between just these 19 proteins and metabolites in the human body.
The human intestine is colonized by a large number of microorganisms that inhabit the intestinal tract and support a variety of physiological functions. Colonization resistance is the term used to describe the microbiota’s capacity to limit the introduction of exogenous microorganisms and is the mechanism in which intestinal microbiota protects itself against colonization by new and harmful microorganisms.
What is the difference between IBD(Inflammatory bowel disease ) and IBS (Irritable bowel Syndrome)?
IBS usually causes no ulcers or lesions in the bowel, and it involves only the colon. IBD is bowel diseases that cause inflammation in the digestive tract. IBS is a common disorder of the large intestine (colon) that causes symptoms of cramping, abdominal pain, bloating, gas, diarrhea, constipation. IBD is a term used to describe a group of inflammatory conditions mainly in the large and small bowels. Abdominal pain in IBS may be spread over a wide area of the abdomen, but it can localize in the lower left area of it. The pain may intensify while eating meals, when gas is present in the GI tract, and from abdominal bloating. Abdominal pain in IBD may occur anywhere in the abdomen, and its location may suggest the type of IBD that you may have (for example, left-sided abdominal pain is a classic symptom of ulcerative colitis).
QUESTION: What is the effect of diet composition on gut microbiota and its impact on gastrointestinal tract health?????? >>>Research is indicating that the gut microbiota has a significant impact on human health. Alterations of gut microbiota have clear consequences on intestinal homeostasis (homeostasis means regulation of any of the large physiological systems in the body, including levels of glucose in blood and body temperature), physiology, gut microbiome, immune system and host metabolic pathways. >>>It is estimated that the human gastrointestinal tract has 10 million genes which are associated with different microbial species and all genes have some beneficial impact on the health of the host, with possible effects on the homeostasis of the immune system, conversion of food into useful nutrients and protection against pathogenic microorganisms invading. However, due to the differences of diets, the microbiota differs widely from individual to individual and each person carries hundreds of microbial species that remain unchanged throughout adulthood. >>>Diet composition plays an important role in the control of gut microbial populations and, thus, in the prevention, management and treatment of certain diseases such as cancer, diabetes. A comprehensive analysis of previously reported results revealed that the gut microbiota can be modulated by diet and the composition of gut microbiota can be influenced by various diet components. The symbiotic relationship between different gut microbial communities regulates the immune system and, therefore, any dysbiosis (Dysbiosis leads to an increased risk of neoplastic transformation which is found to be directly related to chronic inflammation of the gut and the development of colon cancer) can dysregulate the immune system. By, this way diet affects the gut microbiota and it affects the immune system and health of gastrointestinal tract .
Antibiotics are the most commonly prescribed medicine in children. Narrow-spectrum antibiotics target a few types of bacteria. Broad-spectrum antibiotics target many types of bacteria. Both types work well to treat infections. But using broad-spectrum antibiotics when they’re not needed can create antibiotic-resistant bacteria that are hard to treat. They may also have side effects, such as diarrhea or rash.
Treating infections:-Narrow-spectrum antibiotics worked as well as broad-spectrum antibiotics to treat infections. Symptoms improved the same amount in three days.
Side effects:-Children who took narrow-spectrum antibiotics had fewer side effects than those who took broad-spectrum antibiotics.
Quality of life:-There were no differences in quality of life between children who took broad- or narrow-spectrum antibiotics.
Psychobiotics in mental health,neurodegenerative and neurodevelopmental disorders:-
Psychobiotics are a group of probiotics that affect the central nervous system (CNS) related functions and behaviors mediated by the gut-brain-axis (GBA) via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal (GI) function but also the antidepressant and anxiolytic capacity. As a novel class of probiotics, the application of psychobiotics has led researchers to focus on a new area in neuroscience. In the past five years, some psychobiotics strains were reported to inhibit inflammation and decreased cortisol levels, resulting in an amelioration of the symptoms of anxiety and depression. Psychobiotics are efficacious in improving neurodegenerative and neurodevelopmental disorders, including autism spectrum disorder (ASD), Parkinson's disease (PD) and Alzheimer's disease (AD). Use of psychobiotics can improve GI function, ASD symptoms, motor functions of patients with PD and cognition in patients with AD. However, the evidence for the effects of psychobiotics on mental and neurological conditions/disorders remains limited. Further studies of psychobiotics are needed in order to determine into their effectiveness and mechanism as treatments for various psychiatric disorders in the future.
Gut Bacteria Can Influence Your Mood,Thoughts,and Brain:-
The human gut is lined with more than 100 million nerve cells, more than in the spinal cord or in the peripheral nervous system. We have brain cells in our large intestines! This explains why antibiotics which disturb the gut microbial ecosystem might cause neuropsychiatric effects, interact with psychotropic medications, and/or influence our mood. This also explains why mood disorders are so prevalent in patients with irritable bowel syndrome.
Chemicals implicated in depression and happiness such as serotonin are also found in the gut; 90 percent of serotonin is manufactured in the digestive tract and not the brain. Many antidepressants work by increasing serotonin. Scientists have found that gut bacteria produce many other neurotransmitters such as dopamine, norepinephrine, acetylcholine, and GABA, which are critical for mood, anxiety, concentration, reward, and motivation. The gut microbiome can cause changes in how our brains react.
Exposure and consumption of good bacteria are necessary for a balanced brain. Studies found that in germ-free sterile mice, there is an imbalance of depression-related brain chemicals in areas important for emotions and mood. Also, there are significantly more pro-inflammatory cytokines in depressed people compared to non-depressed ones. This effect on the inflammatory system may stem from interactions with a dysfunctional gut microbiome in depressed individuals.
Also, stress makes us more likely to develop mood disorders. And stress makes the gut more permeable to bacteria. Reciprocally, depression causes dysbiosis—an imbalance of good to bad gut bacteria. In sum, depression is maybe caused by dysfunctional gut-brain-immune system interactions.
Good gut bacteria or the absence of some bad ones can make us more resilient to depressive states after stressors or trauma. It is not surprising that chronic exposure to stress is associated with a higher incidence of depression, anxiety.But not everyone who faces stress develops a mood disorder.
Types of human microbiota includes bacteria,archaea,fungi,protists and viruses.
Bacteria: Firmicutes,Bacteriodetes,Protobacteria,Verrumicrobia,Actionobacteria,Fusobacteria and Cyanobacteria are present in human gut. Actinomyces viscosus and A.naeslundii live in mouth. Lactobacillus acidophilus,L.crispatus,L.iners,L.jensenii,L.delbruekii and L.gasseri are present in vaginal microflora.
Archea: Methanobrevibacter smithii,Methanosphaera stadtmanae present in human gut.
Fungi: Yeasts are present in human gut. Malassezia present on the skin.
Viruses: Viruses,especially bacterial viruses such as Bacteriophages colonizes various body sites.
Pyschobiotics are beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that influence bacteria-brain relationships.Pyschobiotics exerts anxiolytic and antidepressant effects characterised by changes in emotions,cognitive,systematic and neural indices.Bacteria-brain communication channels through which pyschobiotics exert effects include the enteric nervous system and the immune system.
Postbiotics: Postbiotics are functional fermentations compounds,like that can be used in combination with nutritional components to promote health.Two commonly used types of postbiotics are parapostbiotics and FIFs.Postbiotics may pave the way towards increasing the potency of active microorganisms or turn them into functional ingredients.Besides that,postbiotics circumvent the technical challange of colonization efficiency and keeping the microorganisms viable and stable in the product at a high dose.The postbiotics concept may bring food,microbiology and personalized treatement even closer.
QUESTION:What is Urolithin? Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. The gut microbiota influences several biological functions including immune responses. Inflammatory bowel disease is favorably influenced by consumption of several dietary natural plant products such as pomegranate, walnuts, and berries containing polyphenolic compounds such as ellagitannins and ellagic acid. The gut microbiota metabolizes ellagic acid resulting in the formation of bioactive urolithins A, B, C, and D. Urolithin A (UA) is the most active and effective gut metabolite and acts as a potent anti-inflammatory and anti-oxidant agent. However, whether gut metabolite UA affects the function of immune cells remains incompletely understood. Since the 2000s, urolithin A has been subject of preliminary studies regarding its possible biological effects. Urolithin A is not known to be found in any food source. Its bioavailability mostly depends on individual microbiota composition, as only some bacteria are able to convert ellagitannins into urolithins.
QUESTION: What is Punicalagin? Punicalagin is an ellagitannin, a type of phenolic compound. It is found in forms alpha and beta in pomegranates (Punica granatum), in Terminalia catappa and Terminalia myriocarpa, and in Combretum molle, the velvet bushwillow, a plant species found in South Africa. These three genera are all Myrtales and the last two are both Combretaceae. Pomegranates have been shown to contain 124 different phytochemicals, and some of them act in concert to exert antioxidant and anti-inflammatory effects on cancer cells. Ellagitannins are bioactive polyphenols present in pomegranate. Pomegranate juice obtained by squeezing the whole fruit has the highest concentration of ellagitannins than any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the known largest molecular weight polyphenol. Pomegranate ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid over several hours in the intestine. Ellagitannins are also metabolized into urolithins by gut flora, which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth. punicalagin, have been characterized to possess antioxidative and anti-genotoxic activities. It is potent immune supressant isolated from pomegranate and has Potential as an antineoplastic.
QUESTION: What Is Glycemic Index (GI)? Carbohydrate is an essential part of our diets, but not all carbohydrate foods are equal. The Glycemic Index (GI) is a relative ranking of carbohydrate in foods according to how they affect blood glucose levels. Carbohydrates with a low GI value (55 or less) are more slowly digested, absorbed and metabolized and cause a lower and slower rise in blood glucose and, therefore usually, insulin levels.
The glycemic index, or GI, was invented in Canada in 1981. It was always intended to be used along with carbohydrate exchanges (which are amounts of food that contain approximately 15 grams of carbohydrate) to help improve blood glucose management. As well as provide much needed insight into the way carbohydrates in food affect blood glucose levels, the GI also helped put an end to the myth that sugars and sugary foods are worse for blood glucose levels than starches and starchy foods.
Since then there have been numerous research papers published not only in the area of diabetes management but also investigating other possible benefits including cardiovascular disease, weight management and even eye health. We have compiled some of the more recent and high level papers for some of the main benefits of GI/GL diets and also some areas where the science is emerging.
The GI value of a food is determined by feeding 10 or more healthy people a portion of the food containing 50 grams of digestible (available) carbohydrate and then measuring the effect on their blood glucose levels over the next two hours. For each person, the area under their two-hour blood glucose response (glucose AUC) for this food is then measured. On another occasion, the same 10 people consume an equal carbohydrate portion of the sugar glucose (the reference food) and their two-hour blood glucose response is also measured. A GI value for the test food is then calculated for each person by dividing their glucose AUC for the test food by their glucose AUC for the reference food. The final GI value for the test food is the average GI value for the 10 people.
Research has proven that a healthy low GI diet helps people with diabetes (type 1 and type 2) manage their blood glucose levels, blood cholesterol levels and reduce insulin resistance – which is important for reducing the risk of long term diabetes related complications. A low GI diet can improve heart health by: Helping to reduce post-meal blood glucose levels, improving the elasticity of blood vessel walls and blood flow, low GI diets can significantly reduce total and LDL cholesterol levels, independent of weight loss, reducing the risk of atherosclerosis, a chronic disease affecting blood vessels, by reducing inflammation. Aiding abdominal fat reduction.
QUESTION: What is gluten, and why is it bad for some people? Gluten is controversial these days. Most sources claim that it is safe for everyone except those who have celiac disease. On the other hand, some health experts believe that gluten is harmful to most people.
Gluten is a family of storage proteins — formally known as prolamins found in grains, including wheat, rye, spelt, and barley. Of the gluten-containing grains, wheat is by far the most common. The two main proteins in gluten are glutenin and gliadin. Gliadin is responsible for most of the adverse health effects of gluten. When flour mixes with water, the gluten proteins form a sticky network that has a glue-like consistency. This glue-like property makes the dough elastic and gives bread the ability to rise during baking. It also provides a chewy, satisfying texture. Interestingly, the name gluten derives from this glue like property of wet dough.
Problems with gluten Most people can tolerate gluten with no adverse effects. However, it can cause problems for people with certain health conditions. This includes celiac disease, gluten sensitivity, wheat allergy, and some other diseases.
Celiac disease Celiac disease, also spelled as coeliac disease, is the most severe form of gluten intolerance. It affects about 1% of the population. It is an autoimmune disorder in which the body treats gluten as a foreign invader. The immune system attacks the gluten, as well as the lining of the gut. This damages the gut wall and may cause nutrient deficiencies, anemia, severe digestive issues, and an increased risk of many diseases. However, some people with celiac disease do not have digestive symptoms but may have other symptoms, such as tiredness or anemia. For this reason, doctors often find it challenging to diagnose celiac disease. In fact, in one study, 80% of people with celiac disease did not know they had it.
Non-celiac gluten sensitivity Many people do not test positive for celiac disease but still react negatively to gluten. This condition is called non-celiac gluten sensitivity. Researchers do not currently know how many people have this condition, but some estimate it to be in the range of 0.5 to 13%.
QUESTION:What is enterotype? Enterotypes are clusters of bacterial communities in the gut that allow researchers to identify common traits that bring people together. Long-term dietary patterns have a powerful influence on the gut microbiota composition, and they are associated with three gut microbiota profile clusters, also known as enterotypes. The enterotypes are divided according to the predominance of Bacteroides (associated with high protein and animal fat diets), Prevotella (associated with carbohydrate-rich diets), or Ruminococcus (associated with a diet high in resistant starch); these enterotypes may correlate with individual health status. The clustering of the gut microbiota has led to the concept of classifying individuals by enterotypes, which is based on the notion that the gut microbiota congregates in a relatively stable composition over time .The discovery of three human enterotypes was announced in the April 2011 issue of Nature by Peer Bork and his associates.
QUESTION:Which types of hormones can be produce by microorganisms? Phytohormones have also been detected and identified in the supernatant of culture medium of many soil and plant-associated bacteria and fungi. In these organisms, the phytohormones do not induce typical hormonal or major physiological changes. Microbial phytohormone production has been linked to changes in root architecture and plant growth promotion. However, the degree of proof for their involvement can vary a lot depending on the phytohormone and the studied microbial strain. Phytohormones (auxins, cytokinins, gibberellins, abscisic acid and ethylene) are elicitors, which can be produced by bacteria and play a role in promoting plant growth Generally, plant hormones are mainly divided into 5 categories: auxins, cytokinins, ethylene, gibberellins (GAs) and abscisic acid (ABA). Gibberellins and abscisic acid accumulated as secondary metabolites in filamentous fungi.
For the industrial production of plant hormones such as GAs and ABA, several processes using fungal fermentation were successfully set up in China. As early as 1950s–1960s, the solid state fermentation of GAs has been applied. However, due to the low yield, tedious operation and other shortcomings, the solid state fermentation was gradually replaced by liquid submerged fermentation, the titer of the process is generally at about 2.0 g/L. Compared with GAs, the industrial microbial fermentation of ABA started relatively late. Until the beginning of this century, the scientist in Chengdu Institute of Biology, Chinese Academy of Sciences, firstly solved the key technical problems and successfully obtained ABA overproducing strain. Through the optimization of liquid submerged fermentation process, the ABA maximum production titer was eventually up to 6.0 g/L. Subsequently, the world's first industrial production line of ABA was formally established through the cooperation with the company Sichuan Lomon Bio Co. Ltd, which greatly reduced the cost and price of ABA and further promoted the application of ABA in agriculture.
QUESTION:What is Peptide YY? The full name for peptide YY is pancreatic peptide YY. It is a hormone that is secreted from endocrine cells called L-cells in the small intestine. There are two major forms of the peptide; one is 36 amino acids long (PYY1-36) and the other lacks the first two amino acids (PYY3-36). It is secreted alongside the hormone glucagon-like peptide 1. Peptide YY is released after eating, circulates in the blood and works by binding to receptors in the brain. Binding of peptide YY to brain receptors decreases appetite and makes people feel full after eating. Peptide YY also acts in the stomach and intestine to slow down the movement of food through the digestive tract. PYY is also anorexigenic, i.e., it reduces appetite.
How is your body able to recognize when you have eaten enough food? After eating, the hormone peptide YY (PYY) will be produced by the small intestine and released into your bloodstream. PYY communicates to your brain that you are full and decreases your appetite. The amount of PPY released depends on the type and quantity of food eaten.
How Does Your Body Use PYY? Peptide YY secretion is mainly stimulated by the presence of food in the digestive tract, particularly fat and protein. The amount of peptide YY that is released into the blood depends on the amount of calories eaten, with higher calorie foods causing more peptide YY release than lower calorie foods. Peptide YY secretion can also be stimulated by digestive juices (such as bile) and another gastrointestinal hormone called cholecystokinin. The highest levels of peptide YY are found in the second hour after eating. Peptide YY levels then gradually decrease. Low levels of peptide YY are seen during long periods without eating, for example overnight.
What happens if I have too much peptide YY? High peptide YY concentrations are unusual. They will cause a decrease in appetite and food intake. High peptide YY concentrations are associated with diseases where there is dramatic weight loss, such as anorexia nervosa, coeliac disease, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and some cancers.
What happens if I have too little peptide YY? Low peptide YY concentrations are associated with an increase in appetite and food intake. Low peptide YY levels are seen in obesity and before the onset of type 2 diabetes and may contribute to weight gain in these conditions. However, low peptide YY concentrations are very unlikely to be the main cause of obesity as the levels decrease after weight gain has started. There has been some research into using peptide YY as a medication for obesity, aiming to decrease the appetite of people who are overweight. This research is still ongoing. It is extremely rare to have a genetic (inherited) deficiency of peptide YY. Low PYY levels mean that you may experience an increase in appetite. Lower PYY levels may contribute to weight gain, however it is not believed to be the main cause of obesity. It is very rare to have a genetic or endocrine disorder of PYY.
QUESTION:What is cholesterol? Overview With all of the bad publicity cholesterol gets, people are often surprised to learn that it’s actually necessary for our existence. What’s also surprising is that our bodies produce cholesterol naturally. But cholesterol isn’t all good, nor is it all bad — it’s a complex topic and one worth knowing more about. Cholesterol is a substance made in the liver that’s vital to human life. You can also get cholesterol through foods. Since it can’t be created by plants, you can only find it in animal products like meat and dairy. Cholesterol is a waxy, fat-like substance that your body needs for good health, but in the right amounts. Unhealthy levels of cholesterol can lead to a condition called high blood cholesterol.
Why Is Cholesterol Needed by the Body? In our bodies, cholesterol serves three main purposes: It aids in the production of sex hormones, it’s a building block for human tissues, and it assists in bile production in the liver.
LDL vs. HDL When people talk about cholesterol, they often use the terms LDL and HDL. Both are lipoproteins, which are compounds made of fat and protein that are responsible for carrying cholesterol throughout the body in the blood. LDL is low-density lipoprotein, often called “bad” cholesterol. HDL is high-density lipoprotein, or “good” cholesterol.
Why is LDL bad? LDL is known as the “bad” cholesterol because too much of it can lead to hardening of the arteries. According to the American Heart Association, LDL leads to plaque accumulation on the walls of your arteries. When this plaque builds up, it can cause two separate, and equally bad, issues. First, it can narrow the blood vessels, straining the flow of oxygen-rich blood throughout the body. Second, it can lead to blood clots, which can break loose and block the flow of blood, causing a heart attack or stroke. When it comes to your cholesterol numbers, your LDL is the one you want to keep low — ideally less than 100 milligrams per deciliter (mg/dL).
Why is HDL good? HDL helps keep your cardiovascular system healthy. It actually aids in the removal of LDL from the arteries. It carries the bad cholesterol back to the liver, where it’s broken down and eliminated from the body. High levels of HDL have also been shown to protect against stroke and heart attack, while low HDL has been shown to increase those risks. According to the National Institutes of Health (NIH), HDL levels of 60 mg/dL and higher are considered protective, while those under 40 mg/dL are a risk factor for heart disease.
QUESTION:What is cytokine storm? Cytokines are small proteins released by many different cells in the body, including those of the immune system where they coordinate the body’s response against infection and trigger inflammation. The name ‘cytokine’ is derived from the Greek words for cell (cyto) and movement (kinos).
A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death. Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1, and SARS-CoV-2 (COVID-19 agent).
Cytokine storm syndrome is diverse set of conditions that can result in cytokine storm. Cytokine storm syndromes include familiar hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.
QUESTION:What is Neutrophil Chemotaxis? Neutrophils undergo a process called chemotaxis via amoeboid movement, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-γ), C3a, C5a, and Leukotriene B4, which these cells use to direct the path of their migration. Neutrophils have a variety of specific receptors, including ones for complement, cytokines like interleukins and IFN-γ, chemokines, lectins, and other proteins. They also express receptors to detect and adhere to endothelium and Fc receptors for opsonin.
In leukocytes responding to a chemoattractant, the cellular polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks regulate activation of Rho GTPases and are required for cell motility. They accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl.
Bile acids are hydroxylated steroids, synthesized in the liver from cholesterol. Glucose, insulin and glucagon also appear to help regulate BA biosynthesis. BAs are ligands for the nuclear farnesoid X receptor (FXR), as well as a G protein-coupled receptor(GPCR's).Bile acids are modified by intestinal bacteria. Primary bile acids are converted to secondary bile acids by dehydroxylation. Bile promotes emulsification of dietary lipids, for digestion and absorption of fatty acids, cholesterol, fat-soluble vitamins, and other hydrophobic components of the diet. Bile acids that are not absorbed in the small intestine reach the large intestine and are metabolized by the microbiota, before being almost totally reabsorbed from the colon. GPBAR1 and FXR modulate the intestinal and liver innate immune system and contribute to the maintenance of a tolerogenic phenotype in entero-hepatic tissues, and how regulation of innate immunity might help to explain beneficial effects exerted by GPBAR1 and FXR ligands in immune and metabolic disorders.
SCFAs are saturated organic acids. They are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota–gut–brain crosstalk. SCFAs directly or indirectly mediate microbiota–gut–brain interactions. They affect cellular systems and their interaction with gut–brain signalling pathways including immune, endocrine, neural and humoral routes. The SCFAs acetate, propionate, and butyrate are the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch. SCFAs have potential to prevent and treat metabolic and inflammatory diseases. They help in maturation of Dendritic cells, enhance T- helper 2 cells, decrease the production of IL12 and IF gamma, also lowers the expression of MHC-2 and costimulatory molecules.
The hypothalamic pituitary adrenal (HPA) axis is our central stress response system.The HPA axis is responsible for the neuroendocrine adaptation component of the stress response. Its dysregulation plays an important role is severe mental disorders. Concentration variance of bile acids through HPA axis affects Gut Brain axis and varies its ability to respond to physiological and psychological stress.
BBB is a semi permeable membrane protecting brain from viruses, bacteria or drugs. Cells within and on either side of the blood-brain barrier are in constant communication about which molecules to let through and when. When the blood-brain barrier breaks down, as is the case in some brain cancers and brain infections or when tiny ruptures to blood vessels occur, some substances that are normally kept out of the brain gain entry and cause problems for the brain. A leaky blood-brain barrier allows too many white blood cells into the brains of people with multiple sclerosis (MS).
Why colon supports the largest number of bacteria?
Ans. The small intestine is followed by the large intestine (colon), which has a larger diameter, but shorter length and is divided into four sections: the ascending colon (cecum), transverse colon, descending colon, and sigmoid colon (123). Water and minerals are continuously absorbed along the colon before excretion. Furthermore, complex foods that cannot be digested by the host are used as growth substrates for the colonic microbiota. Bacteria in the colon account for approximately 70% of all bacteria in the human body because it is the main site for the bacterial fermentation of non-digestible food components such as soluble fiber. Also the food remains for 10 to 12hours in the large intestine thereby giving more contact time.
Human gut microbes perform many metabolic functions that our own bodies cannot carry out, creating a symbiotic relationship. For example, we consume plant polysaccharides that are rich in xylan-, pectin- and arabinose-containing carbohydrate structures, which we are unable to digest. Encoded in the genomes of gut microbiota, however, are a large number of glycoside hydrolases, which break down these plant products and convert them into usable energy sources. At the same time, gut bacteria derive their own energy from fermentation of these glycans.
In addition, microbiota are able to synthesize vitamins and amino acids, degrade dietary oxalates, metabolize host-produced mucosal glycans, and biotransform bile acids.
LACTOBACILLUS RHAMNOSUS PROBIOTIC Lactobacillus rhamnosus probiotic affect in weight reduction,apetite control and eating behaviour in a group of obese men and women.In a group of obese women the consumption of this microorganism provide beneficial effects on mood and behaviour linked to dietary intake ,compared to group of men and those who received placebo. (19MMB028)
Yakult is full of organisms as well as sugars, so why can’t those organisms use present sugar in yakult.... During the process of yakult formation, initially organism is allowed to ferment the milk to form fermented milk base and then it is added to sugar syrup. So, like initially growth is promoted upto it's maximum possible limit and then treatment with high sugar concentration will lead to prevent further growth due to osmolarity, and they might be balancing the sugar concentration upto the limit that organism can survive and no further division is possible to keep cell in viable state.
QUESTION: WHAT ARE THE POSITIVE AND NEGATIVE EFFECTS OF ZINC FOOD ON HUMAN HEALTH? AND WHAT ARE THE GOOD EXAMPLES OF VEGETARIAN AND NON-VEGETARIAN ZINC RICH DIETS?
ANSWER: Zinc is Mostly found in cells throughout the body. It is needed for the body's immune system to properly work. It plays a role in cell division, cell growth, wound healing, and the breakdown of carbohydrates. Zinc is also needed for the senses of smell and taste these are the positive sites.
Negative sites: Immediate symptoms after uptake of toxic amounts of zinc include abdominal pain, nausea, and vomiting. Additional effects include lethargy, anemia, and dizziness.
Good sources of zinc for vegetarians include whole grains, tofu, tempeh, legumes, nuts and seeds, fortified breakfast cereals and dairy products.
For those who consume non-vegetarian food, fish would be an excellent source of zinc. Consume at least twice a week is very effective. Meat and poultry can also be an option. Eggs are also good source of zinc.
This is all about sources and effects of zinc food on human health.
Ans:- whole grains,nuts,seeds(like Flax Seeds,pumpkin seeds,sunflower seeds),cereals , dairy products(like milk and cheese), vegetables and fruits (like banana,potato,avocado ,green peas)they all contain very small amount of zinc but they'll help sneak a small amount into diet.
The term ”phytopharmaceutical” is derived from blend of two words, phyto (referring to plant) and pharmaceutical (refers to medicinal drugs). Plants produce a variety of natural compounds. Herbal crude drugs are processed into herbal extracts which keads to enrichment of bioactive compounds. Phytopharmaceutical drug is defined as purified and standardized fraction with defined minimum four bio-active or phytochemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation, or prevention of any disease or disorder. These are available in dry froms as granules, tablets, capsules etc. Also, medicinal oils can be used from plants or flowers to make ointments.
Nutraceuticals are products, which other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Nutraceuticals may be used to improve health, delay the aging process, prevent chronic diseases, increase life expectancy, or support the structure or function of the body. These are nutritional, safe and show therapeutic effects. Nutraceuticals are nutritional supplements which are also used for health purposes other than nutrition.
QUESTION: What is the meaning of Selective toxicity????? ANSWER: Selective toxicity refers to the power of the drug to targets sites that are relative specific to the microorganism liable for infection. Sometimes these sites are unique to the microorganism or just more essential to survival of the microorganism than to the host.
A newly discovered carbomycine and lesser known complestain kill bacteria by blocking the function of cell wall. Antibiotic like penicilin kill bacteria by preventing the building of cell wall but above two antibiotics work by doing opposite.They prevent wall from being broken down .This is critical for cell to devide.And cell duvision izs very important for cell to grow .And these antibiotics prevent cell division. These antibiotics comesfrom glycopeptide antibiotics which are produced by soil microbes .And it can block infection of drug resistant staphylococcus aureus. (19 MMB 028)
■ Zn containing diet for vegetarian and non vegetarian people. • VEGETARIAN DIET -For a vegetarian,the best option would be to include a handful nuts in daily diet.these can be trail mix of walnuts, almonds, cashews and other fruits & nuts -Seeds,especially sunflower seeds, pumpkin seeds, watermelon seeds. -Legumes -Whole grains -Dairy product (dark chocolate contain reasonable amount of Zn) •NON VEGETARIAN DIET -Meat is excellent source of Zn especially red meat. (beef, lamb, pork) -Shellfish -low calorie source of Zn. -Eggs containing moderate amount of Zn.
■ Zn containing diet for vegetarian and non vegetarian people. • VEGETARIAN DIET -For a vegetarian,the best option would be to include a handful nuts in daily diet.these can be trail mix of walnuts, almonds, cashews and other fruits & nuts -Seeds,especially sunflower seeds, pumpkin seeds, watermelon seeds. -Legumes -Whole grains -Dairy product (dark chocolate contain reasonable amount of Zn) •NON VEGETARIAN DIET -Meat is excellent source of Zn especially red meat. (beef, lamb, pork) -Shellfish -low calorie source of Zn. -Eggs containing moderate amount of Zn.
Q:- Importance of tryptophan in human microbiome? A:- Tryptophan is an essential amino acid which is not synthesized by human body. Therefor it must be provided through regular diet sources which are rich in tryptophan. It is found in two forms in human body. 1) Bounded to albumin 2) free form The transportation of tryptophan across blood - brain - barrier only of free form of tryptophan through nonspecific transporter of amino acids. The recommended amount of tryptophan in human body is 250 - 425 mg/d/adult but through diet individual gets higher concentration of tryptophan that ranges from 850 - 1000 mg/d. Sources of tryptophan. Vegeterian diet - banana, milk, oats,peanuts. Non-vegetarian diet -fish, chicken, chocolate. It is used in protein synthesis. Mainly for serotonin which is 95% synthesized in GI tract. Tryptophan which is consumed through diet out of that approximately 3% used for synthesis of serotonin in GI tract and 1% used for synthesis for serotonin in brain which acts as neurotransmitter and neuromodulator. The enterochromaffin cells of the mucosa are the major source of serotonin in GI tract which use tryptophan. Serotonin is mainly responsible for controlling GI motility and secretion in the gut and play an important role in mood and cognition in the brain.
Chitosan is a sugar that is obtained from the hard outer skeleton of shellfish, including crab, lobster, and shrimp. It is used for medicine.
Chitosan is used to treat obesity, high cholesterol, and Crohn's disease. It is also used to treat complications that kidney failure patients on dialysis often face, including high cholesterol, “tired blood” (anemia), loss of strength and appetite, and trouble sleeping (insomnia).
Some people apply chitosan directly to their gums to treat inflammation that can lead to tooth loss (periodontitis), or chew gum that contains chitosan to prevent “cavities” (dental caries).
Warfarin is a blood thinner. There is some concern that taking chitosan might increase the blood thinning effects of warfarin (Coumadin). Taking chitosan with warfarin (Coumadin) could increase the chance of bruising or bleeding. If you take warfarin, avoid taking chitosan.
Q:- Importance of QUERCETI A:- Quercetin is a plant pigment which is antioxident flavonoid specifically a flavonol. It is found in most of the plant based products. It observed in most of the fruits and vegetables. It highly observed in apple honey, raspberries, onions, red grapes, cherries. It is foun in green leafy vegetables also. It is common compound in citrus fruits. Specifically it is present in onion in abundance amount according to type of onion and also type of compound.
Pan-assay interference compounds (PAINS) cause false-positive assay signals due to reactivity under assay conditions, including covalent modifications or redox effects, chelation, autofluorescence, or degradation.(1-3) More than 450 compound classes have been designated as PAINS to date, including, for example, rhodanines, isothiazolones, enones, and quinonesas well as pharmaceutically intensely explored compounds such as curcuminoids. Classified PAINS are typically small reactive or otherwise liable molecules that are contained as substructures in larger compounds.
Common PAINS include toxoflavin, isothiazolones, hydroxyphenyl hydrazones, curcumin, phenol-sulfonamides, rhodanines, enones, quinones, and catechols.
Basically, functional foods are foods that provide a health benefit in addition to macro and micronutrients. These foods are vital in disease prevention and include fortified foods, phytonutrient-containing fruits and vegetables, fermented foods, fish and chocolate.
Fortified foods are considered functional, as they have vitamins and minerals added to them in order to prevent diseases. Vitamin D is added to milk, as it helps with calcium absorption, which is vital in the prevention of rickets and osteoporosis. Flour and cereals in the U.S. are fortified with folic acid, a B vitamin that is essential in the prevention of neural tube defects in infants. Some types of salt contain iodine, which prevents intellectual and developmental disabilities as well as enlarged thyroid glands. Many of these foods are the result of public health initiatives to prevent many diseases in populations that do not consume a nutrient-dense diet.
Functional foods may include:
Conventional foods such as grains, fruits, vegetables and nuts. Modified foods such as yogurt, cereals and orange juice.
Consider eating more of these nutrient-dense, functional foods.
1. Cold-Water Fish — Sardines and Salmon
These protein-packed fish are lower in mercury and have higher amounts of omega-3 fatty acids, which may help lower risk of heart disease and improve infant health when consumed by women during pregnancy or while breast-feeding. About eight ounces of seafood a week is a good goal for adults, which amounts to two meals per week.
2. Nuts
They make a great snack, help you feel full and may help promote heart health. Bonus: most unsalted nuts, including cashews and almonds, are good sources of magnesium, which plays a role in managing blood pressure.
3. Whole Grains — Barley
Often overshadowed by the fame of oatmeal, barley delivers similar benefits. It's high in dietary fiber, an underconsumed nutrient of public health concern in the U.S., and may help lower cholesterol and assist with blood sugar control.
4. Beans
Beans provide dietary fiber, as well as protein, potassium and folate. While canned beans are fine, look for those with no salt added. If you do choose beans with salt added, rinse and drain them before use, which reduces sodium significantly. Berries Whether you opt for strawberries, cranberries, blueberries, raspberries or blackberries, berries in general are wonderful functional foods. Not only are they low in calories, their anthocyanin pigments, which give them color, may offer health promoting benefits. If you can't get fresh berries, frozen unsweetened berries make a fine alternative.
1. Phytopharmaceuticals = Globally, herbal medicine has been considered an important alternative to modern allopathic medicine. Phytopharmaceuticals are herbal medicines whose efficacy is down to one or several plant substances or active ingredients. Phytopharmaceutical drug is defined as purified and standardized fraction with defined minimum four bio-active or phytochemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation, or prevention of any disease or disorder but does not include administration by parenteral route.
2. Nutraceuticals = Nutraceutic is a term derived from “nutrition” and “pharmaceutics.” The term is applied to products that are isolated from herbal products, dietary supplements (nutrients), specific diets, and processed foods such as cereals, soups, and beverages that other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Emphasis has been made to present herbal nutraceuticals effective on hard curative disorders related to oxidative stress including allergy, Alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory and Parkinson's diseases as well as obesity.
3. Functional foods = Literally, it is another term of Nutraceuticals and Functional foods are foods that have a potentially positive effect on health beyond basic nutrition. Proponents of functional foods say they promote optimal health and help reduce the risk of disease.
Generally, Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good food sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products
There was a strong correlation between Zn serum levels and meat and milk consumption in a Greek population, while no significant association was found with the consumption of fish, green vegetables, legumes, eggs or fruits, because it is well known that Zn bioavailability is decreased by high levels of dietary phytate, which is present in vegetables, cereals and legumes. The Mediterranean diet is characterized by a high content of these types of foods, which increases phytate consumption and, therefore, might affect dietary Zn bioavailability. Also Certain components of the diet, such as fibre, Ca, P, Fe and Cu, have been considered to decrease Zn bioavailability. Another factor to be considered as influencing Zn absorption is the dietary content of Maillard reaction products (MRP). These compounds are formed in heat processes such as frying, a common culinary technique in the Mediterranean diet, and, thus, they are usually present in this diet. Animal balance studies have shown that feeding rats with diets containing the MRP model induces significant reductions in Zn absorption and retention (both net and fractional), compared with animals fed control diets. Therefore, the presence of MRP in the experimental diet may have been a negative factor for dietary Zn utilization.
An ANTIBIOTIC is a low molecular substance produced by a microorganism that at a low concentration inhibits or kills other microorganisms. An ANTIMICROBIAL is any substance of natural, semisynthetic or synthetic origin that kills or inhibits the growth of microorganisms but causes little or no damage to the host.
The name quercetin (3,3',4',5,7-pentahydroxyflavone) comes from the Latin word “Quercetum”, belongs to the class called flavonols that cannot be produced in the human body.It is yellow color and is poorly soluble in hot water, quite soluble in alcohol and lipids and is insoluble in cold water. Quercetin is said to be one of the most widely used bioflavonoids for the treatment of metabolic and inflammatory disorders.The highest concentrations of flavonols were found in vegetables such as onions and broccoli, fruits such as apples, cherries, and berries, and drinks such as tea and red wine.
Pharmacological Importance of Quercetin
Anti-inflammatory One of the core most remarkable properties of quercetin is its ability to modulate inflammation. Quercetin inhibits inflammatory enzymes cyclooxygenase (COX) and lipooxygenase thereby decreasing inflammatory mediators such as prostaglandins and leukotrienes.Elevated C-reactive protein (CRP) levels are associated with numerous disease states such as obesity, heart disease, and lupus. It has been identified through the study that intake of certain foods can lower the levels of the inflammatory risk factor (CRP). In preclinical in vitro studies, quercetin showed a significant reduction in the levels of inflammatory mediators such as NO synthase, COX-2, and CRP in human hepatocyte-derived cell line.
Cardiovascular disease prevention Flavonoids existing over many years such as quercetin possess a wide spectrum of biological activities which may have a positive influence on cardiovascular diseases.Quercetin inhibits the platelet aggregation and improves the health of the endothelium. In addition to that, it also protects against CHD and reduces the risk of mortality caused by low-density lipoprotein (LDL). It is known to exhibit important vasorelaxant properties on isolated arteries which helps to lower blood pressure and prevents the development of cardiac hypertrophy.
Neurodegenerative disorders Flavonoids exert multiple beneficial effects on Neurodegenerative diseases such as Alzheimer's and Parkinson's disease.Quercetin along with with ascorbic acid reduces the incidence of oxidative damage to human lymphocytes and neurovascular structures in the skin and inhibits damage to neurons. It is known to protect brain cells against the oxidative stress, which damages tissue leading to Alzheimer and other neurological conditions.
Ulcer and gastritis The studies have shown that quercetin inhibits gastric acid secretion and lipid peroxidation of gastric cells thereby serves as gastroprotective agents.
Question: classes of antibiotics Ans:Classes of antibiotics include the following:
Aminoglycosides Carbapenems Cephalosporins Fluoroquinolones Glycopeptides and lipoglycopeptides (such as vancomycin) Macrolides (such as erythromycin and azithromycin) Monobactams (aztreonam) Oxazolidinones (such as linezolid and tedizolid) Penicillins Polypeptides Rifamycins Sulfonamides Streptogramins (such as quinupristin and dalfopristin) Tetracyclines Carbapenems, cephalosporins, monobactams, and penicillins are subclasses of beta-lactam antibiotics, a class of antibiotic characterized by a chemical structure called a beta-lactam ring.
Other antibiotics that do not fit into the classes listed above include chloramphenicol, clindamycin, daptomycin, fosfomycin, lefamulin, metronidazole, mupirocin, nitrofurantoin, and tigecycline.
What is Augmentin (amoxicillin and clavulanic acid)?
Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance. The formulation of amoxicillin and clavulanic acid in AUGMENTIN protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics. Thus, AUGMENTIN possesses the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
The majority of riboswitches are regulatory RNAs that regulate gene expression by binding small-molecule metabolites. The discovery of an aminoglycoside-binding riboswitch that is widely distributed among antibiotic-resistant bacterial pathogens. This riboswitch is present in the leader RNA of the resistance genes that encode the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes that confer resistance to aminoglycoside antibiotics through modification of the drugs. The expression of the AAC and AAD resistance genes is regulated by aminoglycoside binding to a secondary structure in their 5′ leader RNA. Reporter gene expression, direct measurements of drug RNA binding, chemical probing, and UV crosslinking combined with mutational analysis demonstrate that the leader RNA functions as an aminoglycoside-sensing riboswitch in which drug binding to the leader RNA leads to the induction of aminoglycosides antibiotic resistance.
SIDEROPHORES : Siderophores are small and high-affinity iron chelating compounds which are secreted by bacteria and fungi and serve primarily to transport iron across cell membrane. Siderophores are among the strongest soluble Fe3+ binding agents known. Siderophores are usually classified by the ligands used to chelate the ferric iron. The major groups of siderophores include the catecholates, hydroxamates and carboxylates. Citric acid can also act as a siderophore.
Once in the cytoplasm of the cell Fe3+-siderophore complex is usually reduced to Fe2+ to release the iron especially in the case of "weaker" siderophore ligands such as hydroxamates and carboxylates. Siderophore decomposition or other biological mechanisms can also release iron.
Siderophores are useful as drugs in facilitating iron mobilization in humans, especially in the treatment of iron diseases, due to their high affinity for iron. One potentially powerful application is to use the iron transport abilities of siderophores to carry drugs into cells by preparation of conjugates between siderophores and antimicrobial agents. Because microbes recognize and utilize only certain siderophores, such conjugates are anticipated to have selective antimicrobial activity.
SIDEROPHORES : Siderophores are small and high-affinity iron chelating compounds which are secreted by bacteria and fungi and serve primarily to transport iron across cell membrane. Siderophores are among the strongest soluble Fe3+ binding agents known. Siderophores are usually classified by the ligands used to chelate the ferric iron. The major groups of siderophores include the catecholates, hydroxamates and carboxylates. Citric acid can also act as a siderophore.
Once in the cytoplasm of the cell Fe3+-siderophore complex is usually reduced to Fe2+ to release the iron especially in the case of "weaker" siderophore ligands such as hydroxamates and carboxylates. Siderophore decomposition or other biological mechanisms can also release iron.
Siderophores are useful as drugs in facilitating iron mobilization in humans, especially in the treatment of iron diseases, due to their high affinity for iron. One potentially powerful application is to use the iron transport abilities of siderophores to carry drugs into cells by preparation of conjugates between siderophores and antimicrobial agents. Because microbes recognize and utilize only certain siderophores, such conjugates are anticipated to have selective antimicrobial activity.
RIBOSWITCHES ans :- Riboswitches are RNA elements that undergo a shift in structure in response to binding of a regulatory molecule. These elements are encoded within the transcript they regulate, and act in cis to control expression of the coding sequence(s) within that transcript; their function is therefore distinct from that of small regulatory RNAs (sRNAs) that act in trans to regulate the activity of other RNA transcripts. Riboswitch RNAs control a broad range of genes in bacterial species, including those involved in metabolism or uptake of amino acids, cofactors, nucleotides, and metal ions. Regulation occurs as a consequence of direct binding of an effector molecule, or through sensing of a physical parameter such as temperature.
Riboswitches as potential antimicrobial drug targets
The ability of the riboswitches to precisely discriminate between different cognate molecules as well as their common existence in bacteria makes them a promising target for antibacterial drug therapy. From a medical point of view this issue is crucial because of a continuously progressing problem of bacterial resistance against regular antibiotics. The potential application of riboswitches as novel antimicrobial drug targets has several important advantages over classic antibiotics. First, they demonstrate potentially lower toxicity due to the fact that riboswitches are not found in higher eukaryotes, including human. Additionally, a lot of them are controlled by small compounds, simple metabolites, easy to deliver into the system, but also to manufacture and modify. The possibility of developing the resistance by bacteria against the antibiotics targeted at riboswitches seems to be more restricted than in the case of commercial drugs. The presence of a single type of riboswitches in multiple bacterial genes makes a single mutation insufficient to neutralize antimicrobial effect.
Augmentin is a well-established and widely-used antibacterial combination product consisting of the semi-synthetic antibiotic amoxicillin (as amoxicillin trihydrate) and the beta-lactamase inhibitor clavulanic acid (as the potassium salt). Amoxicillin/clavulanic acid was originally developed in response to the need for an oral broad-spectrum antibiotic that covered β-lactamase-producing pathogens. Amoxicillin works by inhibiting the transpeptidase enzyme responsible for cross-linking peptidoglycan in the bacterial cell wall, weakening, the cell wall and making the cell swell and rupture. Because amoxicillin is readily hydrolysed by beta lactamase, Augmentin also contains the beta lactamase inhibitor, clavulanic acid, which protects amoxicillin from degradation and extends its antibacterial spectrum to many bacteria normally resistant to penicillins and cephalosporins. A wide range of different presentations of Augmentin with an increasing ratio of amoxicillin to clavulanic acid are approved for oral (2:1, 4:1, 7:1, 8:1, 14:1and16:1) and parenteral (5:1 and 10:1) use in adults and children.
The more common side effects of Augmentin include: diarrhea nausea skin rash vaginitis (caused by problems such as yeast infection) vomiting
Serious side effects : Allergic reaction Liver problem Rash Fatigue Intestinal infection Yeast infection
QUESTION:What is combination therapy? Therapy that combines more than one method of treatment. Also called multimodality therapy and multimodality treatment. Typically, the term refers to using multiple therapies to treat a single disease, and often all the therapies are pharmaceutical (although it can also involve non-medical therapy, such as the combination of medications and talk therapy to treat depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where available, dosage forms that contain more than one active ingredient (such as fixed-dose combinations).
Polypharmacy is a related term, referring to the use of multiple medications (without regard to whether they are for the same or separate conditions/diseases). Sometimes "polymedicine" is used to refer to pharmaceutical combination therapy. Most of these kinds of terms lack a universally consistent definition, so caution and clarification are often advisable.
Combination therapy might achieve efficacy with lower doses or less toxic drugs. It is important to investigate the impacts of drugs beyond what they can achieve alone. Using them in combination can act as a multiplier and increase the sum of their benefits.
Cancer drugs are most effective when given in combination. The rationale for combination therapy is to use drugs that work by different mechanisms, thereby decreasing the likelihood that resistant cancer cells will develop. When drugs with different effects are combined, each drug can be used at its optimal dose, without intolerable side effects
QUESTION:What is Resveratrol? Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Resveratrol is a phytoalexin, a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation. Plants that synthesize resveratrol include knotweeds, pine trees including Scots pine and Eastern white pine, grape vines, peanut plants, cocoa bushes, and Vaccinium shrubs that produce berries, including blueberries, raspberries, mulberries, cranberries, and bilberries. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, and peanuts. Resveratrol is produced in plants by the action of the enzyme, resveratrol synthase, also known as stilbene synthase. Its immediate precursor is a tetraketide derived from malonyl CoA and 4-coumaroyl CoA. The latter is derived from phenylalanine. Although commonly used as a dietary supplement and studied in laboratory models of human diseases, there is no high-quality evidence that resveratrol improves lifespan or has a substantial effect on any human disease.
QUESTION: What is Augmentin? How does it work? And what are the uses of it????? ANSWER: Augmentin contains amoxicillin and clavulanic acid. Amoxicillin is an antibiotic of the penicillin type. It is effective against some bacteria such as H. influenzae, N. gonorrhea, E.coli, Pneumococci, Streptococci, and certain strains of Staphylococci. Chemically, it is closely related to penicillin and ampicillin. Amoxicillin stops bacteria from multiplying by preventing bacteria from forming the walls that surround them. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Bacteria cannot survive without a cell wall. Clavulanic acid enhances the effectiveness of amoxicillin against bacteria that are ordinarily resistant to amoxicillin alone. Augmentin is effective against susceptible bacteria causing infections of the middle ear (otitis media), tonsillitis, throat infections (pharyngitis), laryngitis, bronchitis, sinusitis, and pneumonia. It is also used in treating urinary tract infections, and skin infections. these is all about uses and function of augmentin.
QUESTION:What is immunomodulator? As the name implies, immunomodulators modify the activity of the immune system, in turn, decreasing the inflammatory response. Immunomodulators are most often used in organ transplantation to prevent rejection of the new organ as well as in autoimmune diseases such as rheumatoid arthritis. Since the late 1960s, they have also been used to treat people with IBD, where the normal regulation of the immune system is affected. Immunomodulators are a group of drugs that mainly target the pathways that treat multiple myeloma and a few other cancers. They have many ways to work, including working on the immune system directly by turning down some proteins and turning up others.
Immunomodulators, by themselves or with another agent, may be appropriate in the following treatment situations: Nonresponse or intolerance to aminosalicylates, antibiotics, or corticosteroids, Steroid-dependent disease or frequent need for steroids, Perianal (around the anus) disease that does not respond to antibiotics, Fistulas (abnormal channels between two loops of intestine, or between the intestine and another structure—such as the skin), To bolster or optimize the effect of a biologic drug and prevent the development of resistance to biologic drugs, To prevent recurrence after surgery.
Thalidomide, lenalidomide, and pomalidomide Thalidomide (Thalomid), lenalidomide (Revlimid), and pomalidomide (Pomalyst) are known as immunomodulating drugs (or IMiDs). These drugs can cause side effects such as drowsiness, fatigue, constipation, low blood cell counts, and neuropathy (painful nerve damage). There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). These tend to be more likely with thalidomide than with the other drugs. These drugs can also cause severe birth defects if taken during pregnancy.
Bacillus Calmette-Guérin Bacillus Calmette-Guérin (BCG) is a germ that doesn’t cause serious disease in humans, but it does infect human tissues and helps activate the immune system. This makes BCG useful as a form of cancer immunotherapy. BCG was one of the earliest immunotherapies used against cancer and is still being used today. BCG is used to treat early stage bladder cancer. It is a liquid put into the bladder through a catheter. BCG attracts the body’s immune system cells to the bladder, where they can attack the bladder cancer cells. Treatment with BCG can cause symptoms that are like having the flu, such as fever, chills, and fatigue. It can also cause a burning feeling in the bladder. BCG can also be used to treat some melanoma skin cancers by injecting it directly into the tumors. It's also used as a vaccine against tuberculosis.
Imiquimod Imiquimod is a drug that is applied to the skin as a cream. It stimulates a local immune response against skin cancer cells. It is used to treat some very early stage skin cancers (or pre-cancers), especially if they are in sensitive areas such as on the face. The cream is applied anywhere from once a day to twice a week for several months. Some people have serious skin reactions to this drug.
ANSWER: Iron is an important micronutrient for microbial life. At the beginning of an infection the host environment will normally restrict available iron, and innate immune responses will aim to further reduce iron, thus inhibiting growth of potential pathogens.
Successful pathogens have developed a spread of mechanisms to accumulate iron from the available in vivo sources, using remote and direct capture, to render their environment iron replete. Iron restriction, and therefore the presence of host iron sources like haem, are important drivers of gene regulation controlling the expression of various virulence factors. As an infection progresses the changing iron environment will therefore influence pathogen organic phenomenon and trigger new activities.
How bacteria acquire iron, and the way iron acquisition affects the bacteria, has identified vaccine and antibiotic targets and is now suggesting novel approaches to regulate and treat infection.
QUESTION: What is serum resistance? Serum contains more than thirty proteins of the complement system, a crucial component of the host innate immune response which can also initiate the adaptive response. Deposition of complement factors on the bacterial surface activates the complement cascade and results in the formation of the membrane attack complex (MAC). This complex forms trans-membrane pores in the membranes of susceptible bacteria, thus leading to bacterial death.
Serum resistance is a trait associated with strains that cause bacteraemia. In general, E. coli isolated from blood are more serum-resistant than strains that cause urinary tract infections or strains isolated from faecal samples. Septic shock and death are also more associated with serum-resistant rather than serum-susceptible bacteraemia isolates. Multiple virulence factors of E. coli have been shown to be involved in serum survival. Serum resistance is a major virulence factor of gram-negative bacteria, and K-1 polysaccharide has been shown to contribute to serum resistance in selected strains.
How Escherichia coli evades serum killing? The ability to survive the bactericidal action of serum is advantageous to extraintestinal pathogenic Escherichia coli that gain access to the bloodstream. Evasion of the innate defences present in serum, including complement and antimicrobial peptides, involves multiple factors. Serum resistance mechanisms utilized by E. coli include the production of protective extracellular polysaccharide capsules and expression of factors that inhibit or interfere with the complement cascade. Recent studies have also highlighted the importance of structural integrity of the cell envelope in serum survival.
Leying H, Suerbaum S, Kroll HP, Stahl D, Opferkuch W. The capsular polysaccharide is a major determinant of serum resistance in K-1-positive blood culture isolates of Escherichia coli. Infect Immun. 1990;58(1):222-227. doi:10.1128/IAI.58.1.222-227.1990
QUESTION:Which antibiotics are recently discovered? Corbomycin
The newly-found corbomycin and the lesser-known complestatin have a never-before-seen way to kill bacteria, which is achieved by blocking the function of the bacterial cell wall. The discovery comes from a family of antibiotics called glycopeptides that are produced by soil bacteria.
Teixobactin
Teixobactin is a peptide-like secondary metabolite of some species of bacteria, that kills some gram-positive bacteria. It appears to belong to a new class of antibiotics, and harms bacteria by binding to lipid II and lipid III, important precursor molecules for forming the cell wall. Teixobactin was discovered using a new method of culturing bacteria in soil, which allowed researchers to grow a previously unculturable bacterium now named Eleftheria terrae, which produces the antibiotic. Teixobactin was shown to kill Staphylococcus aureus and Mycobacterium tuberculosis. In January 2015, a collaboration of four institutes in the US and Germany together with two pharmaceutical companies, reported that they had isolated and characterized a new antibiotic, killing "without detectable resistance. Teixobactin was discovered by screening previously unculturable bacteria present in a sample of soil from "a grassy field in Maine, using the isolation chip (iChip).
Halicin
In a paper published in the journal, Cell, MIT researchers took a step in this direction. The team says their machine learning algorithm discovered a powerful new antibiotic. The antibiotic, halicin, successfully wiped out dozens of bacterial strains, including some of the most dangerous drug-resistant bacteria on the World Health Organization’s most wanted list. In a monthlong experiment, E. coli bacteria also failed to develop resistance to halicin, in stark contrast to existing antibiotic ciprofloxacin. The algorithm that discovered halicin was trained on the molecular features of 2,500 compounds. Nearly half were FDA-approved drugs, and another 800 naturally occurring. The researchers specifically tuned the algorithm to look for molecules with antibiotic properties but whose structures would differ from existing antibiotics (as halicin’s does). Using another machine learning program, they screened the results for those likely to be safe for humans. Early study suggests halicin attacks the bacteria’s cell membranes, disrupting their ability to produce energy. Protecting the cell membrane from halicin might take more than one or two genetic mutations, which could account for its impressive ability to prevent resistance.
QUESTION: How Quorum sensing occur in gram-positive bacteria? Gram-positive systems typically use secreted oligopeptides and two-component systems, which consist of membrane-bound sensor kinase receptors and cytoplasmic transcription factors that direct alterations in gene expression. A number of gram-positive bacteria are known to employ quorum-sensing systems. The nature of the signal molecules used in these systems differs from those of gram-negative organisms, and thus far, no gram-positive bacteria have been shown to produce AHLs. Gram-positive quorum-sensing systems typically make use of small posttranslationally processed peptide signal molecules. These peptide signals interact with the sensor element of a histidine kinase two-component signal transduction system. Quorum sensing is used to regulate the development of bacterial competence in Bacillus subtilis and Streptococcus pneumoniae, conjugation inEnterococcus faecalis, and virulence in Staphylococcus aureus. S. aureus causes a wide range of disease states that range from mild to life-threatening. The virulence of this organism is dependent on the temporal expression of a diverse array of virulence factors, including both cell-associated products, such as protein A, collagen- and fibronectin-binding protein, and secreted products including lipases, proteases, alpha-toxin, toxin-1, beta-hemolysin, and enterotoxin. During the early stages of S. aureusinfection, surface proteins involved in attachment (collagen- and fibronectin-binding protein) and defense (protein A) predominate. However, once a high cell density is achieved at the infection site, expression of S. aureus surface proteins is decreased and secreted proteins are preferentially expressed. The genetic basis for this temporal gene expression depends on two pleiotropic regulatory loci called agr (accessory gene regulator) and sar (staphylococcal accessory gene regulator).
QUESTION: How Quorum sensing occur in gram-negative bacteria? Four common features are found in nearly all known Gram-negative quorum sensing systems. First, the autoinducers in such systems are acyl-homoserine lactones (AHLs) or other molecules that are synthesized from S-adenosylmethionine (SAM), and they are able to diffuse freely through the bacterial membrane. Second, autoinducers are bound by specific receptors that reside either in the inner membrane or in the cytoplasm. Third, quorum sensing typically alters dozens to hundreds of genes that underpin various biological processes. Fourth, in a process called autoinduction, autoinducer-driven activation of quorum sensing stimulates the increased synthesis of the autoinducer, which establishes a feed-forward loop that is proposed to promote synchronous gene expression in the population. The vast majority of gram-negative quorum-sensing systems that have been studied thus far utilize N-acyl homoserine lactones (AHL) as signaling molecules. When in high enough concentration, these molecules can bind to and activate a transcriptional activator, or R protein, which in turn induces expression of target genes. The use of biosensors to screen spent culture supernatants has led to the discovery that AHLs are produced by a plethora of unrelated bacteria. Biosensors typically consist of a quorum-sensing-controlled promoter fused to a reporter such aslacZ or the lux operon. These biosensor strains contain a functional R protein but lack the AHL synthase enzyme; therefore, promoter activity depends on the presence of exogenous AHL. Despite the fact that R proteins are exquisitely sensitive to their cognate AHLs, some infidelity does exist and this infidelity enables R proteins to be responsive to a range of AHL molecules, albeit higher concentrations of noncognate AHL are usually required for activation. To date, AHL molecules have been identified containing 4- to 14-carbon acyl side chains and either an oxo, a hydroxy, or no substitution at the third carbon. Only two AHLs bearing double bonds have been identified: 7,8-cis-N-(3-hydroxytetradecenoyl)homoserine lactone from Rhizobium leguminosarum and 7,8-cis-N-(tetradecenoyl)homoserine lactone fromRhodobacter sphaerhoides.
What are the role of AHLs molecules in quorum sensing of Gram negative bacteria and how quorum sensing inhibit by inhibitors?
AHLs are the most common class of autoinducers and are present in approximately 10% of proteobacteria isolated from various ecological niche. AHL signaling molecules possess a homoserine lactone (HSL) moiety, acyl side chains with 4–18 carbons. Three AHL synthase families have been identified so far, and these include the LuxI (see review34), HdtS, and LuxM families. Among the three the LuxI family is the best studied as the LuxI protein in the lux operon in V. fischeri was the first AHL synthase to be identified . LuxI homologs have been described in a large number of Gram-negative bacteria and LuxR proteins combine with AHLs to control target gene expression. This system is the most prevalent QS regulatory system in gram-negative bacteria. LuxR is a cell-density dependent transcription regulator. When the densities reach a particular threshold value, AHL accumulation triggers the corresponding receptors. Binding to AHL stabilizes LuxR allowing the receptor to fold properly, bind DNA and activate transcription of the target genes . The AHL-LuxR protein complexes not only act as co-activators for the promoter sites of the QS responsive operons in a bacterial cell, they also act as positive regulators for the AHL synthesis itself.
QUORUM SENSING INHIBITORS(QSIs) can be used as novel class of antimicrobial drugs. QSIs reduce the activity of the AHL. there many strategies for the Development of QSIs. 1. Inactivation or complete degradation of the AHL signal molecules can be achieved by either of these methods:chemical degradation, enzymatic destruction or metabolism of the AHL molecules. 2. Use an Analogue: Analogues of AHL signal molecules have been designed to block the receptor. These analogues have been designed either by modifications in the acyl side chain or in the lactone ring or in both these moieties of the AHL molecule. 3. Quorum quenching enzymes: AHL lactonase- AHL-lactonases hydrolyse the lactone ring of AHL. And there are many other strategies use for this. also some antibiotic also use as Quorum sensing inhibitiors like Macrolide, ceftazidime, ciprofloxacin and azithromycin have shown strong QSI activity in P. aeruginosa .
What are the role of AIP molecules in quorum sensing of Gram Positive bacteria?
The signaling in gram positive bacteria are controlled by Oligopeptide which is commonly referred as autoinducer peptides [AIPs]. AIPs are produced inside the bacterial cell as pro-AIP which will be processed and modified inside or outside the cell hinge upon the organism [66]. Unlike AHL signaling molecule AIP’s are impermeable to cell membrane hence requires specialized transport proteins for the inward and outward carriage of AIP’s. This transport of AIP’s are generally accomplished by cell membrane bound sensor kinase. Most of the gram positive bacterial linguistics are depending upon membrane bound two component system that identify signaling molecule autoinducer peptides. A classic example for two component quorum sensing system is found in Staphylococcus aureus. Virulence and communication of this bacteria is regulated by Arg locus which is a combination of two transcripts RNA II and RNA III. Extracellular protease processed AIP quorum sensing circuit: In some gram positive bacteria processing of pro AIP is done in the external environment of bacterial cell by extracellular protease enzymes after which AIP will be transported back to cell for regulating transcription.
What are Mammalian Siderophores and what is their role in human body? Mammalian Siderophores are compounds that solubilizes iron and keeps it accessible for transport and systemic utilization. The serum protein transferrin (also called serotransferrin) creates a bacteriostatic environment by sequestering free iron which facilitates the release and internalization of complexed iron following interaction with specific receptors on erythroid cells, lymphocytes, and macrophages. The analogous lactoferrin is widely expressed in secretory fluids (milk, saliva, and tears). Its affinity for iron is 300-times higher than that of transferrin and increases further in acidic conditions. This promotes transfer of iron from transferrin to lactoferrin during inflammation, when the local pH is decreased by accumulation of organic acids. Lactoferrin possesses intrinsic antimicrobial activity owing to both its binding to lipopolysaccharide and its catalyzing formation of peroxides with concomitant reduction of ferric iron, which together increase membrane permeability and trigger lysis. Lactoferrin competes with bacterial siderophores.
What is Clavulanic acid? How it is used with combination of antibiotics?
Clavulanic acid is a naturally occurring β-lactam isolated from Streptomyces clavuligerus and later from other Streptomyces species. It has little antibacterial activity on its own but displays potent inhibitory properties on β- lactamases. It is a β-lactamase inhibitor used together with β-lactam antibiotics to overcome β-lactam resistance. Amoxycillin/clavulanic acid is a combination of two drugs which interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Amoxycillin/clavulanic acid covers skin, enteric flora, and anaerobes. Emergence of resistance to clavulanic acid has not been reported as a clinical problem in bacteria isolated from animals. However, a variety of resistance mechanisms have emerged in human bacterial isolates.
Recently found antibiotics:- Antivirals against COVID-19, drugs are found, which are 1. Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity – it is not approved anywhere globally for any use. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses and are structurally similar to COVID-19. The limited preclinical data on remdesivir in MERS and SARS indicate that remdesivir may have potential activity against COVID-19. Remdesivir is an experimental medicine that does not have established safety or efficacy for the treatment of any condition.
Also
2. Favipiravir is a pyrazinecarboxamide derivative with activity against RNA viruses. Favipiravir is converted to the ribofuranosyltriphosphate derivative by host enzymes and selectively inhibits the influenza viral RNA-dependent RNA polymerase. Favipiravir is a member of pyrazines and a primary carboxamide. Discovered by Toyama Chemical Co., Ltd. in Japan, favipiravir is a modified pyrazine analog that was initially approved for therapeutic use in resistant cases of influenza. The antiviral targets RNA-dependent RNA polymerase (RdRp) enzymes, which are necessary for the transcription and replication of viral genomes. Not only does favipiravir inhibit replication of influenza A and B, but the drug has shown promise in the treatment of avian influenza, and may be an alternative option for influenza strains that are resistant to neuramidase inhibitors. Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19.
Siderophores are small molecules that are produced and secreted by micro-organisms in order to mediate the uptake of essential iron(III) into the cell. The role of these compounds is to obtain iron from the environment and create a soluble complex that is needed to make it available to microbial cells. Siderophores formed by bacteria contribute to their pathogenicity since bacteria require iron for their growth and metabolism and remove it from the host organism during infection. They play an important role as growth-promoting factors in unculturable microorganisms.
INHIBITING SIDEROPHORE PRODUCTION AS AN ANTIMICROBIAL STRATEGY:
One viable mechanism for the development of novel antimicrobial agents is targeting bacterial pathways responsible for acquisition of essential nutrients. Iron serves as an important cofactor for a variety of enzymes that perform crucial reactions, including roles in electron transfer, resistance to reactive oxygen intermediates, and RNA synthesis. Fe(III) is very insoluble and biologically inaccessible such that the concentration of free ferric iron available to pathogens in the human host ranges in estimation from 10−15 to 10−24 M, whereas a typical pathogenic bacterium requires ~1 μM iron for optimal growth. In response, bacterial pathogens have developed siderophore. If inhibition of the biosynthesis of siderophores that are crucial for bacterial survival under iron-limited conditions represents another promising approach. Depriving pathogenic bacteria from iron is another potential antimicrobial strategy.
THERAPEUTIC POTENTIAL OF SIDEROPHORES:
In medicine, siderophores can be used to create complexes with antibiotics, thereby increasing the strength of their attack on bacteria resistant to antibiotics. Medical applications of siderophores include antimalarial activity and treatment of sickle cell anemia.
Q:- PATHOBLOCKERS A:- The rapid development of antimicrobial resistance is threatening mankind to such extent that the WHO expects that there will be more deaths due to drug resistant microbial infections compare to cancer.
To avoid this problem researchers are trying new chemicals and developing new class of antimicrobial that helps to reduce this effect or future condition.
Targeting bacterial virulence as a means of blocking pathogenicity is a new strategy for reduce the pathogenic infection.
This drug resistance prevents efficient treatment of infected patients and surrounding environment of that patient and hospital. Pathogens virulence is the prime determinant for the deterioration of an infected patient's health. This is new approach for development of drug over last decade. Pubmed. Gov database yields 292 references on this approach as of 06/08/2018 with exponential increase over the years.
The traditional thinking of antibiotic that kill or impair the pathogen viability rather than that this pathoblocker concept is not to kill the pathogen but it will disarms the pathogen as keep in live form so that host can itself clear the pathogen from body. This have two benefits 1st - less harm to host cell 2nd - unable the host to clear the microbe from it's system .
Second approach is stop the addhesion of pathogen to host cell. Bacterial adhesion to the host's surface is 1st step of infection. This helps to formation of boifilm for some infectious microbes that is formed by carbohydrate -binding- proteins called lectins. Which recognize glycoconjugates on the host cell or surface. To maintain this adhesion process through carbohydrate binding protein glycomimetics used as pathoblocker to inhibit this adhesion process develop new area of active research in this last decade.
Q:- What is ESKAPE in context of drug resistance? A:- E- Enterococcus faecium S- Staphylococcus aureus K- Klebsiella pneumonia A- Actinobacter baumanii P- Pseudomonas aeruginosa E- Enterobacter species
These are the bacteria strains that are mostly common in all hospitals and also most problematic once in the hospital environment. They are leads to secondary infection in patients due to this they are so called ESKAPE.
Combinatorial chemistry is a laboratory technique in which millions of molecular constructions can be synthesized and tested for biological activity. It has generated massive numbers of targeted molecules for testing and the developing techniques of high throughput screening has automated the screening process so larger numbers of biological assays can be done. All this together has reduced the discovery-to-market time from what used to be 10-14 years to 5-8 years. It involves the generation of a large array of structurally diverse compounds, called a chemical library, through systematic, repetitive and covalent linkage of various “building blocks”. Once prepared, the compounds in the chemical library can be screened, concurrently, for individual interactions with biological targets of interest.
ADVANTAGES (1) The creation of large libraries of molecules in a short time is the main advantage of combinatorial chemistry over traditional. (2)Compounds that cannot be synthesized using traditional methods of medicinal chemistry can be synthesized using combinatorial techniques. (3) Thecost of combinatorial chemistry library generation and analysis of said library is very high, but when considered on a per compound basis the price is significantly lower when compared to the cost of individual synthesis. (4) More opportunities to generate lead compounds. (5)Combinatorial chemistry speeds up drug discovery.
DISADVANTAGES While a large number of compounds are created, the libraries created are often not focused enough to generate a sufficient number of hits during an assay for biological activity. There is a great deal of diversity created, but not often a central synthetic idea in the libraries. One can argue that there should be a focus on the type of molecule developed in order to maximize hits.
1. It should be non-toxic, biocompatible, biodegradable and physiochemical stable in-vivo and in-vitro and should have no side effects. 2. Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution. 3. Controllable and predict the rate of drug release. 4. Drug release should not affect drug action. 5. There should be a therapeutic amount of drug release. 6. Minimal drug leakage during transit. 7. Carriers used must be Biodegradable or readily eliminated from the body without any problem and no carrier induced modulation of a diseased state. 8. The preparation of the delivery system should be easy or reasonably simple reproductive and cost-effective. 9. The drug should be easily eliminated from the body by simple metabolic processes after its action. 10. The drug should not get accumulated in any of the tissues or cells of the body causing inflammation.
In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery. This method became popular after the sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins. This method is the most widely used in drug discovery today. Differently than the classical (forward) pharmacology, with the reverse pharmacology approach in vivo efficacy of identified active (lead) compounds is usually performed in the final drug discovery stages.
Mainly screening is categorized into three named Simple screening, Blind screening and Programmed screening. In simple screening when one or two tests are used to find substances having a particular property, the screening is simple there is no need for battery of tests in which the interpretation of results of one test may depend on those of another test. In blind screening, if a new series of chemical substances available, either through isolation from a natural source or through synthesis, there may be no information on its pharmacological activity. Then blind screening ought to provide clues to potential activity, at least, and preferably, to indicate fields of activity, if they exist. In addition, the blind screening ought to show pharmacological inertness if it exists. The chief purposes of the screening are to demonstrate whether the new group of substances is worthy of further attention, and to indicate which among them have the most interesting pharmacological properties.
Blind screening, the technique for detecting pharmacological activity in a group of substances without pharmacological history, requires considerable planning and skillful execution of the test, in order to be economical of time and money. The strategy of few tests, having simple procedures, to be applied to cheap animals, requires a knowledge of the tests that are known, as well as ingenuity in their combination.
In blind testing, some orientation is sought. By contrast in programmed testing, the screening has aspects beyond orientation. The program may include the use of quantitative assay for immediate study of the most interesting compounds found through a similar semi quantitative assay, or for comparison with drugs recognized to be quite active representatives of other pharmacological class. The program should provide also indications of potential side effects, and it should lead readily into a project for investigating the detailed pharmacology of the most promising substances.
Q:- Polyherbalism A:- Ayurveda is one of the traditional medicinal system of Indians. This involves the use of natural elements to treat the disease fron root cause by restoring balance and also helps to maintain healthy lifestyle to prevent recurrence of imbalance.
Natural medicines also used in ancient Chinese, Greek, Egyptian, and Indian culture for various therapies purpose. Who estimated that 80% of the world's inhabitants still rely mainly on traditional medicines. Based on ayurvedic medicine materials they are divided in three major types. Herbal Mineral Animal Among this the herbal medicines gained great importance for formulation of herbals and cure disease. This herbal plants shows that they are used as drugs for medicines development. The species of plant which have medicinal importance they are classified, characterized and from the plants extracta main effective compounds are purified. But some time it is observed that the pure compounds are not effective compare to crude extract. It is observed that this happens may be due to lack of some supporting material or the backbone of that compound that is released out during purification. So some time this type of compounds are given in the crude extracts without disturbing the composition of that medicinal plant against particular disease. For medicinal purposes various plants have various effects with different body parts like Leaves, flower, seeds, roots, barks, stems, and some naturally producing extracts which secreted out of the body by plants. This complex composition helps to treat disease and cure from root of disease. Various body parts of plants used as medicine. Eg- Root - garlic and ginger Use - Antibiotic Cardiovascular diseases Antioxident.
Stem - Alovera Use - skin infection Skin ailments
Leaves - Neem Use - malaria Rheumatism Skin infection
Flower - Bitter orange Use - nausea Ingestion Constipation
Seeds - Asfoetida Use - cholesterol Breathing problem
Root bark - water ash Use - digestive tract.
This are some planta which are herbal and easily avilable surround us and easy to grow compare to the medicinal plants which are avilable only in some particular area of the earth or in forest.
Q:- Different forms of herbal medicines. A:- Kwatha - decoction Pantha - hot infussion Hima - cold infussion Arka - liquid extract Churna - powder Guggul - resins and balsams Taila - medicated oils.
These are the various forms of herbal medicines. Some of them are given in pure form ( upto 90-95% but not 100% )and some of them are in crude source so that the medicinal importance remains as it is and helps to cure diseases and set up of healthy lifestyle without side-effects.
QUESTION: WHAT IS COMBINATORIAL CHEMISTRY AND WHAT ARE THE APPLICATIONS OF IT????? ANSWER: Combinatorial Chemistry is a new method developed by academics and researchers to reduce the time and cost of producing effective, marketable and competitive new drugs. • Combinatorial chemistry is based on the principle of making a large number of chemical compounds rapidly on a small scale in small reaction cells. This practice is widely adopted by the pharmaceutical sector for use during the drug designing and screening stages. • Scientists use Combinatorial Chemistry to create large numbers of molecules that can be detected efficiently. • This technique is very useful in many areas such as Pharmaceutical chemistry, Biotechnology and Agro chemistry. • Combinatorial chemistry is a technique by which large numbers of different but structurally similar molecules are produced rapidly and submitted for pharmacological assay. • This technique uses the same reaction conditions with the same reaction vessels to produce a large range of analogues. • Technique invented in the late 1980s and early 1990s to enable tasks to be applied to many molecules simultaneously.
Applications: 1)Applications of combinatorial chemistry are very wide Scientists use combinatorial chemistry to create large populations of molecules that can be screened efficiently. 2)By producing larger, more diverse compound libraries, companies increase the probability that they will find novel compounds of significant therapeutic and commercial value. 3)Provides a stimulus for robot-controlled and immobilization strategies that allow high-throughput and multiple parallel approaches to drug discovery.
What is ADMET Profile ? For what purpose is it generated?
ADMET stands for Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET), play key roles in drug discovery and development. A high-quality drug candidate should not only have sufficient efficacy against the therapeutic target, but also show appropriate ADMET properties at a therapeutic dose. The prediction of the ADMET properties plays an important role in the drug design process because these properties account for the failure of about 60% of all drugs in the clinical phases. Where traditionally ADME tools were applied at the end of the drug development pipeline, nowadays ADME is applied at an early phase of the drug development process, in order to remove molecules with poor ADME properties from the drug development pipeline and leads to significant savings in research and development costs.
QUE :VRAS ANS : The acronym, VRSA, stands for vancomycin-resistant Staphylococcus aureus. VRSA can cause an illness from skin infections to severe invasive disease which can result in pneumonia and/or septicemia (bacteria gets in the blood) or even death.
QUE: VRE ANS: Vancomycin-resistant enterococci (VRE) are a type of bacteria called enterococci that have developed resistance to many antibiotics, especially vancomycin. Enterococci bacteria live in our intestines and on our skin, usually without causing problems.
Que.)What is Plasma Medicine? Ans.)Plasma medicine emerged in the last decade as an exciting new field of research at the interface between physics and the life sciences. Physical plasma can be generated by adding energy (heat or electromagnetic fields) to a neutral gas until the ionized gaseous substance becomes increasingly electrically conductive. Plasmas emit electromagnetic radiation, predominately UV radiation and visible light, and contain excited gas molecules, positively and negatively charged ions, free electrons, neutral reactive oxygen/nitrogen species (ROS/RNS), free radicals, and molecule fragments Due to its distinct characteristics compared to ordinary neutral gases, plasma is considered as a fourth state of matter (besides solid, fluid, and gaseous). In modern medicine, high-temperature plasmas are used, e.g., for sterilization of medical devices and implants. Cold atmospheric pressure plasmas (CAP), however, can also be used for the treatment of viable tissues and thus have become a focus of medical research over the past years. Besides therapeutic applications, CAP is also used for surface modification and biological decontamination.
[Concept of Bioavailability enhancers] >>The concept of bioavailability enhancers is derived from the traditional age old system of Ayurveda (science of life). In Ayurveda, black pepper, long pepper and ginger are collectively known as “Trikatu”. In sanskrit “Trikatu” means three acrids. The action of bioenhancers was first documented by Bose (1929) who described the action of long pepper to Adhatoda vasika leaves increased the antiasthamatic properties of Adhatoda vasika leaves.
[Definition and history of bioavailability enhancers] >>The term ‘bioavailability enhancer’ was first coined by Indian scientists at the Regional Research Laboratory, Jammu (RRL, now known as Indian Institute of Integrative Medicine, Jammu), who discovered and scientifically validated piperine as the world’s first bioavailability enhancer in 1979.
>>Bioavailability enhancers are drug facilitators, they are the molecules which by themselves do not show typical drug activity but when used in combination they enhance the activity of drug molecule in several ways including increasing bioavailability of the drug across the membrane, potentiating the drug molecule by conformational interaction, acting as receptors for drug molecule and making target cells more receptive to drugs. A ‘bioenhancer’ is an agent capable of enhancing bioavailability and bioefficacy of a particular drug with which it is combined, without any typical pharmacological activity of its own at the dose used. These are also termed as ‘absorption enhancers’ which are functional excipients included in formulations to improve the absorption of a pharmacologically active drug.
Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Synergistic therapeutic effects may complicate the dosing of long-term medications.When there are any interactions between herbals and drugs occur that can be caused by either pharmaco-kinetic or pharmacodynamic mechanisms. Pharmacokinetic interactions: When an herbal changes the absorption, distribution, metabolism, protein binding, or excretion of a drug that results in altered levels of the drug or its metabolites that is called pharmacokinetic interactions. Pharmaco-dynamic interactions are related to the pharmacologic activity of the interacting agents and can affect organ systems, receptor sites, or enzymes. For e.g. Ginger is used to treat motion sickness, nausea, arthritis. If used with anticoagulants, then can inhibit thromboxane synthetase; may have additive anticoagulant, antiplatelet effects.
Postantibiotic effect(PAE's) (PAE) is the term used to describe suppression of bacterial growth that persists after brief exposure of organisms to antimicrobials. PAE's can vary by drugs and micro-organism. For e.g. macrolides are known for time-dependent kill characteristics, but have a strong post-antibiotic effect which probably inhibits bacterial growth rather than causing cell lysis.
Pathogenecity islands... Pathogenicity islands (PAIs) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species. These mobile genetic elements may range from 10-200 kb and encode genes which contribute to the virulence of the respective pathogen. Typical examples are adherence factors, toxins, iron uptake systems, invasion factors, and secretion systems. Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or tRNA genes, which act as sites for recombination into the DNA. Cryptic mobility genes may also be present, indicating the provenance as transduction. One species of bacteria may have more than one PAI (i.e. Salmonella has at least 5). They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon. Pathogenicity islands carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. They may be located on a bacterial chromosome or may be transferred within a plasmid. The GC-content of pathogenicity islands often differs from that of the rest of the genome, potentially aiding in their detection within a given DNA sequence.They carry functional genes, such as integrases, transposases, or part of insertion sequences, to enable insertion into host DNA. PAIs are often associated with tRNA genes, which target sites for this integration event. They can be transferred as a single unit to new bacterial cells, thus conferring virulence to formerly benign strains.
Ans: This is the persistence of antibiotic effect observed long after the serum concentration has fallen below the MIC. It is seen in antibiotics which inhibit some life-sustaining enzyme, or which bind tightly to cell wall components.
The post-antibiotic effect has some relationship to the kill characteristics of the antibiotic, but the relationship is not straightforward. For instance, macrolides are known for time-dependent kill characteristics, but have a strong post-antibiotic effect which probably inhibits bacterial growth rather than causing cell lysis.
Strong post-antibiotic effect This is mainly seen in drugs which have concentration-dependent kill characteristics.
Aminoglycosides Clindamycin Macrolide antibiotics Tetracyclines Rifampicin Quinupristin/dalfopristin (probably the longest post-antibiotic effect) Such drugs benefit from large intermittent doses; high peak concentrations translate into better post-antibiotic effects.
Moderate post-antibiotic effect This is seen in drugs which have time-dependent kill characteristics
Carbapenems Fluoroquinolones Glycopeptides Linezolid Weak or absent post-antibiotic effect This is usually a feature of drugs which act at some critical point in the bacterial reproductive cycle.
The drug must therefore be present in the over-MIC concentration at that critical point.
Codon usage bias refers to the fact that different organisms have differences in the frequency of occurrence of synonymous codons in their coding DNA, meaning that some codons are rarely used while other codons are frequently used in a particular organism. Differences in codon usage bias may be helpful in identifying genes that have been acquired by horizontal gene transfer.
This technique helps to detect dna differences between the different genomes or between cell types where deletion or genomic rearrangenent took place. PCR based amplification of cDNA or genomic DNA is carried out that differ between control and test strain. Then hybridization is carried out so that dsDNA between control and test DNA of similar abundance can be eliminated and only region of DNA that is different and differentially expressed will b retained. E.g. when a report was generated for isolation and characterization of Shigella species, it was found that they are closely related to non pathogenic E.coli. So after genomic subtraction of similar genome content, a large region of around 42 kb was found to be localized in S. flexneri chromosome and it contained elements with PAI such as IS, bacteriophage genes and Shigella virulence genes.
Question: Efflux pump work on which mechanism??? Answer: Efflux pump are work on the mechanism of competitive inhibition. where the efflux pumps recognize antibiotic as a substrate instead of the target antibiotics (quinolones mainly ciprofloxacin and levofloxacin) and as long as the pumps expel these inhibitors outside the cells, the antibiotic remains intracellular and increasing in concentration.
What is active efflux? Active efflux is a common resistance mechanism in a wide range of bacterial pathogens. It is responsible for the transport of such toxic compounds as drugs, toxins, and detergents. such as BmrR from Bacillus subtilis, or by the global bacterial regulatory system.
Spanish flu The “Spanish” influenza pandemic of 1918–19 caused acute illness in 25–30 percent of the world’s population and resulted in the death of up to an estimated 40 million people. The predominant natural reservoir of influenza viruses is thought to be wild waterfowl.genetic material from avian virus strains is transferred to virus strains infectious to humans by a process called reassortment. Human influenza virus strains with recently acquired avian surface and internal protein-encoding RNA segments were responsible for the pandemic influenza outbreaks in 1957 and 1968. reassortment involving genes encoding surface proteins appears to be a critical event for the production of a pandemic virus, a significant amount of data exists to suggest that influenza viruses must also acquire specific adaptations to spread and replicate efficiently in the new host.Once a new virus strain has acquired the changes that allow it to spread in humans, virulence is affected by the presence of novel surface protein(s) that allow the virus to infect an immunologically naïve population. The degree of illness caused by a particular virus strain, or virulence, is complex and involves host factors like immune status, and viral factors like host adaptation, transmissibility, tissue tropism, or viral replication efficiency.The 1968 pandemic followed with the emergence of a virus strain in which the H2 subtype HA gene was exchanged with an avian-derived H3 HA RNA segment.
Historical Background: Outbreaks of the disease not only swept North America and Europe, but also spread as far as the Alaskan wilderness and the most remote islands of the Pacific.. It has been estimated that one-third of the world’s population (500 million people) may have been clinically infected during the pandemic.The “first wave” or “spring wave” of the 1918 pandemic seemingly arose in the United States in March 1918.The main wave of the global pandemic, the “fall wave” or “second wave,” occurred in September–November 1918.It has been estimated that the influenza epidemic of 1918 killed 675,000 Americans, including 43,000 servicemen mobilized for World War I.persons less than 65 years old accounted for more than 99 percent of all excess influenza-related deaths in 1918–19 .Since the first human and swine influenza A viruses were not isolated until the early 1930. (19mmb028)
The basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible. For e.g. if R0 for COVID-19 is 100 in a population then it can be expected each new case will produce 100 new secondary cases. The basic reproductive number is affected by several factors:
1. The rate of contacts in the host population. 2. The probability of infection being transmitted during contact. 3. The duration of infectiousness.
Amyloid fibers :- formed normally by soluble proteins, which assemble to form insoluble fibers which wil then be resistant to degradation. Their formation leads to diseases which are specifically caused by these fibrils and looking to characteristics, each disease is characterized by a specific protein or peptide that aggregates. Eg = Alzheimer's disease; those fibrils are deposited extracellularly in the tissues and are thought to be responsible for having pathogenic efffect.
Peptidomimetics :-Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect as original molecule. They are designed to find the way out of some of the problems associated with a natural peptide: e.g. stability against proteolysis (duration of activity) and poor bioavailability, etc.
The basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible. For e.g. if R0 for COVID-19 is 100 in a population then it can be expected each new case will produce 100 new secondary cases. (19mmb015)
Remdesivir: Remdesivir (GS-5734) an inhibiu of the viral RNA dependent, RNA polymerase with in vitro inhibitory activity against SARS-CoV-1 and the Middle East respiratory syndrome (MERS-CoV) was identified early as a promising therapeutic candidate for covid-19 because of its ability to inhibit SARS-CoV-2 invitro. In addition in non-humans primate, remdesivir initiate 12 houra after inoculation with MERS-CoV reduced lung virus levels and lung damage.
D-dimer :- D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross-link. A normal D-Dimer is considered less than 0.50. D-dimer levels were higher in COVID-19 patients and were related with markers of inflammation, and after treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis.
What is Reproduction number? -> It is denoted by R and is about how Infectious a disease is. Ro represents the number when no Immunity has been generated from the vaccination. R represents number when immunity generated. R is the mean number of Infections generated during Infectious period of a single infective. We cannot determine the Rate of transmission through R.
Various Therapeutic options of Covid-19. -> Oxygen therapy & ECMO( Extracorporeal Membrane Oxygenation) -> Treatment with convalescent(Person recovered from that disease) plasma & IgG. -> Antiviral treatments: Neuraminidase Inhibitors like Zanamivir, Peramivir, Acyclovir, Remedesivir, Lopinavir. -> Chloroquine, was used as Repurposing drug that means it is actually a drug for Malaria but used as multi purpose drug. -> DRACO that targets viral dsRNA that can induce Apoptosis of the cells having virus. -> Furin as an Antiviral agent as it cleaves the S protein of virus. -> Combinational therapy that is use of Antiviral agents and DRACO might enhance the recovery of patients. -> Recombinant Interferon.
Why do we feel cold while having fever? -When we have fever there are some chemicals produced in our body that causes brain to reset the body’s internal Thermostat at a higher temperature. The new ‘normal’ requires our body to feel cold even if the temperature is high. The high body temperature helps in fighting infection by enhancing white blood cells production and lowering bacterial reproduction rate.
Prepatent Period :- Period between infection with a parasite and the production of eggs by a female; equivalent to the incubation period of microbial infections, but biologically different because the parasite is going through developmental stages in the host.
Incubation period :- The period between exposure to an infection and the appearance of the first symptoms.
Prodormal period :- An early symptom that signals the onset of an illness or disease; a symptom or series of symptoms that precedes the more obvious, diagnosable symptoms that develop along with the condition.
Sequestration Stage :- Sequestration is the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules during malarial infections.
What is Paroxysm ? The classic symptom of malaria is paroxysm, which means cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae; in short at very obvious time interval, and is same at every typical interval of time.
Although vaccination is above all an act of individual prevention, in the case of directly transmissible diseases the vaccination of individuals may contribute indirect protection through the group immunity effect known as collective or herd immunity. The effect is due to the reduced or absent contagiousness of immunized subjects and the reduced likelihood of encounters between contagious and receptive subjects when immunized subjects are numerous. For many diseases, a vaccination coverage of 80% is sufficient to prevent epidemics. Vaccines may be classified as strictly egoistic, strictly altruistic, or simultaneously egoistic and altruistic. Rabies vaccine, which offers 100% protection if administered in time, is an example of a strictly egoistic vaccine that offers no collective benefit. German measles vaccine is strictly altruistic, since it prevents a condition that is dangerous only during fetal development. Vaccines that are both altruistic and egoistic are numerous. Measles, diphtheria, and hepatitis vaccines are examples.
Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.
Poecilia reticulata is the name of fish which is also known as rainbow fish or Guppy. It is most widely distributed tropical fish found on almost every continent except Antarctica. It feeds on mosquito larvae and helps to slow down malaria.
Gembusia also known as mosquitofish which is feed on malaria larvae and has been used more than any other fishes for the biological control of mosquitoes.
Scientific name of mosquitofish : Gambusia affinis.
There are two principal fishes which eat the mosquito larvae and thereby control the spread of Malaria. These are Guppies and Gambusia. Both these fishes are exotic and have been introduced in India from Brazil. The fish Gambusia which is around 3 inches in size voraciously eat the mosquito larvae.
Anopheles species causing malaria:- Anopheles culicifacies s.l. = Rural Malaria (65%) An. fluviatilis s.l. = Plains and foothills (15%) An. minimus breeds = Streams of foothills An. dirus s.l. = Jungle of North-eastern states An. sundaicus = Andaman and Nicobar islands and in brackish water An. stephensi = urban malaria
Larvivorous fish for malarial parasites:- Larvivorous fishes Poecilia reticulata (Guppy), a native of South America and Gambusia affinis (Gambusia), a native of Texas were imported in India in 1908 and 1928, respectively for the control of malaria vectors. Soon after that use of larvivorous fish became a common practice in India.
QUESTION:What are the virulence factors of Pseudomas aeruginosa? Among the pathogenicity caused by virulence factors, can be cited Lipopolysaccharide, Flagellum, Type IV Pili, Type III Secretion System, Exotoxin A, Proteases, Alginate, Quorum Sensing, Biofilm Formation, Type VI Secretion Systems, Oxidant Generation in the Airspace. REFERENCES: Rocha, A. J., Barsottini, M. R. De O., Rocha, R. R., Laurindo, M. V., Moraes, F. L. L. De, & Rocha, S. L. Da. (2019). Pseudomonas Aeruginosa: Virulence Factors and Antibiotic Resistance Genes. Brazilian Archives of Biology and Technology, 62. Doi:10.1590/1678-4324-2019180503
QUESTION:What are the virulence factors of Staphylococcus aureus? It is well known that S. Aureus produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The expression of these factors is tightly regulated during growth. The agr system, known as the quorum-sensing system, is known to play a central role in the regulation of virulence factors. Besides agr, many factors, including other tcss (arl and sae) and transcriptional regulators (the sar family, rot, and mgr), have been demonstrated to be involved in the expression of virulence factors.
REFERENCES: Oogai Y, Matsuo M, Hashimoto M, Kato F, Sugai M, Komatsuzawa H. Expression of virulence factors by Staphylococcus aureus grown in serum. Appl Environ Microbiol. 2011;77(22):8097-8105. Doi:10.1128/AEM.05316-11
QUESTION:What is herb-drug interaction? An herb might increases or decreases the effects of co administered drugs. Consequences can be beneficial, undesirable or harmful effects. Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component.
Mechanism of herbal-drug interactions: When there are any interactions between herbals and drugs occur that can be caused by either pharmaco-kinetic or pharmacodynamic mechanisms.
Pharmacokinetic interactions: When an herbal changes the absorption, distribution, metabolism, protein binding, or excretion of a drug that results in altered levels of the drug or its metabolites that is called pharmacokinetic interactions. Most of the current evidence of pharmacokinetic drug interactions involves metabolizing enzymes and drug transporters.
Example: Aloevera commonly use as Strong cathartic, may interact with Cardiac glycosides, Thiazide diuretics which has potential effect like Can cause electrolyte imbalance and hypokalemia; May potentiate drug toxicity.
Bearberry commonly use as antibacterial, astringent, diuretic, may interact with Urinary acidifiers, Cranberry juice which has potential effect like Inactivated by urinary acidifiers; active compound released only in alkaline urine.
REFERENCES: Pasi AK: Herb-Drug Interaction: An Overview. Int J Pharm Sci Res 2013: 4(10); 3770-3774. Doi: 10.13040/IJPSR. 0975-8232.4(10).3770-74.
QUESTION:What is its region? The internal transcribed spacers (ITS1 and ITS2) regions of the ribosomal RNA gene cluster are the most commonly used nuclear markers for estimating species relationships across many eukaryotic groups including most plant families. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. Internal Transcribed Spacer of nuclear ribosomal RNA and its application in phylogenetic analysis.
REFERENCES: Edger, P. P., Tang, M., Bird, K. A., Mayfield, D. R., Conant, G., Mummenhoff, K. Pires, J. C. (2014). Secondary Structure Analyses of the Nuclear rRNA Internal Transcribed Spacers and Assessment of Its Phylogenetic Utility across the Brassicaceae (Mustards). Plos ONE, 9(7), e101341. Doi:10.1371/journal.pone.0101341
Sarah L. Boyer, Valerie R. Flechtner, Jeffrey R. Johansen, Is the 16S–23S rRNA Internal Transcribed Spacer Region a Good Tool for Use in Molecular Systematics and Population Genetics? A Case Study in Cyanobacteria, Molecular Biology and Evolution, Volume 18, Issue 6, June 2001, Pages 1057-1069, https://doi.org/10.1093/oxfordjournals.molbev.a003877
QUESTION:What is Lysogenic conversion? The ability of some phages to survive in a bacterium as a result of the integration of their DNA into the host chromosome. The integrated DNA is termed a prophage. A regulator gene produces a repressor protein that suppresses the lytic activity of the phage, but various environmental factors, such as ultraviolet irradiation may prevent synthesis of the repressor, leading to normal phage development and lysis of the bacterium. This phenomenon known as Lysogenic conversion. The best example of this is bacteriophage lambda.
QUESTION:What is significance of tcp and ct virulence factor of vibrio cholerae? Acquisition of certain genes encoding virulence factors has enabled certain strains of V. Cholerae to colonize the human intestine and cause disease. The most important of these virulence factors are cholera toxin (CT), which is encoded within the genome of the filamentous bacteriophage ctxφ and thus horizontally transferred, and the intestinal colonization factor toxin-coregulated pilus (TCP). The toxin-coregulated pilus (TCP) of Vibrio cholerae is required for intestinal colonization and cholera toxin acquisition.
REFERENCES: Reguera G, Kolter R. Virulence and the environment: a novel role for Vibrio cholerae toxin-coregulated pili in biofilm formation on chitin. J Bacteriol. 2005;187(10):3551-3555. Doi:10.1128/JB.187.10.3551-3555.2005
QUESTION:What is Pathogenicity islands? Pathogenicity islands (pais) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species. These mobile genetic elements may range from 10-200 kb and encode genes which contribute to the virulence of the respective pathogen. Typical examples are adherence factors, toxins, iron uptake systems, invasion factors, and secretion systems. Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or trna genes, which act as sites for recombination into the DNA. Cryptic mobility genes may also be present, indicating the provenance as transduction. One species of bacteria may have more than one PAI (i.e. Salmonella has at least 5). They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon.
Pathogenicity islands carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. They may be located on a bacterial chromosome or may be transferred within a plasmid. The GC-content of pathogenicity islands often differs from that of the rest of the genome, potentially aiding in their detection within a given DNA sequence. Pais are flanked by direct repeats; the sequence of bases at two ends of the inserted sequence is the same. They carry functional genes, such as integrases, transposases, or part of insertion sequences, to enable insertion into host DNA. Pais are often associated with trna genes, which target sites for this integration event. They can be transferred as a single unit to new bacterial cells, thus conferring virulence to formerly benign strains.
REFERENCES: Schmidt H, Hensel M. Pathogenicity islands in bacterial pathogenesis [published correction appears in Clin Microbiol Rev. 2006 Jan;19(1):257]. Clin Microbiol Rev. 2004;17(1):14-56. Doi:10.1128/cmr.17.1.14-56.2004
QUESTION:What is acute disease? The duration of the period of illness can vary greatly, depending on the pathogen, effectiveness of the immune response in the host, and any medical treatment received. For an acute disease, pathologic changes occur over a relatively short time (e.g., hours, days, or a few weeks) and involve a rapid onset of disease conditions. For example, influenza (caused by Influenzavirus) is considered an acute disease because the incubation period is approximately 1–2 days. Infected individuals can spread influenza to others for approximately 5 days after becoming ill. After approximately 1 week, individuals enter the period of decline.
QUESTION:What is chronic disease? Chronic disease, pathologic changes can occur over longer time spans (e.g., months, years, or a lifetime). For example, chronic gastritis (inflammation of the lining of the stomach) is caused by the gram-negative bacterium Helicobacter pylori. H. Pylori is able to colonize the stomach and persist in its highly acidic environment by producing the enzyme urease, which modifies the local acidity, allowing the bacteria to survive indefinitely. Consequently, H. Pylori infections can recur indefinitely unless the infection is cleared using antibiotics. Hepatitis B virus can cause a chronic infection in some patients who do not eliminate the virus after the acute illness. A chronic infection with hepatitis B virus is characterized by the continued production of infectious virus for 6 months or longer after the acute infection, as measured by the presence of viral antigen in blood samples.
QUESTION:What is latent diseases? In latent diseases, as opposed to chronic infections, the causal pathogen goes dormant for extended periods of time with no active replication. Examples of diseases that go into a latent state after the acute infection include herpes (herpes simplex viruses [HSV-1 and HSV-2]), chickenpox (varicella-zoster virus [VZV]), and mononucleosis (Epstein-Barr virus [EBV]). HSV-1, HSV-2, and VZV evade the host immune system by residing in a latent form within cells of the nervous system for long periods of time, but they can reactivate to become active infections during times of stress and immunosuppression. For example, an initial infection by VZV may result in a case of childhood chickenpox, followed by a long period of latency. The virus may reactivate decades later, causing episodes of shingles in adulthood. EBV goes into latency in B cells of the immune system and possibly epithelial cells; it can reactivate years later to produce B-cell lymphoma.
QUESTION: How does a microbe like P. Aeruginosa make a decision regarding causing acute versus chronic disease? In response to uncharacterized signals, bacteria either initiate an acute infection utilizing factors like TTSS and various toxins or establish a chronic, biofilm-like infection. The route of entry for the infection may impact whether an acute or chronic infection might be initiated. P. Aeruginosa appears to be in a biofilm-like mode of growth when growing in the CF lung. This growth strategy could be a result of the particular environmental signals and/or host factors encountered in the lungs of patients afflicted with this disease. Other factors, such as immune status of the host, tissue integrity, or patient nutrition, might also impact whether microbes initiate an acute versus a chronic infection.
REFERENCES: Furukawa S, Kuchma SL, O'Toole GA. Keeping their options open: acute versus persistent infections. J Bacteriol. 2006;188(4):1211-1217. Doi:10.1128/JB.188.4.1211-1217.2006
QUESTION: What is Coevolution? Coevolution between organisms and their pathogenic agents means that reciprocal and adaptive genetic modifications have occurred in them because of their interaction as biological systems that have shared space and resources over prolonged time periods. Coevolution is a general concept that applies not only to host-parasite relationships but also to other interacting biological species that have shaped biological systems up to the present epoch. Coevolution involves at least three steps: first one species evolves a response to a trait of a second species, and this is followed by a response of the second species to the first. Co-evolution of certain hosts and pathogens for millions of years has resulted in a fine-tuned equilibrium that enables survival of both.
REFERENCES: Interaction of virus populations with their hosts, Esteban domingo.
QUESTION: What is subtractive hybridization? Comparison of DNA from virulent strains of bacterial pathogens with DNA from less virulent or avirulent close relatives allows the identification of those genomic regions that are present only in virulent strains. Such regions are often associated with pathogenicity islands (pis) and their characterisation can lead to a greater understanding of the pathogenesis of infectious diseases. There is now a large database of bacterial genomic sequences that provides useful reference information with which to compare the genomes of strains that exhibit variations in virulence or host preferences. Subtractive hybridisation (SH) is technique designed to identify those regions present in one genome but absent from another. The application of these techniques has led to the identification of pis, mobile genetic elements and variations in virulence gene expression in a range of bacterial pathogens. Subtractive hybridization compares the genes expressed at different stages of a biological/pathological process allowing identification of the all the genes upregulated during the process.
REFERENCES: Winstanley, Craig. (2002). Spot the difference: Applications of subtractive hybridisation to the study of bacterial pathogens. Journal of medical microbiology. 51. 459-67. 10.1099/0022-1317-51-6-459.
Byers RJ, Hoyland JA, Dixon J, Freemont AJ. Subtractive hybridization--genetic takeaways and the search for meaning. Int J Exp Pathol. 2000;81(6):391-404. Doi:10.1046/j.1365-2613.2000.00174.x
QUESTION: What is reproduction number? The basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible.1 For example, if the R0 for measles in a population is 15, then we would expect each new case of measles to produce 15 new secondary cases (assuming everyone around the case was susceptible). R0 excludes new cases produced by the secondary cases.
The basic reproductive number is affected by several factors: The rate of contacts in the host population, the probability of infection being transmitted during contact, the duration of infectiousness.
QUESTION: What is Drug repurposing? Drug repurposing (also called drug repositioning, reprofiling or re-tasking) is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication1. This strategy offers various advantages over developing an entirely new drug for a given indication.
There are usually three kinds of approaches: computational approaches, biological experimental approaches, and mixed approaches, all of which are widely used in drug repositioning.
REFERENCES: Pushpakom, S., Iorio, F., Eyers, P. Et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18, 41–58 (2019). https://doi.org/10.1038/nrd.2018.168
Xue H, Li J, Xie H, Wang Y. Review of Drug Repositioning Approaches and Resources. Int J Biol Sci. 2018;14(10):1232-1244. Published 2018 Jul 13. Doi:10.7150/ijbs.24612
QUESTION: What is DRACO virus treatment? Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsrna, rapidly killing infected cells without harming uninfected cells. DRACO shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. Dracos have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.
QUESTION: Which protozoal diseases is important after malaria? African trypanosomiasis, also known as African sleeping sickness, is caused by parasitic protozoan of the genus Trypanosoma. The two forms, West African and East African trypanosomiasis, are caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. T. B. Gambiense accounts for more than 95% of cases and causes chronic infection which can emerge as severe disease many years after parasite infection. T. B. Rhodesiense causes acute infection, which can rapidly result in central nervous system involvement with parasites crossing the blood–brain barrier. African trypanosomiasis threatens the lives of ∼60 million people in sub-Saharan Africa and, if left untreated, is fatal. Chagas disease, or American trypanosomiasis, is a serious health concern in Latin America and as a result of migration is an emerging disease in traditionally non-endemic countries. Chagas disease is caused by infection with Trypanosoma cruzi and threatens the lives of millions primarily in Mexico, Latin American and the United States. The World Health Organization estimates that 8–10 million people are infected annually. Chagas disease presents as an initial acute phase which is followed by a chronic phase.
REFERENCES: Andrews KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist. 2014;4(2):95-111. Published 2014 Mar 24. Doi:10.1016/j.ijpddr.2014.02.002
QUESTION: What is Cytoadherence? Cytoadherence is the property of Plasmodium falciparum-infected RBC to adhere to various host cell types such as endothelial cells and uninfected red cells, causing the parasite to sequester in deep vascular beds and avoid splenic clearance. Cytoadherence and sequestration are distinct features of P. Falciparum and are thought to account for its greater severity compared to malaria parasite species that lack these properties.
REFERENCES: Duffy P.E., Acharya P., Oleinikov A.V. (2014) Cytoadherence. In: Hommel M., Kremsner P. (eds) Encyclopedia of Malaria. Springer, New York, NY. Https://doi.org/10.1007/978-1-4614-8757-9_39-1
QUESTION: What is sequestration? Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells these phenomena, called sequestration. It involved in both host pathogenesis and parasite survival. Sequestration, the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules, is characteristic of Plasmodium falciparum infections.
REFERENCES: Sherman IW, Eda S, Winograd E. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect. 2003 Aug;5(10):897-909. Doi: 10.1016/s1286-4579(03)00162-x. PMID: 12919858.
David PH, Hommel M, Miller LH, Udeinya IJ, Oligino LD. Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proc Natl Acad Sci U S A. 1983;80(16):5075-5079. Doi:10.1073/pnas.80.16.5075.
QUESTION: What is Rosetting? Rosetting, defined as the binding of two or more uninfected red blood cells (rbc) to an infected rbc, occurs when malarial parasites mature, to trophozoites and schizonts, in the second half of their asexual development. Rosetting is believed to be an important factor in the development of cerebral malaria.
QUESTION: What is RBC knobs? Plasmodium falciparum-infected erythrocytes (RBC) develop surface protrusions (knobs) which consist of electron-dense submembrane cups and the overlying RBC plasma membrane. Knobs mediate cytoadherence to endothelial cells. When P. Falciparum parasites invade red blood cells, several modifications occur in the infected erythrocyte (IE), especially on its surface membrane. One important modification is the formation of nanoscale protrusions, which are known as knobs. Knobs are 50 to 120 nm in diameter and 2 to 20 nm in height and act as a site for anchoring P. Falciparum erythrocyte membrane protein 1 (pfemp1). The role of pfemp1 is to enable adhesion of ies to various host receptors to avoid splenic clearance, and clonal antigenic variation allows ies to evade immune recognition.
REFERENCES: Leech JH, Barnwell JW, Aikawa M, Miller LH, Howard RJ. Plasmodium falciparum malaria: association of knobs on the surface of infected erythrocytes with a histidine-rich protein and the erythrocyte skeleton. J Cell Biol. 1984 Apr;98(4):1256-64. Doi: 10.1083/jcb.98.4.1256. PMID: 6371019; PMCID: PMC2113211.
Plasmodium falciparum-Infected Erythrocyte Knob Density Is Linked to the pfemp1 Variant Expressed, Ramesh Subramani, Katharina Quadt, Anine E. Jeppesen, Casper Hempel, Jens Emil Vang Petersen, Tue Hassenkam, Lars Hviid, Lea Barfod Mbio Oct 2015, 6 (5) e01456-15; DOI: 10.1128/mbio.01456-15
QUESTION: What is Chemoprophylaxis? Chemoprophylaxis is define as, the use of a chemical agent to prevent the development of a disease.
Chemoprophylaxis of Malaria Malaria prevention in travelers to endemic areas remains dependent principally on chemoprophylaxis. Although malaria chemoprophylaxis refers to all malaria species, a distinction should be drawn between falciparum malaria prophylaxis and the prophylaxis of the relapsing malaria species (vivax & ovale). While the emergence of drug resistant strains, as well as the costs and adverse reactions to medications, complicate falciparum prophylaxis use, there are virtually no drugs available for vivax prophylaxis, beside of primaquine. Based on traveler’s malaria data, a revised recommendation for using chemoprophylaxis in low risk areas should be considered.
Chemoprophylaxis does not prevent the infection (as in the case of vaccine preventable diseases), but rather works as having a killing effect against the parasite, either within the erythrocytes or within the hepatocytes, thus preventing the clinical disease.
REFERENCES: Schwartz E. Prophylaxis of malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012045. Doi:10.4084/MJHID.2012.45
QUESTION: What is var gene? Plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) is an important virulence factor encoded by a family of roughly 60 var genes and is used by the parasite to interact with the human host. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. The parasite regularly exchanges the expressed var gene generating antigenic variation of the infected rbcs (prbc) surface which is crucial for successful proliferation and transmission. The multicopy var gene family of Plasmodium falciparum is of crucial importance for pathogenesis and antigenic variation. So far only var2csa, the var gene responsible for placental malaria, was found to be highly conserved among all P. Falciparum strains.
REFERENCES: Dimonte, S., Bruske, E.I., Enderes, C. Et al. Identification of a conserved var gene in different Plasmodium falciparum strains. Malar J 19, 194 (2020). Https://doi.org/10.1186/s12936-020-03257-x
Rubio JP, Thompson JK, Cowman AF. The var genes of Plasmodium falciparum are located in the subtelomeric region of most chromosomes. EMBO J. 1996;15(15):4069-4077.
Flick K, Chen Q. Var genes, pfemp1 and the human host. Mol Biochem Parasitol. 2004 Mar;134(1):3-9. Doi: 10.1016/j.molbiopara.2003.09.010. PMID: 14747137.
QUESTION: What is premunition immunity? Premunition, also known as infection-immunity, is a host response that protects against high numbers of parasite and illness without eliminating the infection. This type of immunity is relatively rapid, progressively acquired, short-lived, and partially effective.
Anopheles species causing malaria:- Anopheles culicifacies s.l. = Rural Malaria (65%) An. fluviatilis s.l. = Plains and foothills (15%) An. minimus breeds = Streams of foothills An. dirus s.l. = Jungle of North-eastern states An. sundaicus = Andaman and Nicobar islands and in brackish water An. stephensi = urban malaria
Larvivorous fish for malarial parasites:- Larvivorous fishes Poecilia reticulata (Guppy), a native of South America and Gambusia affinis (Gambusia), a native of Texas were imported in India in 1908 and 1928, respectively for the control of malaria vectors. Soon after that use of larvivorous fish became a common practice in India.
What do you mean by Prepatent Period? Period between infection with a parasite and the production of eggs by a female; equivalent to the incubation period of microbial infections, but biologically different because the parasite is going through developmental stages in the host.
Prodormal period, in simpler words can be defined as,,,, An early symptom that signals the onset of an illness or disease; a symptom or series of symptoms that precedes the more obvious, diagnosable symptoms that develop along with the condition.
What is Prepatent period? The period between infection with a parasite and demonstration of the parasite in the body especially as determined by the recovery of an infective form from the blood or feces.
I'm Celina Gomez from the UK, I have been cured from genital herpes with herbalist Sakura herbal Remedy. I have been infected with genital herpes for 1 years now , I have done so many medical treatments from different hospitals still not cured. On a very good day , I decided to do research on my computer on how to get rid of genital herpes, I found a post of Sarah Wilson on how she was cured from herpes with herbalist Dr. Sakura herbal remedy. The Herbalist email/contact number was there as well dr.sakuraspellalter@gmail.com/ +2348110114739. I contacted him because of my illness .He needed few of my information which I did, and also sent me his medicine through FedEx courier service. which I received after 3 working days of shipment, I drank the herbal medicine the same way Herbalist Dr Sakura instructed me too. But now my genital herpes is gone totally without any side effect or harm, may God Almighty continue to bless him abundantly . you can contact him on mail/what's app dr.sakuraspellalter@gmail.com +2348110114739 or follow him on Instagram @Herbalist_sakura .you can also mail me for more information celinagomez784@gmail.com
QUESTION:Why Christensenella minuta is important?
ReplyDeleteChristensenella minuta: A bacterium which is the most heritable member of the gut microbiota and which also influences host weight. There has been considerable interest in a particular member of the gut microbiota, a bacterial species named Christensenella minuta, which is a member of the Firmicutes phylum. Three recent findings have generated this interest. First, the Christensenella genus appears to be found so far only in human hosts. Second, C. minuta was found to be the most heritable species in the human gut microbiome, meaning that it is the species whose presence or absence in our gut is mostly determined by the genes of its human host. Third, evidence suggests that the presence of C. minuta can directly affect the weight of its host by as yet unknown mechanisms. C. minuta is more likely to be present in leaner people, and adding C. minuta to the gut tracts of mice resulted in leaner mice. These findings suggest a potential use of C. minuta as a probiotic for weight control.
I'm Celina Gomez from the UK, I have been cured from genital herpes with herbalist Sakura herbal Remedy.
DeleteI have been infected with genital herpes for 1 years now , I have done so many medical treatments from different hospitals still
not cured. On a very good day , I decided to do research on my computer on how to get rid of genital herpes, I found a post of Sarah Wilson on how she was cured from herpes with herbalist Dr. Sakura herbal remedy.
The Herbalist email/contact number was there as well dr.sakuraspellalter@gmail.com/ +2348110114739. I contacted him because of my illness .He needed few of my information which I did, and also sent me his medicine through FedEx courier service.
which I received after 3 working days of shipment, I drank the herbal medicine the same way Herbalist Dr Sakura instructed me too. But now my genital herpes is gone totally without any side effect or harm, may God Almighty continue to bless him abundantly .
you can contact him on mail/what's app dr.sakuraspellalter@gmail.com +2348110114739 or follow him on Instagram @Herbalist_sakura .you can also mail me for more information celinagomez784@gmail.com
Q:- Gut-Brain axis?
ReplyDeleteA:- Gut brain axis shows the link between the gut microbiota and brain behaviour. It linked in the form of the regulation of eachother.It means whenever changes occur in gutmicrobiota that leads to change in the behavior of brain. In last two decades it was studied that stress leads to change in the gutmicrobial flora and that leads to change of host behaviour . However the effects of the microbiota or the absence there of on behaviour remained unclear. It also alter in different composition of gut microflora. With altered or absent gut flora shows various molecular differences. It includes changes in levels of brain derived neurotrophic factors, expression of various neurotransmitter receptors and alterations in the turnover of certain neurotransmitter including serotonin.
QUE):Role of Microbes in Human Health and Diseases?
ReplyDelete>>Microbes are ubiquitous and have ecological interactions with almost all life forms. Likewise, humans invariably engage in host-microbial interactions that could induce short-term or long-term effects. Some of these longterm crossover interactions have allowed successful colonization of microbes within or on the human body, collectively known as the human microbiome or human microbiota. The human microbiome is identified as playing a key role in various physiological processes like digestion, immunity, defense, growth, and development. Any dysbiosis in the human microbiome structure could induce the onset of various metabolic or physiological disorders. Cumulatively the human microbiome is considered as a virtual human organ that is essential for host survival. Additionally short-term biological interactions of the host and microbes have exposed microbes to the human cellular system. This exposure could have allowed the microbes to invade human cells for their growth and reproduction induced onset of various infectious diseases.
What are Probiotics?
ReplyDeleteProbiotics are live microorganisms that are intended to have health benefits when consumed or applied to the body. Many of the microorganisms in probiotic products are the same as or similar to microorganisms that naturally live in our bodies.
What are Prebiotics ?
Probiotics are nondigestible food components that selectively stimulate the growth or activity of desirable microorganisms.
What are Synbiotics ?
Synbiotics are products that combine probiotics and prebiotics.
What are Psychobiotics?
Psychobiotics are beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that influence bacteria–brain relationships. They exert anxiolytic and antidepressant effects characterised by changes in emotional, cognitive, systemic, and neural indices. Bacteria–brain communication channels through which psychobiotics exert effects include the enteric nervous system and the immune system.
What percentage of human body is not human?
ReplyDeleteAns-More than half of our body is not human, say scientists.
Human cells make up only 43% of the body's total cell count. The rest are microscopic colonists.
Understanding this hidden half of ourselves - our microbiome - is rapidly transforming understanding of diseases from allergy to Parkinson's.
QUESTION: How much percent of the human body mass is covered by microorganisms?
ReplyDeleteANSWER: The human body contains trillions of microorganisms Because of their small size; however, microorganisms make up only about 1 to 3 percent of the body's mass (in a 200-pound adult, that’s 2 to 6 pounds of bacteria), but play a vital role in human health.
1. Probiotics = Probiotics are live bacteria and yeasts that are good for body, especially for the digestive system.
ReplyDelete2. Prebiotics = Prebiotics are compounds in food that induce the growth or activity of beneficial microorganisms such as bacteria and yeast.
3. Psychobiotics = Psychobiotics is a term used in preliminary research to refer to live bacteria that, when ingested in appropriate amounts, might confer a mental health benefit by affecting microbiota of the host organism.
4. Synbiotics = When Gibson introduced the concept of prebiotics he speculated as to the additional benefits if prebiotics were combined with probiotics to form what he termed as Synbiotics. A synbiotic product beneficially affects the host in improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract by selectively stimulating the growth and/or activating the metabolism of one or a limited number of health-promoting bacteria.
5. Gut – Brain Axis = The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions.
[The Role Of Gut Microbial Metabolites]
ReplyDelete>The gut microbiome seems to play a key role in the metabolism and degradation of several metabolic compounds.Almost 10% of all circulating metabolites (small molecules of less than 1–1.5 kDa molecular weight) in the human organism are derived from bacteria and participate in human metabolic pathways. Indeed, proteins and carbohydrates constitute the main fuels for microbial fermentation in the gut. Interestingly, in the proximal colon, the carbohydrate fermentation which leads to the production of succinate, short-chain
fatty acids (SCFAs), and gazes takes place. Based on a plethora of animal studies and a handful human studies, the SCFAs are beneficial microbial metabolites in the prevention and therapy of obesity and associated metabolic disorders.On the contrary, in the distal colon, the proteolytic fermentation resulting in the production of several deleterious metabolites such as branched-chain fatty acids (BCFAs), phenols,and ammonia takes place.
Q)What is Functional Redundancy?
ReplyDeleteAns: A characteristic of species within an ecosystem where certain species contribute in equivalent ways to an ecosystem function such that one species may substitute for another.
Q)Pyrosequencing?
Ans: Pyrosequencing is a method of DNA sequencing that differs from Sanger sequencing, in that it relies on the detection of pyrophosphate release and the generation of light on nucleotide incorporation, rather than chain termination with dideoxynucleotides.
QUESTION:What is Molecular Chronometers?
ReplyDeleteNucleic acids or proteins used as “clocks” to measure amount of evolutionary change over time. It's use based on several assumptions like, sequences gradually change over time, changes are selectively neutral and relatively random amount of change increases linearly with time.
QUESTION:What is cause-effect relationship?
ReplyDeleteA cause-effect relationship is a relationship in which one event (the cause) makes another event happen (the effect). One cause can have several effects.
For example, let's say you were conducting an experiment using regular high school students with no athletic ability. The purpose of our experiment is to see if becoming an all-star athlete would increase their attractiveness and popularity ratings among other high school students. Suppose that your results showed that not only did the students view the all-star athletes as more attractive and popular, but the self-confidence of the athletes also improved. Here we see that one cause (having the status of an all-star athlete) has two effects (increased self-confidence and higher attractiveness ratings among other students).
QUESTION:What is functional redundancy?
ReplyDeleteFunctioning can be evaluated in the short-term, in which case the magnitude of the process is of interest, or in the long-term, measured as the probability that this is maintained in the face of environmental change. In both cases, functioning is an emergent property of ecosystems: interactions between the system’s members and coevolution result in functioning which deviates from that expected from a system in which functioning was simply additive. In the case of environmental change, redundancy—the phenomenon in which a function is carried out by multiple species in an ecosystem—buffers functioning, as for any given environmental state there will be multiple organisms within a functional group which can perform optimally at a range of environmental conditions.
Reference: DOI: 10.5772/58981
QUESTION:What is pyrosequencing?
ReplyDeleteDNA sequencing is critical to identifying many human genetic disorders caused by DNA mutations, including cancer. Pyrosequencing is less complex, involves fewer steps, and has a superior limit of detection compared with Sanger sequencing. The fundamental basis of pyrosequencing is that pyrophosphate is released when a deoxyribonucleotide triphosphate is added to the end of a nascent strand of DNA. Because deoxyribonucleotide triphosphates are sequentially added to the reaction and because the pyrophosphate concentration is continuously monitored, the DNA sequence can be determined.
Pyrosequencing is designated as a sequence-by-synthesis technique because DNA synthesis is monitored in real time. It is based on the pioneering and elegant, basic science work of Pål Nyrén, PhD, who first demonstrated in 1987 that DNA polymerization can be monitored by measuring pyrophosphate production, which can be detected by light. Edward Hyman, PhD, capitalized on Dr Nyrén's work to invent pyrosequencing 1 year later, although it took several more years to be fully commercialized and more widely implemented.
Reference: https://doi.org/10.5858/arpa.2012-0463-RA
Factors that Influence Gut Bacterial Composition
ReplyDelete1.Method of delivery at birth.
According to the CDC, as of 2014, 32.2% of all deliveries in the United States are performed by cesarean section. The composition of the gut bacterial community is different in infants delivered by cesarean section from that of infants born by vaginal delivery. Infants born by vaginal delivery are exposed to the mother's bacteria at birth, which influences the infant's gut bacteria and stimulates white blood cells and other components of the immune system. Studies have suggested that infants born by cesarean section are at greater risk of developing obesity and/or diabetes than those born vaginally.
2.Infant feeding.
Infant feeding is another important factor for establishing the bacterial community in the gut, because the mother's milk is not sterile. Human breast milk has been recognized as a source of commensal and potential probiotic bacteria that influence the development of infant gut bacteria. Human breast milk contains >700 species of bacteria. Although human milk bacterial communities are generally complex and vary individually, the median bacterial load is ∼106 bacterial cells/mL through time. Thus, it has been estimated that a lactating infant consuming 800 mL breast milk/d could ingest up to 8 × 108 bacterial cells daily, which is ∼100 times higher than previous estimates, and the composition changes over the course of lactation. It appears that Streptococci and Staphylococci are predominant bacterial genera in human milk both of these are also predominant in the skin microbiota. Therefore, human milk may also contain some skin bacteria.
3.Genetics.
The number of specific bacteria found in the gut microbiota is influenced in part by the genetic makeup of the host in ways that affect host metabolism and ultimately can affect health. Family members have been found to have more similar microbiota communities than unrelated individuals, and the gut microbiota is more similar in monozygotic than in dizygotic twins. However, there are currently no genome-wide studies that have characterized specific genes and pathways that determine the composition of the gut microbiome, although certain genes in the immune system are associated with inflammatory bowel disease.
4.Infections.
A human study of Clostridium difficile patients and asymptomatic carriers with the use of 16S ribosomal RNA gene pyrosequencing found that both had reduced microbial richness and diversity compared with healthy subjects. C. difficile infection is a typical result of severe dysbiosis in the gut microbiota. Interestingly, transplantation of the gut microbiome from healthy donors to infected patients increased microbial richness and diversity, and it is currently applied clinically.
5.Diet.
The role that food-ingested bacteria play in the gut microbiome had been underestimated in the past, possibly because of methodologic limitations that have been overcome in recent years. Numerous studies, both in research mice and in humans, have shown that high-calorie diets contribute to obesity and T2D. However, increasing evidence suggests that the link between diet and obesity lies in the gut microbiota. Understanding that diet is an important contributing factor to the composition of the gut microbiome makes it the most logical target to manipulate. Interventional studies show that dietary changes result in substantial and rapid changes in the make-up of the gut microbiome. Studies in mice have demonstrated that a high-fat diet (60% fat) decreases the number of bacterial species (α diversity) in the gut microbiome, and the composition of the gut microbiome between mice given a high-fat diet (unpurified) and those given a regular unpurified diet is very different (β diversity).
Few definitions of things those were discussed during lecture:-
ReplyDeleteCORE MICROBIOME:- A core microbiome is defined as the group of microbes commonly found within a host's microbiome, using persistence of the association as the criterion to select microbes potentially providing critical function within the habitat in which they are found.
DYSBIOSIS:-Dysbiosis (also called dysbacteriosis) is a term for a microbial imbalance or maladaptation on or inside the body.
CAUSE - EFFECT RELATION :- A cause-effect relationship is a relationship in which one event causes another to happen.
Whenever the cause occurs, the effect must also occur.
RARE BIOSPHERE:- Rare biosphere refers to a large number of rare species of microbial life, i.e. bacteria, archaea and fungi, that can be found in very low concentrations in an environment.
FUNCTIONAL REDUNDANCY:- A characteristic of species within an ecosystem where certain species contribute in equivalent ways to an ecosystem function such that one species may substitute for another.
PYROSEQUENCING:- Pyrosequencing is a method of DNA sequencing based on the "sequencing by synthesis" principle, in which the sequencing is performed by detecting the nucleotide incorporated by a DNA polymerase. Pyrosequencing relies on light detection based on a chain reaction when pyrophosphate is released.
The Human Microbiome Project:-
ReplyDeleteA strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.
To understand the range of human genetic and physiological diversity, the microbiome and the factors that influence the distribution and evolution of the constituent microorganisms must be characterized. This is one of the main goals of the Human Microbiome Project (HMP). The outcome might also provide perspective on contemporary human evolution: that is, on whether and how rapidly advancing technology, and the resultant transformation of human lifestyles and the biosphere, influences the 'micro-evolution' of humans and thereby health and predisposition to various diseases.
Definitions which were discussed in the lecture earlier:-
ReplyDelete1. Probiotics :- Probiotics are the live microorganisms which confer health benefit when they are administered in adequate amount according to the WHO. For example, the organisms from genus Lactobacillus and Bifidobacteria are widely used for gaining health benefits. This bacteria are example of probiotics.
2. Prebiotics - Prebiotics are compounds or substrates which are not digested by humans but these compounds are able to stimulate the growth of selective microorganisms living in colon. It is believed that they stimulate the growth of good bacteria and thus confer benefit to the host. Human breast milk which contains oligosaccharides helps to formulate gut microflora of newborn so they can be a good example of prebiotics.
3. Psychobiotics :- Psychobiotics are probiotics which confer mental health benefits when they are taken in an adequate amount. It is estimated that they might be used in cure of mental health issues like anxiety and depression.
4. Synbiotics :- Synbiotics is a combination of prebiotics and probiotics. It is believed that it benefits the host by improving the survival and activity of microorganisms.
5. Gut-brain axis :- The gut-brain axis is a bidirectional communication system between the GI tract and Central Nervous System.The gut–brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, including the hypothalamic–pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, including the enteric nervous system and the vagus nerve, and the gut microbiota. It is thus believed that gut microbiota plays an important role in changing the CNS system and thus affects mood of a person.
Factors influencing the human microbiome
ReplyDelete# Human genetics and immune interactions in early development.
The composition of the human microbiome is unique in each individual, and the differenceamong individuals are large compared to the typical biochemical differences within a person
over time. Identical twins are barely more similar to one another in microbial composition and structure than are non-identical twins, at least over the range of environmental factors captured in studies to date, suggesting that the effect of the human genome is limited, and that most of microbial community assembly may be determined by environmental factors.
# Body site
When the microbiomes of large cohorts of people at a given body site are compared, individuals fit on a continuum of microbial diversity within a human population, rather than clustering into discrete groups.
During human development, the human microbiome follows body site-specific trajectories, so that each body site develops a specific biogeography.
The skin, for example, shows dramatic variation in microbiome composition and structure across different sites.
The physical and topographical characteristics of skin play a significant role in shaping the microbial community similarity between sites. These factors also play a role in shaping the individuality of the microbiome, so that each person develops a unique microbial signature on their skin, irrespective of the differences between skin sites.
# Diet
Diet has been studied extensively in relation to the gut microbiome, but less so with respect to other microbiomes at other sites across the body. Modulating diet is an ideal opportunity for low-risk, culturally and psychologically acceptable intervention to change
the microbiome. Therefore, this avenue of research could yield noveltherapeutic strategies through targeted dietary interventions should gut microbiota be shown to be causative for certain diseases.
Evidence to date suggests that long-term diet has very large effects on gut
microbiome composition although a sufficiently extreme short-term dietary change can cause people to resemble one another within days.
#Antibiotics
The effect of antibiotics on all microbiomes is expected to be large compared to other factors, and preliminary studies have been performed to determine the impact. The gut microbiome in adults appears not to be resilient to repeated antibiotic administration. The same antibiotic appears to affect particular microbes differently depending on the rest of the
microbiome, perhaps due to different growth phases, metabolic states, or contextual microbial network in which the microorganisms find themselves.
An especially interesting area of research is the increasing evidence that antibiotics in early life have a profound effect of the gut microbiome that can result in the later development of obesity, asthma, inflammatory bowel disease and other disorders.
# Lifestyle
Lifestyle is also thought to have a strong influence on microbiome composition.
Cohabitation with pets, such as dogs, has a statistically significant association with the microbiome. In one study, the skin microbiome of couples living together has a closer resemblance if the couple has a dog, but, intriguingly, a small child did not provide the same trend, so couples with a child but no dog were not significantly more similar to one another than couples without a child. Pet ownership and exposure to livestock have been associated with decreased risk of asthma. Interrupting this exposure in infants from human populations with a known ancestral history of interaction with animals has been shown to lead to a substantial increase in atopy,especially asthma. If these results turn out to be caused by the microbiome, rather than simply correlative, they suggest potential new therapeutic strategies for disease intervention could come from microbial exposure focused on immune activation.
Gnotobiotic mice: Gnotobiotic Mice refers to mice in which every microorganism present is defined and the study of organisms whose every germ is carefully controlled. Germ-free mice are one class of gnotobiotic animals, but mice associated with defined bacterial communities (e.g. Altered Schaedler's Flora) are also considered gnotobiotic. Gnotobiotic animals are kept in isolators for long-term maintenance of their microbiological status.Work on germ-free mice began in 1940's to understand how microorganisms contribute to physiology and disease.
ReplyDeleteList of important gut microbiome, whose activities protect human health and digestive wellbeing.
ReplyDelete1. Christensenella minuta: A highly heritable bacterial species which has been found to be strongly associated with obesity through an unknown biological mechanism. This novel genome provides a valuable resource for future obesity therapeutic study, which is beneficial for weight management.
2. Akkermansia muciniphila: Akkermansia muciniphila is a mucin-degrading bacterium commonly found in human gut. A. muciniphila has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders. Due to its highly promising probiotic activities against obesity and diabetes.
3. Barnesiella: This species has the ability to prevent pathogenic species of antibiotic-resistant bacteria from colonising the gut. Ex: Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization.
4. Adlercreutzia equolifasciens: These bacteria turn compounds found in soy into a special antioxidant that may help prevent cancers and heart disease.
5. Oxalobacter formigenes: Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones.
QUESTION:What is Gnotobiology, Gnotobiosis and Gnotobiotic animals?
ReplyDeleteGnotobiology is the science of study of animals or other organisms raised in environments free of germs or those which contain only specifically known germs. Scientists compare gnotobiotic animals with ordinary animals whose bodies carry many germs, like bacteria, viruses and parasites.
Gnotobiosis is a condition in which all the forms of life present within an organism can be accounted for. Typically gnotobiotic organisms are germ-free or gnotophoric (having only one contaminant).
A gnotobiotic animal is an animal in which only certain known strains of bacteria and other microorganisms are present. Technically, the term also includes germ-free animals, as the status of their microbial communities is also known. However, the term gnotobiotic is often incorrectly contrasted with germ-free.
QUESTION:What is tissue tropism and how it can be used?
ReplyDeleteTissue tropism is the cells and tissues of a host that support growth of a particular virus or bacterium. Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues. Other viruses may infect primarily a single tissue. This concept is central to the radiological evaluation of infectious disease.
Pathology
As infections that display tissue tropism will thrive in certain tissue locations, this characteristic can be helpful in making a diagnosis from radiological imaging. Findings of infection on imaging that are localized in a pattern typical for a particular microbial organism allow for. This is particularly useful when serological confirmation can take days or weeks, as in the cases for many of the viral encephalitides.
Radiographic features
Radiological diagnosis of the underlying microbial pathogen responsible for presenting infection allows for the use of specific antimicrobial therapy much before the causative organism is eventually confirmed. This is particularly true for viruses which are confirmed through the use of PCR, which can take days to weeks. The degree to which microbes display tissue tropism varies and indeed not all of them do.
Examples of tissue tropism include:
Bilateral thalamic involvement in Japanese encephalitis
Medial temporal and limbic involvement in herpes simplex encephalitis
Terminal ileum for gastrointestinal tuberculosis
QUESTION:What is law of minimum?
ReplyDeleteIn the 19th century, the German scientist Justus von Liebig formulated the “Law of the Minimum,” which states that if one of the essential nutrients is deficient, organism will be poor even when all other essential nutrients are abundant. It states that growth is dictated not by total resources available, but by the scarcest resource (limiting factor). The law has also been applied to biological populations and ecosystem models for factors such as sunlight or mineral nutrients.
QUESTION:What is law of tolerance?
ReplyDeleteIt states that an organism's success is based on a complex set of conditions and that each organism has a certain minimum, maximum, and optimum environmental factor or combination of factors that determine success.
It was develop by American zoologist Victor Ernest Shelford in 1911.
The absence of an organism can be limited by the qualitative or quantitative insufficiency from the various environmental factors which may come up to the limits of tolerance for that organism. Environmental factors involved climatic change, topographic location and biological necessities of both plants and animals.
This law is possibly the more precise indication of natural complexity. Each individual or a population is subject to an ecological change that crop up the minimum and maximum capacity to any complex environmental factors. The range wherein it carried out from the minimum to maximum signify the limit of tolerance of an organisms, if all known factors are actually within the particular range of a certain organisms yet it still fails, it is important to consider extra factors of interrelationships with other organisms.
It is been studied that an organisms may have an extensive tolerance for one factor yet a slight array for another. When an organism has a wide range on all factors it indicates that a certain organisms are most widely distributed and are contribute to augment diversity in the community.
QUESTION:What is Phylogenetic inertia?
ReplyDeleteThe concept of ‘phylogenetic inertia’ is routinely deployed in evolutionary biology as an alternative to natural selection for explaining the persistence of characteristics that appear sub-optimal from an adaptationist perspective.
Phylogenetic inertia or phylogenetic constraint refers to the limitations on the future evolutionary pathways that have been imposed by previous adaptations. Charles Darwin first recognized this phenomenon, though the term was later coined by Huber in 1939.
Darwin explained the idea of phylogenetic inertia based on his observations; he spoke about it when explaining the "Law of Conditions of Existence". Darwin also suggested that, after speciation, the organisms do not start over from scratch, but have characteristics that are built upon already existing ones that were inherited from their ancestors; and these characteristics likely limit the amount of evolution seen in that new taxa. This is the main concept of phylogenetic inertia.
Richard Dawkins also explained these constraints by likening natural selection to a river in his 1982 book The Extended Phenotype.
There have been several studies that have been able to effectively test for phylogenetic inertia when looking into shared traits; predominantly with a comparative methods approach. Some have used comparative methods and found evidence for certain traits attributed to adaptation, and some to phylogeny; there were also numerous traits that could be attributed to both. Another study developed a new method of comparative examination that showed to be a powerful predictor of phylogenetic inertia in a variety of situations. It was called Phylogenetic Eigenvector Regression (PVR), which runs principal component analyses between species on a pairwise phylogenetic distance matrix. In another, different study, the authors described methods for measuring phylogenetic inertia, looked at effectiveness of various comparative methods, and found that different methods can reveal different aspects of drivers. Autoregression and PVR showed good results with morphological traits.
About tissue trophism
ReplyDelete#Tissue trophism
Tropism refers to the ability of a given pathogen to infect a specific location. Organ or tissue tropism reflects the ability of a given pathogen to infect a specific organ or sets of organs. Some pathogens are broadly tropic, infecting all or most organs, while others are restricted to a given tissue or even to certain tissue niches.
# Variations in Tropism
S. aureus resides as a commensal in the nose and upper respiratory tract of 30% of individuals . However, it also has the ability to cause a range of diseases, from localized skin abscesses to endocarditis, pneumonia, osteomyelitis, or disseminated infection.
The seasonal influenza viruses mainly infect the upper respiratory tract, while pandemic influenza as well as some highly pathogenic avian influenza viruses (e.g., H5N1) have increased ability to infect the lower respiratory tract. Influenza viruses can also infect extrapulmonary tissues, leading, for example, to conjunctivitis.
# Impact of Tropism on Disease Severity.
As long as S. aureus resides as a commensal in the upper respiratory tract, it does not cause any symptoms . In contrast, S. aureus bacteremia has a 15%–50% case fatality rate. Likewise, mortality from S. aureus infective endocarditis is 22%–66% .
#Impact of Tropism on Disease Transmission
Pathogen location also strongly influences transmission to new hosts. Transmission of S. aureus from bacteremia appears to involve passage through the gastrointestinal tract followed by fecal spread. In contrast, bacterial colonization on the skin and in the nose may facilitate person-to-person transmission.
#Impact of Tropism on Treatment
Drug tissue penetration varies depending on chemical structure, formulation, and delivery. Treatment choices will therefore be influenced by the sites of infection. For example, S. aureus abscesses may be treated by incision and drainage alone, or with topical antibiotics. In contrast, bacteremia will require systemic antibiotics, and endocarditis may require surgery.
Placental Microbiome
ReplyDeleteThe placental microbiome is the nonpathogenic, commensal bacteria claimed to be present in a healthy human placenta and is distinct from bacteria that cause infection and preterm birth in chorioamnionitis.Until recently, the healthy placenta was considered to be a sterile organ but now genera and species have been identified that reside in the basal layer.
It should be stressed that the evidence for a placental microbiome is controversial.Most studies supporting the existence of a placental microbiome lack the appropriate experimental controls, and it has been found that contamination is most likely responsible for reports of a placental microbiome.
The placental microbiome more closely resembles that of the oral microbiome than either the vaginal or rectal microbiome.
In a healthy placental microbiome, the diversity of the species and genera is extensive. A change in the composition of the microbiota in the placenta is associated with excess gestational weight gain, and pre-term birth.The placental microbiota varies between low birth weight infants and those infants with normal birth weights. While bacteria are often found in the amniotic fluid of failed pregnancies, they are also found in particulate matter that is found in about 1% of healthy pregnancies.
In non-human animals, part of the microbiome is passed onto offspring even before the offspring are born. Bacteriologists assume that the same probably holds true for humans.
- Autism Spectrum Disorder (ASD) and role of prevotella species.
ReplyDelete- Autism spectrum disorder (ASD) is a complex developmental condition that involves persistent challenges in social interaction, speech and nonverbal communication, and restricted/repetitive behaviors. One potentially important environmental factor of ASD is abnormal intestinal flora. A large fraction of autistic children suffer from gastrointestinal (GI) problems. Prevotella is a key genus in determining gut microbiome profile. Prevotella plays a key role in digesting carbohydrate-rich food, but also that diet patterns can affect the abundance of Prevotella in human gut. Prevotella species also have essential genes for biosynthesis of vitamin B1, which was reported to mitigate ASD symptoms. A significantly lower abundance of the Prevotella cluster in autistic children could be linked to a low carbohydrate diet, however, autistic and neurotypical children generally consume comparable amounts of carbohydrate and fiber.
QUESTION:What is Asian diet, Mediterranean diet and Western diet?
ReplyDeleteAsian diet
Oldways introduced the Asian Heritage Diet Pyramid in 1995 at the International Conference on the Diets of Asia in San Francisco, developed in conjunction with the Cornell-China-Oxford Project on Nutrition, Health and Environment, and the Harvard School of Public Health. The traditional diet in many Asian countries is often closely tied to both religious practices and long-standing customs, and the record of these eating habits is an excellent source of information and culinary inspiration: Vegetables and more vegetables, strong spices, rice and noodles, seafood, and soy products.
Mediterranean diet
The Mediterranean diet is a diet inspired by the eating habits of Italy and Greece in the 1960s. The principal aspects of this diet include proportionally high consumption of olive oil, legumes, unrefined cereals, fruits, and vegetables, moderate to high consumption of fish, moderate consumption of dairy products (mostly as cheese and yogurt), moderate wine consumption, and low consumption of non-fish meat products. Olive oil has been studied as a potential health factor for reducing all-cause mortality and the risk of chronic diseases.
Western diet
The Western diet or standard American diet (SAD) is a modern dietary pattern that is generally characterized by high intakes of red meat, processed meat, pre-packaged foods, butter, candy and sweets, fried foods, conventionally-raised animal products, high-fat dairy products, eggs, refined grains, potatoes, corn (and high-fructose corn syrup) and high-sugar drinks, and low intakes of fruits, vegetables, whole grains, grass-fed animal products, fish, nuts, and seeds. The modern standard American diet was brought about by fundamental lifestyle changes following the Neolithic Revolution, and, later, the Industrial Revolution.
SHOCKING FACT!!!!!!!!
ReplyDeleteQuestion: Does Gut bacteria really affect human mood??????
Answer: The human gut is lined with more than 100 million nerve cells, more than in the spinal cord or in the peripheral nervous system. Yes, humans have brain cells in large intestines! This explains why antibiotics which disturb the gut microbial ecosystem might cause neuropsychiatric effects, interact with psychotropic medications, and/or influence person’s mood.
Chemicals implicated in depression and happiness such as serotonin are also found in the gut; 90% of serotonin is manufactured in the digestive tract and not the brain. Many antidepressants work by increasing serotonin.
According to Scientists gut bacteria produce many other neurotransmitters such as dopamine, norepinephrine, acetylcholine, and GABA (Gamma aminobutyric acid), which are critical for mood, anxiety, concentration, reward, and motivation. The gut microbiome can cause changes in how our brains react.
So, Yes, gut bacteria really affect human mood.
Dysbiosis
ReplyDeleteDysbiosis is often defined as an “imbalance” in the gut microbial community that is associated with disease. This imbalance could be due to the gain or loss of community members or changes in relative abundance of microbes.
Dysbiosis is a disequilibrium of commensal flora with respect to the endobiogenic needs of the individual organism. This disequilibrium may be due to three basis reasons: (1) insufficiency of commensal flora, (2) loss of diversity: a relative imbalance in the normal commensal flora, and (3) pathogenic flora competing with the commensal microbiome.
Alterations in the microbiota can result from exposure to various environmental factors, including diet, toxins, drugs, and pathogens.
There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity.
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ReplyDeleteQUESTION:What is association vs causation?
ReplyDeleteWhen considering the relationship between exposures and health outcomes, it is important to distinguish between association and causation.
Association: Is a specified outcome more likely in people with a particular exposure. Is there a link? Association is a statistical relationship between two variables. Two variables may be associated without a causal relationship. Association or correlation can be observed between many variable, but causation can only be determined from data collected from a controlled experiments.
Causation: Causation occur when a change in one variation produces a change in another variable. Causation means that the exposure produces the effect. It can be the presence of an adverse exposure, e.g., increased risks from working in a coal mine, using illicit drugs, or breathing in second hand smoke. Causative factors can also be the absence of a preventive exposure, such as not wearing a seatbelt or not exercising. A cause must be associated with the outcome, but simply demonstrating an association is not enough. To conclude that lack of exercise is a cause of heart disease, one needs to review the body of evidence suggesting a causal relationship and also consider other criteria.
For example,
Does exposure to tobacco smoke and air pollution precede the occurrence of lung cancer?
Is there a strong association between smoking and subsequent occurrence of lung cancer?
Is it possible that having lung cancer causes one to smoke?
It is interesting to note that when lifelong smokers are told they have lung cancer or emphysema, many of them quit smoking. This makes it seem as if ex-smokers are more likely to die of emphysema or lung cancer than current smokers.
QUESTION:What is Interactome and Interactomics?
ReplyDeleteThe interactome is the whole set of molecular interactions that occur within a particular cell. The term interactome was originally coined in 1999 by a group of French scientists headed by Bernard Jacq, and is often described in terms of biological networks.
Interactomics is a discipline at the intersection of bioinformatics and biology that deals with studying both the interactions and the consequences of those interactions between and among proteins and other molecules within a cell.
Molecular interactions can occur between molecules belonging to different biochemical families or within a given family, such as proteins, nucleic acids, lipids, and carbohydrates. Interactomes may be described as biological networks, and most commonly, interactome refers to protein-protein interaction (PPI) network and protein-DNA interaction networks (also called gene regulatory networks), or subsets thereof.
Therefore, a typical interactome includes transcription factors, chromatin regulatory proteins, and their target genes. Interactomics aims to compare such networks of interactions between and within species in order to discover patterns of network preservation and/or variation. Interactomic methods are currently being used to predict the function of proteins with no known function, especially in the field of drug discovery.
QUESTION: What are Postbiotics?
ReplyDeleteANSWER: Postbiotics are by-products of the fermentation process carried out by probiotics in the intestine. In other words, as probiotics feed on prebiotics, postbiotics are produced. They are basically the “waste” of probiotics.
Waste products don’t sound like they would be of much use to us. they are responsible for multiple important health-boosting functions in our gut. Some examples of postbiotics include organic acids, bacteriocins, carbonic substances and enzymes. They result naturally from the existence and survival of microorganisms living in our gut, though they can also be added directly through therapeutic processes.
The Gut Brain Connection: How Gut Health Affects Mental Health
ReplyDeleteYour microbiome—the diverse population of microbes (bacteria) that live in your gastrointestinal (GI) tract—plays an important role in the health of your gut, and in other aspects of your physical health, from inflammatory skin disorders to obesity. Researchers now say that this role of promoting good health may extend to include the health of your brain and neurological systems.
What’s the Connection?
The thousands of different types of both “good” and “bad” bacteria that populate the microbiome normally exist in a balance in favor of beneficial bacteria that help prevent overgrowth of bad bacteria that can harm your heath. Studies have shown there is potential harm associated with an imbalance in the microbiome due to inflammation, intestinal permeability or lack of bacterial diversity, any of which may be associated with an overgrowth of unhealthy bacteria. In some cases, researchers are confronted with the classic “chicken or egg” question with respect to the association between gut bacteria and poor health, in terms of which comes first. Does an overgrowth cause the disorder or does the disorder cause an overgrowth of bad bacteria?
Bacteria on the Brain
Current thinking in the field of neuropsychology and the study of mental health problems includes strong speculation that bipolar disorder, schizophrenia, and other psychological or neurological problems may also be associated with alternations in the microbiome. Researchers speculate that any disruption to the normal, healthful balance of bacteria in the microbiome can cause the immune system to overreact and contribute to inflammation of the GI tract, in turn leading to the development of symptoms of disease that occur not only throughout your body, but also in your brain.
This system of connections and communication between the gastrointestinal tract and the brain is referred to as the “gut-brain axis.” Some researchers speculate that infections occurring in early life could negatively affect the mucosal membrane in the GI tract, disrupting the gut-brain axis, and interfering with normal brain development. The mucosal membrane can also be altered in other ways, such as through poor diet choices, radiation treatment, antibiotic use, and chemotherapy.
What You Can Do?
To maintain or restore the health of your microbiome and support good overall health, it is important to maintain a strong balance in favor of beneficial bacteria in your digestive tract. The first step is to eat a well-balanced diet that includes foods with probiotic or prebiotic ingredients that support microbial health by helping to restore balance to the gut microbiome. These are foods that contain live beneficial (probiotic) bacteria and, in the case of prebiotics, contain substances like specific types of fiber that nurture the growth of probiotic bacteria.
Probiotic Foods
Until more is known, look to a variety of readily available probiotic foods that supply varying amounts beneficial live bacteria that grow during carefully controlled fermentation processes. Some of these are common foods you may already be including in diet, while others may seem a bit more exotic, though they are readily available in supermarkets. Probiotic foods and beverages include plain yogurt, kefir, cottage cheese, fresh sauerkraut, kimchi, kombucha, apple cider vinegar, and miso. Keep in mind that the probiotic effects of these foods are destroyed by cooking, processing, or preserving at high temperatures.
Prebiotic Foods.
Unlike probiotic foods, prebiotic foods do not contain living organisms. They contribute to the health of the microbiome because they contain indigestible fibers that ferment in the GI tract, where they are consumed by probiotic bacteria and converted into other healthful substances. Prebiotic foods include artichokes, leeks, onions, garlic, chicory, cabbage, asparagus, legumes, and oats.
The Impact of Postbiotics on Host-Microbiota Interactions
ReplyDeleteProbiotics are viable by definition and their stability and viability were considered to be an essential prerequisite for their health benefits. For postbiotics, however, viability is no longer the most important criterion. Postbiotic efficacy is based on the microbial metabolites, proteins, lipids, carbohydrates, vitamins, organic acids, cell wall components or other complex molecules that are generated in the matrix that is fermented. In some cases the postbiotic composition can be influenced by food processing methods such as heat, sonication, irradiation and high pressure. The microorganisms involved in the fermentation process might respond differently to these methods. For example, some proteins originating from bacteria that are inactivated by heat might denature, while irradiation might cause mutations in nucleic acids.
Therefore, the composition of the postbiotic product and thus the host response to the postbiotic products depends on the complete food production process.
The molecular mechanisms underlying the effects of postbiotics seem to be mediated through an interaction between the host and microbial products. This in turn can trigger the host immune system, and thereby trigger e.g., anti-inflammatory responses. Studies describing these molecular mechanisms are often performed in vitro, mechanisms of action leading to these benefits in humans have not been fully elucidated. An example of a possible mechanism immunomodulation by postbiotics in humans could be derived from an in vitro experiment showing the innate response of macrophages to non viable Lactobacillus casei cells. A suspension with heat-killed bacterial cells resulted in an increase in the expression of pro-inflammatory cytokines and enhanced the transcription of Toll-like receptors (TLR-2, TLR-3, TLR-4 and TLR-9).
Moreover, several in vitro studies have shown that heat treated Bifidobacterium cells induce cellular immune and anti-inflammatory responses by inhibiting IL-8 secretion in intestinal epithelial cells obtained from patients with UC. It was suggested that these effects in UC patient derived cells are induced by released microbial soluble anti-inflammatory factors that inhibit IL-8 secretion in intestinal epithelial cells. This was not caused by one single factor. Furthermore, it is hypothesized that postbiotic compounds from Lactobacilli spp. can exert immunomodulation activity by increasing levels of Th1-associated cytokines and reducing Th2-associated cytokines.
IMP.. STUDY!!!!!!!!
ReplyDeleteQUESTION: What is the Relationship Between Prebiotics, Probiotics, and Postbiotics???
ANSWER: According to recent research that most of the positive effects of the probiotics are actually due to postbiotics. They may also provide the bases for the proper processing of prebiotics, promoting a healthy prebiotic population in yet another manner.
Simply, Prebiotics proceed probiotics, which proceed postbiotics.
Postbiotics, in turn, promote the use of prebiotics. Prebiotics are like the “food”, probiotics are the microorganisms themselves, and postbiotics are the results of probiotics consuming that “food”. Postbiotics, while being a sort of probiotic waste, are what may be exerting many of the health effects on humans. This relationship is helps us to understand the symbiotic relationship between gut microorganisms and humans on an even deeper level.
1. Microbial consortia = A microbial consortium is two or more microbial groups living symbiotically. Consortiums can be endosymbiotic or ectosymbiotic. The concept of consortium was first introduced by Johannes Reinke in 1872.
ReplyDelete2. Interactome = The sum of these host and microbe metabolite interactions is referred to as the human interactome. Human and microbial metabolites interact so often that the interactome is almost impossible to quantify.
Eg :- Consider that the genome of the pathogen HIV codes for nine genes, which generate 19 proteins. According to Fu and team, there are 1,443 direct interactions (3,300 total interactions) between just these 19 proteins and metabolites in the human body.
Post biotics = Postbiotics are byproducts of probiotic bacterial fermentation. When probiotics feed on certain types of fiber molecules in order to thrive, they leave behind “waste products” that are collectively called postbiotics. The microbiota therefore naturally releases postbiotics, which in turn help regulate the composition of the microbiome. Post biotics are immobilised probiotics which when ingested, may have the ability to exert positive biological responses and restore intestinal homeostasis in a similar manner to probiotics. Postbiotics are currently being referred to as modified, inactivated, non-viable, para- or ghost probiotics.
ReplyDelete1. Microbial consortia = A microbial consortium is two or more microbial groups living symbiotically. Consortiums can be endosymbiotic or ectosymbiotic. The concept of consortium was first introduced by Johannes Reinke in 1872.
ReplyDelete2. Interactome = The sum of these host and microbe metabolite interactions is referred to as the human interactome. Human and microbial metabolites interact so often that the interactome is almost impossible to quantify.
Eg :- Consider that the genome of the pathogen HIV codes for nine genes, which generate 19 proteins. According to Fu and team, there are 1,443 direct interactions (3,300 total interactions) between just these 19 proteins and metabolites in the human body.
What is Colonization Resistance?
ReplyDeleteThe human intestine is colonized by a large number of microorganisms that inhabit the intestinal tract and support a variety of physiological functions. Colonization resistance is the term used to describe the microbiota’s capacity to limit the introduction of exogenous microorganisms and is the mechanism in which intestinal microbiota protects itself against colonization by new and harmful microorganisms.
What is the difference between IBD(Inflammatory bowel disease ) and IBS (Irritable bowel Syndrome)?
ReplyDeleteIBS usually causes no ulcers or lesions in the bowel, and it involves only the colon. IBD is bowel diseases that cause inflammation in the digestive tract.
IBS is a common disorder of the large intestine (colon) that causes symptoms of cramping, abdominal pain, bloating, gas, diarrhea, constipation. IBD is a term used to describe a group of inflammatory conditions mainly in the large and small bowels. Abdominal pain in IBS may be spread over a wide area of the abdomen, but it can localize in the lower left area of it. The pain may intensify while eating meals, when gas is present in the GI tract, and from abdominal bloating.
Abdominal pain in IBD may occur anywhere in the abdomen, and its location may suggest the type of IBD that you may have (for example, left-sided abdominal pain is a classic symptom of ulcerative colitis).
QUESTION: What is the effect of diet composition on gut microbiota and its impact on gastrointestinal tract health??????
ReplyDelete>>>Research is indicating that the gut microbiota has a significant impact on human health. Alterations of gut microbiota have clear consequences on intestinal homeostasis (homeostasis means regulation of any of the large physiological systems in the body, including levels of glucose in blood and body temperature), physiology, gut microbiome, immune system and host metabolic pathways.
>>>It is estimated that the human gastrointestinal tract has 10 million genes which are associated with different microbial species and all genes have some beneficial impact on the health of the host, with possible effects on the homeostasis of the immune system, conversion of food into useful nutrients and protection against pathogenic microorganisms invading. However, due to the differences of diets, the microbiota differs widely from individual to individual and each person carries hundreds of microbial species that remain unchanged throughout adulthood.
>>>Diet composition plays an important role in the control of gut microbial populations and, thus, in the prevention, management and treatment of certain diseases such as cancer, diabetes. A comprehensive analysis of previously reported results revealed that the gut microbiota can be modulated by diet and the composition of gut microbiota can be influenced by various diet components. The symbiotic relationship between different gut microbial communities regulates the immune system and, therefore, any dysbiosis (Dysbiosis leads to an increased risk of neoplastic transformation which is found to be directly related to chronic inflammation of the gut and the development of colon cancer) can dysregulate the immune system.
By, this way diet affects the gut microbiota and it affects the immune system and health of gastrointestinal tract .
Broad Spectrum And Narrow Spectrum Antibiotics:-
ReplyDeleteAntibiotics are the most commonly prescribed medicine in children. Narrow-spectrum antibiotics target a few types of bacteria. Broad-spectrum antibiotics target many types of bacteria. Both types work well to treat infections. But using broad-spectrum antibiotics when they’re not needed can create antibiotic-resistant bacteria that are hard to treat. They may also have side effects, such as diarrhea or rash.
Treating infections:-Narrow-spectrum antibiotics worked as well as broad-spectrum antibiotics to treat infections. Symptoms improved the same amount in three days.
Side effects:-Children who took narrow-spectrum antibiotics had fewer side effects than those who took broad-spectrum antibiotics.
Quality of life:-There were no differences in quality of life between children who took broad- or narrow-spectrum antibiotics.
Psychobiotics in mental health,neurodegenerative and neurodevelopmental disorders:-
ReplyDeletePsychobiotics are a group of probiotics that affect the central nervous system (CNS) related functions and behaviors mediated by the gut-brain-axis (GBA) via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal (GI) function but also the antidepressant and anxiolytic capacity. As a novel class of probiotics, the application of psychobiotics has led researchers to focus on a new area in neuroscience. In the past five years, some psychobiotics strains were reported to inhibit inflammation and decreased cortisol levels, resulting in an amelioration of the symptoms of anxiety and depression. Psychobiotics are efficacious in improving neurodegenerative and neurodevelopmental disorders, including autism spectrum disorder (ASD), Parkinson's disease (PD) and Alzheimer's disease (AD). Use of psychobiotics can improve GI function, ASD symptoms, motor functions of patients with PD and cognition in patients with AD. However, the evidence for the effects of psychobiotics on mental and neurological conditions/disorders remains limited. Further studies of psychobiotics are needed in order to determine into their effectiveness and mechanism as treatments for various psychiatric disorders in the future.
Gut Bacteria Can Influence Your Mood,Thoughts,and Brain:-
ReplyDeleteThe human gut is lined with more than 100 million nerve cells, more than in the spinal cord or in the peripheral nervous system. We have brain cells in our large intestines! This explains why antibiotics which disturb the gut microbial ecosystem might cause neuropsychiatric effects, interact with psychotropic medications, and/or influence our mood. This also explains why mood disorders are so prevalent in patients with irritable bowel syndrome.
Chemicals implicated in depression and happiness such as serotonin are also found in the gut; 90 percent of serotonin is manufactured in the digestive tract and not the brain. Many antidepressants work by increasing serotonin. Scientists have found that gut bacteria produce many other neurotransmitters such as dopamine, norepinephrine, acetylcholine, and GABA, which are critical for mood, anxiety, concentration, reward, and motivation. The gut microbiome can cause changes in how our brains react.
Exposure and consumption of good bacteria are necessary for a balanced brain. Studies found that in germ-free sterile mice, there is an imbalance of depression-related brain chemicals in areas important for emotions and mood. Also, there are significantly more pro-inflammatory cytokines in depressed people compared to non-depressed ones. This effect on the inflammatory system may stem from interactions with a dysfunctional gut microbiome in depressed individuals.
Also, stress makes us more likely to develop mood disorders. And stress makes the gut more permeable to bacteria. Reciprocally, depression causes dysbiosis—an imbalance of good to bad gut bacteria. In sum, depression is maybe caused by dysfunctional gut-brain-immune system interactions.
Good gut bacteria or the absence of some bad ones can make us more resilient to depressive states after stressors or trauma. It is not surprising that chronic exposure to stress is associated with a higher incidence of depression, anxiety.But not everyone who faces stress develops a mood disorder.
Name of few microorganisms present in body:
ReplyDeleteTypes of human microbiota includes bacteria,archaea,fungi,protists and viruses.
Bacteria: Firmicutes,Bacteriodetes,Protobacteria,Verrumicrobia,Actionobacteria,Fusobacteria and Cyanobacteria are present in human gut.
Actinomyces viscosus and A.naeslundii live in mouth.
Lactobacillus acidophilus,L.crispatus,L.iners,L.jensenii,L.delbruekii and L.gasseri are present in vaginal microflora.
Archea:
Methanobrevibacter smithii,Methanosphaera stadtmanae present in human gut.
Fungi:
Yeasts are present in human gut.
Malassezia present on the skin.
Viruses:
Viruses,especially bacterial viruses such as Bacteriophages colonizes various body sites.
Pyschobiotics and Post-biotics:
ReplyDeletePyschobiotics are beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that influence bacteria-brain relationships.Pyschobiotics exerts anxiolytic and antidepressant effects characterised by changes in emotions,cognitive,systematic and neural indices.Bacteria-brain communication channels through which pyschobiotics exert effects include the enteric nervous system and the immune system.
Postbiotics:
Postbiotics are functional fermentations compounds,like that can be used in combination with nutritional components to promote health.Two commonly used types of postbiotics are parapostbiotics and FIFs.Postbiotics may pave the way towards increasing the potency of active microorganisms or turn them into functional ingredients.Besides that,postbiotics circumvent the technical challange of colonization efficiency and keeping the microorganisms viable and stable in the product at a high dose.The postbiotics concept may bring food,microbiology and personalized treatement even closer.
QUESTION:What is Urolithin?
ReplyDeleteUrolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. The gut microbiota influences several biological functions including immune responses. Inflammatory bowel disease is favorably influenced by consumption of several dietary natural plant products such as pomegranate, walnuts, and berries containing polyphenolic compounds such as ellagitannins and ellagic acid. The gut microbiota metabolizes ellagic acid resulting in the formation of bioactive urolithins A, B, C, and D. Urolithin A (UA) is the most active and effective gut metabolite and acts as a potent anti-inflammatory and anti-oxidant agent. However, whether gut metabolite UA affects the function of immune cells remains incompletely understood. Since the 2000s, urolithin A has been subject of preliminary studies regarding its possible biological effects. Urolithin A is not known to be found in any food source. Its bioavailability mostly depends on individual microbiota composition, as only some bacteria are able to convert ellagitannins into urolithins.
QUESTION: What is Punicalagin?
ReplyDeletePunicalagin is an ellagitannin, a type of phenolic compound. It is found in forms alpha and beta in pomegranates (Punica granatum), in Terminalia catappa and Terminalia myriocarpa, and in Combretum molle, the velvet bushwillow, a plant species found in South Africa. These three genera are all Myrtales and the last two are both Combretaceae. Pomegranates have been shown to contain 124 different phytochemicals, and some of them act in concert to exert antioxidant and anti-inflammatory effects on cancer cells. Ellagitannins are bioactive polyphenols present in pomegranate. Pomegranate juice obtained by squeezing the whole fruit has the highest concentration of ellagitannins than any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the known largest molecular weight polyphenol. Pomegranate ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid over several hours in the intestine. Ellagitannins are also metabolized into urolithins by gut flora, which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth. punicalagin, have been characterized to possess antioxidative and anti-genotoxic activities. It is potent immune supressant isolated from pomegranate and has Potential as an antineoplastic.
QUESTION: What Is Glycemic Index (GI)?
ReplyDeleteCarbohydrate is an essential part of our diets, but not all carbohydrate foods are equal. The Glycemic Index (GI) is a relative ranking of carbohydrate in foods according to how they affect blood glucose levels. Carbohydrates with a low GI value (55 or less) are more slowly digested, absorbed and metabolized and cause a lower and slower rise in blood glucose and, therefore usually, insulin levels.
The glycemic index, or GI, was invented in Canada in 1981. It was always intended to be used along with carbohydrate exchanges (which are amounts of food that contain approximately 15 grams of carbohydrate) to help improve blood glucose management. As well as provide much needed insight into the way carbohydrates in food affect blood glucose levels, the GI also helped put an end to the myth that sugars and sugary foods are worse for blood glucose levels than starches and starchy foods.
Since then there have been numerous research papers published not only in the area of diabetes management but also investigating other possible benefits including cardiovascular disease, weight management and even eye health. We have compiled some of the more recent and high level papers for some of the main benefits of GI/GL diets and also some areas where the science is emerging.
The GI value of a food is determined by feeding 10 or more healthy people a portion of the food containing 50 grams of digestible (available) carbohydrate and then measuring the effect on their blood glucose levels over the next two hours. For each person, the area under their two-hour blood glucose response (glucose AUC) for this food is then measured. On another occasion, the same 10 people consume an equal carbohydrate portion of the sugar glucose (the reference food) and their two-hour blood glucose response is also measured. A GI value for the test food is then calculated for each person by dividing their glucose AUC for the test food by their glucose AUC for the reference food. The final GI value for the test food is the average GI value for the 10 people.
Research has proven that a healthy low GI diet helps people with diabetes (type 1 and type 2) manage their blood glucose levels, blood cholesterol levels and reduce insulin resistance – which is important for reducing the risk of long term diabetes related complications. A low GI diet can improve heart health by: Helping to reduce post-meal blood glucose levels, improving the elasticity of blood vessel walls and blood flow, low GI diets can significantly reduce total and LDL cholesterol levels, independent of weight loss, reducing the risk of atherosclerosis, a chronic disease affecting blood vessels, by reducing inflammation. Aiding abdominal fat reduction.
QUESTION: What is gluten, and why is it bad for some people?
ReplyDeleteGluten is controversial these days. Most sources claim that it is safe for everyone except those who have celiac disease. On the other hand, some health experts believe that gluten is harmful to most people.
Gluten is a family of storage proteins — formally known as prolamins found in grains, including wheat, rye, spelt, and barley. Of the gluten-containing grains, wheat is by far the most common. The two main proteins in gluten are glutenin and gliadin. Gliadin is responsible for most of the adverse health effects of gluten. When flour mixes with water, the gluten proteins form a sticky network that has a glue-like consistency. This glue-like property makes the dough elastic and gives bread the ability to rise during baking. It also provides a chewy, satisfying texture. Interestingly, the name gluten derives from this glue like property of wet dough.
Problems with gluten
Most people can tolerate gluten with no adverse effects. However, it can cause problems for people with certain health conditions. This includes celiac disease, gluten sensitivity, wheat allergy, and some other diseases.
Celiac disease
Celiac disease, also spelled as coeliac disease, is the most severe form of gluten intolerance. It affects about 1% of the population. It is an autoimmune disorder in which the body treats gluten as a foreign invader. The immune system attacks the gluten, as well as the lining of the gut. This damages the gut wall and may cause nutrient deficiencies, anemia, severe digestive issues, and an increased risk of many diseases. However, some people with celiac disease do not have digestive symptoms but may have other symptoms, such as tiredness or anemia. For this reason, doctors often find it challenging to diagnose celiac disease. In fact, in one study, 80% of people with celiac disease did not know they had it.
Non-celiac gluten sensitivity
Many people do not test positive for celiac disease but still react negatively to gluten. This condition is called non-celiac gluten sensitivity. Researchers do not currently know how many people have this condition, but some estimate it to be in the range of 0.5 to 13%.
QUESTION:What is enterotype?
ReplyDeleteEnterotypes are clusters of bacterial communities in the gut that allow researchers to identify common traits that bring people together. Long-term dietary patterns have a powerful influence on the gut microbiota composition, and they are associated with three gut microbiota profile clusters, also known as enterotypes. The enterotypes are divided according to the predominance of Bacteroides (associated with high protein and animal fat diets), Prevotella (associated with carbohydrate-rich diets), or Ruminococcus (associated with a diet high in resistant starch); these enterotypes may correlate with individual health status. The clustering of the gut microbiota has led to the concept of classifying individuals by enterotypes, which is based on the notion that the gut microbiota congregates in a relatively stable composition over time .The discovery of three human enterotypes was announced in the April 2011 issue of Nature by Peer Bork and his associates.
QUESTION:Which types of hormones can be produce by microorganisms?
ReplyDeletePhytohormones have also been detected and identified in the supernatant of culture medium of many soil and plant-associated bacteria and fungi. In these organisms, the phytohormones do not induce typical hormonal or major physiological changes. Microbial phytohormone production has been linked to changes in root architecture and plant growth promotion. However, the degree of proof for their involvement can vary a lot depending on the phytohormone and the studied microbial strain. Phytohormones (auxins, cytokinins, gibberellins, abscisic acid and ethylene) are elicitors, which can be produced by bacteria and play a role in promoting plant growth Generally, plant hormones are mainly divided into 5 categories: auxins, cytokinins, ethylene, gibberellins (GAs) and abscisic acid (ABA). Gibberellins and abscisic acid accumulated as secondary metabolites in filamentous fungi.
For the industrial production of plant hormones such as GAs and ABA, several processes using fungal fermentation were successfully set up in China. As early as 1950s–1960s, the solid state fermentation of GAs has been applied. However, due to the low yield, tedious operation and other shortcomings, the solid state fermentation was gradually replaced by liquid submerged fermentation, the titer of the process is generally at about 2.0 g/L. Compared with GAs, the industrial microbial fermentation of ABA started relatively late. Until the beginning of this century, the scientist in Chengdu Institute of Biology, Chinese Academy of Sciences, firstly solved the key technical problems and successfully obtained ABA overproducing strain. Through the optimization of liquid submerged fermentation process, the ABA maximum production titer was eventually up to 6.0 g/L. Subsequently, the world's first industrial production line of ABA was formally established through the cooperation with the company Sichuan Lomon Bio Co. Ltd, which greatly reduced the cost and price of ABA and further promoted the application of ABA in agriculture.
QUESTION:What is Peptide YY?
ReplyDeleteThe full name for peptide YY is pancreatic peptide YY. It is a hormone that is secreted from endocrine cells called L-cells in the small intestine. There are two major forms of the peptide; one is 36 amino acids long (PYY1-36) and the other lacks the first two amino acids (PYY3-36). It is secreted alongside the hormone glucagon-like peptide 1. Peptide YY is released after eating, circulates in the blood and works by binding to receptors in the brain. Binding of peptide YY to brain receptors decreases appetite and makes people feel full after eating. Peptide YY also acts in the stomach and intestine to slow down the movement of food through the digestive tract. PYY is also anorexigenic, i.e., it reduces appetite.
How is your body able to recognize when you have eaten enough food?
After eating, the hormone peptide YY (PYY) will be produced by the small intestine and released into your bloodstream. PYY communicates to your brain that you are full and decreases your appetite. The amount of PPY released depends on the type and quantity of food eaten.
How Does Your Body Use PYY?
Peptide YY secretion is mainly stimulated by the presence of food in the digestive tract, particularly fat and protein. The amount of peptide YY that is released into the blood depends on the amount of calories eaten, with higher calorie foods causing more peptide YY release than lower calorie foods. Peptide YY secretion can also be stimulated by digestive juices (such as bile) and another gastrointestinal hormone called cholecystokinin. The highest levels of peptide YY are found in the second hour after eating. Peptide YY levels then gradually decrease. Low levels of peptide YY are seen during long periods without eating, for example overnight.
What happens if I have too much peptide YY?
High peptide YY concentrations are unusual. They will cause a decrease in appetite and food intake. High peptide YY concentrations are associated with diseases where there is dramatic weight loss, such as anorexia nervosa, coeliac disease, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and some cancers.
What happens if I have too little peptide YY?
Low peptide YY concentrations are associated with an increase in appetite and food intake. Low peptide YY levels are seen in obesity and before the onset of type 2 diabetes and may contribute to weight gain in these conditions. However, low peptide YY concentrations are very unlikely to be the main cause of obesity as the levels decrease after weight gain has started. There has been some research into using peptide YY as a medication for obesity, aiming to decrease the appetite of people who are overweight. This research is still ongoing. It is extremely rare to have a genetic (inherited) deficiency of peptide YY. Low PYY levels mean that you may experience an increase in appetite. Lower PYY levels may contribute to weight gain, however it is not believed to be the main cause of obesity. It is very rare to have a genetic or endocrine disorder of PYY.
QUESTION:What is cholesterol?
ReplyDeleteOverview
With all of the bad publicity cholesterol gets, people are often surprised to learn that it’s actually necessary for our existence. What’s also surprising is that our bodies produce cholesterol naturally. But cholesterol isn’t all good, nor is it all bad — it’s a complex topic and one worth knowing more about. Cholesterol is a substance made in the liver that’s vital to human life. You can also get cholesterol through foods. Since it can’t be created by plants, you can only find it in animal products like meat and dairy. Cholesterol is a waxy, fat-like substance that your body needs for good health, but in the right amounts. Unhealthy levels of cholesterol can lead to a condition called high blood cholesterol.
Why Is Cholesterol Needed by the Body?
In our bodies, cholesterol serves three main purposes: It aids in the production of sex hormones, it’s a building block for human tissues, and it assists in bile production in the liver.
LDL vs. HDL
When people talk about cholesterol, they often use the terms LDL and HDL. Both are lipoproteins, which are compounds made of fat and protein that are responsible for carrying cholesterol throughout the body in the blood. LDL is low-density lipoprotein, often called “bad” cholesterol. HDL is high-density lipoprotein, or “good” cholesterol.
Why is LDL bad?
LDL is known as the “bad” cholesterol because too much of it can lead to hardening of the arteries. According to the American Heart Association, LDL leads to plaque accumulation on the walls of your arteries. When this plaque builds up, it can cause two separate, and equally bad, issues. First, it can narrow the blood vessels, straining the flow of oxygen-rich blood throughout the body. Second, it can lead to blood clots, which can break loose and block the flow of blood, causing a heart attack or stroke. When it comes to your cholesterol numbers, your LDL is the one you want to keep low — ideally less than 100 milligrams per deciliter (mg/dL).
Why is HDL good?
HDL helps keep your cardiovascular system healthy. It actually aids in the removal of LDL from the arteries. It carries the bad cholesterol back to the liver, where it’s broken down and eliminated from the body. High levels of HDL have also been shown to protect against stroke and heart attack, while low HDL has been shown to increase those risks. According to the National Institutes of Health (NIH), HDL levels of 60 mg/dL and higher are considered protective, while those under 40 mg/dL are a risk factor for heart disease.
QUESTION:What is cytokine storm?
ReplyDeleteCytokines are small proteins released by many different cells in the body, including those of the immune system where they coordinate the body’s response against infection and trigger inflammation. The name ‘cytokine’ is derived from the Greek words for cell (cyto) and movement (kinos).
A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death. Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1, and SARS-CoV-2 (COVID-19 agent).
Cytokine storm syndrome is diverse set of conditions that can result in cytokine storm. Cytokine storm syndromes include familiar hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.
QUESTION:What is Neutrophil Chemotaxis?
ReplyDeleteNeutrophils undergo a process called chemotaxis via amoeboid movement, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-γ), C3a, C5a, and Leukotriene B4, which these cells use to direct the path of their migration. Neutrophils have a variety of specific receptors, including ones for complement, cytokines like interleukins and IFN-γ, chemokines, lectins, and other proteins. They also express receptors to detect and adhere to endothelium and Fc receptors for opsonin.
In leukocytes responding to a chemoattractant, the cellular polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks regulate activation of Rho GTPases and are required for cell motility. They accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl.
Role of Bile Acids
ReplyDeleteBile acids are hydroxylated steroids, synthesized in the liver from cholesterol. Glucose, insulin and glucagon also appear to help regulate BA biosynthesis. BAs are ligands for the nuclear farnesoid X receptor (FXR), as well as a G protein-coupled receptor(GPCR's).Bile acids are modified by intestinal bacteria. Primary bile acids are converted to secondary bile acids by dehydroxylation. Bile promotes emulsification of dietary lipids, for digestion and absorption of fatty acids, cholesterol, fat-soluble vitamins, and other hydrophobic components of the diet. Bile acids that are not absorbed in the small intestine reach the large intestine and are metabolized by the microbiota, before being almost totally reabsorbed from the colon.
GPBAR1 and FXR modulate the intestinal and liver innate immune system and contribute to the maintenance of a tolerogenic phenotype in entero-hepatic tissues, and how regulation of innate immunity might help to explain beneficial effects exerted by GPBAR1 and FXR ligands in immune and metabolic disorders.
Role of SCFA (Short chain Fatty acids)
ReplyDeleteSCFAs are saturated organic acids. They are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota–gut–brain crosstalk. SCFAs directly or indirectly mediate microbiota–gut–brain interactions. They affect cellular systems and their interaction with gut–brain signalling pathways including immune, endocrine, neural and humoral routes. The SCFAs acetate, propionate, and butyrate are the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch. SCFAs have potential to prevent and treat metabolic and inflammatory diseases. They help in maturation of Dendritic cells, enhance T- helper 2 cells, decrease the production of IL12 and IF gamma, also lowers the expression of MHC-2 and costimulatory molecules.
What is HPA axis?
ReplyDeleteThe hypothalamic pituitary adrenal (HPA) axis is our central stress response system.The HPA axis is responsible for the neuroendocrine adaptation component of the stress response. Its dysregulation plays an important role is severe mental disorders. Concentration variance of bile acids through HPA axis affects Gut Brain axis and varies its ability to respond to physiological and psychological stress.
What is Blood- Brain barrier (BBB)?
ReplyDeleteBBB is a semi permeable membrane protecting brain from viruses, bacteria or drugs. Cells within and on either side of the blood-brain barrier are in constant communication about which molecules to let through and when. When the blood-brain barrier breaks down, as is the case in some brain cancers and brain infections or when tiny ruptures to blood vessels occur, some substances that are normally kept out of the brain gain entry and cause problems for the brain. A leaky blood-brain barrier allows too many white blood cells into the brains of people with multiple sclerosis (MS).
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ReplyDeleteWhy colon supports the largest number of bacteria?
ReplyDeleteAns. The small intestine is followed by the large intestine (colon), which has a larger diameter, but shorter length and is divided into four sections: the ascending colon (cecum), transverse colon, descending colon, and sigmoid colon (123). Water and minerals are continuously absorbed along the colon before excretion. Furthermore, complex foods that cannot be digested by the host are used as growth substrates for the colonic microbiota.
Bacteria in the colon account for approximately 70% of all bacteria in the human body because it is the main site for the bacterial fermentation of non-digestible food components such as soluble fiber.
Also the food remains for 10 to 12hours in the large intestine thereby giving more contact time.
Functions of The Human Gut Microbiota
ReplyDeleteHuman gut microbes perform many metabolic functions that our own bodies cannot carry out, creating a symbiotic relationship. For example, we consume plant polysaccharides that are rich in xylan-, pectin- and arabinose-containing carbohydrate structures, which we are unable to digest. Encoded in the genomes of gut microbiota, however, are a large number of glycoside hydrolases, which break down these plant products and convert them into usable energy sources. At the same time, gut bacteria derive their own energy from fermentation of these glycans.
In addition, microbiota are able to synthesize vitamins and amino acids, degrade dietary oxalates, metabolize host-produced mucosal glycans, and biotransform bile acids.
LACTOBACILLUS
ReplyDeleteRHAMNOSUS PROBIOTIC
Lactobacillus rhamnosus probiotic affect in weight reduction,apetite control and eating behaviour in a group of obese men and women.In a group of obese women the consumption of this microorganism provide beneficial effects on mood and behaviour linked to dietary intake ,compared to group of men and those who received placebo.
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Yakult is full of organisms as well as sugars, so why can’t those organisms use present sugar in yakult....
ReplyDeleteDuring the process of yakult formation, initially organism is allowed to ferment the milk to form fermented milk base and then it is added to sugar syrup. So, like initially growth is promoted upto it's maximum possible limit and then treatment with high sugar concentration will lead to prevent further growth due to osmolarity, and they might be balancing the sugar concentration upto the limit that organism can survive and no further division is possible to keep cell in viable state.
Reference :- https://www.yakult.com.ph/production-process
QUESTION: WHAT ARE THE POSITIVE AND NEGATIVE EFFECTS OF ZINC FOOD ON HUMAN HEALTH? AND WHAT ARE THE GOOD EXAMPLES OF VEGETARIAN AND NON-VEGETARIAN ZINC RICH DIETS?
ReplyDeleteANSWER: Zinc is Mostly found in cells throughout the body. It is needed for the body's immune system to properly work. It plays a role in cell division, cell growth, wound healing, and the breakdown of carbohydrates. Zinc is also needed for the senses of smell and taste these are the positive sites.
Negative sites: Immediate symptoms after uptake of toxic amounts of zinc include abdominal pain, nausea, and vomiting. Additional effects include lethargy, anemia, and dizziness.
Good sources of zinc for vegetarians include whole grains, tofu, tempeh, legumes, nuts and seeds, fortified breakfast cereals and dairy products.
For those who consume non-vegetarian food, fish would be an excellent source of zinc. Consume at least twice a week is very effective. Meat and poultry can also be an option. Eggs are also good source of zinc.
This is all about sources and effects of zinc food on human health.
Que:- Zinc rich foods for vegetarian people:
ReplyDeleteAns:- whole grains,nuts,seeds(like Flax Seeds,pumpkin seeds,sunflower seeds),cereals , dairy products(like milk and cheese), vegetables and fruits (like banana,potato,avocado ,green peas)they all contain very small amount of zinc but they'll help sneak a small amount into diet.
What are Phytopharmaceuticals?
ReplyDeleteThe term ”phytopharmaceutical” is derived from blend of two words, phyto (referring to plant) and pharmaceutical (refers to medicinal drugs). Plants produce a variety of natural compounds. Herbal crude drugs are processed into herbal extracts which keads to enrichment of bioactive compounds. Phytopharmaceutical drug is defined as purified and standardized fraction with defined minimum four bio-active or phytochemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation, or prevention of any disease or disorder. These are available in dry froms as granules, tablets, capsules etc. Also, medicinal oils can be used from plants or flowers to make ointments.
What are Nutraceuticals?
ReplyDeleteNutraceuticals are products, which other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Nutraceuticals may be used to improve health, delay the aging process, prevent chronic diseases, increase life expectancy, or support the structure or function of the body. These are nutritional, safe and show therapeutic effects. Nutraceuticals are nutritional supplements which are also used for health purposes other than nutrition.
QUESTION: What is the meaning of Selective toxicity?????
ReplyDeleteANSWER: Selective toxicity refers to the power of the drug to targets sites that are relative specific to the microorganism liable for infection. Sometimes these sites are unique to the microorganism or just more essential to survival of the microorganism than to the host.
A newly discovered carbomycine and lesser known complestain kill bacteria by blocking the function of cell wall.
ReplyDeleteAntibiotic like penicilin kill bacteria by preventing the building of cell wall but above two antibiotics work by doing opposite.They prevent wall from being broken down .This is critical for cell to devide.And cell duvision izs very important for cell to grow .And these antibiotics prevent cell division.
These antibiotics comesfrom glycopeptide antibiotics which are produced by soil microbes .And it can block infection of drug resistant staphylococcus aureus.
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■ Zn containing diet for vegetarian and non vegetarian people.
ReplyDelete• VEGETARIAN DIET
-For a vegetarian,the best option would be to include a handful nuts in daily diet.these can be trail mix of walnuts, almonds, cashews and other fruits & nuts
-Seeds,especially sunflower seeds, pumpkin seeds, watermelon seeds.
-Legumes
-Whole grains
-Dairy product (dark chocolate contain reasonable amount of Zn)
•NON VEGETARIAN DIET
-Meat is excellent source of Zn especially red meat. (beef, lamb, pork)
-Shellfish -low calorie source of Zn.
-Eggs containing moderate amount of Zn.
■ Zn containing diet for vegetarian and non vegetarian people.
ReplyDelete• VEGETARIAN DIET
-For a vegetarian,the best option would be to include a handful nuts in daily diet.these can be trail mix of walnuts, almonds, cashews and other fruits & nuts
-Seeds,especially sunflower seeds, pumpkin seeds, watermelon seeds.
-Legumes
-Whole grains
-Dairy product (dark chocolate contain reasonable amount of Zn)
•NON VEGETARIAN DIET
-Meat is excellent source of Zn especially red meat. (beef, lamb, pork)
-Shellfish -low calorie source of Zn.
-Eggs containing moderate amount of Zn.
Q:- Importance of tryptophan in human microbiome?
ReplyDeleteA:- Tryptophan is an essential amino acid which is not synthesized by human body. Therefor it must be provided through regular diet sources which are rich in tryptophan.
It is found in two forms in human body.
1) Bounded to albumin
2) free form
The transportation of tryptophan across blood - brain - barrier only of free form of tryptophan through nonspecific transporter of amino acids.
The recommended amount of tryptophan in human body is 250 - 425 mg/d/adult but through diet individual gets higher concentration of tryptophan that ranges from 850 - 1000 mg/d.
Sources of tryptophan.
Vegeterian diet - banana, milk, oats,peanuts.
Non-vegetarian diet -fish, chicken,
chocolate.
It is used in protein synthesis. Mainly for serotonin which is 95% synthesized in GI tract. Tryptophan which is consumed through diet out of that approximately 3% used for synthesis of serotonin in GI tract and 1% used for synthesis for serotonin in brain which acts as neurotransmitter and neuromodulator.
The enterochromaffin cells of the mucosa are the major source of serotonin in GI tract which use tryptophan.
Serotonin is mainly responsible for controlling GI motility and secretion in the gut and play an important role in mood and cognition in the brain.
What is chitosan?
ReplyDeleteChitosan is a sugar that is obtained from the hard outer skeleton of shellfish, including crab, lobster, and shrimp. It is used for medicine.
Chitosan is used to treat obesity, high cholesterol, and Crohn's disease. It is also used to treat complications that kidney failure patients on dialysis often face, including high cholesterol, “tired blood” (anemia), loss of strength and appetite, and trouble sleeping (insomnia).
Some people apply chitosan directly to their gums to treat inflammation that can lead to tooth loss (periodontitis), or chew gum that contains chitosan to prevent “cavities” (dental caries).
Interactions of chitosan with medication
ReplyDeleteWarfarin (Coumadin) interacts with CHITOSAN
Warfarin is a blood thinner. There is some concern that taking chitosan might increase the blood thinning effects of warfarin (Coumadin). Taking chitosan with warfarin (Coumadin) could increase the chance of bruising or bleeding. If you take warfarin, avoid taking chitosan.
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ReplyDeleteQ:- Importance of QUERCETI
ReplyDeleteA:- Quercetin is a plant pigment which is antioxident flavonoid specifically a flavonol.
It is found in most of the plant based products. It observed in most of the fruits and vegetables.
It highly observed in apple honey, raspberries, onions, red grapes, cherries.
It is foun in green leafy vegetables also.
It is common compound in citrus fruits.
Specifically it is present in onion in abundance amount according to type of onion and also type of compound.
Quercetin
Yellow onion - 94.95 mg/g/Dw
Red onion - 73.83 mg/g/DW
Quercetin - 3 -glucoside
Red onion - 32.21 mg/g/DW
chartreuse onion - 127.92 mg/g/DW.
Importance
- tissue injuries
- drug toxicities
- reduced inflammation
- helps to control blood pressure
- helps to control sugar level
- antiallergic substances
- anticancer properties.
Pan-assay interference compounds (PAINS)
ReplyDeletePan-assay interference compounds (PAINS) cause false-positive assay signals due to reactivity under assay conditions, including covalent modifications or redox effects, chelation, autofluorescence, or degradation.(1-3) More than 450 compound classes have been designated as PAINS to date, including, for example, rhodanines, isothiazolones, enones, and quinonesas well as pharmaceutically intensely explored compounds such as curcuminoids.
Classified PAINS are typically small reactive or otherwise liable molecules that are contained as substructures in larger compounds.
Common PAINS include toxoflavin, isothiazolones, hydroxyphenyl hydrazones, curcumin, phenol-sulfonamides, rhodanines, enones, quinones, and catechols.
What are functional foods?
ReplyDeleteBasically, functional foods are foods that provide a health benefit in addition to macro and micronutrients. These foods are vital in disease prevention and include fortified foods, phytonutrient-containing fruits and vegetables, fermented foods, fish and chocolate.
Fortified foods are considered functional, as they have vitamins and minerals added to them in order to prevent diseases. Vitamin D is added to milk, as it helps with calcium absorption, which is vital in the prevention of rickets and osteoporosis. Flour and cereals in the U.S. are fortified with folic acid, a B vitamin that is essential in the prevention of neural tube defects in infants. Some types of salt contain iodine, which prevents intellectual and developmental disabilities as well as enlarged thyroid glands.
Many of these foods are the result of public health initiatives to prevent many diseases in populations that do not consume a nutrient-dense diet.
Functional foods may include:
Conventional foods such as grains, fruits, vegetables and nuts.
Modified foods such as yogurt, cereals and orange juice.
Consider eating more of these nutrient-dense, functional foods.
1. Cold-Water Fish — Sardines and Salmon
These protein-packed fish are lower in mercury and have higher amounts of omega-3 fatty acids, which may help lower risk of heart disease and improve infant health when consumed by women during pregnancy or while breast-feeding. About eight ounces of seafood a week is a good goal for adults, which amounts to two meals per week.
2. Nuts
They make a great snack, help you feel full and may help promote heart health. Bonus: most unsalted nuts, including cashews and almonds, are good sources of magnesium, which plays a role in managing blood pressure.
3. Whole Grains — Barley
Often overshadowed by the fame of oatmeal, barley delivers similar benefits. It's high in dietary fiber, an underconsumed nutrient of public health concern in the U.S., and may help lower cholesterol and assist with blood sugar control.
4. Beans
Beans provide dietary fiber, as well as protein, potassium and folate. While canned beans are fine, look for those with no salt added. If you do choose beans with salt added, rinse and drain them before use, which reduces sodium significantly.
Berries
Whether you opt for strawberries, cranberries, blueberries, raspberries or blackberries, berries in general are wonderful functional foods. Not only are they low in calories, their anthocyanin pigments, which give them color, may offer health promoting benefits. If you can't get fresh berries, frozen unsweetened berries make a fine alternative.
Five Basic Mechanisms of Antibiotic Action against Bacterial Cells:
ReplyDeleteA. Inhibition of Cell Wall Synthesis
Beta-Lactams ---> Inhibition of peptidoglycan synthesis (bactericidal)
Resistance --->
(1) fails to cross membrane (gram negatives)
(2) fails to bind to altered PBP�s
(3) hydrolysis by beta-lactamases
Vancomycin ---> Disrupts peptidoglycan cross-linkage
Resistance --->
(1) fails to cross gram negative outer membrane (too large)
(2) some intrinsically resistant (pentapeptide terminus)
Bacitracin ---> Disrupts movement of peptidoglycan precursors (topical use)
Resistance ---> fails to penetrate into cell
Antimycobacterial agents ---> Disrupt mycolic acid or arabinoglycan synthesis (bactericidal)
Resistance --->
(1) reduced uptake
(2) alteration of target sites
B. Inhibition of Protein Synthesis (Translation)
30S Ribosome site
Aminoglycosides ---> Irreversibly bind 30S ribosomal proteins (bactericidal)
Resistance --->
(1) mutation of ribosomal binding site
(2) decreased uptake
(3) enzymatic modification of antibiotic
Tetracyclines ---> Block tRNA binding to 30S ribosome-mRNA complex (b-static)
Resistance --->
(1) decreased penetration
(2) active efflux of antibiotic out of cell
(3) protection of 30S ribosome
50S Ribosome site
Chloramphenicol ---> Binds peptidyl transferase component of 50S ribosome, blocking peptide elongation (bacteriostatic)
Resistance --->
(1) plasmid-encoded chloramphenicol transferase
(2) altered outer membrane (chromosomal mutations)
Macrolides ---> Reversibly bind 50S ribosome, block peptide elongation (b-static)
Resistance --->
(1) methylation of 23S ribosomal RNA subunit
(2) enzymatic cleavage (erythromycin esterase)
(3) active efflux
Clindamycin ---> Binds 50S ribosome, blocks peptide elongation; Inhibits peptidyl transferase by interfering with binding of amino acid-acyl-tRNA complex
Resistance ---> methylation of 23S ribosomal RNA subunit
C. Alteration of Cell Membranes
Polymyxins (topical) ---> Cationic detergent-like activity (topical use)
Resistance ---> inability to penetrate outer membrane
Bacitracin (topical) ---> Disrupt cytoplasmic membranes
Resistance ---> inability to penetrate outer membrane
D. Inhibition of Nucleic Acid Synthesis
DNA Effects
Quinolones ---> Inhibit DNA gyrases or topoisomerases required for supercoiling of DNA; bind to alpha subunit
Resistance --->
(1) alteration of alpha subunit of DNA gyrase (chromosomal)
(2) decreased uptake by alteration of porins (chromosomal)
Metronidazole ---> Metabolic cytotoxic byproducts disrupt DNA
Resistance --->
(1) decreased uptake
(2) elimination of toxic compounds before they interact
RNA Effects (Transcription)
Rifampin ---> Binds to DNA-dependent RNA polymerase inhibiting initiation & Rifabutin of RNA synthesis
Resistance --->
(1) altered of beta subunit of RNA polymerase (chromosomal)
(2) intrinsic resistance in gram negatives (decreased uptake)
Bacitracin (topical) ---> Inhibits RNA transcription
Resistance ---> inability to penetrate outer membrane
E. Antimetabolite Activity
Sulfonamides & Dapsone ---> Compete with p-aminobenzoic acid (PABA) preventing synthesis of folic acid
Resistance ---> permeability barriers (e.g., Pseudomonas)
Trimethoprim ---> Inhibit dihydrofolate reductase preventing synthesis of folic acid
Resistance --->
(1) decreased affinity of dihydrofolate reductase
(2) intrinsic resistance if use exogenous thymidine
Trimethoprim-Sulfamethoxazole synergism
1. Phytopharmaceuticals = Globally, herbal medicine has been considered an important alternative to modern allopathic medicine. Phytopharmaceuticals are herbal medicines whose efficacy is down to one or several plant substances or active ingredients. Phytopharmaceutical drug is defined as purified and standardized fraction with defined minimum four bio-active or phytochemical compounds (qualitatively and quantitatively assessed) of an extract of a medicinal plant or its part, for internal or external use of human beings or animals for diagnosis, treatment, mitigation, or prevention of any disease or disorder but does not include administration by parenteral route.
ReplyDelete2. Nutraceuticals = Nutraceutic is a term derived from “nutrition” and “pharmaceutics.” The term is applied to products that are isolated from herbal products, dietary supplements (nutrients), specific diets, and processed foods such as cereals, soups, and beverages that other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Emphasis has been made to present herbal nutraceuticals effective on hard curative disorders related to oxidative stress including allergy, Alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory and Parkinson's diseases as well as obesity.
3. Functional foods = Literally, it is another term of Nutraceuticals and Functional foods are foods that have a potentially positive effect on health beyond basic nutrition. Proponents of functional foods say they promote optimal health and help reduce the risk of disease.
Generally, Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good food sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products
ReplyDeleteThere was a strong correlation between Zn serum levels and meat and milk consumption in a Greek population, while no significant association was found with the consumption of fish, green vegetables, legumes, eggs or fruits, because it is well known that Zn bioavailability is decreased by high levels of dietary phytate, which is present in vegetables, cereals and legumes. The Mediterranean diet is characterized by a high content of these types of foods, which increases phytate consumption and, therefore, might affect dietary Zn bioavailability. Also Certain components of the diet, such as fibre, Ca, P, Fe and Cu, have been considered to decrease Zn bioavailability.
Another factor to be considered as influencing Zn absorption is the dietary content of Maillard reaction products (MRP). These compounds are formed in heat processes such as frying, a common culinary technique in the Mediterranean diet, and, thus, they are usually present in this diet. Animal balance studies have shown that feeding rats with diets containing the MRP model induces significant reductions in Zn absorption and retention (both net and fractional), compared with animals fed control diets. Therefore, the presence of MRP in the experimental diet may have been a negative factor for dietary Zn utilization.
Reference -
(https://www.cambridge.org/core/journals/public-health-nutrition/article/is-the-mediterranean-diet-adequate-to-satisfy-zinc-requirements-during-adolescence/2173F6B628AA34161D2C67112ECD84D5/core-reader#:~:text=found%20a%20strong%20correlation%20between,%2C%20legumes%2C%20eggs%20or%20fruits)
An ANTIBIOTIC is a low molecular substance produced by a microorganism that at a low concentration inhibits or kills other microorganisms. An ANTIMICROBIAL is any substance of natural, semisynthetic or synthetic origin that kills or inhibits the growth of microorganisms but causes little or no damage to the host.
ReplyDeleteQuercetin and its uses
ReplyDeleteThe name quercetin (3,3',4',5,7-pentahydroxyflavone) comes from the Latin word “Quercetum”, belongs to the class called flavonols that cannot be produced in the human body.It is yellow color and is poorly soluble in hot water, quite soluble in alcohol and lipids and is insoluble in cold water. Quercetin is said to be one of the most widely used bioflavonoids for the treatment of metabolic and inflammatory disorders.The highest concentrations of flavonols were found in vegetables such as onions and broccoli, fruits such as apples, cherries, and berries, and drinks such as tea and red wine.
Pharmacological Importance of Quercetin
Anti-inflammatory
One of the core most remarkable properties of quercetin is its ability to modulate inflammation. Quercetin inhibits inflammatory enzymes cyclooxygenase (COX) and lipooxygenase thereby decreasing inflammatory mediators such as prostaglandins and leukotrienes.Elevated C-reactive protein (CRP) levels are associated with numerous disease states such as obesity, heart disease, and lupus. It has been identified through the study that intake of certain foods can lower the levels of the inflammatory risk factor (CRP). In preclinical in vitro studies, quercetin showed a significant reduction in the levels of inflammatory mediators such as NO synthase, COX-2, and CRP in human hepatocyte-derived cell line.
Cardiovascular disease prevention
Flavonoids existing over many years such as quercetin possess a wide spectrum of biological activities which may have a positive influence on cardiovascular diseases.Quercetin inhibits the platelet aggregation and improves the health of the endothelium. In addition to that, it also protects against CHD and reduces the risk of mortality caused by low-density lipoprotein (LDL). It is known to exhibit important vasorelaxant properties on isolated arteries which helps to lower blood pressure and prevents the development of cardiac hypertrophy.
Neurodegenerative disorders
Flavonoids exert multiple beneficial effects on Neurodegenerative diseases such as Alzheimer's and Parkinson's disease.Quercetin along with with ascorbic acid reduces the incidence of oxidative damage to human lymphocytes and neurovascular structures in the skin and inhibits damage to neurons. It is known to protect brain cells against the oxidative stress, which damages tissue leading to Alzheimer and other neurological conditions.
Ulcer and gastritis
The studies have shown that quercetin inhibits gastric acid secretion and lipid peroxidation of gastric cells thereby serves as gastroprotective agents.
Que : what is the newest antibiotics?
ReplyDeleteAns:- Ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin are relatively new antibiotics.
Question: classes of antibiotics
ReplyDeleteAns:Classes of antibiotics include the following:
Aminoglycosides
Carbapenems
Cephalosporins
Fluoroquinolones
Glycopeptides and lipoglycopeptides (such as vancomycin)
Macrolides (such as erythromycin and azithromycin)
Monobactams (aztreonam)
Oxazolidinones (such as linezolid and tedizolid)
Penicillins
Polypeptides
Rifamycins
Sulfonamides
Streptogramins (such as quinupristin and dalfopristin)
Tetracyclines
Carbapenems, cephalosporins, monobactams, and penicillins are subclasses of beta-lactam antibiotics, a class of antibiotic characterized by a chemical structure called a beta-lactam ring.
Other antibiotics that do not fit into the classes listed above include chloramphenicol, clindamycin, daptomycin, fosfomycin, lefamulin, metronidazole, mupirocin, nitrofurantoin, and tigecycline.
What is Augmentin (amoxicillin and clavulanic acid)?
ReplyDeleteAmoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms.
Amoxicillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not include organisms which produce these enzymes.
Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins.
In particular, it has good activity against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred
drug resistance.
The formulation of amoxicillin and clavulanic acid in AUGMENTIN protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics.
Thus, AUGMENTIN possesses the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
Riboswitches
ReplyDeleteThe majority of riboswitches are regulatory RNAs that regulate gene expression by binding small-molecule metabolites.
The discovery of an aminoglycoside-binding riboswitch that is widely distributed among antibiotic-resistant bacterial pathogens.
This riboswitch is present in the leader RNA of the resistance genes that encode the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes that confer resistance to aminoglycoside antibiotics through modification of the drugs.
The expression of the AAC and AAD resistance genes is regulated by aminoglycoside binding to a secondary structure in their 5′ leader RNA. Reporter gene expression, direct measurements of drug RNA binding, chemical probing, and UV crosslinking combined with mutational analysis demonstrate that the leader RNA functions as an aminoglycoside-sensing riboswitch in which drug binding to the leader RNA leads to the induction of aminoglycosides antibiotic resistance.
SIDEROPHORES :
ReplyDeleteSiderophores are small and high-affinity iron chelating compounds which are secreted by bacteria and fungi and serve primarily to transport iron across cell membrane. Siderophores are among the strongest soluble Fe3+ binding agents known. Siderophores are usually classified by the ligands used to chelate the ferric iron. The major groups of siderophores include the catecholates, hydroxamates and carboxylates. Citric acid can also act as a siderophore.
Once in the cytoplasm of the cell Fe3+-siderophore complex is usually reduced to Fe2+ to release the iron especially in the case of "weaker" siderophore ligands such as hydroxamates and carboxylates. Siderophore decomposition or other biological mechanisms can also release iron.
Siderophores are useful as drugs in facilitating iron mobilization in humans, especially in the treatment of iron diseases, due to their high affinity for iron. One potentially powerful application is to use the iron transport abilities of siderophores to carry drugs into cells by preparation of conjugates between siderophores and antimicrobial agents. Because microbes recognize and utilize only certain siderophores, such conjugates are anticipated to have selective antimicrobial activity.
SIDEROPHORES :
ReplyDeleteSiderophores are small and high-affinity iron chelating compounds which are secreted by bacteria and fungi and serve primarily to transport iron across cell membrane. Siderophores are among the strongest soluble Fe3+ binding agents known. Siderophores are usually classified by the ligands used to chelate the ferric iron. The major groups of siderophores include the catecholates, hydroxamates and carboxylates. Citric acid can also act as a siderophore.
Once in the cytoplasm of the cell Fe3+-siderophore complex is usually reduced to Fe2+ to release the iron especially in the case of "weaker" siderophore ligands such as hydroxamates and carboxylates. Siderophore decomposition or other biological mechanisms can also release iron.
Siderophores are useful as drugs in facilitating iron mobilization in humans, especially in the treatment of iron diseases, due to their high affinity for iron. One potentially powerful application is to use the iron transport abilities of siderophores to carry drugs into cells by preparation of conjugates between siderophores and antimicrobial agents. Because microbes recognize and utilize only certain siderophores, such conjugates are anticipated to have selective antimicrobial activity.
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ReplyDeleteRIBOSWITCHES
ReplyDeleteans :- Riboswitches are RNA elements that undergo a shift in structure in response to binding of a regulatory molecule. These elements are encoded within the transcript they regulate, and act in cis to control expression of the coding sequence(s) within that transcript; their function is therefore distinct from that of small regulatory RNAs (sRNAs) that act in trans to regulate the activity of other RNA transcripts. Riboswitch RNAs control a broad range of genes in bacterial species, including those involved in metabolism or uptake of amino acids, cofactors, nucleotides, and metal ions. Regulation occurs as a consequence of direct binding of an effector molecule, or through sensing of a physical parameter such as temperature.
Riboswitches as potential antimicrobial drug targets
ReplyDeleteThe ability of the riboswitches to precisely discriminate between different cognate molecules as well as their common existence in bacteria makes them a promising target for antibacterial drug therapy.
From a medical point of view this issue is crucial because of a continuously progressing problem of bacterial resistance against regular antibiotics.
The potential application of riboswitches as novel antimicrobial drug targets has several important advantages over classic antibiotics.
First, they demonstrate potentially lower toxicity due to the fact that riboswitches are not found in higher eukaryotes, including human. Additionally, a lot of them are controlled by small compounds, simple metabolites, easy to deliver into the system, but also to manufacture and modify. The possibility of developing the resistance by bacteria against the antibiotics targeted at riboswitches seems to be more restricted than in the case of commercial drugs.
The presence of a single type of riboswitches in multiple bacterial genes makes a single mutation insufficient to neutralize antimicrobial effect.
ReplyDeleteWhat is Augmentin?
Augmentin is a well-established and widely-used antibacterial combination product consisting of the semi-synthetic antibiotic amoxicillin (as amoxicillin trihydrate) and the beta-lactamase inhibitor clavulanic acid (as the potassium salt). Amoxicillin/clavulanic acid was originally developed in response to the need for an oral broad-spectrum antibiotic that covered β-lactamase-producing pathogens.
Amoxicillin works by inhibiting the transpeptidase enzyme responsible for cross-linking peptidoglycan in the bacterial cell wall, weakening, the cell wall and making the cell swell and rupture. Because amoxicillin is readily hydrolysed by beta lactamase, Augmentin also contains the beta lactamase inhibitor, clavulanic acid, which protects amoxicillin from degradation and extends its antibacterial spectrum to many bacteria normally resistant to penicillins and cephalosporins.
A wide range of different presentations of Augmentin with an increasing ratio of amoxicillin to clavulanic acid are approved for oral (2:1, 4:1, 7:1, 8:1, 14:1and16:1) and parenteral (5:1 and 10:1) use in adults and children.
The more common side effects of Augmentin include:
diarrhea
nausea
skin rash
vaginitis (caused by problems such as yeast infection)
vomiting
Serious side effects :
Allergic reaction
Liver problem
Rash
Fatigue
Intestinal infection
Yeast infection
QUESTION:What is combination therapy?
ReplyDeleteTherapy that combines more than one method of treatment. Also called multimodality therapy and multimodality treatment. Typically, the term refers to using multiple therapies to treat a single disease, and often all the therapies are pharmaceutical (although it can also involve non-medical therapy, such as the combination of medications and talk therapy to treat depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where available, dosage forms that contain more than one active ingredient (such as fixed-dose combinations).
Polypharmacy is a related term, referring to the use of multiple medications (without regard to whether they are for the same or separate conditions/diseases). Sometimes "polymedicine" is used to refer to pharmaceutical combination therapy. Most of these kinds of terms lack a universally consistent definition, so caution and clarification are often advisable.
Combination therapy might achieve efficacy with lower doses or less toxic drugs. It is important to investigate the impacts of drugs beyond what they can achieve alone. Using them in combination can act as a multiplier and increase the sum of their benefits.
Cancer drugs are most effective when given in combination. The rationale for combination therapy is to use drugs that work by different mechanisms, thereby decreasing the likelihood that resistant cancer cells will develop. When drugs with different effects are combined, each drug can be used at its optimal dose, without intolerable side effects
QUESTION:What is Resveratrol?
ReplyDeleteResveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Resveratrol is a phytoalexin, a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation. Plants that synthesize resveratrol include knotweeds, pine trees including Scots pine and Eastern white pine, grape vines, peanut plants, cocoa bushes, and Vaccinium shrubs that produce berries, including blueberries, raspberries, mulberries, cranberries, and bilberries. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, and peanuts. Resveratrol is produced in plants by the action of the enzyme, resveratrol synthase, also known as stilbene synthase. Its immediate precursor is a tetraketide derived from malonyl CoA and 4-coumaroyl CoA. The latter is derived from phenylalanine. Although commonly used as a dietary supplement and studied in laboratory models of human diseases, there is no high-quality evidence that resveratrol improves lifespan or has a substantial effect on any human disease.
QUESTION: What is Augmentin? How does it work? And what are the uses of it?????
ReplyDeleteANSWER: Augmentin contains amoxicillin and clavulanic acid. Amoxicillin is an antibiotic of the penicillin type. It is effective against some bacteria such as H. influenzae, N. gonorrhea, E.coli, Pneumococci, Streptococci, and certain strains of Staphylococci. Chemically, it is closely related to penicillin and ampicillin. Amoxicillin stops bacteria from multiplying by preventing bacteria from forming the walls that surround them. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Bacteria cannot survive without a cell wall. Clavulanic acid enhances the effectiveness of amoxicillin against bacteria that are ordinarily resistant to amoxicillin alone.
Augmentin is effective against susceptible bacteria causing infections of the middle ear (otitis media), tonsillitis, throat infections (pharyngitis), laryngitis, bronchitis, sinusitis, and pneumonia. It is also used in treating urinary tract infections, and skin infections.
these is all about uses and function of augmentin.
QUESTION:What is immunomodulator?
ReplyDeleteAs the name implies, immunomodulators modify the activity of the immune system, in turn, decreasing the inflammatory response. Immunomodulators are most often used in organ transplantation to prevent rejection of the new organ as well as in autoimmune diseases such as rheumatoid arthritis. Since the late 1960s, they have also been used to treat people with IBD, where the normal regulation of the immune system is affected. Immunomodulators are a group of drugs that mainly target the pathways that treat multiple myeloma and a few other cancers. They have many ways to work, including working on the immune system directly by turning down some proteins and turning up others.
Immunomodulators, by themselves or with another agent, may be appropriate in the following treatment situations: Nonresponse or intolerance to aminosalicylates, antibiotics, or corticosteroids, Steroid-dependent disease or frequent need for steroids, Perianal (around the anus) disease that does not respond to antibiotics, Fistulas (abnormal channels between two loops of intestine, or between the intestine and another structure—such as the skin), To bolster or optimize the effect of a biologic drug and prevent the development of resistance to biologic drugs, To prevent recurrence after surgery.
Thalidomide, lenalidomide, and pomalidomide
Thalidomide (Thalomid), lenalidomide (Revlimid), and pomalidomide (Pomalyst) are known as immunomodulating drugs (or IMiDs).
These drugs can cause side effects such as drowsiness, fatigue, constipation, low blood cell counts, and neuropathy (painful nerve damage). There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). These tend to be more likely with thalidomide than with the other drugs.
These drugs can also cause severe birth defects if taken during pregnancy.
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin (BCG) is a germ that doesn’t cause serious disease in humans, but it does infect human tissues and helps activate the immune system. This makes BCG useful as a form of cancer immunotherapy. BCG was one of the earliest immunotherapies used against cancer and is still being used today.
BCG is used to treat early stage bladder cancer. It is a liquid put into the bladder through a catheter. BCG attracts the body’s immune system cells to the bladder, where they can attack the bladder cancer cells. Treatment with BCG can cause symptoms that are like having the flu, such as fever, chills, and fatigue. It can also cause a burning feeling in the bladder. BCG can also be used to treat some melanoma skin cancers by injecting it directly into the tumors. It's also used as a vaccine against tuberculosis.
Imiquimod
Imiquimod is a drug that is applied to the skin as a cream. It stimulates a local immune response against skin cancer cells. It is used to treat some very early stage skin cancers (or pre-cancers), especially if they are in sensitive areas such as on the face.
The cream is applied anywhere from once a day to twice a week for several months. Some people have serious skin reactions to this drug.
ReplyDeleteQUESTION: What is the Iron starvation???
ANSWER: Iron is an important micronutrient for microbial life. At the beginning of an infection the host environment will normally restrict available iron, and innate immune responses will aim to further reduce iron, thus inhibiting growth of potential pathogens.
Successful pathogens have developed a spread of mechanisms to accumulate iron from the available in vivo sources, using remote and direct capture, to render their environment iron replete. Iron restriction, and therefore the presence of host iron sources like haem, are important drivers of gene regulation controlling the expression of various virulence factors.
As an infection progresses the changing iron environment will therefore influence pathogen organic phenomenon and trigger new activities.
How bacteria acquire iron, and the way iron acquisition affects the bacteria, has identified vaccine and antibiotic targets and is now suggesting novel approaches to regulate and treat infection.
QUESTION: What is serum resistance?
ReplyDeleteSerum contains more than thirty proteins of the complement system, a crucial component of the host innate immune response which can also initiate the adaptive response. Deposition of complement factors on the bacterial surface activates the complement cascade and results in the formation of the membrane attack complex (MAC). This complex forms trans-membrane pores in the membranes of susceptible bacteria, thus leading to bacterial death.
Serum resistance is a trait associated with strains that cause bacteraemia. In general, E. coli isolated from blood are more serum-resistant than strains that cause urinary tract infections or strains isolated from faecal samples. Septic shock and death are also more associated with serum-resistant rather than serum-susceptible bacteraemia isolates. Multiple virulence factors of E. coli have been shown to be involved in serum survival. Serum resistance is a major virulence factor of gram-negative bacteria, and K-1 polysaccharide has been shown to contribute to serum resistance in selected strains.
How Escherichia coli evades serum killing?
The ability to survive the bactericidal action of serum is advantageous to extraintestinal pathogenic Escherichia coli that gain access to the bloodstream. Evasion of the innate defences present in serum, including complement and antimicrobial peptides, involves multiple factors. Serum resistance mechanisms utilized by E. coli include the production of protective extracellular polysaccharide capsules and expression of factors that inhibit or interfere with the complement cascade. Recent studies have also highlighted the importance of structural integrity of the cell envelope in serum survival.
References:
https://doi.org/10.1111/1574-6968.12419
Leying H, Suerbaum S, Kroll HP, Stahl D, Opferkuch W. The capsular polysaccharide is a major determinant of serum resistance in K-1-positive blood culture isolates of Escherichia coli. Infect Immun. 1990;58(1):222-227. doi:10.1128/IAI.58.1.222-227.1990
QUESTION:Which antibiotics are recently discovered?
ReplyDeleteCorbomycin
The newly-found corbomycin and the lesser-known complestatin have a never-before-seen way to kill bacteria, which is achieved by blocking the function of the bacterial cell wall. The discovery comes from a family of antibiotics called glycopeptides that are produced by soil bacteria.
Teixobactin
Teixobactin is a peptide-like secondary metabolite of some species of bacteria, that kills some gram-positive bacteria. It appears to belong to a new class of antibiotics, and harms bacteria by binding to lipid II and lipid III, important precursor molecules for forming the cell wall. Teixobactin was discovered using a new method of culturing bacteria in soil, which allowed researchers to grow a previously unculturable bacterium now named Eleftheria terrae, which produces the antibiotic. Teixobactin was shown to kill Staphylococcus aureus and Mycobacterium tuberculosis. In January 2015, a collaboration of four institutes in the US and Germany together with two pharmaceutical companies, reported that they had isolated and characterized a new antibiotic, killing "without detectable resistance. Teixobactin was discovered by screening previously unculturable bacteria present in a sample of soil from "a grassy field in Maine, using the isolation chip (iChip).
Halicin
In a paper published in the journal, Cell, MIT researchers took a step in this direction. The team says their machine learning algorithm discovered a powerful new antibiotic.
The antibiotic, halicin, successfully wiped out dozens of bacterial strains, including some of the most dangerous drug-resistant bacteria on the World Health Organization’s most wanted list. In a monthlong experiment, E. coli bacteria also failed to develop resistance to halicin, in stark contrast to existing antibiotic ciprofloxacin. The algorithm that discovered halicin was trained on the molecular features of 2,500 compounds. Nearly half were FDA-approved drugs, and another 800 naturally occurring. The researchers specifically tuned the algorithm to look for molecules with antibiotic properties but whose structures would differ from existing antibiotics (as halicin’s does). Using another machine learning program, they screened the results for those likely to be safe for humans.
Early study suggests halicin attacks the bacteria’s cell membranes, disrupting their ability to produce energy. Protecting the cell membrane from halicin might take more than one or two genetic mutations, which could account for its impressive ability to prevent resistance.
QUESTION: How Quorum sensing occur in gram-positive bacteria?
ReplyDeleteGram-positive systems typically use secreted oligopeptides and two-component systems, which consist of membrane-bound sensor kinase receptors and cytoplasmic transcription factors that direct alterations in gene expression. A number of gram-positive bacteria are known to employ quorum-sensing systems. The nature of the signal molecules used in these systems differs from those of gram-negative organisms, and thus far, no gram-positive bacteria have been shown to produce AHLs. Gram-positive quorum-sensing systems typically make use of small posttranslationally processed peptide signal molecules. These peptide signals interact with the sensor element of a histidine kinase two-component signal transduction system. Quorum sensing is used to regulate the development of bacterial competence in Bacillus subtilis and Streptococcus pneumoniae, conjugation inEnterococcus faecalis, and virulence in Staphylococcus aureus. S. aureus causes a wide range of disease states that range from mild to life-threatening. The virulence of this organism is dependent on the temporal expression of a diverse array of virulence factors, including both cell-associated products, such as protein A, collagen- and fibronectin-binding protein, and secreted products including lipases, proteases, alpha-toxin, toxin-1, beta-hemolysin, and enterotoxin. During the early stages of S. aureusinfection, surface proteins involved in attachment (collagen- and fibronectin-binding protein) and defense (protein A) predominate. However, once a high cell density is achieved at the infection site, expression of S. aureus surface proteins is decreased and secreted proteins are preferentially expressed. The genetic basis for this temporal gene expression depends on two pleiotropic regulatory loci called agr (accessory gene regulator) and sar (staphylococcal accessory gene regulator).
QUESTION: How Quorum sensing occur in gram-negative bacteria?
ReplyDeleteFour common features are found in nearly all known Gram-negative quorum sensing systems. First, the autoinducers in such systems are acyl-homoserine lactones (AHLs) or other molecules that are synthesized from S-adenosylmethionine (SAM), and they are able to diffuse freely through the bacterial membrane. Second, autoinducers are bound by specific receptors that reside either in the inner membrane or in the cytoplasm. Third, quorum sensing typically alters dozens to hundreds of genes that underpin various biological processes. Fourth, in a process called autoinduction, autoinducer-driven activation of quorum sensing stimulates the increased synthesis of the autoinducer, which establishes a feed-forward loop that is proposed to promote synchronous gene expression in the population. The vast majority of gram-negative quorum-sensing systems that have been studied thus far utilize N-acyl homoserine lactones (AHL) as signaling molecules. When in high enough concentration, these molecules can bind to and activate a transcriptional activator, or R protein, which in turn induces expression of target genes. The use of biosensors to screen spent culture supernatants has led to the discovery that AHLs are produced by a plethora of unrelated bacteria. Biosensors typically consist of a quorum-sensing-controlled promoter fused to a reporter such aslacZ or the lux operon. These biosensor strains contain a functional R protein but lack the AHL synthase enzyme; therefore, promoter activity depends on the presence of exogenous AHL. Despite the fact that R proteins are exquisitely sensitive to their cognate AHLs, some infidelity does exist and this infidelity enables R proteins to be responsive to a range of AHL molecules, albeit higher concentrations of noncognate AHL are usually required for activation. To date, AHL molecules have been identified containing 4- to 14-carbon acyl side chains and either an oxo, a hydroxy, or no substitution at the third carbon. Only two AHLs bearing double bonds have been identified: 7,8-cis-N-(3-hydroxytetradecenoyl)homoserine lactone from Rhizobium leguminosarum and 7,8-cis-N-(tetradecenoyl)homoserine lactone fromRhodobacter sphaerhoides.
What are the role of AHLs molecules in quorum sensing of Gram negative bacteria and how quorum sensing inhibit by inhibitors?
ReplyDeleteAHLs are the most common class of autoinducers and are present in approximately 10% of proteobacteria isolated from various ecological niche. AHL signaling molecules possess a homoserine lactone (HSL) moiety, acyl side chains with 4–18 carbons.
Three AHL synthase families have been identified so far, and these include the LuxI (see review34), HdtS, and LuxM families. Among the three the LuxI family is the best studied as the LuxI protein in the lux operon in V. fischeri was the first AHL synthase to be identified . LuxI homologs have been described in a large number of Gram-negative bacteria and LuxR proteins combine with AHLs to control target gene expression. This system is the most prevalent QS regulatory system in gram-negative bacteria.
LuxR is a cell-density dependent transcription regulator. When the densities reach a particular threshold value, AHL accumulation triggers the corresponding receptors. Binding to AHL stabilizes LuxR allowing the receptor to fold properly, bind DNA and activate transcription of the target genes . The AHL-LuxR protein complexes not only act as co-activators for the promoter sites of the QS responsive operons in a bacterial cell, they also act as positive regulators for the AHL synthesis itself.
QUORUM SENSING INHIBITORS(QSIs) can be used as novel class of antimicrobial drugs. QSIs reduce the activity of the AHL. there many strategies for the Development of QSIs.
1. Inactivation or complete degradation of the AHL signal molecules can be achieved by either of these methods:chemical degradation, enzymatic destruction or metabolism
of the AHL molecules.
2. Use an Analogue: Analogues of AHL signal molecules have been designed to block the receptor. These analogues have been designed either by modifications in the acyl side chain or in the lactone ring or in both these moieties of the AHL molecule.
3. Quorum quenching enzymes: AHL lactonase- AHL-lactonases hydrolyse the lactone ring of AHL.
And there are many other strategies use for this. also some antibiotic also use as Quorum sensing inhibitiors like Macrolide, ceftazidime, ciprofloxacin and azithromycin have shown strong QSI activity in P. aeruginosa .
What are the role of AIP molecules in quorum sensing of Gram Positive bacteria?
ReplyDeleteThe signaling in gram positive bacteria are controlled by Oligopeptide which is commonly referred as autoinducer peptides [AIPs]. AIPs are produced inside the bacterial cell as pro-AIP which will be processed and modified inside or outside the cell hinge upon the organism [66]. Unlike AHL signaling molecule AIP’s are impermeable to cell membrane hence requires specialized transport proteins for the inward and outward carriage of AIP’s. This transport of AIP’s are generally accomplished by cell membrane bound sensor kinase.
Most of the gram positive bacterial linguistics are depending upon membrane bound two component system that identify signaling molecule autoinducer peptides. A classic example for two component quorum sensing system is found in Staphylococcus aureus. Virulence and communication of this bacteria is regulated by Arg locus which is a combination of two transcripts RNA II and RNA III.
Extracellular protease processed AIP quorum sensing circuit: In some gram positive bacteria processing of pro AIP is done in the external environment of bacterial cell by extracellular protease enzymes after which AIP will be transported back to cell for regulating transcription.
What are Mammalian Siderophores and what is their role in human body?
ReplyDeleteMammalian Siderophores are compounds that solubilizes iron and keeps it accessible for transport and systemic utilization. The serum protein transferrin (also called serotransferrin) creates a bacteriostatic environment by sequestering free iron which facilitates the release and internalization of complexed iron following interaction with specific receptors on erythroid cells, lymphocytes, and macrophages. The analogous lactoferrin is widely expressed in secretory fluids (milk, saliva, and tears). Its affinity for iron is 300-times higher than that of transferrin and increases further in acidic conditions. This promotes transfer of iron from transferrin to lactoferrin during inflammation, when the local pH is decreased by accumulation of organic acids. Lactoferrin possesses intrinsic antimicrobial activity owing to both its binding to lipopolysaccharide and its catalyzing formation of peroxides with concomitant reduction of ferric iron, which together increase membrane permeability and trigger lysis. Lactoferrin competes with bacterial siderophores.
What is Clavulanic acid? How it is used with combination of antibiotics?
ReplyDeleteClavulanic acid is a naturally occurring β-lactam isolated from Streptomyces clavuligerus and later from other Streptomyces species. It has little antibacterial activity on its own but displays potent inhibitory properties on β- lactamases. It is a β-lactamase inhibitor used together with β-lactam antibiotics to overcome β-lactam resistance. Amoxycillin/clavulanic acid is a combination of two drugs which interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms.
Amoxycillin/clavulanic acid covers skin, enteric flora, and anaerobes. Emergence of resistance to clavulanic acid has not been reported as a clinical problem in bacteria isolated from animals. However, a variety of resistance mechanisms have emerged in human bacterial isolates.
Recently found antibiotics:-
ReplyDeleteAntivirals against COVID-19, drugs are found, which are
1. Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity – it is not approved anywhere globally for any use. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses and are structurally similar to COVID-19. The limited preclinical data on remdesivir in MERS and SARS indicate that remdesivir may have potential activity against COVID-19.
Remdesivir is an experimental medicine that does not have established safety or efficacy for the treatment of any condition.
Also
2. Favipiravir is a pyrazinecarboxamide derivative with activity against RNA viruses. Favipiravir is converted to the ribofuranosyltriphosphate derivative by host enzymes and selectively inhibits the influenza viral RNA-dependent RNA polymerase.
Favipiravir is a member of pyrazines and a primary carboxamide.
Discovered by Toyama Chemical Co., Ltd. in Japan, favipiravir is a modified pyrazine analog that was initially approved for therapeutic use in resistant cases of influenza. The antiviral targets RNA-dependent RNA polymerase (RdRp) enzymes, which are necessary for the transcription and replication of viral genomes. Not only does favipiravir inhibit replication of influenza A and B, but the drug has shown promise in the treatment of avian influenza, and may be an alternative option for influenza strains that are resistant to neuramidase inhibitors. Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19.
What is Siderophores?
ReplyDeleteSiderophores are small molecules that are produced and secreted by micro-organisms in order to mediate the uptake of essential iron(III) into the cell.
The role of these compounds is to obtain iron from the environment and create a soluble complex that is needed to make it available to microbial cells. Siderophores formed by bacteria contribute to their pathogenicity since bacteria require iron for their growth and metabolism and remove it from the host organism during infection. They play an important role as growth-promoting factors in unculturable microorganisms.
INHIBITING SIDEROPHORE PRODUCTION AS AN ANTIMICROBIAL STRATEGY:
One viable mechanism for the development of novel antimicrobial agents is targeting bacterial pathways responsible for acquisition of essential nutrients. Iron serves as an important cofactor for a variety of enzymes that perform crucial reactions, including roles in electron transfer, resistance to reactive oxygen intermediates, and RNA synthesis. Fe(III) is very insoluble and biologically inaccessible such that the concentration of free ferric iron available to pathogens in the human host ranges in estimation from 10−15 to 10−24 M, whereas a typical pathogenic bacterium requires ~1 μM iron for optimal growth. In response, bacterial pathogens have developed siderophore. If inhibition of the biosynthesis of siderophores that are crucial for bacterial survival under iron-limited conditions represents another promising approach. Depriving pathogenic bacteria from iron is another potential antimicrobial strategy.
THERAPEUTIC POTENTIAL OF SIDEROPHORES:
In medicine, siderophores can be used to create complexes with antibiotics, thereby increasing the strength of their attack on bacteria resistant to antibiotics. Medical applications of siderophores include antimalarial activity and treatment of sickle cell anemia.
Q:- PATHOBLOCKERS
ReplyDeleteA:- The rapid development of antimicrobial resistance is threatening mankind to such extent that the WHO expects that there will be more deaths due to drug resistant microbial infections compare to cancer.
To avoid this problem researchers are trying new chemicals and developing new class of antimicrobial that helps to reduce this effect or future condition.
Targeting bacterial virulence as a means of blocking pathogenicity is a new strategy for reduce the pathogenic infection.
This drug resistance prevents efficient treatment of infected patients and surrounding environment of that patient and hospital.
Pathogens virulence is the prime determinant for the deterioration of an infected patient's health. This is new approach for development of drug over last decade.
Pubmed. Gov database yields 292 references on this approach as of 06/08/2018 with exponential increase over the years.
The traditional thinking of antibiotic that kill or impair the pathogen viability rather than that this pathoblocker concept is not to kill the pathogen but it will disarms the pathogen as keep in live form so that host can itself clear the pathogen from body. This have two benefits
1st - less harm to host cell
2nd - unable the host to clear the microbe from it's system .
Second approach is stop the addhesion of pathogen to host cell.
Bacterial adhesion to the host's surface is 1st step of infection. This helps to formation of boifilm for some infectious microbes that is formed by carbohydrate -binding- proteins called lectins. Which recognize glycoconjugates on the host cell or surface. To maintain this adhesion process through carbohydrate binding protein glycomimetics used as pathoblocker to inhibit this adhesion process develop new area of active research in this last decade.
Q:- What is ESKAPE in context of drug resistance?
ReplyDeleteA:-
E- Enterococcus faecium
S- Staphylococcus aureus
K- Klebsiella pneumonia
A- Actinobacter baumanii
P- Pseudomonas aeruginosa
E- Enterobacter species
These are the bacteria strains that are mostly common in all hospitals and also most problematic once in the hospital environment.
They are leads to secondary infection in patients due to this they are so called ESKAPE.
What is Combinatorial Chemistry?
ReplyDeleteCombinatorial chemistry is a laboratory technique in which millions of molecular constructions can be synthesized and tested for biological activity. It has generated massive numbers of targeted molecules for testing and the developing techniques of high throughput screening has automated the screening process so larger numbers of biological assays can be done. All this together has reduced the discovery-to-market time from what used to be 10-14 years to 5-8 years.
It involves the generation of a large array of structurally diverse compounds, called a chemical library, through systematic, repetitive and covalent linkage of various “building blocks”. Once prepared, the compounds in the chemical library can be screened, concurrently, for individual interactions with biological targets of interest.
ADVANTAGES
(1) The creation of large libraries of molecules in a short time is the main advantage of combinatorial chemistry over traditional.
(2)Compounds that cannot be synthesized using traditional methods of medicinal chemistry can be synthesized using combinatorial techniques.
(3) Thecost of combinatorial chemistry library generation and analysis of said library is very high, but when considered on a per compound basis the price is significantly lower when compared to the cost of individual synthesis.
(4) More opportunities to generate lead compounds.
(5)Combinatorial chemistry speeds up drug discovery.
DISADVANTAGES
While a large number of compounds are created, the libraries created are often not focused enough to generate a sufficient number of hits during an assay for biological activity. There is a great deal of diversity created, but not often a central synthetic idea in the libraries. One can argue that there should be a focus on the type of molecule developed in order to maximize hits.
Characteristics of an ideal antibiotic :
ReplyDelete1. It should be non-toxic, biocompatible, biodegradable and physiochemical stable in-vivo and in-vitro and should have no side effects.
2. Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution.
3. Controllable and predict the rate of drug release.
4. Drug release should not affect drug action.
5. There should be a therapeutic amount of drug release.
6. Minimal drug leakage during transit.
7. Carriers used must be Biodegradable or readily eliminated from the body without any problem and no carrier induced modulation of a diseased state.
8. The preparation of the delivery system should be easy or reasonably simple reproductive and cost-effective.
9. The drug should be easily eliminated from the body by simple metabolic processes after its action.
10. The drug should not get accumulated in any of the tissues or cells of the body causing inflammation.
Reverse pharmacology
ReplyDeleteIn the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery. This method became popular after the sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins. This method is the most widely used in drug discovery today. Differently than the classical (forward) pharmacology, with the reverse pharmacology approach in vivo efficacy of identified active (lead) compounds is usually performed in the final drug discovery stages.
Blind Screening
ReplyDeleteMainly screening is categorized into three named Simple screening, Blind screening and Programmed screening. In simple screening when one or two tests are used to find substances having a particular property, the screening is simple there is no need for battery of tests in which the interpretation of results of one test may depend on those of another test. In blind screening, if a new series of chemical substances available, either through isolation from a natural source or through synthesis, there may be no information on its pharmacological activity. Then blind screening ought to provide clues to potential activity, at least, and preferably, to indicate fields of activity, if they exist. In addition, the blind screening ought to show pharmacological inertness if it exists. The chief purposes of the screening are to demonstrate whether the new group of substances is worthy of further attention, and to indicate which among them have the most interesting pharmacological properties.
Blind screening, the technique for detecting pharmacological activity in a group of substances without pharmacological history, requires considerable planning and skillful execution of the test, in order to be economical of time and money. The strategy of few tests, having simple procedures, to be applied to cheap animals, requires a knowledge of the tests that are known, as well as ingenuity in their combination.
In blind testing, some orientation is sought. By contrast in programmed testing, the screening has aspects beyond orientation. The program may include the use of quantitative assay for immediate study of the most interesting compounds found through a similar semi quantitative assay, or for comparison with drugs recognized to be quite active representatives of other pharmacological class. The program should provide also indications of potential side effects, and it should lead readily into a project for investigating the detailed pharmacology of the most promising substances.
Q:- Polyherbalism
ReplyDeleteA:- Ayurveda is one of the traditional medicinal system of Indians. This involves the use of natural elements to treat the disease fron root cause by restoring balance and also helps to maintain healthy lifestyle to prevent recurrence of imbalance.
Natural medicines also used in ancient Chinese, Greek, Egyptian, and Indian culture for various therapies purpose.
Who estimated that 80% of the world's inhabitants still rely mainly on traditional medicines.
Based on ayurvedic medicine materials they are divided in three major types.
Herbal
Mineral
Animal
Among this the herbal medicines gained great importance for formulation of herbals and cure disease. This herbal plants shows that they are used as drugs for medicines development. The species of plant which have medicinal importance they are classified, characterized and from the plants extracta main effective compounds are purified. But some time it is observed that the pure compounds are not effective compare to crude extract. It is observed that this happens may be due to lack of some supporting material or the backbone of that compound that is released out during purification. So some time this type of compounds are given in the crude extracts without disturbing the composition of that medicinal plant against particular disease.
For medicinal purposes various plants have various effects with different body parts like
Leaves, flower, seeds, roots, barks, stems, and some naturally producing extracts which secreted out of the body by plants. This complex composition helps to treat disease and cure from root of disease.
Various body parts of plants used as medicine.
Eg-
Root - garlic and ginger
Use - Antibiotic
Cardiovascular diseases
Antioxident.
Stem - Alovera
Use - skin infection
Skin ailments
Leaves - Neem
Use - malaria
Rheumatism
Skin infection
Fruits -
Marijuana - Alzheimer's
Dementia
Chilli (cayenne) - heart attack
Fibronolytic actions
Flower - Bitter orange
Use - nausea
Ingestion
Constipation
Seeds - Asfoetida
Use - cholesterol
Breathing problem
Root bark - water ash
Use - digestive tract.
This are some planta which are herbal and easily avilable surround us and easy to grow compare to the medicinal plants which are avilable only in some particular area of the earth or in forest.
Q:- Different forms of herbal medicines.
ReplyDeleteA:-
Kwatha - decoction
Pantha - hot infussion
Hima - cold infussion
Arka - liquid extract
Churna - powder
Guggul - resins and balsams
Taila - medicated oils.
These are the various forms of herbal medicines. Some of them are given in pure form ( upto 90-95% but not 100% )and some of them are in crude source so that the medicinal importance remains as it is and helps to cure diseases and set up of healthy lifestyle without side-effects.
QUESTION: WHAT IS COMBINATORIAL CHEMISTRY AND WHAT ARE THE APPLICATIONS OF IT?????
ReplyDeleteANSWER: Combinatorial Chemistry is a new method developed by academics and researchers to reduce the time and cost of producing effective, marketable and competitive new drugs.
• Combinatorial chemistry is based on the principle of making a large number of chemical compounds rapidly on a small scale in small reaction cells. This practice is widely adopted by the pharmaceutical sector for use during the drug designing and screening stages.
• Scientists use Combinatorial Chemistry to create large numbers of molecules that can be detected efficiently.
• This technique is very useful in many areas such as Pharmaceutical chemistry, Biotechnology and Agro chemistry.
• Combinatorial chemistry is a technique by which large numbers of different but structurally similar molecules are produced rapidly and submitted for pharmacological assay.
• This technique uses the same reaction conditions with the same reaction vessels to produce a large range of analogues.
• Technique invented in the late 1980s and early 1990s to enable tasks to be applied to many molecules simultaneously.
Applications:
1)Applications of combinatorial chemistry are very wide Scientists use combinatorial chemistry to create large populations of molecules that can be screened efficiently.
2)By producing larger, more diverse compound libraries, companies increase the probability that they will find novel compounds of significant therapeutic and commercial value.
3)Provides a stimulus for robot-controlled and immobilization strategies that allow high-throughput and multiple parallel approaches to drug discovery.
What is ADMET Profile ? For what purpose is it generated?
ReplyDeleteADMET stands for Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET), play key roles in drug discovery and development. A high-quality drug candidate should not only have sufficient efficacy against the therapeutic target, but also show appropriate ADMET properties at a therapeutic dose. The prediction of the ADMET properties plays an important role in the drug design process because these properties account for the failure of about 60% of all drugs in the clinical phases. Where traditionally ADME tools were applied at the end of the drug development pipeline, nowadays ADME is applied at an early phase of the drug development process, in order to remove molecules with poor ADME properties from the drug development pipeline and leads to significant savings in research and development costs.
QUE :VRAS
ReplyDeleteANS : The acronym, VRSA, stands for vancomycin-resistant Staphylococcus aureus. VRSA can cause an illness from skin infections to severe invasive disease which can result in pneumonia and/or septicemia (bacteria gets in the blood) or even death.
QUE: VRE
ReplyDeleteANS: Vancomycin-resistant enterococci (VRE) are a type of bacteria called enterococci that have developed resistance to many antibiotics, especially vancomycin. Enterococci bacteria live in our intestines and on our skin, usually without causing problems.
Que.)What is Plasma Medicine?
ReplyDeleteAns.)Plasma medicine emerged in the last decade as an exciting new field of research at the interface between physics and the life sciences. Physical plasma can be generated by adding energy (heat or electromagnetic fields) to a neutral gas until the ionized gaseous substance becomes increasingly electrically conductive. Plasmas emit electromagnetic radiation, predominately UV radiation and visible light, and contain excited gas molecules, positively and negatively charged ions, free electrons, neutral reactive oxygen/nitrogen species (ROS/RNS), free radicals, and molecule fragments Due to its distinct characteristics compared to ordinary neutral gases, plasma is considered as a fourth state of matter (besides solid, fluid, and gaseous). In modern medicine, high-temperature plasmas are used, e.g., for sterilization of medical devices and implants. Cold atmospheric pressure plasmas (CAP), however, can also be used for the treatment of viable tissues and thus have become a focus of medical research over the past years. Besides therapeutic applications, CAP is also used for surface modification and biological decontamination.
ReplyDelete[Concept of Bioavailability enhancers]
>>The concept of bioavailability enhancers is derived from the traditional age old system of Ayurveda (science of life). In Ayurveda, black pepper, long pepper and ginger are collectively known as “Trikatu”. In sanskrit “Trikatu” means three acrids. The action of bioenhancers was first documented by Bose (1929) who described the action of long pepper to Adhatoda vasika leaves increased the antiasthamatic properties of Adhatoda vasika leaves.
[Definition and history of bioavailability enhancers]
ReplyDelete>>The term ‘bioavailability enhancer’ was first coined by Indian scientists at the Regional Research Laboratory, Jammu (RRL, now known as Indian Institute of Integrative Medicine, Jammu), who discovered and scientifically validated piperine as the world’s first bioavailability enhancer in 1979.
>>Bioavailability enhancers are drug facilitators, they are the molecules which by themselves do not show typical drug activity but when used in combination they enhance the activity of drug molecule in several ways including increasing bioavailability of the drug across the membrane, potentiating the drug molecule by conformational interaction, acting as receptors for drug molecule and making target cells more receptive to drugs. A ‘bioenhancer’ is an agent capable of enhancing bioavailability and bioefficacy of a particular drug with which it is combined, without any typical pharmacological activity of its own at the dose used. These are also termed as ‘absorption enhancers’ which are functional excipients included in formulations to improve the absorption of a pharmacologically active drug.
What are Herb- drug interactions?
ReplyDeleteInteractions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Synergistic therapeutic effects may complicate the dosing of long-term medications.When there are any interactions between herbals and drugs occur that can be caused by either pharmaco-kinetic or pharmacodynamic mechanisms.
Pharmacokinetic interactions: When an herbal changes the absorption, distribution, metabolism, protein binding, or excretion of a drug that results in altered levels of the drug or its metabolites that is called pharmacokinetic interactions.
Pharmaco-dynamic interactions are related to the pharmacologic activity of the interacting agents and can affect organ systems, receptor sites, or enzymes. For e.g. Ginger is used to treat motion sickness, nausea, arthritis. If used with anticoagulants, then can inhibit thromboxane synthetase; may have additive anticoagulant, antiplatelet effects.
What is Post Antibiotic Effect?
ReplyDeletePostantibiotic effect(PAE's) (PAE) is the term used to describe suppression of bacterial growth that persists after brief exposure of organisms to antimicrobials. PAE's can vary by drugs and micro-organism. For e.g. macrolides are known for time-dependent kill characteristics, but have a strong post-antibiotic effect which probably inhibits bacterial growth rather than causing cell lysis.
Pathogenecity islands...
ReplyDeletePathogenicity islands (PAIs) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species. These mobile genetic elements may range from 10-200 kb and encode genes which contribute to the virulence of the respective pathogen. Typical examples are adherence factors, toxins, iron uptake systems, invasion factors, and secretion systems. Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or tRNA genes, which act as sites for recombination into the DNA. Cryptic mobility genes may also be present, indicating the provenance as transduction. One species of bacteria may have more than one PAI (i.e. Salmonella has at least 5). They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon.
Pathogenicity islands carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. They may be located on a bacterial chromosome or may be transferred within a plasmid. The GC-content of pathogenicity islands often differs from that of the rest of the genome, potentially aiding in their detection within a given DNA sequence.They carry functional genes, such as integrases, transposases, or part of insertion sequences, to enable insertion into host DNA. PAIs are often associated with tRNA genes, which target sites for this integration event. They can be transferred as a single unit to new bacterial cells, thus conferring virulence to formerly benign strains.
Que: Post Antibiotic Effect
ReplyDeleteAns: This is the persistence of antibiotic effect observed long after the serum concentration has fallen below the MIC. It is seen in antibiotics which inhibit some life-sustaining enzyme, or which bind tightly to cell wall components.
The post-antibiotic effect has some relationship to the kill characteristics of the antibiotic, but the relationship is not straightforward. For instance, macrolides are known for time-dependent kill characteristics, but have a strong post-antibiotic effect which probably inhibits bacterial growth rather than causing cell lysis.
Strong post-antibiotic effect
This is mainly seen in drugs which have concentration-dependent kill characteristics.
Aminoglycosides
Clindamycin
Macrolide antibiotics
Tetracyclines
Rifampicin
Quinupristin/dalfopristin (probably the longest post-antibiotic effect)
Such drugs benefit from large intermittent doses; high peak concentrations translate into better post-antibiotic effects.
Moderate post-antibiotic effect
This is seen in drugs which have time-dependent kill characteristics
Carbapenems
Fluoroquinolones
Glycopeptides
Linezolid
Weak or absent post-antibiotic effect
This is usually a feature of drugs which act at some critical point in the bacterial reproductive cycle.
The drug must therefore be present in the over-MIC concentration at that critical point.
Such drugs include:
β-lactams
Cephalosporins
Monobactams
CODON USES BIAS
ReplyDeleteCodon usage bias refers to the fact that different organisms have differences in the frequency of occurrence of synonymous codons in their coding DNA, meaning that some codons are rarely used while other codons are frequently used in a particular organism. Differences in codon usage bias may be helpful in identifying genes that have been acquired by horizontal gene transfer.
Subtractive hybridization technique
ReplyDeleteThis technique helps to detect dna differences between the different genomes or between cell types where deletion or genomic rearrangenent took place. PCR based amplification of cDNA or genomic DNA is carried out that differ between control and test strain. Then hybridization is carried out so that dsDNA between control and test DNA of similar abundance can be eliminated and only region of DNA that is different and differentially expressed will b retained.
E.g. when a report was generated for isolation and characterization of Shigella species, it was found that they are closely related to non pathogenic E.coli. So after genomic subtraction of similar genome content, a large region of around 42 kb was found to be localized in S. flexneri chromosome and it contained elements with PAI such as IS, bacteriophage genes and Shigella virulence genes.
Question: Efflux pump work on which mechanism???
ReplyDeleteAnswer: Efflux pump are work on the mechanism of competitive inhibition. where the efflux pumps recognize antibiotic as a substrate instead of the target antibiotics (quinolones mainly ciprofloxacin and levofloxacin) and as long as the pumps expel these inhibitors outside the cells, the antibiotic remains intracellular and increasing in concentration.
What is active efflux?
ReplyDeleteActive efflux is a common resistance mechanism in a wide range of bacterial pathogens. It is responsible for the transport of such toxic compounds as drugs, toxins, and detergents. such as BmrR from Bacillus subtilis, or by the global bacterial regulatory system.
Spanish flu
ReplyDeleteThe “Spanish” influenza pandemic of 1918–19 caused acute illness in 25–30 percent of the world’s population and resulted in the death of up to an estimated 40 million people.
The predominant natural reservoir of influenza viruses is thought to be wild waterfowl.genetic material from avian virus strains is transferred to
virus strains infectious to humans by a process called reassortment. Human influenza virus strains with recently acquired avian surface and internal protein-encoding RNA segments were responsible for the pandemic influenza outbreaks in 1957 and 1968.
reassortment involving genes encoding surface proteins appears to be a critical event for the production of a pandemic virus, a significant amount of data exists to suggest that influenza viruses must also acquire specific adaptations to spread and replicate efficiently in the new host.Once a new virus strain has acquired the changes that allow it to spread in humans, virulence is affected by the presence of novel surface protein(s) that allow the virus to infect an immunologically naïve population.
The degree of illness caused by a particular virus strain, or
virulence, is complex and involves host factors like immune status, and viral factors like host adaptation, transmissibility, tissue tropism, or viral replication efficiency.The 1968 pandemic followed with the emergence of a virus strain in which the H2 subtype HA gene was exchanged with an avian-derived H3 HA RNA segment.
Historical Background:
Outbreaks of the disease not only swept North America and Europe, but also spread as far as the Alaskan wilderness and the most remote islands of the Pacific.. It has been estimated that one-third of the world’s population (500 million people) may have been clinically infected during the pandemic.The “first wave” or “spring wave” of the 1918 pandemic seemingly arose in the United States in March 1918.The main wave of the global pandemic, the “fall wave” or “second wave,” occurred in September–November 1918.It has been estimated that the influenza epidemic of 1918 killed 675,000 Americans, including 43,000 servicemen mobilized for World War I.persons less than 65 years old accounted for more than 99 percent of all excess influenza-related deaths in 1918–19 .Since the first human and swine influenza A viruses were not isolated until the early 1930.
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What is Reproduction Number?
ReplyDeleteThe basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible. For e.g. if R0 for COVID-19 is 100 in a population then it can be expected each new case will produce 100 new secondary cases. The basic reproductive number is affected by several factors:
1. The rate of contacts in the host population.
2. The probability of infection being transmitted during contact.
3. The duration of infectiousness.
Amyloid fibers :- formed normally by soluble proteins, which assemble to form insoluble fibers which wil then be resistant to degradation.
ReplyDeleteTheir formation leads to diseases which are specifically caused by these fibrils and looking to characteristics, each disease is characterized by a specific protein or peptide that aggregates.
Eg = Alzheimer's disease; those fibrils are deposited extracellularly in the tissues and are thought to be responsible for having pathogenic efffect.
Peptidomimetics :-Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect as original molecule. They are designed to find the way out of some of the problems associated with a natural peptide: e.g. stability against proteolysis (duration of activity) and poor bioavailability, etc.
ReplyDeleteWhat is Reproduction Number?
ReplyDeleteThe basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible. For e.g. if R0 for COVID-19 is 100 in a population then it can be expected each new case will produce 100 new secondary cases.
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Remdesivir:
ReplyDeleteRemdesivir (GS-5734) an inhibiu of the viral RNA dependent, RNA polymerase with in vitro inhibitory activity against SARS-CoV-1 and the Middle East respiratory syndrome (MERS-CoV) was identified early as a promising therapeutic candidate for covid-19 because of its ability to inhibit SARS-CoV-2 invitro. In addition in non-humans primate, remdesivir initiate 12 houra after inoculation with MERS-CoV reduced lung virus levels and lung damage.
D-dimer :- D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross-link.
ReplyDeleteA normal D-Dimer is considered less than 0.50.
D-dimer levels were higher in COVID-19 patients and were related with markers of inflammation, and after treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis.
What is Reproduction number?
ReplyDelete-> It is denoted by R and is about how Infectious a disease is. Ro represents the number when no Immunity has been generated from the vaccination. R represents number when immunity generated. R is the mean number of Infections generated during Infectious period of a single infective.
We cannot determine the Rate of transmission through R.
Various Therapeutic options of Covid-19.
ReplyDelete-> Oxygen therapy & ECMO( Extracorporeal Membrane Oxygenation)
-> Treatment with convalescent(Person recovered from that disease) plasma & IgG.
-> Antiviral treatments: Neuraminidase Inhibitors like Zanamivir, Peramivir, Acyclovir, Remedesivir, Lopinavir.
-> Chloroquine, was used as Repurposing drug that means it is actually a drug for Malaria but used as multi purpose drug.
-> DRACO that targets viral dsRNA that can induce Apoptosis of the cells having virus.
-> Furin as an Antiviral agent as it cleaves the S protein of virus.
-> Combinational therapy that is use of Antiviral agents and DRACO might enhance the recovery of patients.
-> Recombinant Interferon.
Why do we feel cold while having fever?
ReplyDelete-When we have fever there are some chemicals produced in our body that causes brain to reset the body’s internal Thermostat at a higher temperature. The new ‘normal’ requires our body to feel cold even if the temperature is high. The high body temperature helps in fighting infection by enhancing white blood cells production and lowering bacterial reproduction rate.
Prepatent Period :- Period between infection with a parasite and the production of eggs by a female; equivalent to the incubation period of microbial infections, but biologically different because the parasite is going through developmental stages in the host.
ReplyDeleteIncubation period :- The period between exposure to an infection and the appearance of the first symptoms.
Prodormal period :- An early symptom that signals the onset of an illness or disease; a symptom or series of symptoms that precedes the more obvious, diagnosable symptoms that develop along with the condition.
Sequestration Stage :- Sequestration is the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules during malarial infections.
ReplyDeleteWhat is Paroxysm ?
ReplyDeleteThe classic symptom of malaria is paroxysm, which means cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae; in short at very obvious time interval, and is same at every typical interval of time.
Egoistic vaccines-Altruistic vaccines
ReplyDeleteAlthough vaccination is above all an act of individual prevention, in the case of directly transmissible diseases the vaccination of individuals may contribute indirect protection through the group immunity effect known as collective or herd immunity. The effect is due to the reduced or absent contagiousness of immunized subjects and the reduced likelihood of encounters between contagious and receptive subjects when immunized subjects are numerous. For many diseases, a vaccination coverage of 80% is sufficient to prevent epidemics. Vaccines may be classified as strictly egoistic, strictly altruistic, or simultaneously egoistic and altruistic. Rabies vaccine, which offers 100% protection if administered in time, is an example of a strictly egoistic vaccine that offers no collective benefit. German measles vaccine is strictly altruistic, since it prevents a condition that is dangerous only during fetal development. Vaccines that are both altruistic and egoistic are numerous. Measles, diphtheria, and hepatitis vaccines are examples.
Angiotensin Converting Enzyme-2 (ACE2)
ReplyDeleteAngiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.
Scientific name of the Fish feeding on Mosquito larvae.
ReplyDelete- Gambusia affinis(western mosquitofish) & Gambusia holbrooki (eastern mosquitofish).
Fish feedding on mosquito larvae
ReplyDeletePoecilia reticulata is the name of fish which is also known as rainbow fish or Guppy. It is most widely distributed tropical fish found on almost every continent except Antarctica. It feeds on mosquito larvae and helps to slow down malaria.
Gembusia also known as mosquitofish which is feed on malaria larvae and has been used more than any other fishes for the biological control of mosquitoes.
ReplyDeleteScientific name of mosquitofish : Gambusia affinis.
Que: scientific and common name of fish feed on mosquito larvae:
ReplyDeleteAns : Scientific name: Gambusia affinis
Common name:Gambezi (mosquitofish)
SCIENTIFIC NAME OF FISH FEED ON MISQUITO LARVAE :
ReplyDeleteANSWER :
Scientific Name : Gambusia affinis
Common Name:Gambezi (mosquitofish)
Fish feed on mosquito larvae:
ReplyDeleteThere are two principal fishes which eat the mosquito larvae and thereby control the spread of Malaria. These are Guppies and Gambusia. Both these fishes are exotic and have been introduced in India from Brazil. The fish Gambusia which is around 3 inches in size voraciously eat the mosquito larvae.
Anopheles species causing malaria:-
ReplyDeleteAnopheles culicifacies s.l. = Rural Malaria (65%)
An. fluviatilis s.l. = Plains and foothills (15%)
An. minimus breeds = Streams of foothills
An. dirus s.l. = Jungle of North-eastern states
An. sundaicus = Andaman and Nicobar islands and in brackish water
An. stephensi = urban malaria
Larvivorous fish for malarial parasites:-
Larvivorous fishes Poecilia reticulata (Guppy), a native of South America and Gambusia affinis (Gambusia), a native of Texas were imported in India in 1908 and 1928, respectively for the control of malaria vectors. Soon after that use of larvivorous fish became a common practice in India.
Reference https://www.intechopen.com/books/anopheles-mosquitoes-new-insights-into-malaria-vectors/the-dominant-mosquito-vectors-of-human-malaria-in-india
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741835/
This comment has been removed by the author.
ReplyDeleteQUESTION:What are the virulence factors of Pseudomas aeruginosa?
ReplyDeleteAmong the pathogenicity caused by virulence factors, can be cited Lipopolysaccharide, Flagellum, Type IV Pili, Type III Secretion System, Exotoxin A, Proteases, Alginate, Quorum Sensing, Biofilm Formation, Type VI Secretion Systems, Oxidant Generation in the Airspace.
REFERENCES:
Rocha, A. J., Barsottini, M. R. De O., Rocha, R. R., Laurindo, M. V., Moraes, F. L. L. De, & Rocha, S. L. Da. (2019). Pseudomonas Aeruginosa: Virulence Factors and Antibiotic Resistance Genes. Brazilian Archives of Biology and Technology, 62. Doi:10.1590/1678-4324-2019180503
QUESTION:What are the virulence factors of Staphylococcus aureus?
ReplyDeleteIt is well known that S. Aureus produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The expression of these factors is tightly regulated during growth. The agr system, known as the quorum-sensing system, is known to play a central role in the regulation of virulence factors. Besides agr, many factors, including other tcss (arl and sae) and transcriptional regulators (the sar family, rot, and mgr), have been demonstrated to be involved in the expression of virulence factors.
REFERENCES:
Oogai Y, Matsuo M, Hashimoto M, Kato F, Sugai M, Komatsuzawa H. Expression of virulence factors by Staphylococcus aureus grown in serum. Appl Environ Microbiol. 2011;77(22):8097-8105. Doi:10.1128/AEM.05316-11
QUESTION:What is herb-drug interaction?
ReplyDeleteAn herb might increases or decreases the effects of co administered drugs. Consequences can be beneficial, undesirable or harmful effects. Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component.
Mechanism of herbal-drug interactions:
When there are any interactions between herbals and drugs occur that can be caused by either pharmaco-kinetic or pharmacodynamic mechanisms.
Pharmacokinetic interactions:
When an herbal changes the absorption, distribution, metabolism, protein binding, or excretion of a drug that results in altered levels of the drug or its metabolites that is called pharmacokinetic interactions. Most of the current evidence of pharmacokinetic drug interactions involves metabolizing enzymes and drug transporters.
Example:
Aloevera commonly use as Strong cathartic, may interact with Cardiac glycosides, Thiazide diuretics which has potential effect like Can cause electrolyte imbalance and hypokalemia; May potentiate drug toxicity.
Bearberry commonly use as antibacterial, astringent, diuretic, may interact with Urinary acidifiers, Cranberry juice which has potential effect like Inactivated by urinary acidifiers; active compound released only in alkaline urine.
REFERENCES:
Pasi AK: Herb-Drug Interaction: An Overview. Int J Pharm Sci Res 2013: 4(10); 3770-3774. Doi: 10.13040/IJPSR. 0975-8232.4(10).3770-74.
QUESTION:What is its region?
ReplyDeleteThe internal transcribed spacers (ITS1 and ITS2) regions of the ribosomal RNA gene cluster are the most commonly used nuclear markers for estimating species relationships across many eukaryotic groups including most plant families. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. Internal Transcribed Spacer of nuclear ribosomal RNA and its application in phylogenetic analysis.
REFERENCES:
Edger, P. P., Tang, M., Bird, K. A., Mayfield, D. R., Conant, G., Mummenhoff, K. Pires, J. C. (2014). Secondary Structure Analyses of the Nuclear rRNA Internal Transcribed Spacers and Assessment of Its Phylogenetic Utility across the Brassicaceae (Mustards). Plos ONE, 9(7), e101341. Doi:10.1371/journal.pone.0101341
Sarah L. Boyer, Valerie R. Flechtner, Jeffrey R. Johansen, Is the 16S–23S rRNA Internal Transcribed Spacer Region a Good Tool for Use in Molecular Systematics and Population Genetics? A Case Study in Cyanobacteria, Molecular Biology and Evolution, Volume 18, Issue 6, June 2001, Pages 1057-1069, https://doi.org/10.1093/oxfordjournals.molbev.a003877
QUESTION:What is Lysogenic conversion?
ReplyDeleteThe ability of some phages to survive in a bacterium as a result of the integration of their DNA into the host chromosome. The integrated DNA is termed a prophage. A regulator gene produces a repressor protein that suppresses the lytic activity of the phage, but various environmental factors, such as ultraviolet irradiation may prevent synthesis of the repressor, leading to normal phage development and lysis of the bacterium. This phenomenon known as Lysogenic conversion. The best example of this is bacteriophage lambda.
QUESTION:What is significance of tcp and ct virulence factor of vibrio cholerae?
ReplyDeleteAcquisition of certain genes encoding virulence factors has enabled certain strains of V. Cholerae to colonize the human intestine and cause disease. The most important of these virulence factors are cholera toxin (CT), which is encoded within the genome of the filamentous bacteriophage ctxφ and thus horizontally transferred, and the intestinal colonization factor toxin-coregulated pilus (TCP). The toxin-coregulated pilus (TCP) of Vibrio cholerae is required for intestinal colonization and cholera toxin acquisition.
REFERENCES:
Reguera G, Kolter R. Virulence and the environment: a novel role for Vibrio cholerae toxin-coregulated pili in biofilm formation on chitin. J Bacteriol. 2005;187(10):3551-3555. Doi:10.1128/JB.187.10.3551-3555.2005
QUESTION:What is Pathogenicity islands?
ReplyDeletePathogenicity islands (pais) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species. These mobile genetic elements may range from 10-200 kb and encode genes which contribute to the virulence of the respective pathogen. Typical examples are adherence factors, toxins, iron uptake systems, invasion factors, and secretion systems. Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or trna genes, which act as sites for recombination into the DNA. Cryptic mobility genes may also be present, indicating the provenance as transduction. One species of bacteria may have more than one PAI (i.e. Salmonella has at least 5). They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon.
Pathogenicity islands carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. They may be located on a bacterial chromosome or may be transferred within a plasmid. The GC-content of pathogenicity islands often differs from that of the rest of the genome, potentially aiding in their detection within a given DNA sequence. Pais are flanked by direct repeats; the sequence of bases at two ends of the inserted sequence is the same. They carry functional genes, such as integrases, transposases, or part of insertion sequences, to enable insertion into host DNA. Pais are often associated with trna genes, which target sites for this integration event. They can be transferred as a single unit to new bacterial cells, thus conferring virulence to formerly benign strains.
REFERENCES:
Schmidt H, Hensel M. Pathogenicity islands in bacterial pathogenesis [published correction appears in Clin Microbiol Rev. 2006 Jan;19(1):257]. Clin Microbiol Rev. 2004;17(1):14-56. Doi:10.1128/cmr.17.1.14-56.2004
QUESTION:What is acute disease?
ReplyDeleteThe duration of the period of illness can vary greatly, depending on the pathogen, effectiveness of the immune response in the host, and any medical treatment received. For an acute disease, pathologic changes occur over a relatively short time (e.g., hours, days, or a few weeks) and involve a rapid onset of disease conditions. For example, influenza (caused by Influenzavirus) is considered an acute disease because the incubation period is approximately 1–2 days. Infected individuals can spread influenza to others for approximately 5 days after becoming ill. After approximately 1 week, individuals enter the period of decline.
QUESTION:What is chronic disease?
ReplyDeleteChronic disease, pathologic changes can occur over longer time spans (e.g., months, years, or a lifetime). For example, chronic gastritis (inflammation of the lining of the stomach) is caused by the gram-negative bacterium Helicobacter pylori. H. Pylori is able to colonize the stomach and persist in its highly acidic environment by producing the enzyme urease, which modifies the local acidity, allowing the bacteria to survive indefinitely. Consequently, H. Pylori infections can recur indefinitely unless the infection is cleared using antibiotics. Hepatitis B virus can cause a chronic infection in some patients who do not eliminate the virus after the acute illness. A chronic infection with hepatitis B virus is characterized by the continued production of infectious virus for 6 months or longer after the acute infection, as measured by the presence of viral antigen in blood samples.
QUESTION:What is latent diseases?
ReplyDeleteIn latent diseases, as opposed to chronic infections, the causal pathogen goes dormant for extended periods of time with no active replication. Examples of diseases that go into a latent state after the acute infection include herpes (herpes simplex viruses [HSV-1 and HSV-2]), chickenpox (varicella-zoster virus [VZV]), and mononucleosis (Epstein-Barr virus [EBV]). HSV-1, HSV-2, and VZV evade the host immune system by residing in a latent form within cells of the nervous system for long periods of time, but they can reactivate to become active infections during times of stress and immunosuppression. For example, an initial infection by VZV may result in a case of childhood chickenpox, followed by a long period of latency. The virus may reactivate decades later, causing episodes of shingles in adulthood. EBV goes into latency in B cells of the immune system and possibly epithelial cells; it can reactivate years later to produce B-cell lymphoma.
QUESTION: How does a microbe like P. Aeruginosa make a decision regarding causing acute versus chronic disease?
ReplyDeleteIn response to uncharacterized signals, bacteria either initiate an acute infection utilizing factors like TTSS and various toxins or establish a chronic, biofilm-like infection. The route of entry for the infection may impact whether an acute or chronic infection might be initiated. P. Aeruginosa appears to be in a biofilm-like mode of growth when growing in the CF lung. This growth strategy could be a result of the particular environmental signals and/or host factors encountered in the lungs of patients afflicted with this disease. Other factors, such as immune status of the host, tissue integrity, or patient nutrition, might also impact whether microbes initiate an acute versus a chronic infection.
REFERENCES:
Furukawa S, Kuchma SL, O'Toole GA. Keeping their options open: acute versus persistent infections. J Bacteriol. 2006;188(4):1211-1217. Doi:10.1128/JB.188.4.1211-1217.2006
QUESTION: What is Coevolution?
ReplyDeleteCoevolution between organisms and their pathogenic agents means that reciprocal and adaptive genetic modifications have occurred in them because of their interaction as biological systems that have shared space and resources over prolonged time periods. Coevolution is a general concept that applies not only to host-parasite relationships but also to other interacting biological species that have shaped biological systems up to the present epoch. Coevolution involves at least three steps: first one species evolves a response to a trait of a second species, and this is followed by a response of the second species to the first. Co-evolution of certain hosts and pathogens for millions of years has resulted in a fine-tuned equilibrium that enables survival of both.
REFERENCES:
Interaction of virus populations with their hosts, Esteban domingo.
Antigen Presentation, E.I.Zuniga, D.B.mcgavern, M.B.A.Oldstone.
Geographic Mosaic of Coevolution, T.P.Craig.
QUESTION: What is subtractive hybridization?
ReplyDeleteComparison of DNA from virulent strains of bacterial pathogens with DNA from less virulent or avirulent close relatives allows the identification of those genomic regions that are present only in virulent strains. Such regions are often associated with pathogenicity islands (pis) and their characterisation can lead to a greater understanding of the pathogenesis of infectious diseases. There is now a large database of bacterial genomic sequences that provides useful reference information with which to compare the genomes of strains that exhibit variations in virulence or host preferences. Subtractive hybridisation (SH) is technique designed to identify those regions present in one genome but absent from another. The application of these techniques has led to the identification of pis, mobile genetic elements and variations in virulence gene expression in a range of bacterial pathogens. Subtractive hybridization compares the genes expressed at different stages of a biological/pathological process allowing identification of the all the genes upregulated during the process.
REFERENCES:
Winstanley, Craig. (2002). Spot the difference: Applications of subtractive hybridisation to the study of bacterial pathogens. Journal of medical microbiology. 51. 459-67. 10.1099/0022-1317-51-6-459.
Byers RJ, Hoyland JA, Dixon J, Freemont AJ. Subtractive hybridization--genetic takeaways and the search for meaning. Int J Exp Pathol. 2000;81(6):391-404. Doi:10.1046/j.1365-2613.2000.00174.x
QUESTION: What is reproduction number?
ReplyDeleteThe basic reproduction number (R0) is used to measure the transmission potential of a disease. It is the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible.1 For example, if the R0 for measles in a population is 15, then we would expect each new case of measles to produce 15 new secondary cases (assuming everyone around the case was susceptible). R0 excludes new cases produced by the secondary cases.
The basic reproductive number is affected by several factors: The rate of contacts in the host population, the probability of infection being transmitted during contact, the duration of infectiousness.
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ReplyDeleteQUESTION: What is Drug repurposing?
ReplyDeleteDrug repurposing (also called drug repositioning, reprofiling or re-tasking) is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication1. This strategy offers various advantages over developing an entirely new drug for a given indication.
There are usually three kinds of approaches: computational approaches, biological experimental approaches, and mixed approaches, all of which are widely used in drug repositioning.
REFERENCES:
Pushpakom, S., Iorio, F., Eyers, P. Et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18, 41–58 (2019). https://doi.org/10.1038/nrd.2018.168
Xue H, Li J, Xie H, Wang Y. Review of Drug Repositioning Approaches and Resources. Int J Biol Sci. 2018;14(10):1232-1244. Published 2018 Jul 13. Doi:10.7150/ijbs.24612
QUESTION: What is DRACO virus treatment?
ReplyDeleteDouble-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsrna, rapidly killing infected cells without harming uninfected cells. DRACO shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. Dracos have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.
REFERENCES:
Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, Zusman BD. Broad-spectrum antiviral therapeutics. Plos One. 2011;6(7):e22572. Doi:10.1371/journal.pone.0022572
QUESTION: Which protozoal diseases is important after malaria?
ReplyDeleteAfrican trypanosomiasis, also known as African sleeping sickness, is caused by parasitic protozoan of the genus Trypanosoma. The two forms, West African and East African trypanosomiasis, are caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. T. B. Gambiense accounts for more than 95% of cases and causes chronic infection which can emerge as severe disease many years after parasite infection. T. B. Rhodesiense causes acute infection, which can rapidly result in central nervous system involvement with parasites crossing the blood–brain barrier. African trypanosomiasis threatens the lives of ∼60 million people in sub-Saharan Africa and, if left untreated, is fatal.
Chagas disease, or American trypanosomiasis, is a serious health concern in Latin America and as a result of migration is an emerging disease in traditionally non-endemic countries. Chagas disease is caused by infection with Trypanosoma cruzi and threatens the lives of millions primarily in Mexico, Latin American and the United States. The World Health Organization estimates that 8–10 million people are infected annually. Chagas disease presents as an initial acute phase which is followed by a chronic phase.
REFERENCES:
Andrews KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist. 2014;4(2):95-111. Published 2014 Mar 24. Doi:10.1016/j.ijpddr.2014.02.002
QUESTION: What is Cytoadherence?
ReplyDeleteCytoadherence is the property of Plasmodium falciparum-infected RBC to adhere to various host cell types such as endothelial cells and uninfected red cells, causing the parasite to sequester in deep vascular beds and avoid splenic clearance. Cytoadherence and sequestration are distinct features of P. Falciparum and are thought to account for its greater severity compared to malaria parasite species that lack these properties.
REFERENCES:
Duffy P.E., Acharya P., Oleinikov A.V. (2014) Cytoadherence. In: Hommel M., Kremsner P. (eds) Encyclopedia of Malaria. Springer, New York, NY. Https://doi.org/10.1007/978-1-4614-8757-9_39-1
QUESTION: What is sequestration?
ReplyDeleteInfected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells these phenomena, called sequestration. It involved in both host pathogenesis and parasite survival. Sequestration, the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules, is characteristic of Plasmodium falciparum infections.
REFERENCES:
Sherman IW, Eda S, Winograd E. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect. 2003 Aug;5(10):897-909. Doi: 10.1016/s1286-4579(03)00162-x. PMID: 12919858.
David PH, Hommel M, Miller LH, Udeinya IJ, Oligino LD. Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proc Natl Acad Sci U S A. 1983;80(16):5075-5079. Doi:10.1073/pnas.80.16.5075.
QUESTION: What is Rosetting?
ReplyDeleteRosetting, defined as the binding of two or more uninfected red blood cells (rbc) to an infected rbc, occurs when malarial parasites mature, to trophozoites and schizonts, in the second half of their asexual development. Rosetting is believed to be an important factor in the development of cerebral malaria.
QUESTION: What is RBC knobs?
ReplyDeletePlasmodium falciparum-infected erythrocytes (RBC) develop surface protrusions (knobs) which consist of electron-dense submembrane cups and the overlying RBC plasma membrane. Knobs mediate cytoadherence to endothelial cells. When P. Falciparum parasites invade red blood cells, several modifications occur in the infected erythrocyte (IE), especially on its surface membrane. One important modification is the formation of nanoscale protrusions, which are known as knobs. Knobs are 50 to 120 nm in diameter and 2 to 20 nm in height and act as a site for anchoring P. Falciparum erythrocyte membrane protein 1 (pfemp1). The role of pfemp1 is to enable adhesion of ies to various host receptors to avoid splenic clearance, and clonal antigenic variation allows ies to evade immune recognition.
REFERENCES:
Leech JH, Barnwell JW, Aikawa M, Miller LH, Howard RJ. Plasmodium falciparum malaria: association of knobs on the surface of infected erythrocytes with a histidine-rich protein and the erythrocyte skeleton. J Cell Biol. 1984 Apr;98(4):1256-64. Doi: 10.1083/jcb.98.4.1256. PMID: 6371019; PMCID: PMC2113211.
Plasmodium falciparum-Infected Erythrocyte Knob Density Is Linked to the pfemp1 Variant Expressed, Ramesh Subramani, Katharina Quadt, Anine E. Jeppesen, Casper Hempel, Jens Emil Vang Petersen, Tue Hassenkam, Lars Hviid, Lea Barfod Mbio Oct 2015, 6 (5) e01456-15; DOI: 10.1128/mbio.01456-15
QUESTION: What is Chemoprophylaxis?
ReplyDeleteChemoprophylaxis is define as, the use of a chemical agent to prevent the development of a disease.
Chemoprophylaxis of Malaria
Malaria prevention in travelers to endemic areas remains dependent principally on chemoprophylaxis. Although malaria chemoprophylaxis refers to all malaria species, a distinction should be drawn between falciparum malaria prophylaxis and the prophylaxis of the relapsing malaria species (vivax & ovale). While the emergence of drug resistant strains, as well as the costs and adverse reactions to medications, complicate falciparum prophylaxis use, there are virtually no drugs available for vivax prophylaxis, beside of primaquine. Based on traveler’s malaria data, a revised recommendation for using chemoprophylaxis in low risk areas should be considered.
Chemoprophylaxis does not prevent the infection (as in the case of vaccine preventable diseases), but rather works as having a killing effect against the parasite, either within the erythrocytes or within the hepatocytes, thus preventing the clinical disease.
REFERENCES:
Schwartz E. Prophylaxis of malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012045. Doi:10.4084/MJHID.2012.45
QUESTION: What is var gene?
ReplyDeletePlasmodium falciparum erythrocyte membrane protein 1 (pfemp1) is an important virulence factor encoded by a family of roughly 60 var genes and is used by the parasite to interact with the human host. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. The parasite regularly exchanges the expressed var gene generating antigenic variation of the infected rbcs (prbc) surface which is crucial for successful proliferation and transmission. The multicopy var gene family of Plasmodium falciparum is of crucial importance for pathogenesis and antigenic variation. So far only var2csa, the var gene responsible for placental malaria, was found to be highly conserved among all P. Falciparum strains.
REFERENCES:
Dimonte, S., Bruske, E.I., Enderes, C. Et al. Identification of a conserved var gene in different Plasmodium falciparum strains. Malar J 19, 194 (2020). Https://doi.org/10.1186/s12936-020-03257-x
Rubio JP, Thompson JK, Cowman AF. The var genes of Plasmodium falciparum are located in the subtelomeric region of most chromosomes. EMBO J. 1996;15(15):4069-4077.
Flick K, Chen Q. Var genes, pfemp1 and the human host. Mol Biochem Parasitol. 2004 Mar;134(1):3-9. Doi: 10.1016/j.molbiopara.2003.09.010. PMID: 14747137.
QUESTION: What is premunition immunity?
ReplyDeletePremunition, also known as infection-immunity, is a host response that protects against high numbers of parasite and illness without eliminating the infection. This type of immunity is relatively rapid, progressively acquired, short-lived, and partially effective.
Anopheles species causing malaria:-
ReplyDeleteAnopheles culicifacies s.l. = Rural Malaria (65%)
An. fluviatilis s.l. = Plains and foothills (15%)
An. minimus breeds = Streams of foothills
An. dirus s.l. = Jungle of North-eastern states
An. sundaicus = Andaman and Nicobar islands and in brackish water
An. stephensi = urban malaria
Larvivorous fish for malarial parasites:-
ReplyDeleteLarvivorous fishes Poecilia reticulata (Guppy), a native of South America and Gambusia affinis (Gambusia), a native of Texas were imported in India in 1908 and 1928, respectively for the control of malaria vectors. Soon after that use of larvivorous fish became a common practice in India.
What do you mean by Prepatent Period?
ReplyDeletePeriod between infection with a parasite and the production of eggs by a female; equivalent to the incubation period of microbial infections, but biologically different because the parasite is going through developmental stages in the host.
What exactly is Incubation period?
ReplyDeleteThe period between exposure to an infection and the appearance of the first symptoms.
Prodormal period, in simpler words can be defined as,,,,
ReplyDeleteAn early symptom that signals the onset of an illness or disease; a symptom or series of symptoms that precedes the more obvious, diagnosable symptoms that develop along with the condition.
Q: which fish feed on mosquito larvae?A:Gambusia effinis is feed on mosquito larvae and helps to control mosquito.
ReplyDeleteQ: which fish feed on mosquito larvae?A:Gambusia effinis is feed on mosquito larvae and helps to control mosquito.
ReplyDeleteQ: which fish feed on mosquito larvae?A:Gambusia effinis is feed on mosquito larvae and helps to control mosquito.
ReplyDeleteWhat is Prepatent period?
ReplyDeleteThe period between infection with a parasite and demonstration of the parasite in the body especially as determined by the recovery of an infective form from the blood or feces.
I'm Celina Gomez from the UK, I have been cured from genital herpes with herbalist Sakura herbal Remedy.
ReplyDeleteI have been infected with genital herpes for 1 years now , I have done so many medical treatments from different hospitals still
not cured. On a very good day , I decided to do research on my computer on how to get rid of genital herpes, I found a post of Sarah Wilson on how she was cured from herpes with herbalist Dr. Sakura herbal remedy.
The Herbalist email/contact number was there as well dr.sakuraspellalter@gmail.com/ +2348110114739. I contacted him because of my illness .He needed few of my information which I did, and also sent me his medicine through FedEx courier service.
which I received after 3 working days of shipment, I drank the herbal medicine the same way Herbalist Dr Sakura instructed me too. But now my genital herpes is gone totally without any side effect or harm, may God Almighty continue to bless him abundantly .
you can contact him on mail/what's app dr.sakuraspellalter@gmail.com +2348110114739 or follow him on Instagram @Herbalist_sakura .you can also mail me for more information celinagomez784@gmail.com