I remember studying the parasympathetic system in high school back in the 70’s. Basically we were taught that it exists and it balances the sympathetic system. Also recall we were taught that the nervous system and immune systems were separate, one did not “talk” to the other.
Kevin Tracey, a neurosurgeon based in New York, is a man haunted by personal events – a man with a mission. “My mother died from a brain tumor when I was five years old. It was very sudden and unexpected,” he says. “And I learned from that experience that the brain – nerves – are responsible for health.”
This background made him a neurosurgeon who thinks a lot about inflammation. He believes it was this perspective that enabled him to interpret the results of an accidental experiment in a new way.
In the late 1990s, Tracey was experimenting with a rat’s brain. “We’d injected an anti-inflammatory drug into the brain because we were studying the beneficial effect of blocking inflammation during a stroke,” he recalls. “We were surprised to find that when the drug was present in the brain, it also blocked inflammation in the spleen and in other organs in the rest of the body. Yet the amount of drug we’d injected was far too small to have got into the bloodstream and traveled to the rest of the body.”
After months puzzling over this, he finally hit upon the idea that the brain might be using the nervous system – specifically the vagus nerve – to tell the spleen to switch off inflammation everywhere.
It was an extraordinary idea – if Tracey was right, inflammation in body tissues was being directly regulated by the brain. Communication between the immune system’s specialist cells in our organs and bloodstream and the electrical connections of the nervous system had been considered impossible. Now Tracey was apparently discovering that the two systems were intricately linked.
The awe we feel when we’re in nature may help lower levels of pro-inflammatory proteins, a new study suggests (iStockphoto)
Taking in such spine-tingling wonders as the Grand Canyon, Sistine Chapel ceiling or Schubert’s “Ave Maria” may give a boost to the body’s defense system, according to new research from UC Berkeley.
Researchers have linked positive emotions – especially the awe we feel when touched by the beauty of nature, art and spirituality – with lower levels of pro-inflammatory cytokines, which are proteins that signal the immune system to work harder.
“Our findings demonstrate that positive emotions are associated with the markers of good health,” said Jennifer Stellar, a postdoctoral researcher at the University of Toronto and lead author of the study, which she conducted while at UC Berkeley.
While cytokines are necessary for herding cells to the body’s battlegrounds to fight infection, disease and trauma, sustained high levels of cytokines are associated with poorer health and such disorders as type-2 diabetes, heart disease, arthritis and even Alzheimer’s disease and clinical depression.
It has long been established that a healthy diet and lots of sleep and exercise bolster the body’s defenses against physical and mental illnesses. But the Berkeley study, whose findings were just published in the journal Emotion, is one of the first to look at the role of positive emotions in that arsenal.
PITTSBURGH, Nov. 1, 2013 – The red, swollen and painful gums and bone destruction of periodontal disease could be effectively treated by beckoning the right kind of immune system cells to the inflamed tissues, according to a new animal study conducted by researchers at the University of Pittsburgh. Their findings, published this week in the early online version of the Proceedings of the National Academy of Sciences, offer a new therapeutic paradigm for a condition that afflicts 78 million people in the U.S. alone.
Periodontal disease currently is treated by keeping oral bacteria in check with daily brushing and flossing as well as regular professional deep cleaning with scaling and root planing, which remove tartar above and below the gum line. In some hard-to-treat cases, antibiotics are given. These strategies of mechanical tartar removal and antimicrobial delivery aim to reduce the amount of oral bacteria on the tooth surface, explained co-author and co-investigator Charles Sfeir, D.D.S., Ph.D., director, Center for Craniofacial Regeneration and associate professor, Departments of Periodontics and Oral Biology, Pitt’s School of Dental Medicine.
“Currently, we try to control the build-up of bacteria so it doesn’t trigger severe inflammation, which could eventually damage the bone and tissue that hold the teeth in place,” Dr. Sfeir said. “But that strategy doesn’t address the real cause of the problem, which is an overreaction of the immune system that causes a needlessly aggressive response to the presence of oral bacteria. There is a real need to design new approaches to treat periodontal disease.”
In the healthy mouth, a balance exists between bacteria and the immune system response to forestall infection without generating inflammation, said senior author Steven Little, Ph.D., associate professor and chair of the Department of Chemical and Petroleum Engineering, Pitt’s Swanson School of Engineering. But in many people, a chronic overload of bacteria sets up the immune system to stay on red alert, causing harm to the oral tissues while it attempts to eradicate germs.
“There is a lot of evidence now that shows these diseased tissues are deficient in a subset of immune cells called regulatory T-cells, which tells attacking immune cells to stand down, stopping the inflammatory response,” Dr. Little said. “We wanted to see what would happen if we brought these regulatory T-cells back to the gums.”
To do so, the researchers developed a system of polymer microspheres to slowly release a chemokine, or signaling protein, called CCL22 that attracts regulatory T-cells, and placed tiny amounts of the paste-like agent between the gums and teeth of animals with periodontal disease. The team found that even though the amount of bacteria was unchanged, the treatment led to improvements of standard measures of periodontal disease, including decreased pocket depth and gum bleeding, reflecting a reduction in inflammation as a result of increased numbers of regulatory T-cells. MicroCT-scanning showed lower rates of bone loss.
“Mummified remains from ancient Egypt show evidence of teeth scraping to remove plaque,” Dr. Little noted. “The tools are better and people are better trained now, but we’ve been doing much the same thing for hundreds of years. Now, this homing beacon for Treg cells, combined with professional cleaning, could give us a new way of preventing the serious consequences of periodontal disease by correcting the immune imbalance that underlies the condition.”
Next steps include developing the immune modulation strategy for human trials. In addition to Drs. Sfeir and Little, the research team included Ph.D. candidate Andrew J. Glowacki,, Sayuri Yoshizawa, D.D.S., Ph.D., Siddharth Jhunjhunwala, Ph.D., all of the University of Pittsburgh; and Andreia E Vieira, Ph.D., and Gustavo P. Garlet, D.D.S., Ph.D., of Sao Paulo University, Brazil.
The project was funded by National Institutes of Health Grants 1R01DE021058-01 A1, 1R56DE021058-01, the Wallace H. Coulter Foundation, the Camille and Henry Dreyfus Foundation, the Arnold and Mabel Beckman Foundation and the Commonwealth of Pennsylvania.
The gut mucosa is the largest and most dynamic immunological environment of the body. It hosts the body’s largest population of immune cells. It is often the first point of pathogen exposure and many microbes use it as a beachhead into the rest of the body.
The gut immune system therefore needs to be ready to respond to pathogens but at the same time it is constantly exposed to innocuous environmental antigens, food particles and commensal microflora which need to be tolerated.
Misdirected immune responses to harmless antigens are the underlying cause of food allergies and debilitating conditions such as inflammatory bowel disease. This animation introduces the key cells and molecular players involved in gut immunohomeostasis and disease.
Nature Immunology in collaboration with Arkitek Studios have produced an animation unraveling the complexities of mucosal immunology in health and disease:
Doing yoga is way more than just an excuse to buy expensive leggings. Aside from improving fitness and flexibility, yoga has been used to treat many ailments including depression, arthritis, anxiety, asthma, type II diabetes, fatigue, chronic pain, IBS, and sleep disruptions. Recent research suggests that hatha yoga can also play a role in reducing risk for diabetes and cardiovascular disease. So how might twisting yourself into a pretzel lower your risk for two prominent chronic diseases?
Systemic Inflammation: the silent risk factor
You are probably familiar with acute inflammation if you have ever had an infection or sprained ankle. Swelling and pain are an effective way for our bodies to let us know that something is wrong. Chronic systemic inflammation, however, is not so apparent. It can persist undetected at a low level for years as it slowly damages body tissue while elevating risk for type II diabetes, atherosclerosis, cardiovascular disease, and age-related diseases.
Systemic inflammation is mediated by numerous chemicals inside the body. Two such chemicals are Leptin and adiponectin. These hormones are made in the adipose tissue and have recently been recognized to have a ….
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Yoga’s Effect on Inflammation
In 2012, Kiecolt-Glaser et. al. present in their paper Adiponectin, leptin, and yoga practice that “expert” hatha yoga practitioners have significantly different levels of leptin and adiponectin when compared to “novice” practitioners. Specifically, experts are shown to have 28% higher blood level adiponectin and a leptin concentration 26% lower than that of novices. Furthermore, the experts’ average adiponectin to leptin ratios were nearly twice that of the novices. Given that leptin and adiponectin are correlated with C-reactive protein, a potent marker of inflammation, this means that those who do more yoga seem to have lower systemic inflammation….
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A 2008 study by the Yoga Journal found that 6.9% of U.S. adults, or 15.8 million people, practice yoga and that 4.1% of non-practitioners, or about 9.4 million people, say they are hoping to try yoga within the next year. On this scale, if regular yoga practice can reduce systemic inflammation in healthy adult women, this is definitely an area worth further research!
According to the World Health Organization (WHO), 63 percent of the deaths that occurred in 2008 were attributed to non-communicable chronic diseases such as cardiovascular disease, certain cancers, Type 2 diabetes and obesity — for which poor diets are contributing factors. Yet people that live in societies that eat healthy, plant-based diets rarely fall victim to these ailments. Research studies have long indicated that a high consumption of plant foods is associated with lower incidents of chronic disease. In the October issue of Food Technology magazine, Senior Writer/Editor Toni Tarver discusses recent discoveries in nutritional genomics that explain how plant-based diets are effective at warding off disease.
The article indicates that bioactive compounds in plant foods play a role in controlling genetic and other biological factors that lead to chronic disease. For example, antioxidants in plant foods counter free radicals that can cause chronic inflammation and damage cells. And other plant compounds help control a gene linked to cardiovascular disease and plaque buildup in arteries and the genes and other cellular components responsible for forming and sustaining tumors…
All dietary fats are not created equal. Some types of fats have been linked to ailments like heart disease and diabetes, while others, like those often found in plants and fish, have well documented health benefits.
So why do our bodies respond so destructively to some fats but not others?
A new hypothesis described in latest issue of The Quarterly Review of Biologysuggests the answer may lie in how different fats interact with the microbes in our guts. According to researchers from the University of New Mexico and Northwestern University, some fats may encourage the growth of harmful bacteria in the digestive system. Our bodies have evolved to recognize those fats and launch an immune response to preempt the impeding changes in harmful bacteria. The result is low-levelinflammation that, over the long term, causes chronic disease.
“Although the inflammatory effects of [fats] are well documented, it is less well appreciated that they also influence bacterial survival and proliferation in the gastrointestinal tract,” write the researchers, led by Joe Alcock, of the University of New Mexico Department of Emergency Medicine and VA Medical Center.
Some fats – mostly unsaturated fats – actually have strong antimicrobial properties. They react chemically with bacterial cell membranes, weakening them. “If you expose unsaturated fats on bacteria, the bacteria have a tendency to lyse. The combination of long chain unsaturated fats, especially omega-3 fatty acids, and innate host defenses like gastric acid and antimicrobial peptides, is particularly lethal to pathogenic bacteria,” Alcock said. Saturated fats on the other hand generally lack those antimicrobial properties, and in fact can provide a carbon source that bacteria need to grow and flourish….
Overview of biological circadian clock in humans. Biological clock affects the daily rhythm of many physiological processes. This diagram depicts the circadian patterns typical of someone who rises early in morning, eats lunch around noon, and sleeps at night (10 p.m.). Although circadian rhythms tend to be synchronized with cycles of light and dark, other factors – such as ambient temperature, meal times, napping schedule and duration, stress and exercise – can influence the timing as well. (Photo credit: Wikipedia)
Disruptions to the circadian rhythm can affect the growth of blood vessels in the body, thus causing illnesses such asdiabetes, obesity, and cancer, according to a new study from Linkoping University and Karolinska Institutet.
The circadian rhythm is regulated by a “clock” that reacts to both incoming light and genetic factors.
In an article now being published in the scientific journal Cell Reports, it is demonstrated for the first time that disruption of the circadian rhythm immediately inhibits blood vessel growth in zebra fish embryos.
Professor Yihai Cao leads a research group, which has demonstrated that the breaking point is the production of a very important signalling substance: vascular endothelial growth factor (VEGF). The formation of this substance requires a normal circadian rhythm…
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“The results can definitely be translated into clinical circumstances. Individuals with disrupted circadian rhythms – for example, shift workers who work under artificial lights at night, people with sleep disorders or a genetic predisposition – should be on guard against illnesses associated with disrupted blood vessel growth,” says Lasse Dahl Jensen (pictured), researcher in Cardiovascular Physiology at Linköping University (LiU), and lead writer of the article.
Such diseases include heart attack, stroke, chronic inflammation, and cancer. Disruptions in blood vessel growth can also affect foetal development, women’s reproductive cycles, and the healing of wounds.
What do heart disease, diabetes, Alzheimer’s, stroke and cancer have in common? Scientists have linked each of these to a condition known as chronic inflammation, and they are studying how high-fat foods and excess body weight may increase the risk for fatal disorders.
While much focus has been on fighting inflammation with drugs, researchers are getting a better understanding of the links connecting diet, inflammation and illness and discovering ways that foods can help keep inflammation in check. Laura Landro has details on Lunch Break.
Inflammation is the body’s natural response to injury and outside irritants. But when the irritants don’t let up, because of a diet of high-fat foods, too much body fat and smoking, for example, the immune system can spiral out of control and increase the risk for disease. Experts say when inflammation becomes chronic it can damage heart valves and brain cells, trigger strokes, and promote resistance to insulin, which leads to diabetes. It also is associated with the development of cancer.
Much of the research on chronic inflammation has focused on fighting it with drugs, such as cholesterol-lowering statins for heart disease. A growing body of research is revealing how abdominal fat and an unhealthy diet can lead to inflammation. Some scientists are investigating how certain components in foods might help. Dietary fiber from whole grains, for instance, may play a protective role against inflammation, a recent study found. And dairy foods may help ease inflammation in patients with a combination of risk factors…
…A substance known as C-reactive protein, measured with a simple blood test, is an indicator of inflammation in the body. A report published in Archives of Internal Medicine in 2007, which analyzed results of 33 separate studies, found that losing weight can lower C-reactive protein levels. For each one kilogram, or 2.2 pounds, of weight loss, whether by dieting, exercise or surgery, the mean reduction in C-reactive protein among participants was 0.13 milligram per liter…
..At a meeting in Quebec City last week on abdominal obesity and its health risks, experts in cardiology, endocrinology, nutrition and related specialties presented a wide range of new research linking obesity to inflammation-related diseases…
One of the biggest risk factors for liver, colon or stomach cancer is chronic inflammation of those organs, often caused by viral or bacterial infections. A new study from MIT offers the most comprehensive look yet at how such infections provoke tissues into becoming cancerous.
The study, which is in the online edition ofProceedings of the National Academy of Sciences the week of June 11, tracked a variety of genetic and chemical changes in the livers and colons of mice infected with Helicobacter hepaticus, a bacterium similar to Helicobacter pylori, which causes stomach ulcers and cancer in humans.
The findings could help researchers develop ways to predict the health consequences of chronic inflammation, and design drugs to halt such inflammation.
“If you understand the mechanism, then you can design interventions,” says Peter Dedon, an MIT professor of biological engineering. “For example, what if we develop ways to block or interrupt the toxic effects of the chronic inflammation?” …
Declining biodiversity may be contributing to the rise of asthma, allergies, and other chronic inflammatory diseases among people living in cities worldwide, a Finnish study suggests. Emerging evidence indicates that commensal microbes inhabiting the skin, airway, and gut protect against inflammatory disorders. However, little is known about the environmental determinants of the microbiome.
Ilkka Hanski et al. from the Department of Biosciences, University of Helsinki, investigated whether reduced human contact with nature and biodiversity influences the composition of commensal skin bacteria and allergen sensitivity in a random sample of 118 teenagers living in eastern Finland. The authors found that subjects living on farms or near forests had more diverse bacteria on their skin and lower allergen sensitivity than individuals living in areas with less environmental biodiversity, such as urban areas or near bodies of water. …
Concerns are being raised as to how modern lifestyles may cause physiological defense mechanisms in light of the dramatic increase of people suffering from chronic inflammatory diseases, such as allergies,asthma and irritable bowel syndrome.
…Determining the factors responsible for the development of chronic inflammatory diseases remains challenging. Even though epidemiological evidence clearly indicates environmental influence as being responsible, not everyone within these environments develops diseases; and despite the fact that susceptibility to chronic inflammatory disease evidently play an important role, genetics alone may not be the only determining factor, as susceptibility to disease in later life can be influenced by prenatal exposures. Another influencing factor that determines the likelihood of a person developing diseases like asthma and allergies in later life is whether or not a person is breastfed and exposed to microorganisms after birth. …
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The supplement called “Gene-Environment Interaction in Chronic Disease – An ESF Forward Look,” by H. Renz, I.B. Autenrieth, P. Brandtzaeg, W.O. Cookson, S. Holgate, E. von Mutius, R. Valenta, and D. Haller appears as The Journal of Allergy and Clinical Immunology, Volume 128, Supplement (December 2011) published by Elsevier. It is freely available via the JACI website.
Age-old remedies could hold the key to treating a wide range of serious medical problems, as well as keeping skin firmer and less wrinkled, according to scientists. Experts have discovered that white tea, witch hazel and the simple rose hold potential health and beauty properties which could be simply too good to ignore.
The research suggests a number of naturally-occurring substances may offer the hope of new treatments to block the progression of inflammation. It is credited with a major role in both the initiation and development of diseases ranging from cancer, diabetes and arthritis through to neuro-degenerative conditions and cardiovascular and pulmonary problems.
“For thousands of years people used natural remedies to try — and sometimes succeed — in curing their ailments and preserving their youth,” Professor Declan Naughton, from the University’s School of Life Sciences, said. “Now the latest research we have carried out suggests a number of naturally-occurring substances may offer the hope of new treatments to block the progression of inflammation.”….
….The new study builds on work undertaken by Professor Naughton and Kingston University PhD student Tamsyn Thring, along with the technical team from Neal’s Yard. They tested 21 plant extracts for evidence of their efficiency in fighting cancer and also in the battle against aging. Of the 21 extracts, three — white tea, witch hazel and rose — showed considerable potential, with white tea displaying the most marked results. “Indeed it appeared that drinking a simple cup of white tea might well help reduce an individual’s risk of cancer, rheumatoid arthritis or even just age-associated wrinkles,” Professor Naughton said.
The image depicts symbiotic microbes in the process of colonizing the mucosal surface of the mouse colon. Yellow cells are Escherichia coli; red cells are Bacteroides fragilis. Intestinal tissues are labeled in green with blue nuclei.
ScienceDaily (Apr. 22, 2011) — The human gut is filled with 100 trillion symbiotic bacteria — ten times more microbial cells than our own cells — representing close to one thousand different species. “And yet, if you were to eat a piece of chicken with just a few Salmonella, your immune system would mount a potent inflammatory response,” says Sarkis K. Mazmanian, assistant professor of biology at the California Institute of Technology (Caltech).
Salmonella and its pathogenic bacterial kin don’t look that much different from the legion of bacteria in our gut that we blissfully ignore, which raises the question: What decides whether we react or don’t? Researchers have pondered this paradox for decades.
In the case of a common “friendly” gut bacterium, Bacteroides fragilis, Mazmanian and his colleagues have figured out the surprising answer: “The decision is not made by us,” he says. “It’s made by the bacteria. Since we are their home, they hold the key to our immune system.”
What’s more, the bacteria enforce their “decision” by hijacking cells of the immune system, say Mazmanian and his colleagues, who have figured out the mechanism by which the bacteria accomplish this feat — and revealed an explanation for how the immune system distinguishes between beneficial and pathogenic organisms….
…bacteria actually live in a unique ecological niche, deep within the crypts of the colon, “and thus in intimate contact with the gut mucosal immune system,” he says.
“The closeness of this association highlights that an active communication is occurring between the bacteria and their host,” says Caltech postdoctoral scholar June L. Round.
From that vantage point, the bacteria are able to orchestrate control over the immune system — and, specifically, over the behavior of immune cells known as regulatory T cells, or Treg cells. …
…”Our immune system arose in the face of commensal colonization and thus likely evolved specialized molecules to recognize good bacteria,” says Round. Mazmanian suspects that genetic mutations in these pathways could be responsible for certain types of immune disorders, including inflammatory bowel disease: “The question is, do patients get sick because they are rejecting bacteria they shouldn’t reject?”
On a more philosophical level, Mazmanian says, the findings suggest that our concept of “self” should be broadened to include our many trillions of microbial residents. “These bacteria live inside us for our entire lives, and they’ve evolved to look and act like us, as part of us,” he says. “As far as our immune system is concerned, the molecules made by gut bacteria should be tolerated similarly to our own molecules. Except in this case, the bacteria ‘teaches’ us to tolerate them, for both our benefit and theirs.”…
Journal Reference:
June L. Round, S. Melanie Lee, Jennifer Li, Gloria Tran, Bana Jabri, Talal A. Chatila, and Sarkis K. Mazmanian.The Toll-Like Receptor 2 Pathway Establishes Colonization by a Commensal of the Human Microbiota. Science, 21 April 2011 DOI:10.1126/science.1206095
“The three enterotypes show various categories of bacteria with a different impact of the gut. Enterotype 1 is dominated by the Bacteroides intestinal bacteria, which together with a few other species of bacteria, forms a distinctive cluster of gut flora. The dominant bacteria in enterotype 2 is Prevotella. And in enterotype 3, Ruminococcus is the main bacteria, along with other species such as Staphylococcus, Gordonibacter and a species discovered in Wageningen previously, Akkermansia. Enterotype 3 is the most common.
Furthermore, every cluster of bacteria has its own way of supplying energy. Enterotype 3, for example, specialises in breaking down mucin, a carbohydrate that enters the gut via our food. This allows the gut to absorb these fragments asnutrition for the body. All three enterotypes also produce vitamins, albeit in varying amounts. Enterotype 1 produces the most vitamin B7 (biotin), B2 (riboflavin) and C (ascorbic acid), and enterotype 2 produces mainly vitamin B1 (thiamin) and folic acid. Every enterotype, with its distinctive clusters of bacteria and functional differences, reflects a distinctive way of generating energy that is closely compatible with its host. It is also possible that the enterotypes may interact with their host on various levels, having an impact on the individual’s health.
In March of last year, the MetaHIT consortium published the first catalogue of genes of human intestinal bacteria (also known as the second genome). These bacteria populations encode 150 times more genes than our own genome. It was shown that from a range of more than a thousand species of bacteria that live in the human gut, every individual is host to several hundred types of bacteria.
The discovery of the enterotypes will influence the fields of biology, medicine and nutrition, making it much easier to analyse an individual’s needs. The research team sees future opportunities for personal and preventive dietary and medicinal advice.”
Genes linked to the immune system can affect healthy people’s personality traits as well as the risk of developing mental illness and suicidal behaviour, reveals a thesis from the University of Gothenburg, Sweden.
Inflammation is part of the immune system and is responsible for defending humans against infection as well as fascilitating the healing of injuries, and is therefore vital for our survival. Research has demonstrated that inflammatory processes also have other roles to play as inflammatory substances produced by the body influence mechanisms in the brain involving learning and memory.
Inflammatory substances produced in moderate quantities in the brain can be beneficial during the formation of new brain cells, for example. However, an increase in the levels of these substances as is the case during illness, can result in damage to the brain.
“Previous studies have shown that individuals suffering from various mental illnesses have an increased peripheral inflammation, but the reason behind this increase is not known,” says Petra Suchankova Karlsson, who wrote the thesis. “It has been suggested that the stress that goes with mental illness activates the body’s immune system, but it is also possible that inflammation in the body affects the brain, which in turn results in mental illness.”
Previous studies have focused on how environmental and psychological factors affect the immune system’s impact on the brain. Suchankova’s thesis presents, for the first time, results that suggest that several different genes linked to the immune system are associated with healthy people’s personality traits. It also demonstrates that some of these genes are associated with an increased risk of developing schizophrenia or suicidal behaviour….
WASHINGTON, Feb. 5, 2011 — With millions of people warding off winter’s chill with blazing fireplaces and wood-burning stoves, scientists are raising red flags about the potential health effects of the smoke released from burning wood. Their study, published in the American Chemical Society‘s (ACS’) journal, Chemical Research in Toxicology, found that the invisible particles inhaled into the lungs from wood smoke may have several adverse health effects. It is among 39 peer-reviewed scientific journals published by ACS, the world’s largest scientific society.
Steffen Loft, Ph.D., and colleagues cite the abundant scientific evidence linking inhalation of fine particles of air pollution — so-called “particulate matter” — from motor vehicle exhaust, coal-fired electric power plants, and certain other sources with heart disease, asthma, bronchitis and other health problems. However, relatively little information of that kind exists about the effects of wood smoke particulate matter (WSPM), even though millions of people around the world use wood for home heating and cooking and routinely inhale WSPM.
The scientists analyzed and compared particulate matter in air from the center of a village in Denmark where most residents used wood stoves to a neighboring rural area with few wood stoves, as well as to pure WSPM collected from a wood stove. Airborne particles in the village and pure WSPM tended to be of the most potentially hazardous size — small enough to be inhaled into the deepest parts of the lungs. WSPM contained higher levels of polycyclic aromatic hydrocarbons (PAHs), which include “probable” human carcinogens. When tested on cultures of human cells, WSPM also caused more damage to the genetic material, DNA; more inflammation; and had greater activity in turning on genes in ways linked to disease.
Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.
Under standard laboratory conditions, the human beta-defensin 1 (hBD-1), a human antibiotic naturally produced in the body, had always shown only little activity against microbes. Nevertheless the human body produces it in remarkable quantities. The solution to the puzzle was the investigation process itself, as the research group led by Dr. Jan Wehkamp at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology of the Stuttgart-based Robert Bosch Hospital found out.
Before the research group took a new approach to this research, defensins were usually tested in the presence of oxygen, although little oxygen is present, for example, in the human intestine. Starting out from the discovery that a special antibiotic-activating protein of the human body is diminished in patients with inflammatory bowel diseases, Crohn’s Disease and Ulcerative Colitis, the working group investigated how defensins act under low-oxygen conditions. During their investigations the scientists found out that under these conditions hBD-1 unfolds a strong antibiotic activity against lactic acid bacteria and yeast.
Furthermore the researchers discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Technical University of Munich, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein.
Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.
So far the cause of inflammatory bowel disease is unclear. Genetic as well as environmental factors seem to play a role, finally leading to a weakening of the antimicrobial barrier, which is mainly mediated by defensins. Accordingly the identified mechanism might contribute to the development of new therapies to treat affected patients.
This blog presents a sampling of health and medical news and resources for all. Selected articles and resources will hopefully be of general interest but will also encourage further reading through posted references and other links. Currently I am focusing on public health, basic and applied research and very broadly on disease and healthy lifestyle topics.
Several times a month I will post items on international and global health issues. My Peace Corps Liberia experience (1980-81) has formed me as a global citizen in many ways and has challenged me to think of health and other topics in a more holistic manner.
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My professional work experience and education includes over 15 years experience as a medical librarian and a Master’s in Library Science. In my most recent position I enjoyed contributing to our library’s blog, performing in depth literature searches, and collaborating with faculty, staff, students, and the general public.
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