Articles which explain aspects of Inflammatory Bowel Disease, why it develops in the first place etc.

Prevention Is Better Than Cure: Fighting Autoimmune Diseases

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11 Jul 2006

Centenary scientist Associate Professor Barbara Fazekas de St. Groth, a leader in inflammatory bowel disease research, has demonstrated for the first time the important role of T cells in the prevention of autoimmune diseases in humans.

In a study involving 38 patients with Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), and 43 healthy controls, Assoc Prof Fazekas and colleagues found that healthy individuals have up to twice the number of disease-fighting regulatory T cells compared with IBD patients at the onset of disease.

"It is important to have more regulatory T cells, especially when you are young, as individuals with a deficiency are more susceptible to disease and frequency of disease is higher in the young," says Assoc Prof Fazekas.

"Our results also indicate that the activity of these cells is increased in IBD patients during the later stages of disease in an attempt to fight it."

IBD is usually diagnosed in children and young adults. It affects 1 in 200 people and an estimated 100,000 Australians and there is no cure.

"Regulatory T cells have previously been difficult to quantify in humans and conventional methods could identify fewer than a third of the total number. The blood test we have developed allows us for the first time to accurately count the number of regulatory T cells in the body," says Assoc Prof Fazekas.

The highly accurate identification and isolation of regulatory T cells was made possible using sophisticated flow cytometry equipment at the Centenary Institute.

The machines use laser beams and advanced optics and electronics to analyse and purify many kinds of cells at a rate of over 25,000 cells every second. This technology is able to produce results that cannot be obtained by any other method as it allows every cell to be identified and sorted on an individual basis.

"The ability to detect regulatory T cell deficits in inflammatory diseases such as IBD means that we can now identify individuals at risk of developing disease. The test can also be used to assess the effect of new preventative treatments in the future."

The researchers are using the test to study regulatory T cell levels in autoimmune, inflammatory and allergic diseases such as multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, asthma and eczema, to determine the risk of disease in patients and their families.
http://www.medilexicon.com/medicalnews.php?newsid=46860∞

Scientists Show How Immune System Chooses Best Way To Fight Infection

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18 Nov 2006

A new study has suggested a novel way of combating diseases related to the immune system, including cancer and autoimmune diseases such as type I diabetes and arthritis. The study, funded by the Wellcome Trust, appears online in the journal Nature.

T cells are produced by the body to fight infection. Scientists previously identified two types of T cell, both produced in the thymus: "effector T cells", which attack infected cells, and "regulatory T cells", which suppress the immune system, protecting the body from inflammatory damage during infection. Regulatory T cells, if given to individuals receiving transplants, may help suppress the rejection response.

Now, a team of researchers has discovered a novel mechanism determining whether a maturing T cell is likely to emerge from the thymus as an effector cell or a regulatory cell. The research suggests that new treatments could be developed to deliberately affect the type of T cells produced, allowing scientists to tackle a number of diseases which are influenced by these different types of T cells.

"Our team has shown that a process known as 'trans-conditioning', which we knew to be involved in T cell development, actually has a profound influence on whether a T cell becomes an effector or a regulatory cell," explains Professor Adrian Hayday of King's College London. "This may be clinically significant; if we can find a way to influence this process, it may be possible to make the body produce effector T cells in a cancer patient or regulatory T cells in someone suffering from autoimmune disease, both of which are caused by the immune system malfunctioning."

Professor Hayday and his team believe that the findings may also answer one of medical research's mysteries: why autoimmune diseases in women commonly go into remission in pregnancy.

"We believe that trans-conditioning is less active during pregnancy," says Professor Hayday. "This means that most T cells emerging at that time will be regulatory. Regulatory T cells prevent an over-active immune system from causing inflammatory damage to the body. This may be one of the key steps in preventing the mother from rejecting the foetus growing inside her."
http://www.medilexicon.com/medicalnews.php?newsid=56692∞

Note by Kathy - many women report that their symptoms subside during pregnancy, only to re-appear once the baby is born. Others have first symptoms following a pregnancy. Maybe this starts to explain why.

Molecular Basis Of Inflammatory Bowel Disease Identified By Researchers

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17 Mar 2007

Inflammatory bowel diseases, such as Crohn's disease and Ulcerative Colitis, severely impair the lives of more than four million people worldwide. The development of effective therapies against these diseases requires an understanding of their underlying molecular mechanisms. Researchers from the Universities of Cologne and Mainz in Germany, the Mouse Biology Unit of the European Molecular Biology Laboratory (EMBL) in Italy and their collaborators, have now deciphered a molecular signal that triggers chronic intestinal inflammation. The study, which is published in the current online issue of Nature, shows that blocking a signaling molecule causes severe intestinal inflammation in mice and reveals a molecular mechanism that is likely to also underpin human inflammatory bowel disease.

Our gut is home to an enormous number of bacteria, which live in harmony with us and help in food digestion. If they penetrate the wall of the intestine, however, these bacteria can become harmful and cause diseases. This is why a thin, continuous layer of interconnected cells, called an epithelium, lines the intestinal surface creating a barrier that prevents bacteria from crossing that border. The mechanisms that control the integrity of the epithelium and contribute to maintaining a healthy gut have remained unknown.

Arianna Nenci from the group of Manolis Pasparakis at the University of Cologne and Christoph Becker, a member of Markus Neurath's group in Mainz, investigated the role of NF-kB, a signaling molecule that helps cells cope with stress, in the intestinal epithelium. Using sophisticated genetic methods, they generated a mouse model that does not express NEMO, a protein needed to activate NF-kB, in intestinal epithelial cells. As a result, these mice developed severe chronic intestinal inflammation very similar to Colitis in humans.

"A close look at the mice revealed that their gut epithelium was damaged," says Manolis Pasparakis, who recently moved from heading a lab at EMBL to becoming a professor at the University of Cologne. "NF-kB acts as a survival signal for cells. Without the molecule cells are much more likely to die and this is what happened in the intestines of our mice; individual epithelial cells died disrupting the gut lining."

Through these gaps bacteria could penetrate the intestinal wall. Right behind the gut epithelium lie cells of the intestinal immune system, the biggest immune system of our body. It detects the invading bacteria and generates a strong immune response to fight off the invaders. In the process of combating the bacteria, the immune cells secrete a cocktail of signals that bring about the symptoms of inflammation.

"This is where the vicious cycle closes," explains Markus Neurath, professor at the University of Mainz. "Inflammatory signals also reach the epithelial cells that due to the lack of NF-kB are very sensitive to them and die. The death of more epithelial cells creates bigger gaps in the gut lining so that more bacteria enter. The result is a constant immune response leading to chronic inflammation as we know it from inflammatory bowel diseases in humans."

The finding that defective NF-kB signaling in the gut epithelium initiates the outbreak of inflammation in the intestine provides a new paradigm for the pathogenesis of inflammatory bowel disease. Since the immune systems of mice and humans are very similar, the insights gained through the mouse model are steps towards a better understanding of the mechanisms causing human inflammatory bowel diseases and may pave the way for novel therapeutic approaches.
http://www.medicalnewstoday.com/medicalnews.php?newsid=65303∞

Alternative article:

Researchers identify molecular basis of inflammatory bowel disease

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Scientists decipher a signaling pathway crucially involved in Crohn's disease and Ulcerative Colitis

Inflammatory bowel diseases, such as Crohn?s disease and Ulcerative Colitis, severely impair the lives of more than four million people worldwide. The development of effective therapies against these diseases requires an understanding of their underlying molecular mechanisms. Researchers from the Universities of Cologne and Mainz in Germany, the Mouse Biology Unit of the European Molecular Biology Laboratory (EMBL) in Italy and their collaborators, have now deciphered a molecular signal that triggers chronic intestinal inflammation. The study, which is published in the current online issue of Nature, shows that blocking a signaling molecule causes severe intestinal inflammation in mice and reveals a molecular mechanism that is likely to also underpin human inflammatory bowel disease.

Our gut is home to an enormous number of bacteria, which live in harmony with us and help in food digestion. If they penetrate the wall of the intestine, however, these bacteria can become harmful and cause diseases. This is why a thin, continuous layer of interconnected cells, called an epithelium, lines the intestinal surface creating a barrier that prevents bacteria from crossing that border. The mechanisms that control the integrity of the epithelium and contribute to maintaining a healthy gut have remained unknown.

Arianna Nenci from the group of Manolis Pasparakis at the University of Cologne and Christoph Becker, a member of Markus Neurath?s group in Mainz, investigated the role of NF-kB, a signaling molecule that helps cells cope with stress, in the intestinal epithelium. Using sophisticated genetic methods, they generated a mouse model that does not express NEMO, a protein needed to activate NF-kB, in intestinal epithelial cells. As a result, these mice developed severe chronic intestinal inflammation very similar to Colitis in humans.

"A close look at the mice revealed that their gut epithelium was damaged," says Manolis Pasparakis, who recently moved from heading a lab at EMBL to becoming a professor at the University of Cologne. "NF-kB acts as a survival signal for cells. Without the molecule cells are much more likely to die and this is what happened in the intestines of our mice; individual epithelial cells died disrupting the gut lining."

Through these gaps bacteria could penetrate the intestinal wall. Right behind the gut epithelium lie cells of the intestinal immune system, the biggest immune system of our body. It detects the invading bacteria and generates a strong immune response to fight off the invaders. In the process of combating the bacteria, the immune cells secrete a cocktail of signals that bring about the symptoms of inflammation.

"This is where the vicious cycle closes," explains Markus Neurath, professor at the University of Mainz. "Inflammatory signals also reach the epithelial cells that due to the lack of NF-kB are very sensitive to them and die. The death of more epithelial cells creates bigger gaps in the gut lining so that more bacteria enter. The result is a constant immune response leading to chronic inflammation as we know it from inflammatory bowel diseases in humans."

The finding that defective NF-kB signaling in the gut epithelium initiates the outbreak of inflammation in the intestine provides a new paradigm for the pathogenesis of inflammatory bowel disease. Since the immune systems of mice and humans are very similar, the insights gained through the mouse model are steps towards a better understanding of the mechanisms causing human inflammatory bowel diseases and may pave the way for novel therapeutic approaches.
http://www.eurekalert.org/pub_releases/2007-03/embl-rim031407.php∞

Patients With Inflammatory Bowel Disease More Likely To Die From Clostridium Difficile Infection

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Article Date: 27 Sep 2007 - 7:00 PDT

A patient with inflammatory bowel disease is four times as likely to die from Clostridium difficile infection compared to a person who does not have the disease, according to an article published ahead of print in the journal Gut (BMJ).

The number of new cases of C difficile infection has been steadily rising over the last few years. C difficile is a major cause of diarrhea among inpatients, say the writers.

The researchers examined a representative sample of community hospital admissions in The United States for 2003, covering 994 hospitals in 37 states, including 124,570 patients.

44,400 of these patients had been hospitalized with C difficile infection, while 77,366 had inflammatory bowel disease (IBD). Inflammatory bowel disease includes Crohn's disease or ulcerative colitis. 2,804 of the patients had both C difficile infection and IBD.

The average age of those who had just the infection was 73. The average age of those with IBD was 42. The researchers found that the risk of death was higher for those with C difficile infection alone, or in combination with IBD, than patients with IBD alone. However, those who had both IBD and C difficile infection were four times more likely to die than the other patients - this was regardless of age.

Patients with both IBD and C difficile infection also remained in hospital for three days longer than the other patients, their rates of endoscopy were also higher.

The writers report that patients with ulcerative colitis tended to suffer from more serious C difficile infections and had worse outcomes than patients with Crohn's disease. They concluded that a patient with IBD may be especially susceptible to C difficile infection.
http://www.medicalnewstoday.com/articles/83869.php∞

Cancer Protection and Mesalamine Linked For High Risk Inflammatory Bowel Disease Patients

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Article Date: 16 Oct 2007 - 6:00 PDT

Colorectal screening remains essential for those with IBD

Researchers found that mesalamine use among patients with inflammatory bowel disease was associated with a decrease in incidence of colorectal cancer when comparing cases and controls. In the study presented at the 72nd Annual Scientific Meeting of the American College of Gastroenterology, researchers from Henry Ford Hospital in Detroit matched 16 patients with ulcerative colitis and Crohn's disease to 23 controls with similar body mass index, family history of IBD, family history of colorectal cancer and smoking.

Among those with ulcerative colitis who did not get colorectal cancer, researchers found that 100 percent used mesalamine. While among those with UC who developed colorectal cancer only 76.9 percent used mesalamine. "This finding suggests an association between mesalamine use and reduced risk of colorectal cancer," according to Jeffrey Tang, M.D. Dr. Tang and his colleagues, including Ann L. Silverman, M.D., conducted conditional logistic regression analysis which revealed that at doses greater than 5068 grams mesalamine use in patients with IBD was associated with an 89 percent reduction in risk of colorectal cancer, compared to IBD patients matched for other major risk factors. While these are provocative findings, it should be noted that this is a small study and further investigation is needed on the chemoprevention potential of mesalamine.

Patients with inflammatory bowel disease including ulcerative colitis and Crohn's disease are at significantly higher than average risk for colorectal cancer and should be screened for colorectal cancer according to accepted guidelines, which recommend more frequent screening among those with IBD. However, some research suggests this is not happening.

Poor Adherence to Recommended Screenings for Colorectal Cancer Among IBD Patients

In another study conducted at the University of California, San Francisco and Kaiser Permanente of Northern California and presented at the ACG Annual Meeting, researchers looked at rates of participation in colorectal cancer screening by patients with IBD in an integrated health system with access to colonoscopy. An intensive program of colonoscopic screening and surveillance is recommended to prevent colorectal cancer in patients with ulcerative colitis, who are at higher than average risk.

In this study of 358 patients with ulcerative colitis who were eligible for screening, only one third were screened once during the period 2001 to 2005. Of these 123 patients, only 52 percent had an additional surveillance colonoscopy within the recommended period of one to two years. Overall, only 18 percent of the eligible patients at high risk for colorectal cancer due to history of ulcerative colitis adhered to recommended surveillance guidelines.
http://www.medicalnewstoday.com/articles/85646.php?nfid=30587∞

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