Newly Identified Immune Protein Could Stop Diabetes in Its Tracks: Melbourne Researchers

The discovery has wider repercussions, as the protein is responsible for protecting the body against excessive immune responses, and could be used to treat, or even prevent, other immune disorders such as multiple sclerosis and rheumatoid arthritis.

Professor Len Harrison, Dr Esther Bandala-Sanchez and Dr Yuxia Zhang led the research team from the Walter and Eliza Hall Institute's Molecular Medicine division that identified the immune protein CD52 as responsible for suppressing the immune response, and its potential for protecting against autoimmune diseases.

So-called autoimmune diseases develop when the immune system goes awry and attacks the body's own tissues. Professor Harrison said CD52 held great promise as a therapeutic agent for preventing and treating autoimmune diseases such as type 1 diabetes.

"Immune suppression by CD52 is a previously undiscovered mechanism that the body uses to regulate itself, and protect itself against excessive or damaging immune responses," Professor Harrison said.

"We are excited about the prospect of developing this discovery to clinical trials as soon as possible, to see if CD52 can be used to prevent and treat type 1 diabetes and other autoimmune diseases. This has already elicited interest from pharmaceutical companies," he noted.

Type 1 diabetes is an autoimmune disease that develops when immune cells attack and destroy insulin-producing beta cells in the pancreas.

Professor Harrison said that T cells that have or release high levels of CD52 are necessary to maintain normal balance in the immune system.

"In a preclinical model of type 1 diabetes, we showed that removal of CD52-producing immune cells led to rapid development of diabetes. We think that cells that release CD52 are essential to prevent the development of autoiummune disease, and that CD52 has great potential as a therapeutic agent," he said.

CD52 appears to play a dominant role in controlling or suppressing immune activity in the early stages of the immune response, Professor Harrison said.

"We identified a specialised population of immune cells (T cells) that carry high levels of CD52, which they release to dampen the activity of other T cells and prevent uncontrolled immune responses," Professor Harrison said.

"The cells act as an early 'braking' mechanism," he added.

Professor Harrison said his goal is to prevent and ultimately cure type 1 diabetes.

He revealed that they can prevent and cure type 1 diabetes in animal models and he's hopeful that these results will be translatable into humans, hopefully in the not-too-distant future.

The research was published today in the journal Nature Immunology.

Source-ANI

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New Compounds to Curb Staph Infection Identified

Writing online in the Journal of the American Chemical Society, a group led by University of Wisconsin-Madison chemistry Professor Helen Blackwell describes agents that effectively interfere with the "quorum sensing" behavior of Staphylococcus aureus, a bacterium at the root of a host of human infections ranging from acne to life-threatening conditions such as pneumonia, toxic shock syndrome and sepsis.

"It's a whole new world for us," says Blackwell, whose group identified peptide-based signaling molecules that effectively outcompete the native molecules the bacterium uses to communicate and activate the genes that cause disease.

Bacteria use quorum sensing to assess their population density and coordinate certain behaviors. They do so through the use of pheromone-like chemicals, which bind to receptors either in the bacterial cell or on its surface and tell it if there are enough companion bacteria around to switch on genes that perform certain functions. In the case of Staphylococcus aureus, quorum sensing activates toxin production, manifesting disease in the host.

Interfering with bacterial quorum sensing to stymie disease is considered a promising new antibiotic strategy, says Blackwell. Staph, she adds, is an excellent target as the bacterium is not only a prevalent pathogen, but some strains, notably methicillin-resistant Staphylococcus aureus or MRSA, have developed resistance to commonly used antibiotics such as penicillin and its derivatives.

The new compounds synthesized by Blackwell and her colleagues are peptides that work at very low concentrations by blocking the chemical receptors the bacterium uses to regulate quorum sensing. The new agents devised by Blackwell and her group work on the four subtypes of staph, all of which use different quorum sensing signals and are found in different infection types.

"We had not worked much in this area because the (signaling molecules) are somewhat challenging to synthesize," explains Blackwell. "We now have developed methods to make these molecules and analogs much more efficiently, which helped fuel this new study."

For now, the compounds devised by the Wisconsin team will have their greatest impact in the lab as research probes to further study the role of quorum sensing in Staphylococcus aureus. In addition, the gritty details of how these synthetic agents work in the cell need to be determined in order to optimize their potential use in both the lab and clinic. Such studies are ongoing.

"The impact of these new peptides could be significant because staph is an important and increasingly scary pathogen. There is plenty of scope," notes Blackwell.

Source-Eurekalert

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Risks and Interventions for Children's GI Health Identified

by Kathy Jones on? May 19, 2013 at 3:28 PM Child Health News Gastrointestinal issues that require interventions are being experienced by an increasing number of children in the US, according to research presented at Digestive Disease Week? (DDW).
In one study targeting obesity, researchers at the Cleveland Clinic Children's Hospital found that obese children have a unique pattern of exhaled breath compared to their lean counterparts. The pattern showed differences in volatile organic compound levels that can be correlated to potential complications associated with obesity, such as diabetes and fatty liver disease.

"Childhood obesity has reached epidemic levels in the U.S., with 17 percent of children being obese and at risk for serious health complications," said Naim Alkhouri, MD, director of the Pediatric Preventive Cardiology and Metabolic Clinic at Cleveland Clinic's Children's Hospital. "A quick, non-invasive breath test that identifies specific risks could help clinicians identify effective interventions while also motivating families to take preventative action."

Funded by the Cleveland Clinic Respiratory Institute and the Ohio Third Frontier program, the study compared the volatile organic compounds in the breath of obese and lean children and found differences in the concentration of more than 50 compounds. The test identified the obese children with a 92 percent rate of accuracy. Dr. Alkhouri said that while more research is needed to validate the findings, the breath test could be an invaluable research tool.

"The findings promise to shed more light on the causes and complications of childhood obesity," he said. "Ultimately, this could have huge implications for early interventions for obesity-related complications that could be effectively targeted to combat risk as these children get older."

Study identifies high rate of surgical intervention for magnet ingestions

DDW is also featuring research in a very different area of pediatric risk: the ingestion of high-powered magnets.

What started as a concern posted by a few pediatric gastroenterologists on a community bulletin board became the first study to document the frequency of medical and surgical interventions for children and adolescents who swallow magnets, a common component of adult desk toys. Investigators found that more than 79 percent of magnet ingestion cases ultimately required surgical and/or endoscopic procedures. Only 21 percent of cases could be managed by observation alone or by observation and pumping of the stomach, or lavage.

"We seemed to be seeing more and more of these cases, some of which were very serious, even life-threatening," said R. Adam Noel, associate professor of pediatrics at Louisiana State University Children's Hospital. "Our research not only confirms our concern, but also shows that early intervention is particularly important with these magnet ingestions."

Funded by the department of pediatrics at the Louisiana State University Health Science Center in New Orleans, the study surveyed pediatric gastroenterologists around the country, tracking their medical and surgical interventions with patients who had swallowed neodymium magnets. These magnets are 10 to 20 times stronger than typical refrigerator magnets and are typically found in desk toys marketed to adults as stress relievers. If ingested, the magnets can become lodged in the digestive system and perforate the intestine. Severe damage can be fatal.

In 31 percent of cases, the study found, surgery was only needed to remove the magnets. But 43 percent of surgical cases required another major procedure, including fistula (abnormal connection between an organ, vessel or intestine and another structure) repair, and 15 percent needed a bowel resection.

The high surgical rate may be explained by the magnets' unique potential for harm. In cases involving other foreign objects, 85 percent of the time, those objects pass through a child's digestive track without complication. But the neodymium magnets, which are often swallowed in multiples, can pull together through the wall of the intestine.

"The findings send a strong message to clinicians and parents," said Dr. Noel. "Although they look harmless on an X-Ray, these magnets are powerful enough to cause serious damage to the digestive track in a short amount of time."

While children between the ages of 13 months and 6 years are at the highest risk for ingestion, older children's risk also appears to be increased as adolescents use the magnets for body jewelry and fake piercings. Analyzing the same data, a companion study found that 24 percent of children treated had ingested magnets as a result.

Last month, in response to the increasing reports of this hazard, the U.S. Consumer Product Safety Commission and several retailers announced the voluntary recall of high-powered magnet sets.

Source-Eurekalert

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Infection and Sepsis-related Mortality Hotspots Identified Across US

Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have created the first U.S. map that pinpoints hotspots for infection and severe sepsis related-deaths - with notable clusters located in the Midwest, mid-Atlantic, and the South. The research is a critical first step in helping to determine which areas of the country require vital public health resources to fight these deadly diseases. The new research will be presented at the annual meeting of Society for Academic Emergency Medicine in Atlanta, Ga.

"Infection-related deaths are a leading cause of morbidity and mortality in the U.S., affecting over 1 million people a year, and costing $17 billion annually," said lead study author David Gaieski, MD, an associate professor of Emergency Medicine at Penn. "And while our understanding of the causes of infection-related death rates has improved, we are still struggling to prevent these diseases and indentify individuals who are most susceptible. We need to be able to pinpoint the geographic distribution of infection-related death rates in order to further study how and why these infections are happening in these areas and the best methods to prevent these deaths."

Sepsis is the tenth leading cause of death in the United States. With an estimated 750,000 cases annually and a nearly 40 percent mortality rate, severe sepsis is also one of the most common causes of death in hospital critical care units.

To better understand what areas of the country are most at risk for severe sepsis and other infection-related deaths, the research team collected U.S. county death data from the 2010 Multiple Cause of Death data files (compiled by the National Center for Health Statistics) and combined it with 2010 Area Resource File demographic data for a comprehensive view of national variations. The authors note that previous research had only been able to identify potential trends on a state level.

Infection-related deaths were identified using ICD-10 primary cause of death codes for infection and severe sepsis. "Hotspots" were defined as regions where the infection death rate was significantly higher than the national mean and surrounding counties. The analysis revealed four hotspots: 1) two regions that had three times the national mean of infection-related deaths located across the Midwest and mid-Atlantic and 2) two regions that had four times the national death rate from severe sepsis, located in the South and mid-Atlantic.

In addition to the hotspots, the research team also indentified one "coolspot" cluster, an area that had disproportionately low rates of deaths caused by these infections. The coolspot cluster consisted of 157 counties located across the Southwest and Mountain states. The research team notes that these "coolspot" counties might yield important insights as well, including particular screening and treatment protocols that may be in place in these areas.

"This analysis may help target focused geographical interventions to improve the dissemination and implementation of evidence-based care," said senior study author Brendan G. Carr, MD, MA, assistant professor of Emergency Medicine, Surgery, & Epidemiology at Penn. "Further study is required to clarify the geographic variability we observed, but we believe this new resource will be a helpful tool for researchers and public health officials."

Source-Eurekalert

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