October 15, 2006, 6:41 PM CT

New Mechanisms For Dopamine Release

The neurotransmitter dopamine continues to be released for nearly an hour after neurons are stimulated, suggesting the existence of secondary mechanisms that allow for sustained availability of dopamine in different regions of the brain including areas critical for memory consolidation, drug induced plasticity and maintaining active networks during working memory, as per a University of Pittsburgh study being presented today at the 36th Annual Meeting of the Society for Neuroscience, held at the Georgia World Congress Center in Atlanta.

Determining the mechanisms that cause what is being called "post-stimulus activated release" and how they maintain dopamine levels could have important implications for understanding and treating neurological and psychiatric disorders caused by an imbalance of dopamine function including schizophrenia, attention deficit hyperactivity disorder, Tourette's syndrome, Parkinson's disease and addiction.

As per Bita Moghaddam, Ph.D., professor of neuroscience and psychiatry, who led the study, in addition to its clinical benefits, post-stimulus activated release can be used to explain how brief events that activate neurons for short periods of time can influence brain function long after the events. For example, it can be used to explain how smelling freshly baked cookies could evoke childhood memories of spending time with a beloved grandparent, leading a person to reminisce long after the smell is gone and take the unplanned or impulsive action of baking or buying cookies.........

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October 15, 2006, 6:20 PM CT

Commonplace Sugar Controls Seizures

This sugar has been in clinical use for decades, but now it is finding new uses, a potential cure for epilepsy.

2-deoxy-glucose, or 2DG, has long been used in radio labeling, medical scanning and cancer imaging studies in humans. But now, researchers at the University of Wisconsin-Madison have found the substance also blocks the onset of epileptic seizures in laboratory rats.

Reported in the journal Nature Neuroscience, the findings have potentially huge implications for up to half of all epileptic patients who currently have no access to treatment, says senior author Avtar Roopra, a UW-Madison assistant professor of neurology.

"We pumped the rats full [of 2DG] and still saw no side effects," says Roopra, who estimates that the compound may be available for human use within five years. "I see 2DG as an epilepsy management treatment much like insulin is used to treat diabetes".

"All the available epilepsy treatments have focused on suppressing seizures," says co-author and renowned epilepsy expert Tom Sutula, a UW-Madison professor of neurology. "There has been hope that [new drugs] will not only suppress seizures, but modify their consequences. [2DG] appears to be a novel treatment that offers great promise to achieve that vision".

About 1 percent of the world's population suffers from epilepsy, a neurological condition that makes people susceptible to seizures. Scientists believe that seizures, of which there are many kinds, occur due to sudden changes in how brain cells send electrical signals to each other. In about 30 to 50 percent of epilepsy patients, available treatments - including the removal of parts of the brain's temporal lobe - are largely ineffective.........

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October 12, 2006, 5:11 AM CT

Potential New Drug For Multiple Sclerosis

Virginia Commonwealth University researchers have identified a unique mechanism of action of a new drug that shows great promise for the treatment of multiple sclerosis.

The researchers report the unique action of FTY720, or Fingolimod, an immunosuppressant drug that was already known to affect the functioning of the immune system by preventing the egress of white blood cells from the lymph nodes into the blood. The article was pre-published as a First Edition Paper in Blood, The Journal of the American Society of Hematology, which appeared online on Sept. 28.

In this study, the research team observed that FTY720 also inhibited the activity of a key enzyme called cPLA2, which is necessary for the production of inflammatory mediators, known as eicosanoids. Eicosanoids drive inflammatory disorders such as asthma and multiple sclerosis.

According to Sarah Spiegel, Ph.D., professor and chair in the VCU Department of Biochemistry, and lead author on the study, the inhibition of cPLA2 would shut down the entire inflammatory pathway, possibly without the side-effects caused by medications such as Vioxx, that have been withdrawn from the pharmaceutical market.

FTY720, a drug developed by Novartis, has shown considerable therapeutic effects in a recent small, placebo-controlled clinical trial involving patients with relapsing multiple sclerosis. The study was published in the September 2006 issue of the New England Journal (NEJM) by an international research team. With its novel mode of action and the added benefit of an oral formulation, further clinical development of FTY720 might have a major impact on treatment of MS, said Spiegel.........

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October 11, 2006, 5:18 AM CT

Hiv Gets A Makeover

The slow pace of AIDS research can be pinned, in no small part, on something akin to the square-peg-round-hole conundrum. The HIV-1 virus won't replicate in monkey cells, so researchers use a monkey virus - known as SIVmac, or the macaque version of simian immunodeficiency virus - to test potential therapies and vaccines in animals. But therapies and vaccines that are effective on SIV don't necessarily translate into human success. Now, using a combination of genetic engineering and forced adaptation, researchers at Rockefeller and the Aaron Diamond AIDS Research Center have created a version of the AIDS virus that replicates vigorously in both human and monkey cells - an advance that has the potential to revolutionize vaccine research.

In a paper published in today's issue of Science, Paul Bieniasz, associate professor and head of the Laboratory of Retrovirology, describes how he and his colleagues maneuvered around the intrinsic immunity of primate cells by replacing just a few parts of the human virus - the ones responsible for blocking replication in monkey cells - with components from SIV. "Overall, the virus is a mixture of engineering and forced evolution," Bieniasz says. "It sounds simple, in theory, but it took us two years to do".

Bieniasz and Theodora Hatziioannou, a research scientist in the lab and the paper's first author, had to overcome two major obstacles: the first was a protein called TRIM5 that, in monkeys, recognizes the outer shell or "capsid" of HIV-1 but not that of SIV. By swapping out the capsid region of the HIV-1 genome for that of the monkey virus, and then selectively growing the viruses that replicated most robustly, over several generations Hatziioannou created an HIV-1 mutant that could evade the monkey cells' TRIM5 recognition.........

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October 10, 2006, 10:18 PM CT

New Hope For Borderline Personality Disorder

For the first time, a major outcome study has shown that a high percentage of patients with Borderline Personality Disorder can achieve full recovery across the complete range of symptoms. The controlled study, appearing in a recent issue of the Archives of General Psychiatry published by the American Medical Association, shows that a new approach -- Schema Therapy -- is more than twice as effective as a widely practiced psychodynamic approach, Transference Focused Psychotherapy (TFP). Schema Therapy was also found to be less costly and to have a much lower drop out rate. Borderline Personality Disorder (BPD) has until recent years been considered untreatable, with little scientific justification for longer-term therapy.

This study demonstrates that schema therapy leads to complete recovery in about 50% of the patients, and to significant improvement in two-thirds. The success of the therapy is strongly related to its duration and intensity (two sessions a week for 3 years). The results clearly contradict the prevailing opinion that BPD cannot be fully cured, and that longer-term psychotherapy is ineffective.

According to the National Institute of Mental Health, Borderline Personality Disorder is found in about 1 to 2.5 percent of the general population--about 5.8 to 8.7 million Americans, most of whom are young women. Patients with the disorder live life on the edge: they're typically impulsive, unstable, exquisitely sensitive to rejection, have regular outbursts of anger, and live daily with extreme emotional pain. They often self-mutilate and make repeated suicide attempts. Identity problems, low stress tolerance, and fears of abandonment also make the disorder difficult for patients and for those who live with them. Many with BPD either cannot work or do not function at levels that could be expected in light of their intellectual capacities. As a result, the disorder carries high medical and societal costs, accounting for more than one in every five inpatient psychiatric admissions.........

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October 10, 2006, 9:58 PM CT

Material That Stops Bleeding In Seconds

MIT and Hong Kong University scientists have shown that some simple biodegradable liquids can stop bleeding in wounded rodents within seconds, a development that could significantly impact medicine.

When the liquid, composed of protein fragments called peptides, is applied to open wounds, the peptides self-assemble into a nanoscale protective barrier gel that seals the wound and halts bleeding. Once the injury heals, the nontoxic gel is broken down into molecules that cells can use as building blocks for tissue repair.

"We have found a way to stop bleeding, in less than 15 seconds, that could revolutionize bleeding control," said Rutledge Ellis-Behnke, research scientist in the MIT Department of Brain and Cognitive Sciences.

This study, which will appear in the online edition of the journal Nanomedicine on Oct. 10, marks the first time that nanotechnology has been used to achieve complete hemostasis, the process of halting bleeding from a damaged blood vessel.

Doctors currently have few effective methods to stop bleeding without causing other damage. More than 57 million Americans undergo nonelective surgery each year, and as much as 50 percent of surgical time is spent working to control bleeding. Current tools used to stop bleeding include clamps, pressure, cauterization, vasoconstriction and sponges.........

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October 9, 2006, 9:28 PM CT

Celiac Disease And Cognitive Decline

Mayo Clinic researchers have uncovered a new link between celiac disease, a digestive condition triggered by consumption of gluten, and dementia or other forms of cognitive decline. The investigators' case series analysis -- an examination of medical histories of a group of patients with a common problem -- of 13 patients would be published in the recent issue of Archives of Neurology.

"There has been very little known about this connection between celiac disease and cognitive decline until now," says Keith Josephs, M.D., Mayo Clinic neurologist and study investigator. "This is the largest case series to date of patients demonstrating cognitive decline within two years of the onset of celiac disease symptom onset or worsening".

Says Joseph Murray, M.D., Mayo Clinic gastroenterologist and study investigator, "There has been a fair amount written before about celiac disease and neurological issues like peripheral neuropathy (nerve problems causing numbness or pain) or balance problems, but this degree of brain problem -- the cognitive decline we've found here -- has not been recognized before. I was not expecting there would be so many celiac disease patients with cognitive decline".

The next step in the research will be to investigate the measure and nature of the connection between the two conditions.........

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October 9, 2006, 9:13 PM CT

Progress In HIV Research

How a harmless virus called GB Virus type C (GBV-C) protects against HIV infection is now better understood. Researchers at the Department of Veterans Affairs (VA) Iowa City Health Care System and the University of Iowa have identified a protein segment that strongly inhibits HIV from growing in cell models.

The team found that an 85-amino acid segment within a GBV-C viral protein called NS5A greatly slows down HIV from replicating in cells grown in labs. The study results will appear online this week in the Proceedings of the National Academy of Sciences.

The finding builds on earlier VA and UI work showing that people with HIV who also are infected GBV-C live longer than those infected only with HIV, said Jinhua Xiang, M.D., a VA research health scientific specialist, UI researcher and the current study's principal author.

GBV-C and its role in HIV infection have been studied for nearly a decade by Xiang, along with another study author Jack Stapleton, M.D., staff doctor and researcher at the VA Iowa City Health Care System and professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine.

"Identifying a specific protein made by GBV-C that inhibits HIV growth in cell culture strengthens the argument that GBV-C is responsible for the prolonged survival observed in several studies of HIV-positive people," Xiang said. "Understanding how the protein works may allow us to develop target-specific therapies that can mimic these effects and inhibit HIV.........

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October 9, 2006, 8:35 PM CT

Antibiotic Resistance In Hospitals

In one of the first national studies on guidelines that control antibiotics and antibiotic resistance in hospitals, scientists from the Indiana University School of Medicine, the Regenstrief Institute, Inc. and the Richard Roudebush Veterans.

Administration Medical Center report that hospitals that follow national guidelines on controlling antibiotic use have lower rates of antibiotic resistance.

As per a research findings reported in the recent issue of Infection Control and Hospital Epidemiology, the scientists studied four major types of antibiotic resistance at almost 450 hospitals, looking at what each hospital did to control antibiotic use and how this affected the rate of antibiotic resistance.

"We saw in this study, as in other work we have done, that antibiotic resistance is increasing rapidly. This increase is seen in all types of hospitals across the country - large and small, teaching and non-teaching, VA and non-VA," said Bradley N. Doebbeling, M.D., M.Sc., who led the study. He directs the IU Center for Health Services and Outcomes Research at the Regenstrief Institute and the IU School of Medicine. He also directs the VA Center for Implementing Evidence-Based Practice.

The study looked at measures to prevent development of antibiotic resistance as well as ways to stop its spread. The scientists reported that if hospitals implemented specific measures to control the use of antibiotics they were more likely to have succeeded in controlling antibiotic resistance.........

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October 8, 2006, 7:10 PM CT

Genes Diet And Heart Disease

Researchers from the Jean Mayer USDA Human Nutrition Research Center (USDA HNRCA) at Tufts University and colleagues have found another link among genes, heart disease and diet. The study, published in Circulation, examined apolipoprotein A5 (APOA5), a gene that codes for a protein, which in turn plays a role in the metabolism of fats in the blood. The results show that people who carry a particular variant of APOA5 may have elevated risk factors that are associated with heart disease, but only if they also consumed high amounts of omega-6 fatty acids in their diets.

Corresponding author Chao-Qiang Lai, PhD, a USDA-Agricultural Research Service (ARS) scientist at the USDA HNRCA, and colleagues analyzed lipid levels and dietary assessment questionnaires of more than 2,000 participants in the Framingham Heart Study and quantified their intake of different types of fats.

Omega-6 fatty acids, as well as omega-3 fatty acids, are polyunsaturated fatty acids (PUFAs) and, according to a report from the National Institutes of Health Office of Dietary Supplements, most Americans consume about 10 times more omega-6s than omega-3s. Omega-3s are found in nuts, leafy green vegetables, fatty fish, and vegetable oils like canola and flaxseed, while omega-6s are found in grains, meats, vegetable oils like corn and soy, and also processed foods made with these oils. Both omega-3s and omega-6s, known as essential fatty acids, must be consumed in the diet because they are not made by the body.........

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