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April 21, 2007, 6:49 AM CT

Brain networks strengthened by ion channels

Brain networks strengthened by ion channels
Yale School of Medicine and University of Crete School of Medicine scientists report in Cell April 20 the first evidence of a molecular mechanism that dynamically alters the strength of higher brain network connections.

This discovery may help the development of drug therapies for the cognitive deficits of normal aging, and for cognitive changes in schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder (ADHD).

"Our data reveal how the brains arousal systems influence the cognitive networks that subserve working memorywhich plays a key role in abstract thinking, planning, and organizing, as well as suppressing attention to distracting stimuli," said Amy Arnsten, lead author and neurobiology professor at Yale.

The brains prefrontal cortex (PFC) normally is responsible for so-called executive functions. The ability of the PFC to maintain such memory-based functions declines with normal aging, is weakened in people with ADHD, and is severely disrupted in disorders such as schizophrenia and bipolar disorder.

The current study observed that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN), that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected. Arnsten said inhibiting cAMP closes the channels and allows the network to reconnect.........

Posted by: Daniel      Read more         Source


April 21, 2007, 6:44 AM CT

Family turmoil and domestic violence

Family turmoil and domestic violence
Adolescents who are chronically exposed to family turmoil, violence, noise, poor housing or other chronic risk factors show more stress-induced physiological strain on their organs and tissues than other young people.

However, when they have responsive, supportive mothers, they do not experience these negative physiological changes, reports a new study from Cornell.

But the research group also observed that the cardiovascular systems of youths who are exposed to chronic and multiple risk factors are compromised, regardless of their mothers' responsiveness.

The study, led by environmental and developmental psychology expert Gary Evans, is reported in the recent issue of Developmental Psychology. It is the first study to look at how maternal responsiveness may protect against cumulative risk as well as the first, as per the researchers, to look at cardiovascular recovery from stress in children or youths.

Evans said that the findings suggest that the physiological toll of coping with multiple risk factors is significantly greater than with that of coping with a single event, even if that event was rather severe. "Moreover the burden appears to register in physiological systems that help us regulate our responses to stress," said Evans, the Elizabeth Lee Vincent Professor of Human Ecology and professor of human development and of design and environmental analysis in Cornell's College of Human Ecology.........

Posted by: JoAnn      Read more         Source


April 19, 2007, 7:42 PM CT

How Viruses Invade The Brain

How Viruses Invade The Brain
A molecule thought crucial to ferrying the deadly rabies virus into the brain, where it eventually kills, apparently isnt. The surprising finding, say scientists at Jefferson Medical College in Philadelphia, may change the way researchers think about how central nervous system-attacking viruses such as herpes viruses invade the brain and cause disease.

As per Matthias Schnell, Ph.D., professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University, viruses such as rabies must be actively transported to the brain and central nervous system. The LC8 protein was thought to tether viruses to the cellular transport machinery in order to get there.

But Dr. Schnell and his co-workers observed that this protein complex is instead a "transcription factor" that plays a role in virus reproduction. "We believe that this finding has implications not only for rabies but a number of viruses that previously were thought to use this complex for transport, such as herpes viruses," he says. They report their results online this week in the journal Proceedings of the National Academy of Sciences.

To understand the role of LC8 in rabies disease in the brain, the team compared a rabies virus strain with the LC8 "binding domain" (where the rabies virus and LC8 protein interact) to a virus lacking it. They showed that in mice that were infected with rabies without the LC8 binding domain, the virus was still able to infect the brain, but did not cause disease. The virus ability to reproduce was greatly diminished.........

Posted by: Daniel      Read more         Source


April 19, 2007, 7:38 PM CT

Novel transfusion strategy for pediatric patients

Novel transfusion strategy for pediatric patients
In its April 19th, 2007 edition, the New England Journal (NEJM) published an article about the findings of a multi-center randomized clinical trial that compared transfusion strategies for patients in pediatric intensive care units. The study, led by Dr. Jacques Lacroix, a full professor in the Department of Pediatrics at the Universit de Montral and a pediatric intensivist as well as researcher at the CHU Sainte-Justine, a university hospital center, was conducted in 637 children in 19 intensive care units in Canada, England, Belgium and the USA.

Determining the Transfusion Requirements of Pediatric Patients

Before this study, entitled TRIPICU (Transfusion Requirements for Patients in Pediatric Intensive Care Units), no precise data were available to guide intensive care specialists when deciding about whether or not to transfuse critically ill children. In fact, up until now, the optimal threshold for transfusion using packed red blood cells in children admitted to intensive care was not known.

A prior study carried out in adult patients suggested that a restrictive transfusion strategy could provide a better outcome than a liberal strategy. However, the study was conducted previous to the introduction of new practices involving the systematic removal of leukocytes from packed red blood cells before storage.........

Posted by: JoAnn      Read more         Source


April 19, 2007, 7:34 PM CT

Novel drug for treating leukemia

Novel drug for treating leukemia
Scientists from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have observed that a novel targeted treatment effectively treats acute leukemia in animal models by preventing cancer cells from being purged of damaged proteins.

In the March online issue of the journal Blood, researchers reported that the new proteasome inhibitor, NPI-0052, not only successfully kills leukemia cells, but also shows greater efficacy than its predecessor bortezomib when combined with other agents in animal models.

As per researchers, proteasomes clean out mutated or damaged proteins within cells, which promotes cell growth and allows cancer cells to rapidly reproduce. Proteasome inhibitors block this process, resulting in apoptosis, or cell death, of the cancerous cells.

Bortezomib is the first and only FDA-approved proteasome inhibitor. Eventhough it is effective for treating multiple myeloma and mantle cell lymphoma, it was proven to be ineffective as a single agent against leukemia in clinical trials. NPI-0052 varies from bortezomib in ways that scientists at M. D. Anderson hope will make NPI-0052 effective in a human clinical trial.

"NPI-0052 targets the proteasome through different intermediaries and is more potent than bortezomib in leukemia cells," says senior author Joya Chandra, Ph.D., assistant professor of pediatrics from the Children's Cancer Hospital at M. D. Anderson. "Therefore we can use less of the drug to inhibit the proteasome".........

Posted by: Janet      Read more         Source


April 18, 2007, 11:07 PM CT

Smoking indicator of alcohol misuse

Smoking indicator of alcohol misuse
Where there is cigarette smoking there is probably misuse of alcohol too, as per a research studyby Yale School of Medicine scientists in the Archives of Internal Medicine.

"This means cigarette smoking status can be used as a clinical indicator for alcohol misuse, which presents an opportunity for intervention," said the principal investigator, Sherry McKee, assistant professor of psychiatry.

She said that eventhough brief screening and brief intervention provided in primary care settings are effective, clinicians do not frequently screen for alcohol misuse. This is a matter of concern because 26 percent of the U.S. population is drinking at hazardous levels, which puts them at increased risk for alcohol-related consequences such as injuries from motor vehicle crashes, hypertension, depression, and certain cancers.

"Only an estimated 30 percent of individuals who had a primary care visit reported being screened for an alcohol or drug use problem," McKee said. "Physicians are much more likely to ask patients whether and how often they smoke".

She and her collaborators arrived at their conclusions after analyzing data obtained from 42,374 adults in a national epidemiological survey on alcohol misuse and other related conditions. Following guidelines that physicians use to assess tobacco and alcohol use, they observed that non-daily smokers are five times more likely to have a problem with alcohol in comparison to people who have never smoked. Daily smokers are three times more likely to have an alcohol problem.........

Posted by: Janet      Read more         Source


April 17, 2007, 11:13 PM CT

Stem cells decrease ischemic injury

Stem cells decrease ischemic injury
This is the impressive result of a study carried out by a group of scientists coordinated by Dr. Maria Grazia De Simoni of the Mario Negri Institute in Milan, Italy in cooperation with the Istituto Neurologico Besta (Milan) and the University of Lausanne. The study appears in the April 18th issue of the international, peer-evaluated, open-access online journal of the Public Library of Science, PLoS ONE.

Stroke is the first cause of permanent invalidity and the third cause of death in industrialized countries.

Despite the recent advancements in the management of ischemic patients (early diagnosis, thrombolysis, stroke units and rehabilitation centers), stroke still represents a major and unresolved medical issue.

"Stroke causes the death of a number of nervous cells that, in theory, could be substituted by stem cells. A few studies have shown that these cells can be effective, eventhough various issues about their use and the mechanisms of their protective action remained unsolved," says Maria Grazia De Simoni.

"Our research has underlined a possible mechanism of action. Once introduced in the area of the brain hit by a stroke, stem cells induce the development of a protective effect in this same area," explains De Simoni. "Therefore, it is not necessary, as proposed in past studies, for stem cells to turn into neurons in order to protect the brain from ischemic injury and restore brain functions. Their presence in brain tissue is sufficient to induce a protective reaction".........

Posted by: Daniel      Read more         Source


April 17, 2007, 10:58 PM CT

Insights Into Multiple Sclerosis

Insights Into Multiple Sclerosis Myelin Sheath and Astroglial Filaments
Scientists have developed a way to use three types of microscopic imaging techniques simultaneously to analyze living tissue and learn more about the molecular mechanisms of multiple sclerosis, information that could help lead to earlier detection and new therapys.

The combined imaging method is enabling the scientists to study how multiple sclerosis causes an overproduction of "astroglial filaments," which form bundles between critical nerve fibers and interfere with proper spinal cord functioning. The technique also promises to yield new information about how the disease degrades the myelin sheath, which insulates nerve fibers and enables them to properly conduct impulses in the spinal cord, brain and in the "peripheral nervous system" throughout the body, said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.

The three imaging techniques - called sum frequency generation, two-photon-excitation fluorescence and coherent anti-Stokes Raman scattering - ordinarily are used alone. Purdue scientists have developed a way to combine all three methods in the same platform, promising to reveal new details about the spinal cord and myelin sheath, Cheng said.

"Combining these three methods allows us to conduct more specific and precise molecular analyses," he said. "Ultimately, this work paves the way toward studying the degradation of the myelin sheath as a result of multiple sclerosis and analyzing living tissue to study the mechanisms of disease".........

Posted by: Daniel      Read more         Source


April 17, 2007, 10:56 PM CT

Treating Alzheimer's Disease

Treating Alzheimer's Disease Arun Ghosh, at right, and Xiaoming Xu
molecule designed by a Purdue University researcher could lead to the first drug therapy for Alzheimer's disease.

"There are a number of people suffering, and no effective therapy is available to them," said Arun Ghosh, the Purdue professor who designed the molecule. "There is an urgent need for a drug to treat this devastating disease, and the scientific community has been working on this problem for a number of years".

The National Institute on Aging estimates that as a number of as 4.5 million Americans suffer from Alzheimer's disease, which leads to dementia by affecting parts of the brain that control thought, memory and language.

The new molecule prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. The material at various stages of plaque formation is made up of fibrous clumps of toxic proteins that cause the devastating symptoms of Alzheimer's disease, said Ghosh, who has a dual appointment in the chemistry and medicinal chemistry and molecular pharmacology departments.

"Interdisciplinary research and the tools available today allowed us to build a molecule that is both highly potent and highly selective, meaning it does not affect other enzymes important to brain function," he said.

Jordan Tang, head of the Protein Studies Research Program at the Oklahoma Medical Research Foundation, is one of the discoverers of the critical enzyme and target for intervention, Ghosh said.........

Posted by: Daniel      Read more         Source


April 17, 2007, 5:07 AM CT

Increased Survival In Metastatic Colorectal Cancer

Increased Survival In Metastatic Colorectal Cancer
A phase III trial of 1,298 colorectal cancer patients has observed that a combination of the drugs cetuximab (Erbitux) and irinotecan showed a significant improvement in progression-free survival over just irinotecan alone, as per an international team of researchers.

The Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) study looked at survival in metastatic colorectal cancer patients who had already shown resistance to conventional therapies. The research was presented today at the 2007 Annual Meeting of the American Association for Cancer Research.

By the end of the study, a significantly larger number of patients who received the combination of cetuximab, an antibody against the epidermal growth factor and irinotecan, an enzyme-inhibiting cancer drug, survived without their cancers progressing further. The tumor response rate in this group was also significantly higher. The study was sponsored, in part, by Bristol-Myers Squibb and Merck KGaA.

"Patients who received both cetuximab and irinotecan experienced longer periods of time spent, on average, without further progression of the disease," said Alberto F. Sobrero, M.D., of the San Martino Hospital's Department of Medical Oncology in Genoa, Italy. "From a patient perspective, any improvement in progression-free survival, as well as tumor shrinkage, is worthwhile. These data confirm that, despite a moderate increase in side effects, cetuximab is a key therapeutic agent in the optimal therapy of advanced colorectal cancer".........

Posted by: Sue      Read more         Source



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Did you know?
Studies in monkeys and women suggest that unlike traditional estrogen therapy, a diet high in the natural plant estrogens found in soy does not increase the risk of uterine cancer in postmenopausal women, according to Mark Cline, D.V.M., Ph.D., an associate professor of comparative medicine at Wake Forest University Baptist Medical Center.

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