December 6, 2006, 8:47 PM CT

Statin Users Risk Heart Attacks By Dropping Treatment

Thousands of statin users worldwide are suffering preventable heart attacks, simply because they are not complying with their treatment or are taking too low a dose, according to new research published on-line (Thursday 7 December) in European Heart Journal[1].

These life-saving drugs, used to lower cholesterol levels in people at risk of coronary heart disease (CHD), can only be optimally effective if patients use them properly - and many are not.

That is the conclusion by the research team, who followed the prescription records of nearly 60,000 patients in the Netherlands for up to 14 years.

Dr Fernie Penning-van Beest and colleagues from the PHARMO Institute[2], the Utrecht Institute of Pharmaceutical Sciences and the Academic Hospital in Amsterdam, analysed 548,084 prescriptions of statin treatment issued over the first two years of treatment[3] in 59,094 new users in the period January 1991-December 2004, and followed the patients until their first hospital admission for heart attack, death, or the end of the study in December 2004.

The aim was to see how effective robust statin treatment was for primary and secondary CHD in the 'real world' - as opposed to in clinical trials. Their results enabled them to calculate the absolute number of avoidable heart attacks that occurred because patients had stopped taking their drugs or were not taking them consistently. They were also able to compare the preventive effects of different doses and types of statins.........

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December 6, 2006, 8:20 PM CT

Sticky Proteins And Drug Action

How drugs such as adrenalin do primarily one thing - in this case, increase the heart rate - now makes more sense to scientists.

"Any time you get a sudden jolt, adrenaline (a.k.a. epinephrine) is why your heart rate goes up," says Dr. Nevin A. Lambert, a biophysicist at the Medical College of Georgia. "If your heart is about to stop and the doctor administers epinephrine, that is what he or she is trying to do".

New research, would be reported in the Nov. 21 print issue of Proceedings of the National Academy of Sciences and already available online in Early Edition, may help explain how cells respond correctly to epinephrine.

Most drugs never get inside cells; they interact with external receptors that activate G proteins roaming inside cells. "If you are going to change the way the cell works, you have to transduce a signal from outside a cell inside," says Dr. Lambert. "It's like a relay. G proteins interact with receptors; they run into them, they collide with them. The receptor itself does not do anything other than turn on these G proteins".

There are only four classes of G proteins, but cells contain thousands of copies of them which interact with hundreds of surface receptors. Each G protein is actually three protein subunits stuck together: alpha, beta and gamma.........

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December 5, 2006, 8:32 PM CT

Steps In The Development Of Taste

Of the five senses, taste is one of the least understood, but now scientists at the University of Pennsylvania School of Medicine have come one step closer to understanding how the sense of taste develops. They have pinpointed a molecular pathway that regulates the development of taste buds. Using genetically engineered mice, they discovered that a signaling pathway activated by small proteins called Wnts is mandatory for initiating taste-bud formation. They have also determined that Wnt proteins are mandatory for hooking up the wiring of taste signals to the brain.

Senior author Sarah E. Millar, PhD, Associate Professor in the Departments of Dermatology and Cell and Developmental Biology, Penn postdoctoral fellow Fei Liu, PhD, and his colleagues report their findings in the most recent online issue of Nature Genetics. "The developmental biology of taste is underexplored," says Millar of her team's impetus for the study.

The scientists demonstrated that blocking the action of Wnt proteins in surface cells of the developing tongue prevents taste-bud formation, while stimulating Wnt activity causes the formation of excessive numbers of enlarged taste papillae that are able to attract taste-related nerve fibers. This study represents the first genetic analysis of taste-organ initiation in mammals. While these studies were performed in mice, the scientists think that their findings will also hold true for understanding the basis of taste-bud development in humans.........

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December 5, 2006, 4:15 AM CT

Arsenic Have Broad Impact On Hormone Activity

Dartmouth Medical School researchers are learning more about how low doses of arsenic, such as the levels found in drinking water in a number of areas of the United States, affect human physiology. In a paper published online on Dec. 2 in the journal Chemical Research in Toxicology, the scientists report that three different steroid hormones all show similar responses to arsenic, suggesting a broader effect and a common mechanism of arsenic on how these hormones function.

"Since most of the health consequences of exposure to arsenic - various cancers, diabetes, heart and vascular disease, reproductive and developmental effects, etc. - involve these same steroid receptors, we believe that disruption of their normal function could explain, in large part, how arsenic can influence so a number of disease risks," says Joshua Hamilton, one of the authors on this study and the director of the Center for Environmental Health Sciences at Dartmouth and Dartmouth's Superfund Basic Research Program on Toxic Metals.

Hamilton's laboratory had earlier observed that arsenic disrupts the activity of the glucocorticoid receptor, and this follow up study considered the progesterone and mineralocorticoid receptors, which regulate a wide range of biological processes. This work was done in collaboration with Jack Bodwell, the lead author on this paper and a research associate professor of physiology at Dartmouth Medical School.........

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December 1, 2006, 4:41 AM CT

PTSD Drug Is No More Effective Than Placebo

Guanfacine, a medicine usually prescribed to alleviate symptoms of post-traumatic stress disorder, is no more effective than a placebo, as per a research studyled by scientists at the San Francisco VA Medical Center.

There was no benefit at all, and there were several adverse side effects, says lead author Thomas Neylan, MD, medical director of the PTSD therapy program at SFVAMC. People with symptoms of PTSD should probably stay away from this drug and others of its type.

The study appears in the December 1, 2006 issue of the American Journal of Psychiatry.

Guanfacine belongs to a class of medications known as alpha-2 agonists, which lower the brains supply of the neurotransmitter norepinephrine. Neurotransmitters are chemicals that transmit electrical signals between nerve cells. They are responsible for a number of aspects of behavior.

Norepinephrine is released in the brain during states of excited arousal, and PTSD is linked to that state patients startle easily, have trouble sleeping, and are hypervigilant and anxious, explains Neylan, who is also an associate professor of psychiatry at the University of California, San Francisco.

Guanfacine and clonidine, another alpha-2 agonist, are usually prescribed for PTSD symptoms. There are at least 20 peer-evaluated articles reported in the field of PTSD that recommend drugs which lower norepinephrine, Neylan says. However, ours was the first randomized, controlled study of alpha-2 agonists for symptoms of PTSD.........

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December 1, 2006, 4:31 AM CT

Huntington's And Abnormal Cholesterol Levels In Brain

Mayo Clinic scientists have discovered a protein interaction that may explain how the deadly Huntington's disease affects the brain. The findings, published in and featured on the cover of the current issue of Human Molecular Genetics, show how the mutated Huntington's protein interacts with another protein to cause dramatic accumulation of cholesterol in the brain.

"Cholesterol is essential for promoting the connection network among brain cells and in maintaining their membrane integrity. Both the level of cholesterol and its delivery to the proper locations in the cell are essential for the survival of neurons," explains Mayo Clinic molecular biologist Cynthia McMurrary, Ph.D.

"Our discovery that the mutant Huntington's disease protein derails the cholesterol delivery system and causes cholesterol accumulation in neurons provides us with key results and solid clues to the mechanism of this disease," says Dr. McMurray. "Fully understanding the mechanism of toxicity is the key to developing therapys".

Huntington's disease -- sometimes called Huntington's chorea or St. Vitus' dance -- is a progressive, degenerative condition that causes nerve cells in the brain to waste away. Symptoms include uncontrolled movements, emotional disturbances and mental deterioration.........

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November 30, 2006, 4:50 AM CT

Finding Cause And Cure For Asthma

A $7.7 million grant will establish a new center for asthma research at Washington University School of Medicine in St. Louis. Directed by Michael J. Holtzman, M.D., the Selma and Herman Seldin Professor of Medicine, the center will investigate the causes of asthma to develop new therapys for the disease. The center's funding comes from the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health.

Named the Asthma and Allergic Diseases Cooperative Research Center, the center will conduct research specifically focused on how the body's protective mechanism, the immune system, contributes to asthma.

"Normally, immunity is under tight control," says Holtzman, who directs the Division of Pulmonary and Critical Care Medicine. "But if the immune response goes too far, it can cause inflammatory diseases like asthma."

Prior research showed that viral infections of the lungs at an early age could trigger long-term asthma. The researchers will test children with respiratory infections, measuring their body's response to the virus, and they will follow their respiratory health for five years.

"We will look at the cell biology and the biochemistry of the children's response to respiratory virus infection," Holtzman says. "We know the more severe the infection is, the more likely a patient is to develop asthma later. We want to know at the cell level what determines the severity of the infection and how we can intervene to prevent asthma."........

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November 30, 2006, 4:39 AM CT

Metabolic Syndrome Could Be Treated With Chloroquine

Studies of a rare genetic condition that increases cancer risk have unveiled a potential treatment for metabolic syndrome, a common disorder that afflicts as many as one in every four American adults and puts them at sharply increased risk of type 2 diabetes and clogged arteries.

Scientists know relatively little about metabolic syndrome, which is linked to a range of symptoms that include obesity, insulin resistance, high blood pressure, low levels of good cholesterol and high blood sugar levels. The number of adults and children with the condition is rising sharply in industrial countries, and diagnoses are also increasing in developing countries like India and China as they adopt Western standards of living.

In findings published in the recent issue of Cell Metabolism, researchers at Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tenn. report that a small dose of the malaria drug chloroquine eased many symptoms of metabolic syndrome in mice, reducing blood pressure, decreasing hardening and narrowing of the arteries and improving blood sugar tolerance.

"We just received funding for a clinical trial, and we're very excited to see if the processes activated by chloroquine can effectively treat one of the most common health problems of modern industrialized society," says senior author Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology at Washington University. "We already know that chloroquine is safe and well-tolerated, and our mouse results suggest we may only need very low and perhaps infrequent doses to achieve similar effects in humans".........

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November 29, 2006, 9:37 PM CT

Risks Increase On Episodic Antiretroviral Therapy

Results from one of the largest HIV/AIDS treatment trials ever conducted show that a specific strategy of interrupting antiretroviral therapy more than doubles the risk of AIDS or death from any cause. In the study, the scientists used two predetermined levels of CD4+ T cells, the primary immune cell targeted by HIV, to guide them in respectively suspending or restarting the study participants on antiretroviral therapy.

A report describing this researchwhich involved 318 clinical sites in 33 countriesappears in this week's issue of The New England Journal (NEJM). The trial, known as Strategies for Management of Anti-Retroviral Therapies, or SMART, was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"The SMART trial has provided important new data that will help physicians and their HIV-infected patients make treatment decisions," says NIAID Director Anthony S. Fauci, M.D. "The study reflects an extraordinary global collaboration among hundreds of dedicated AIDS clinicians and thousands of their patients, all of whom should be commended for their contributions to this pivotal HIV/AIDS treatment study".

As HIV/AIDS has evolved into a chronic disease without a cure, lifelong antiretroviral therapy has become the norm. Lifelong therapy, however, can be difficult to adhere to as well as expensive. For these reasons, there has been a concerted research effort to test treatment interruption strategies that may enhance patients' quality of life and limit adverse drug effects. The experimental strategies vary in their approach to when to interrupt therapy. Some, like SMART, use a specific CD4+ count as a guide; others schedule regular time periods during which treatment is stopped (for example, alternating one month off and three months on).........

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November 29, 2006, 5:03 AM CT

Predicting Outcome of Child Heart Surgery

Georgia Tech and Emory University researchers have developed an innovative new technology that will help pediatric cardiac surgeons design and test a customized surgical procedure before they ever pick up a scalpel. With a better understanding of each child's unique heart defect, surgeons could greatly improve the likelihood that children with complex defects requiring multiple surgeries over a period of several years could have smoother recoveries and an improved quality of life after their operations.

The technology, known as image-based surgical planning and developed with the help of pediatric cardiologists and pediatric surgeons at The Children's Hospital of Philadelphia (CHOP) and Emory University, creates a three-dimensional model of the child's heart with data from the child's MRI scans at different times in the cardiac cycle, also called a 4D MRI. The models allow surgeons to visualize the direction of blood flow and determine any energy loss in the heart. So if a surgeon were planning a certain correction to an area of a child's heart, a model created by the system would show the surgeon how well blood would flow through the newly configured heart.

The goal of the Georgia Tech/Emory project is to create a complete system that allows surgeons to get a detailed look at the child's heart functions with the new MRI system, design surgical procedures for optimum post-operative performance and evaluate the heart's performance with a sophisticated blood flow computer simulation.........

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