November 10, 2006, 4:34 AM CT

How Genes Affect Antipsychotic Drug Response?

Researchers at the University of Illinois at Chicago College of Pharmacy are attempting to discover how genes determine how well an antipsychotic medicine works in adults and children and the side effects it will cause.

Risperidone, a popular "atypical" antipsychotic medication, is used to treat mental illnesses such as schizophrenia and bipolar disorder.

Jeffrey Bishop, assistant professor of pharmacy practice, is examining the effects of one gene, catechol-o-methyltransferase, on brain activity, cognition and symptom response to the drug.

The study is being done in adults who are experiencing their first episode of schizophrenia who are treated with risperidone for six weeks as part of UIC's First Episode Program.

"Allowing patients with schizophrenia an increased chance at medicine response literally could change their lives," Bishop said.

"While we know a great deal about the pharmacology of antipsychotics like risperidone, there is still much to learn about their influence on cognition and brain function, as well as how genetics affect overall medicine response," he said.

Bishop says the project will serve as a first step toward a comprehensive pharmacogenetic analysis of metabolic pathways affecting response to the drug. He was presented with an award for new scientists from the American College of Clinical Pharmacy for the project.........

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November 7, 2006, 10:27 PM CT

Novel Treatment of Sickle Cell Disease

Virginia Commonwealth University scientists have developed a unique anti-sickling agent that may one day be effective in treating sickle cell disease, a painful and debilitating genetic blood disorder that affects approximately 80,000 Americans.

The research team led by Donald Abraham, Ph.D., the Alfred and Frances Burger Professor of Biological and Medicinal Chemistry, in the Department of Medicinal Chemistry in VCU's School of Pharmacy, has shown that 5-HMF, a pure compound developed by the team, has a high affinity for sickle cell hemoglobin and holds promise for the therapy of sickle cell disease.

"Our findings suggest that this anti-sickling agent may lead to new drug therapys and may one day help those suffering with sickle cell disease. This molecule, 5-HMF, is the most promising molecule to treat sickle cell anemia to come from our research group in more than 30 years," said Abraham, who is also the director of the Institute of Structural Biology and Drug Discovery.

The United States Patent and Trademark Office recently issued VCU a Notice of Allowance for a patent relating to a method of treating sickle cell disease with 5-HMF compound. A Notice of Allowance is a written notification that a patent application has cleared an internal review and it has been approved for issuance.........

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November 7, 2006, 7:10 PM CT

Enzyme To Treat Diabetic Kidney Disease

Northwestern University Feinberg School of Medicine researchers have found that an enzyme called ACE2 may hold the potential to treat diabetic kidney disease, the most common form of kidney disease.

In the laboratory, researchers led by Daniel Batlle, professor of medicine in the Feinberg School, chief of the nephrology/hypertension division and staff nephrologist at Northwestern Memorial Hospital, have found low levels of the ACE2 enzyme in the glomeruli of the kidneys of diabetic mice. When ACE2 was further decreased with an inhibitor drug, kidney disease worsened. Studies are now needed using compounds that increase the level of ACE2 in the kidneys of diabetic mice to see if it reverses or prevents kidney disease from developing, Batlle said.

The experiments appear in a report by Ye et. al in the recent issue of the Journal of the American Society of Nephrology.

Diabetes, which affects 230 million people worldwide and 21 million in the United States, is the leading cause of kidney failure. About one-third of patients with diabetes will go on to develop kidney disease. In diabetes, the small blood vessels in the kidneys are injured and the kidneys cannot clean the blood properly. In 2002, a total of 153,000 people in the U.S. with kidney failure due to diabetes were living on chronic dialysis or with a kidney transplant.........

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November 7, 2006, 4:16 AM CT

Missing Link In Sudden Cardiac Death

An electrical imbalance caused by a malfunctioning gene triggers a potentially fatal heart rhythm disorder, according to researchers at Baylor College of Medicine (BCM) and Texas Children's Hospital in Houston.

Findings are reported in the Nov. 21 print edition of the journal Circulation, a publication of the American Heart Association. The journal has posted the findings online.

Electrical impulses originate in the top of the heart's right atrium and travel through the muscle fibers, causing the heart to contract. The genetic and molecular basis of sudden cardiac arrest, which occurs when these impulses are disrupted, is not well understood.

Study scientists began to close this gap of understanding by becoming the first to isolate a gene called Caveolin-3, which influences the electrical-muscular impulses that drive the heart's rhythm. A mutation of the gene can trigger arrhythmia associated with long QT syndrome, a hereditary disorder that can occur in otherwise-healthy people of all ages, and increases the risk of sudden cardiac death.

"This is part of a totally new concept in which the structural part of the heart is intertwined and connected with the electrical part," said first author Dr. Matteo Vatta, assistant professor of pediatrics at BCM and pediatric cardiac researcher at Texas Children's Hospital. "This is the missing link between the heart's electrical and muscular activities".........

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November 6, 2006, 7:54 PM CT

Most Ear Infections Host Both Bacteria And Viruses

Ear infections are among the most common diseases seen in pediatric practice. They have generally been considered bacterial diseases and are therefore usually treated with antibiotics. New research, published in the December 15 issue of Clinical Infectious Diseases and currently available online, provides evidence that viruses are found in a great many ear infection cases and may complicate treatment.

The researchers used a variety of laboratory techniques to identify the pathogen that caused ear infections, known clinically as acute otitis media (AOM), in 79 young children. They found bacteria in 92 percent of the cases, viruses in 70 percent, and both bacteria and viruses in 66 percent.

According to Aino Ruohola, MD, PhD, from the Turku University Hospital in Finland and lead author of the study, "the major finding of the study is that acute otitis media is a coinfection of bacteria and viruses in the great majority of children. This is actually logical since acute otitis media is virtually always connected to viral respiratory infection".

Antibiotics, which are effective against the bacteria that cause AOM, have no effect on the viruses found in AOM infections. Therefore, the standard treatment for AOM--antibiotics--can be, at best, partially effective in the majority of cases. "Based on this and previous research," said Dr. Ruohola, "it is possible that viruses cause a considerable proportion of clinical treatment failures. Thus, in these cases a new antibiotic is not necessarily the best choice although bacteria resistant to common antibiotics are wide-spread".........

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November 6, 2006, 4:33 AM CT

Children's Belly Fat Increases More Than 65 Percent

Abdominal obesity increased more than 65 percent among boys and almost 70 percent among girls between 1988 and 2004. The finding of growing girth is significant because abdominal obesity has emerged as a better predictor of cardiovascular disease and type 2 diabetes risk than the more usually used Body Mass Index, a weight to height ratio that can sometimes be misleading.

As the first nationally representative study to document the increase in children's belly fat, the study in today's Pediatrics paints a bleak picture for these children who have a higher risk of heart disease, adult-onset diabetes and metabolic syndrome. The good news is that, for children and adolescents, the health effects are often reversible through improved lifestyle for weight loss.

"Kids, teens and adults who have early stages of atherosclerosis in their arteries can have a healthy cardiovascular system again," said Stephen Cook, M.D., an assistant professor of Pediatrics at the University of Rochester Medical Center's Golisano Children's Hospital at Strong and an author of the study about childhood abdominal obesity. "Elderly adults who have plaque build up have a much harder battle, particularly if the plaque has calcified".

Measuring waist circumference is not a "vital sign" normally taken in a visit to the doctor. A BMI is usually calculated at a well visit, but there are limitations to those measurements. A very muscular person may register a high BMI score, even if he is very healthy and has an average waist circumference. On the flip side, a sedentary child may not register a very high BMI score, but if he carries a lot of fat around his middle, he may be at a higher risk for health problems than other children with the same BMI score.........

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November 3, 2006, 4:59 AM CT

Heart Catheters Do Not Benefit Patients

Doctors should probably stop using pulmonary artery catheters because they do not benefit patients, say doctors from Australia in this week's BMJ.

The pulmonary artery catheter was invented in 1968. It enabled bedside monitoring in critically ill patients by measuring heart output and capillary pressure in the lungs and became widely used in intensive care units.

But reports of serious complications soon appeared and arguments for and against its use have continued ever since.

The most recent evaluation, commissioned by the NHS Health Technology Assessment (HTA) programme, observed that pulmonary artery catheters do not benefit patients and concluded that withdrawing them from UK intensive care units would be cost effective.

Another recent trial in patients with acute lung injury confirmed these findings, while an analysis of 13 trials reported no overall effect of using these devices on mortality or length of hospital stay.

So what should clinicians do with all this information?

Given that the use of pulmonary artery catheters increases the risk of important complications, continued use of these devices is difficult to defend, say the authors.

The onus is now on the proponents of the pulmonary artery catheter and related devices to limit their use to clinical trials and to show that protocols based on such devices do benefit patients, they conclude.........

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November 3, 2006, 4:45 AM CT

Strong Link Between Uric Acid And Hypertension

New research shows that higher levels of uric acid are strongly associated with high blood pressure in blacks, suggesting that a simple blood test could predict risk and that treatments to lower uric acid may be a novel way to reduce hypertension-related complications in this population.

"The novel angle of our study is that the association between uric acid and hypertension is much stronger in blacks, a group that disproportionately suffers from kidney disease, stroke and other complications of hypertension," said Philip B. Mellen, M.D., M.S., assistant professor internal medicine, and lead investigator.

The results are reported online in Hypertension, a journal of the American Heart Association.

Uric acid levels are influenced by dietary factors, such as high levels of protein, and by the breakdown of the body's cells. Most uric acid is eliminated in urine. However, if excess uric acid is being produced or if the kidneys cannot remove enough of it, levels build up in the blood.

Very high levels of uric acid cause gout, but recent animal and human studies suggest that modest elevations of uric acid are one cause of hypertension. Currently, studies are under way to evaluate whether lowering uric acid prevents hypertension.

"If these studies show that lowering uric acid is an effective treatment, our research suggests that it may be especially appropriate for blacks," said Mellen.........

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November 2, 2006, 8:58 PM CT

Common Antacids To Fight Gingivitis

Chemicals commonly used to treat heartburn also display fighting power against the oral bacteria linked with gum disease, according to researchers at the University of Rochester Medical Center and Gteborg University in Sweden.

A study published in November's Archives of Oral Biology explores how the active ingredients in popular antacids could help fend off gingivitis. If the work holds up in subsequent studies in people, the compounds could one day find themselves widely available in oral care products like toothpaste and mouthwashes.

"The American diet and the constant drip of sugar allows little time for the natural repair of teeth. All day, it's a cycle of acidic erosion and repair or at least, it should be but our constant sucking on hard candy and guzzling sodas with high fructose syrups leaves little time for repair," said Robert Marquis, Ph.D., of the University of Rochester Medical Center. Marquis, an internationally recognized expert on the bacteria that inhabit our mouths, is the study's lead author.

The team studied a compound known as lansoprazole, part of a family of compounds known as benzimidazoles that already have a range of uses, primarily controlling stomach hyperacidity and killing Helicobacter pylori (the bacteria responsible for stomach ulcers). Now, the compounds are brandishing potent antimicrobial actions that interfere with the dirty work of other types of bacteria that cause plaque buildup and gingivitis.........

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November 2, 2006, 8:44 PM CT

Towards Cure For Multiple Sclerosis

A breakthrough finding on the mechanism of myelin formation by Jonah Chan, assistant professor of cell and neurobiology at the Keck School of Medicine of the University of Southern California, could have a major impact on the treatment of diseases such as multiple sclerosis and demyelination as a result of spinal cord injuries.

Myelin, the white matter that coats all nerves, allows long-distance communication in the nervous system. "It plays a vital role in the overall health and function of the nervous system, and its degeneration plays a role in a number of diseases, such as multiple sclerosis, peripheral neuropathies, and even in spinal cord injury," Chan explained.

The study, "The Polarity Protein Par-3 Directly Interacts with p75NTR to Regulate Myelination", appears in the Nov. 3 issue of Science. Chan, who works at the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC, collaborated on the study with Michel Cayouette and researchers at the Institut de Recherches Cliniques de Montreal in Canada.

At a basic level, the nervous system functions like a collection of wires that transmit electrical signals encoding our thoughts, feelings, and actions. Just as an electrical wire needs insulation, myelin is wrapped around axons - the wire-like extensions of neurons that make up nerve fibers. The sheath helps to propagate the electrical signal and maximize the efficiency and velocity of these signals in our brain and body.........

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