Edmund's Newsletter
April 22, 2008

Issue: #17

Volume 8

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In This Issue

World Map of Metabolism Finds Blood Pressure Clues

Patients Receive Heart Valve Replacements Without Surgery Using High-tech Device

Harmless Virus May Aid in Knocking Out Deadly Bird Flu

How Arsenic Cures Leukemia

Einstein Researchers Find That Vitamin D May Protect Against Peripheral Artery Disease

Gene Therapy Reduces Cocaine Use in Rats

Launching a Global Alliance for Pharmacogenomics

Believe It Or Not

News From MedWatch

Recently Approved Drugs/Indications

FDA Recalls and Safety Alerts in the Past 60 Days

Drug Shortages

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World Map of Metabolism Finds Blood Pressure Clues

Researchers creating a map of human metabolism around the world have found compounds in urine that point to some surprising differences affecting blood pressure, based not on genes but on what people eat and their gut bacteria.

They hope their findings, published in the journal Nature on Sunday, can help lead to the development of new drugs to fight high blood pressure or perhaps even non-drug therapy.

They analyzed urine samples from 4,630 people in the United States, Britain, Japan and China to find some surprising new links to blood pressure differences.

"On one end of the metabolic world we have got people in southern China and at the other end we have got people from Corpus Christi, Texas," said Jeremy Nicholson of Imperial College London, who led the study.

"And you can geographically map people according to their metabolic patterns," he added.

"Britain is the '51st state' as we are really in the middle of America. Our lifestyle and our diets and our ethnic mixes are quite similar in many ways to America."

Patients Receive Heart Valve Replacements Without Surgery Using High-tech Device

Interventional cardiologists at Rush University Medical Center now offer a minimally-invasive transcatheter valve replacement procedure for patients with congenital heart disease that doesn't involve open heart surgery.

Rush is one of three sites taking part in the investigational device exemption (IDE) feasibility study of minimally-invasive pulmonic valves and successfully implanted the first three patients enrolled in the trial on Thursday, April 17.

"We were able to successfully implant the Edwards SAPIEN transcatheter heart valve percutaneously in the first three patients treated in this trial. All of the patients are recovering and are expected to go home today," said Dr. Ziyad M. Hijazi, director of the Rush Center for Congenital and Structural Heart Disease, chief of the section of pediatric cardiology and professor in the departments of pediatrics and internal medicine at Rush University, Chicago. "Patients with congenital right ventricular outflow tract problems typically face the burden of multiple open-heart surgeries throughout their lives, either to replace their 'native' diseased valves or, as they age, their bioprosthetic replacement valves."

Harmless Virus May Aid in Knocking Out Deadly Bird Flu

A harmless virus used as a delivery vehicle may help set a roadblock for a potentially catastrophic human outbreak of bird flu, according to researchers at Purdue University and the Centers for Disease Control and Prevention (CDC).

Purdue molecular virologist Suresh Mittal and his collaborators are investigating a new way to provide immunity against avian influenza viruses, or bird flu, the most lethal of which, H5N1, has a 50 percent fatality rate in humans. Under a $1.6 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), the researchers are focusing on using a harmless virus, called adenovirus, as a transmitting agent for a vaccine to fight off highly virulent strains of the avian influenza viruses.

Current vaccines are designed for strains of flu found in local areas and are effective only as long as the virus doesn't change form. Existing vaccines will have limited success against new strains of avian influenza, he said. Every time a bird flu mutates, vaccines must be redesigned.

An additional important advantage to using an adenovirus as a vector, or transporter of vaccine into cells, is that is could be mass produced much more quickly than with current methods.

How Arsenic Cures Leukemia

Arsenic is a remarkably effective treatment against a rare form of leukemia.. Researchers from a CNRS / Universit� Paris Diderot research unit, based at the Institut Universitaire d'H�matologie at H�pital Saint Louis, have shown how arsenic cures this type of leukemia. This research should lead to a better understanding of the therapy, and thus to medical strategies which are better adapted to this disease. This work was supported by the Ligue contre le cancer and published on April 13 2008 on the website for Nature Cell Biology.
Arsenic is a poison which has been used in medicine for more than 3000 years. It is now regularly used to treat acute promyelocytic leukemia. This type of leukemia is characterized by the fusion of PML and RARA proteins, which is sufficient to make cells leukemic. Earlier, Pr. Hugues de Th�'s team had shown that arsenic induces the SUMOylation of PML/RARA, SUMO being a peptide that regulates interaction between proteins. But the nature of the degradation pathway remained a mystery, because SUMO generally works against degradation.

A new enzyme which participates in this mechanism, RNF4, has recently been identified by the researchers. This enzyme plays a key role in the recognition and degradation of PML/RARA forms which have been modified by arsenic (PML/RARA-SUMO). The work of the French team, like that of an English team publishing in the same journal, shows that RNF4 binds to PML-SUMO or PML/RARA-SUMO. It then fixes another peptide, ubiquitin, onto this complex. Ubiquitin is known to lead to the degradation of proteins to which is binds. Ubiquitin then modifies the PML/RARA-SUMO protein.

Einstein Researchers Find That Vitamin D May Protect Against Peripheral Artery Disease

People with low vitamin D levels may face an increased risk for peripheral artery disease (PAD), according to researchers at the Albert Einstein College of Medicine of Yeshiva University. The scientists reported their findings at the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2008.

PAD is a common disease that occurs when arteries in the legs become narrowed by fatty deposits, causing pain and numbness and impairing the ability to walk. PAD affects about eight million Americans and is associated with significant disease and death, according to the American Heart Association.

People obtain vitamin D by making it themselves (through skin exposure to sunlight), by ingesting foods such as fish and fortified dairy products that contain vitamin D, or by taking dietary supplements. Adequate vitamin D levels are necessary for bone health, but scientists are only beginning to explore vitamin D's connection to cardiovascular disease.

"We know that in mice, vitamin D regulates one of the hormone systems that affects blood pressure," said Dr. Michal Melamed, lead author of the study and assistant professor in the departments of Medicine and Epidemiology & Population Health at Einstein. "Since cells in the blood vessels have receptors for vitamin D, it may directly affect the vessels, although this has not been fully worked out."

Gene Therapy Reduces Cocaine Use in Rats

Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have shown that increasing the brain level of receptors for dopamine, a pleasure-related chemical, can reduce use of cocaine by 75 percent in rats trained to self-administer it. Earlier research by this team had similar findings for alcohol intake. Treatments that increase levels of these chemicals - dopamine D2 receptors -- may prove useful in treating addiction, according to the authors. The study will be published online April 16 and will appear in the July 2008 issue of Synapse.
Peter Thanos

"By increasing dopamine D2 receptor levels, we saw a dramatic drop in these rats' interest in cocaine," said lead author Panayotis (Peter) Thanos, a neuroscientist with Brookhaven Lab and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging. "This provides new evidence that low levels of dopamine D2 receptors may play an important role in not just alcoholism but in cocaine abuse as well. It also shows a potential direction for addiction therapies."

The D2 receptor receives signals in the brain triggered by dopamine, a neurotransmitter needed to experience feelings of pleasure and reward. Without receptors for dopamine, these signals get "jammed" and the pleasure response is blunted. Previous studies at Brookhaven Lab have shown that chronic abuse of alcohol and other addictive drugs increases the brain's production of dopamine. Over time, however, these drugs deplete the brain's D2 receptors and rewire the brain so that normal pleasurable activities that stimulate these pathways no longer do - leaving the addictive drug as the only way to achieve this stimulation.

Launching a Global Alliance for Pharmacogenomics

Leaders at the National Institutes of Health and the Center for Genomic Medicine in Japan have signed a letter of intent creating a Global Alliance for Pharmacogenomics. The effort aims to identify genetic factors that contribute to individual responses to medicines, including rare and dangerous side effects. The results of such work will eventually help doctors optimize the safety and effectiveness of drugs for each patient.

U.S. scientists joining the alliance are members of the NIH Pharmacogenetics Research Network, a consortium of research groups that study how genetic factors influence the way drugs work in and are handled by the body.

Japanese scientists in the alliance represent the newly created Center for Genomic Medicine, a component of the RIKEN Yokohama Institute that conducts high-throughput analyses of human genes involved in diseases and drug responses.

Signers of the agreement include the directors of three of the National Institutes of Health: Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences; Elizabeth G. Nabel, M.D., director of the National Heart, Lung, and Blood Institute; and John E. Niederhuber, M.D., director of the National Cancer Institute.

"By bringing together our resources, we will advance the understanding of how changes in DNA affect our responses to medicines. Thus we can begin to realize the promise of personalized medicine," said Yusuke Nakamura, M.D., Ph.D., director of the Center for Genomic Medicine at RIKEN.

Believe it or not

Alleged drug dealer calls police to report robbery

Nassau County Police said Christopher Canonico, 23, of Seaford, called at 8:19 p.m. Wednesday to say he had just been robbed in North New Hyde Park.

Police said Canonico was set up by two women who agreed to buy heroin at a local gas station. While they were sitting in Canonico's car, a third person with a gun came up to the car and robbed him of $340, a cell phone and wallet.

Police said Canonico is charged with criminal sale and criminal possession of a controlled substance. The women and man with the gun are charged with robbery and other charges.

News From MedWatch

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Recently Approved Drugs/Indications

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FDA Recalls and Safety Alerts in the Past 60 Days:

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Drug Shortages:

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