September 14, 2006, 5:03 AM CT

Transplant Cures Type 2 Diabetes In Rat

An approach proven to cure a rat model of type 1 or juvenile-onset diabetes also works in a rat model of type 2 or adult-onset diabetes, according to a new report from researchers at Washington University School of Medicine in St. Louis.

"Finding that we can cure type 2 diabetes in the same way is very significant because in humans type 2 diabetes is almost 20 times more prevalent than type 1 diabetes," says senior author Marc R. Hammerman, M.D., the Chromalloy Professor of Renal Diseases in Medicine. "There are about 200 million type 2 diabetics worldwide, and the incidence is rapidly increasing".

The treatment approach transplants precursors of the pancreas from embryonic pigs. In a previous study, Hammerman and co-developer Sharon A. Rogers, research instructor in medicine, showed that they could transplant the cells in a way that lets them grow into insulin producers without triggering attacks by the rats' immune systems. This cured the rats' diabetes without the risky immune suppression drugs required to prevent rejection in other transplant-based treatments.

The results appear online and will be published in Transplant Immunology.

Hammerman and Rogers are leaders in the emerging field of organogenesis, which focuses on growing organs from stem cells and other embryonic cell clusters known as organ primordia. Unlike embryonic stem cells, which can become virtually any cell type, primordia are locked into becoming cells of a particular organ.........

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September 13, 2006, 9:35 PM CT

Teens and depression

There has been much controversy in recent years regarding the correlation between teenage suicide and the use of antidepressant drugs. At an FDA meeting reviewing this topic, the majority of clinical trials examined did not show that the drugs were effective in treating depression in children and adolescents.

In a recent study published in the recent issue of the Journal of Clinical Pharmacology, Dr. Richard Malone, from the Department of Psychiatry at Drexel University College of Medicine and Philadelphia Health & Education Corporation, and colleagues suggest that the short duration of depressive symptoms in this age group makes it difficult to distinguish drug efficacy from placebo.

Using a naturalistic study design, the researchers advise using multiple assessments to establish a continuous baseline before randomizing patients to treatment, which would remove those who spontaneously recover in a very short period of time. In addition to having an impact on the accuracy of future clinical trials, this approach may help decrease the number of children who are exposed to unnecessary long-term drug therapy and possible side effects, since those who spontaneously recover quickly would not be started on drug therapy.

The article "Impersistence of Depression in Youth: Implications for Drug Study Design" can be accessed at no-charge for a limited time at The Journal of Clinical Pharmacology's web site at www.jclinpharm.org/cgi/reprint/46/9/1044.........

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September 13, 2006, 4:20 AM CT

Fighting Diarrhea In Kids

University of Leicester scientists are heading a worldwide research project which could revolutionise the diagnosis and treatment of diarrhoea in children in developing countries.

The four-year project, the results of which are now being piloted in four hospitals in India, will offer a means of identifying the two most deadly forms of the disease quickly, cheaply and with little training necessary for practitioners.

The implications for improving children's health could be enormous. Diarrhoea is a major killer in developing countries. World Health Organisation statistics indicate that more than 2 million people die each year from the effects of diarrhoea, most of them children under five years old.

Diarrhoea is caused by a range of bacterial, viral and parasitic organisms, and is usually spread by contaminated water and poor sanitation. Two particular bacteria , enteropathogenic E.coli (EPEC), which causes a persistent infection lasting more than 14 days, and Shigella, the cause of dysentery - are the most deadly in terms of killing children. They cause only 20% of cases of diarrhoea but result in 60% of deaths. It is these two killers - EPEC and Shigella - that the Leicester-led project is targeting.........

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September 12, 2006, 4:58 AM CT

Parkinson's Gene And The Disease

A group of Parkinson's disease scientists concluded there are no observable differences between those who have two copies of the most common mutation of the recently discovered LRRK2 gene and those who have only one copy. Their study would be reported in the September edition of the Archives of Neurology.

In most diseases with a genetic cause or component, two copies of a bad gene lead to more severe visible manifestation of the disease. Scientists expected to see worse symptoms, the disease start earlier in life and a shorter life span for those with two copies of the LRRK2 gene with the G2019S mutation. "That proved not to be the case," says Mayo Clinic neurologist Zbigniew Wszolek, M.D.

Wszolek formed an international consortium that compared the clinical features of Parkinson's disease in the two groups. "It's puzzling," he says. "More research is needed. More patients need to be identified and, hopefully, more basic science research is going to be performed to find out why".

The G2019S mutation is the most common of the 20 identified LRRK2 diseasecausing mutations. There are six known genes that cause familial Parkinson's disease, but only one, the G2019S mutation of the LRRK2 gene, has been linked to previously unexplained cases of Parkinson's disease. Wszolek and colleagues hope that studying the ways in which these genes cause disease, particularly the G2019S mutation, will lead to improved therapys and even a cure. "We are all united by the common drive to learn more about this disease, to help the people with this illness and to bring us closer to curative therapys," Wszolek says. "And this may be a step in that direction".........

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September 11, 2006, 10:20 PM CT

Artificial Cornea In Sight

If eyes are "the windows of the soul," corneas are the panes in those windows. They shield the eye from dust and germs. They also act as the eye's outermost lens, contributing up to 75 percent of the eye's focusing power. On Sept. 11 in San Francisco at the annual meeting of the American Chemical Society, chemical engineer Curtis W. Frank will present a novel biomimetic material that's finding its way into artificial corneas. It's a hydrogel, or polymer that holds a lot of water. That material may promise a new view for at least 10 million people worldwide who are blind due to damaged or diseased corneas or many millions more who are nearsighted or farsighted due to misshapen corneas.

Called Duoptix^TM, the material can swell to a water content of 80 percent--about the same as biological tissues. It's made of two interwoven networks of hydrogels. One network, made of polyethylene glycol molecules, resists the accumulation of surface proteins and inflammation. The other network is made of molecules of polyacrylic acid, a relative of the superabsorbent material in diapers.

"Think of a fishnet, but think of a 3-D fishnet," says Frank, the W. M. Keck, Sr. Professor in Engineering and a professor, by courtesy, of chemistry and of materials science and engineering. "It's a strong, stretchy material." That makes it able to survive suturing during surgery. The biocompatible hydrogel is transparent and permeable to nutrients, including glucose, the cornea's favorite food.........

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September 11, 2006, 9:30 PM CT

Enzyme Builds Neurotransmitters

The study, which was directed by Scripps Research Professor Benjamin Cravatt, Ph.D., is being reported in the September 8 issue of The Journal of Biological Chemistry.

The new study describes a pathway-different than the one previously suggested-for the biosynthesis of neurotransmitter lipids, N-acyl ethanolamines (NAEs), which include the endogenous cannabinoid ("endocannabinoid") anandamide. The high activity of the enzyme a/b hydrolase4 (Abh4) in areas such as the central nervous system suggests that the pathway makes a "potentially major contribution" to endocannabinoid signaling.

Endocannabinoids are naturally produced substances similar to the active ingredient D9-tetrahydrocannabinol (THC) in marijuana. Cannabinoid receptors were first discovered in 1988; the first endocannabinoid, anandamide, which shares some of the pharmacologic properties of THC, was identified in 1992.

Other research has shown that the endogenous cannabinoid system helps control food intake, among other critical processes, by acting on cannabinoid receptors in the central nervous system. The system drives consumption of fat and calorie-rich foods and the amount of fat stored or expended and plays a significant role in energy homeostasis.

"At least one cannabinoid receptor antagonist is on the verge of approval for the therapy of obesity-metabolic disorders," said Cravatt. "Enzymes involved in endocannabinoid biosynthesis, such as the one highlighted in our study, can be viewed as complementary drug targets. One potential advantage of this approach is that it may prove more selective than a receptor antagonist. By inhibiting enzymes such as Abh4, we may be able to disrupt the activity of a single class of endocannabinoids, rather than all of them".........

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September 11, 2006, 8:26 PM CT

A Look At The Antibiotic Drug Development

University of Minnesota and University of Michigan researchers have discovered a new method of developing antibiotics, an important step in fighting the growing number of drug-resistant infections.

In two articles published in the current online issue of Nature Chemical Biology, researchers describe an approach that is more efficient--and environmentally friendly--in developing new antibiotics, those needed to kill the increasing number of infections resistant to multiple drugs.

"We're striving to create new drugs that can have a positive impact on the growing threat of infectious diseases," says Robert Fecik, Ph.D., an assistant professor of Medicinal Chemistry at the University of Minnesota College of Pharmacy and one of the lead authors of the study. "This type of research can help us make new antibiotic molecules".

Officials at the Centers for Disease Control and Prevention have called antibiotic resistance one of the world's most pressing public health problems. Once only found in hospitals, these "superbugs" are now being found in community settings, including schools, nursing homes, and locker rooms.

These infections don't respond to common antibiotics such as erythromycin, which belong to a ring-shaped class of antibiotics called macrolides.........

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September 9, 2006, 6:40 AM CT

Selection Of Embryos

As Chad Kingsbury watches his daughter playing in the sandbox behind their Chicago house, the thought that has flashed through his mind a million times in her two years of life comes again: Chloe will never be sick.

Not, at least, with the inherited form of colon cancer that has devastated his family, killing his mother, her father and her two brothers, and that he too may face because of a genetic mutation that makes him uncommonly susceptible.

By subjecting Chloe to a genetic test when she was an eight-cell embryo in a petri dish, Kingsbury and his wife, Colby, were able to determine that she did not harbor the defective gene. That was the reason they selected her, from among the other embryos they had conceived through elective in vitro fertilization, to implant in her mother's uterus.........

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September 9, 2006, 6:01 AM CT

Women At Higher Risk Of Heart Disease

We all assume that older men are at a higher risk of heat disease and heart attacks compared to older women. It seems that we need to rethink this model. A surprising new study finds that women in their 60s have as a number of risk factors for heart disease as men, and by their 70s have more, as per research led by demographers at the University of Southern California.

The findings, reported in the current issue of the Journal of Women's Health, reflect a change from prior decades when older men were at greater risk for heart disease. Instead this research shows over the last 10 years, older women are doing worse, while men are doing better.

Women's risk for heart disease is still lower than men's through middle age. But the break-even point at which women catch up to men is now at age 60, 10 years earlier than before.

"Women are no longer protected from heart disease risk relative to men," said Eileen Crimmins, corresponding author and professor in USC Leonard Davis School of Gerontology. "Reports indicating that men are more likely to have more high-risk levels of blood pressure and cholesterol are no longer true in the U.S. population over 60 years of age".

Crimmins and her colleagues examined changes between 1988 and 2002 in indicators correlation to cardiovascular disease. The research team used data on men and women 40 and older from two broadly representative samples of the US population, approximately 10 years apart.........

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September 9, 2006, 5:42 AM CT

Hair loss oily skin and cancer.

A pathway through which a gene's over-expression causes skin stem cells to switch from creating hair follicles to creating sebaceous glands have been uncovered by Scientists from Oregon Health & Science University.

The discovery by the laboratory of Xiao-Jing Wang, M.D., Ph.D., professor of otolaryngology/head and neck surgery, OHSU School of Medicine, and member of the OHSU Cancer Institute, points to a new pathway that could some day be used as a therapeutic target for not only treating hair loss and oily skin, but prevent and treat cancer.

The study's results are reported in the current issue of the journal Developmental Cell.

Epidermal stem cells give rise to the outer layer of the skin that serves as a barrier for the body, as well as follicles that produce hairs and sebaceous glands that produce lipid oil to lubricate the skin. In aged skin, a protein called Smad7 is overproduced, which triggers hair loss and sebaceous gland growth.

The Developmental Cell study is the first to definitively link Smad7 over-expression and the pathological changes that occur in aged skin.

"In humans, researchers and medical doctors documented the aging skin phenotype a long time ago, and the Smad7 over-expression in aged skin was reported a few years ago, but nobody knew whether these two events had any link," said Wang, who also serves in the OHSU departments of Cell and Developmental Biology, and Dermatology. "We found the mechanism that links these two together".........

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