April 24, 2007, 10:57 PM CT

Unravel Clue in Cortisol Production

When a person's under stress or injured, the adrenal gland releases cortisol to help restore the body's functions to normal. But the hormone's effects are many and varied, lowering the activity of the immune system, helping create memories with short-term exposure, while impairing learning if there's too much for too long. Given the variety of its effects,understanding how cortisol is made is essential to producing medications that can alter its production.

Scientists at the Georgia Institute of Technology have discovered an important step in cortisol production, finding that although the output of the hormone is continuous, the molecular production is cyclic in nature - involving a rhythmic binding and unbinding of a protein essential to its production. The research, which increases understanding of how the brain and the endocrine system work together to regulate health, appears in the recent issue of the journal Molecular Endocrinology.

Turning cholesterol into the stress hormone cortisol involves many reactions and begins when the hypothalamus sends a signal to the adrenal glands. Proteins then flood into the nucleus to bind to the DNA, creating the gene CYP 17. What happens next is well understood; CYP 17, along with a battery of other enzymes, transforms cholesterol into cortisol. But what isn't understood is how this protein binding creates CYP 17, or which proteins are important. So, graduate students Eric Dammer and Adam Leon, along with Marion Sewer, assistant professor in Georgia Tech's School of Biology, decided to model the events that occur after the adrenal gland receives the signal......... Posted by: Emily      Read more         Source

April 24, 2007, 10:48 PM CT

Enzyme linked to Friedreich's ataxia

Friedreich's ataxia is one of those diseases few have heard of unless you know someone with the condition. For that individual -- commonly a child or teenager -- it is devastating. Symptoms are mild at first: muscle weakness in the arms and legs, vision impairment and slurred speech, but eventually the symptoms progress and most patients become wheelchair-bound and succumb to heart failure during the later part of life. There is no cure at this time, but Mayo Clinic scientists have identified mutations in an enzyme that may contribute to the disease.

"Children and teens want to be on top of the world and having a disease like this is devastating for them and their families in so a number of different respects," says Grazia Isaya, M.D., Ph.D., senior author of the study and a basic scientist at Mayo Clinic who specializes in Friedreich's ataxia. "Their cognitive functions are not impaired so they understand exactly what is happening to them".

Friedreich's ataxia is an inherited neurodegenerative disease of children and teens and is considered an orphan disease by the National Institutes of Health because of its rarity -- affecting one in 40,000. It is linked to a deficiency of frataxin, a protein that balances iron in mitochondria, which are the structures that convert nutrients into energy for cells. A new Mayo Clinic study reported in the recent issue of the Proceedings of the National Academy of Sciences (PNAS) shows that mutations in a moonlighting enzyme, dihydrolipoamide dehydrogenase (DLD), are responsible for decreasing the enzyme's primary role as a metabolizer, while increasing its role in breaking down frataxin, its second job......... Posted by: Emily      Read more         Source

April 24, 2007, 10:26 PM CT

High insulin levels impair intestinal metabolic function

Nutritional researchers at the University of Alberta are the first to establish a correlation between high insulin levels and dysfunction of intestinal lipid metabolism in an animal model. They believe this finding supports their contention that impaired intestinal metabolic function plays a critical role in the development of cardiovascular disease.

The research was published recently in the journal Atherosclerosis.

The scientists have observed that excessive insulin appears to slow the removal of chylomicrons from the blood stream following a fatty meal. Chylomicrons transport dietary fat from the intestine to the rest of the body.

The scientists note that excessive insulin appears to alter the mechanics of blood vessel walls, allowing chylomicrons and cholesterol to build up in them, which, over time, creates blockages in the blood stream, leading to heart problems.

"Now that we know high levels of insulin are linked to altered intestinal chylomicron metabolism and a build up of these particles in the blood vessel walls, our next step is to use this animal model to look closer at the cellular mechanisms and try to figure out how this happens," said Dr. Donna Vine, a nutritional scientist at the U of A and co-author of the paper in Atherosclerosis......... Posted by: Emily      Read more         Source

April 23, 2007, 9:48 PM CT

Overcrowded hospitals may increase risk

Hospitals that operate at or over their capacity may be at increased risk of adverse events that injure patients, as per a research studyled by researchers from Massachusetts General Hospital (MGH) and Brigham and Woman's Hospital (BWH). The report in the recent issue of the journal Medical Care suggests that efforts to meet two primary challenges facing hospitals today reducing costs and improving patient safety may work against each other.

"While financial and political pressures to make health care more efficient are leading to increased hospital occupancy and greater patient turnover, patients and policymakers are quite rightly demanding that health delivery systems be made safer," says Joel Weissman, PhD, of the MGH Institute of Health Policy, the report's lead author. "Our study suggests that pushing efficiency efforts to their limits could be a double-edged sword that may jeopardize patient safety".

In order to examine their hypothesis that increased workload could raise the likelihood of adverse events, the researchers examined data from four hospitals in two states two large urban teaching hospitals and two suburban teaching hospitals over the 12 months from October 2000 through September 2001. To compile patient care information they evaluated patient charts and billing records on almost 25,000 patients, selecting 6,841 for comprehensive review, and analyzed that data against information on hospital workloads and staffing patterns, with a focus on variations within each hospital......... Posted by: Emily      Read more         Source

April 17, 2007, 11:02 PM CT

Proteins Important in Alzheimer's and Parkinson's Disease

Using a novel video-imaging system, scientists at the University of Pennsylvania School of Medicine have been able to observe proteins important in Alzheimer's and Parkinson's disease moving along axons, extensions of nerve cells that carry proteins away from the cell body. Understanding this process of axonal transport is important for studying a number of neurodegenerative diseases. The study appeared in the Journal of Neuroscience.

Typically axonal transport often breaks down and a number of neurodegenerative diseases are characterized by defects in this process. Of particular interest is a group of transported proteins called slow component-b that includes synuclein and tau, disease proteins involved in Parkinson's and Alzheimer's disease, respectively, in addition to a number of other proteins critical for axonal growth and regeneration.

"There are two basic transport groups called fast and slow components, with a 200 to 300 fold difference in average velocities," says first author Subhojit Roy, MD, PhD, a neuropathologist and Research Associate in the Department of Pathology and Laboratory Medicine. "While researchers have seen proteins in the fast component move rapidly to the tip of the axon, until now, mechanisms of the slow movement of these disease-related proteins have been unclear as their transport had not been directly visualized"......... Posted by: Emily      Read more         Source

April 15, 2007, 9:48 PM CT

ATR checkpoint-activating DNA structure

As reported in the April 15th issue of Genes & Development, Dr. Karlene Cimprich and his colleagues at Stanford University have determined the minimal DNA structure sufficient to activate the ATR-mediated DNA damage checkpoint.

"We are very excited about these results," says Dr. Cimprich. "The ability to precisely define and manipulate the nature of the checkpoint activating structure in an experimental system will enable us to control, quantitative and probe checkpoint signaling responses in unprecedented ways".

Using Xenopus egg extracts as a cell-free system, the scientists observed that single-stranded DNA annealed with primers specifically triggers the ATR-mediated checkpoint response. While a number of proteins involved in the DNA damage response have been uncovered, this type of structural information is quite novel and valuable. The elucidation of the first defined DNA structure capable of eliciting the ATR checkpoint will aid scientists to further identify additional checkpoint proteins, as well as understand how checkpoint signals are generated and regulated inside the cell......... Posted by: Emily      Read more         Source

April 15, 2007, 9:16 PM CT

More Insomnia-related Symptoms

Those persons who are labeled a night owl report more pathological symptoms correlation to insomnia, despite a number of having the opportunity to compensate for their nocturnal sleeplessness by extending their time in bed and being able to gain more total sleep time, as per a research studyreported in the April 15th issue of the Journal of Clinical Sleep Medicine (JCSM).

The study, authored by Jason C. Ong, PhD, and his colleagues at Stanford University, consisted of 312 patients, who were categorized as morning, intermediate and evening chronotypes based upon scores on the Morningness-Eveningness Composite Scale. Group comparisons were made on self-report measures of nocturnal sleep, sleep period variability and waking correlates and consequences of insomnia.

In comparison to the morning and intermediate types, people with insomnia who prefer evening activities (i.e., night owls) reported the most sleep/wake irregularities and waking distress, even after adjusting for severity of sleep disturbance.

Our findings indicate that further research should investigate the relationship between circadian rhythms and insomnia, particularly with the severity of the night owl group, said Ong. These factors may serve to perpetuate the insomnia disorder, and might be especially important to consider when treating this subgroup of insomniacs......... Posted by: Emily      Read more         Source

April 15, 2007, 8:31 PM CT

Scientists find new genes for Crohn's disease

Just a few months after their landmark article in Science magazine reporting the discovery of strong links between variations in a gene that codes for a cellular receptor involved in controlling inflammation and Crohn's disease, a consortium of U.S. and Canadian scientists is reporting in today's online issue of Nature Genetics that they have discovered several more genetic variations that are strongly associated with an increased risk for the disease. The discovery of these Crohn's disease-associated genetic variants has identified several key biological pathways that will be the focus of further research to understand how the debilitating inflammatory process is initiated and maintained in a number of cases of the disease.

"As we collect more and more data from these genome-wide association studies, we continue to discover susceptibility genes for Crohn's and other inflammatory bowel diseases (IBDs). More importantly, those genes are leading us to the biological pathways that relate to IBD pathogenesis. By understanding these pathways, we may be better able to develop more effective therapies for IBD," said consortium member Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh, co-director of the Inflammatory Bowel Disease Center and director of the IBD Genetics Program......... Posted by: Emily      Read more         Source

April 11, 2007, 11:09 PM CT

Stress may help cancer cells resist treatment

Scientists from Wake Forest University School of Medicine are the first to report that the stress hormone epinephrine causes changes in prostate and breast cancer cells that may make them resistant to cell death.

"These data imply that emotional stress may contribute to the development of cancer and may also reduce the effectiveness of cancer treatments," said George Kulik, D.V.M., Ph.D., an assistant professor of cancer biology and senior researcher on the project.

The study results are reported on-line in the Journal of Biological Chemistry and will appear in a future print issue.

Levels of epinephrine, which is produced by the adrenal glands, are sharply increased in response to stressful situations and can remain continuously elevated during persistent stress and depression, according to previous research. The goal of the current study was to determine whether there is a direct link between stress hormones and changes in cancer cells.

While a link between stress and cancer has been suggested, studies in large groups of people have been mixed.

"Population studies have had contradictory results," said Kulik. "We asked the question, If stress is linked to cancer, what is the cellular mechanism? There had been no evidence that stress directly changes cancer cells"......... Posted by: Emily      Read more         Source

April 10, 2007, 6:24 PM CT

Protecting Brains Of Premature Infants

A study of how the brain of a premature infant responds to injury has found vulnerabilities similar to those in the mature brain but also identified at least one significant difference, according to neuroscientists and neonatologists at Washington University School of Medicine in St. Louis.

In an animal model of brain injury, researchers showed for the first time that parts of the developing brain are vulnerable to damage from glutamate, a nervous system messenger compound. Glutamate is already well-known for its links to injury in the mature brain. But scientists also found damage in the developing brain that could not be linked to glutamate, suggesting that different treatments are needed to prevent brain injury in premature infants.

More than two percent of babies are born before the completion of their eighth month of gestation, and up to half of these infants suffer brain injury. Unlike adults, premature infants receive the most damage in the white matter, the portions of the brain that connect different brain regions.

"These injuries can lead to behavioral problems, developmental delay, cognitive impairment or cerebral palsy," says senior author Mark P. Goldberg, M.D., professor of neurology and of neurobiology. "In this study, we've identified a unique vulnerability in the developing brain's white matter that likely contributes to those disabilities. We will be looking for new drug treatments to prevent injury"......... Posted by: Emily      Read more         Source