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News 24 march 2009

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Hopkins scientists ID 10 genes associated with a risk factor for sudden cardiac death

One minute, he's a strapping 40-year-old with an enviable cholesterol level, working out on his treadmill. The next, he's dead. That an abnormality in his heart's electrical system had managed to stay on the Q.T. — until it proved lethal — is characteristic of sudden cardiac death, which annually claims more than a quarter million Americans. A dearth of discernable symptoms and lack of detectable molecules circulating in the blood makes the prediction of sudden cardiac death largely dependent on genetic risk factors. Having identified 10 common variants of genes that modify the timing of the contraction of the heart, known as the QT interval, scientists in the Johns Hopkins University School of Medicine, in collaboration with an international contingent of researchers, now provide new insight about the underpinnings of the QT interval which, when prolonged or shortened, predisposes to sudden cardiac death. QT interval, which is determined from a standard electrocardiogram (ECG), reflects the time it takes for the heart (ventricles) to contract and then reset for the next heartbeat. Publishing March 22 in Nature Genetics, the international team including researchers from the Technical University in Munich, Johns Hopkins and others, used DNA samples previously collected for epidemiological studies to analyze the genomes of 15,842 individuals whose QT intervals had been measured by electrocardiogram. With DNA microarray chips, each able to assess hundreds of thousands of markers in each sample, followed by bioinformatic techniques to increase the number of markers, the researchers screened approximately 2.5 million markers to detect subtle alterations in the sequences of these genomes that modify the QT interval. By focusing on 2.5 million sites in a genome of 3 billion sites, the scientists surveyed one-one-thousandth of nearly 16,000 genomes. This relatively small but "still extremely powerful" screen correlates genomic architecture with QT intervals, according to Aravinda Chakravarti, Ph.D., a professor in the McKusick-Nathans Institute of Genetic Medicine.

New method of assessing women's eggs could enhance IVF success

Many couples who have trouble conceiving a child have turned to a process known as in vitro fertilization. The resulting embryos are then transferred back into the woman or placed in storage. More than 400,000 embryos are currently in storage in the United States. The quality of the egg is often the single greatest factor in the viability of the embryo, yet fertility experts lack a good method for assessing the eggs.
Barry Behr, PhD, HCLD, associate professor of obstetrics and gynecology at the Stanford University School of Medicine and director of Stanford's IVF laboratory, recently published findings on a way to "profile" the eggs to determine which are more likely to result in pregnancies.The question - Can a non-invasive test of a woman's eggs be used to predict in vitro fertilization success? Background - In vitro fertilization involves retrieving eggs from a woman's ovaries and fertilizing the eggs in a dish by incubating them with sperm or injecting sperm directly into them. The resulting embryos are then transferred back into the woman or placed in storage. The quality of the egg is often the single biggest determinant in the viability of the embryo.The need - There is currently no good tool to available to assess eggs. "We would stand on our head and hop on our left leg if we could find a way to give us some information about viability of embryo," said Behr. The technology - Metabolomic testing reveals trace molecules remaining after an array of cellular processes. Previous studies have shown that metabolomic profiling can be used to identify unique biomarkers left behind by embryos in culture, which foretell the embryos with the highest reproductive potential in IVF. "Think of it as a sort of smog test for the embryo," said Behr. "It tells you how clean the engine is burning, and whether there are any problems."The study - The study involved extracting eggs from 43 women, incubating them in culture for three hours and then examining their metabolomic results before fertilization. The researchers then documented what happened to each egg: Whether it was fertilized, the quality of the resulting embryo on days three and five, and whether it led to a successful pregnancy.

Stanford study improves insights into Parkinson's disease and possible treatments

About the only thing doctors have understood about deep-brain stimulation, which is widely used to treat Parkinson’s disease symptoms, is that somehow it works for many patients. In a new study that was published March 19 in the online journal Science Express, Stanford University researchers used light to illuminate how the treatment works, generating surprising insights into the diseased circuitry and also suggesting new ideas to improve Parkinson’s therapy.Parkinson’s disease is a brain disorder that affects an estimated 1.5 million Americans, causing tremors, stiffness and difficulty balancing. In those who undergo deep-brain stimulation, pulses of electricity are applied to the circuitry of a tiny brain region called the subthalamic nucleus. Naturally, researchers suspected that cells within that region are somehow stimulated, or calmed, by the shocks, leading to reduced Parkinson’s symptoms. In the new study, which will also appear in an upcoming print issue of Science, the medical and engineering researchers found that by far the biggest effect in “Parkinsonian” rodents occurs not by stimulating cells in the subthalamic nucleus, but by stimulating the neural wires, called axons, that connect directly to it from areas closer to the surface of the brain.

Scientists find cellular process that fights virus

Scientists have discovered a new way for our immune system to combat the elusive virus responsible for cold sores: Type 1 herpes simplex (HSV-1). As reported in the advance online edition of Nature Immunology, a group of virus hunters from the Université de Montréal, in collaboration with American colleagues, have identified a cellular process that seeks out and fights herpes. The five-year study, partially supported by the Canadian Institutes of Health Research, was a joint project with Washington University and Pennsylvania State University. "Once human cells are infected with Type 1 herpes simplex, the virus comes back because it hides and blocks protection from our immune system," says Luc English, the study's lead author and a doctoral student at the Université de Montréal's Department of Pathology and Cell Biology. "For the first time, our research team has indentified a combative cellular mechanism in this game of hide-and-seek." "We've found that the nuclear membrane of an infected cell can unmask Type 1 herpes simplex and stimulate the immune system to disintegrate the virus," says English. The team made its discovery while conducting various tests in HSV-1 infected mice cells. They replicated environments when Type 1 herpes simplex thrives, namely periods of low-grade fever between 38.5 to 39 degrees, and found that herpes-fighting mechanisms were unleashed. The research team now plans to study how activation of the herpes-combating cellular process could be applied to other illnesses. The outcome could hasten the development of therapies to prevent other immune-evading bacteria, parasites and viruses. "Our goal is to further study the molecules implicated in this mechanism to eventually develop therapies against diseases such as HIV or even cancer," says English.

Special gold nanoparticles show promise for 'cooking' cancer cells

Researchers are describing a long-awaited advance toward applying the marvels of nanotechnology in the battle against cancer. They have developed the first hollow gold nanospheres — smaller than the finest flecks of dust — that search out and "cook" cancer cells. The cancer-destroying nanospheres show particular promise as a minimally invasive future treatment for malignant melanoma, the most serious form of skin cancer, the researchers say. Melanoma now causes more than 8,000 deaths annually in the United States alone and is on the increase globally. The topic of a report presented here today at the American Chemical Society's 237th National Meeting, the hollow gold nanospheres are equipped with a special "peptide." That protein fragment draws the nanospheres directly to melanoma cells, while avoiding healthy skin cells. After collecting inside the cancer, the nanospheres heat up when exposed to near-infrared light, which penetrates deeply through the surface of the skin. In recent studies in mice, the hollow gold nanospheres did eight times more damage to skin tumors than the same nanospheres without the targeting peptides, the researchers say. "This technique is very promising and exciting," explains study co-author Jin Zhang, Ph.D., a professor of chemistry and biochemistry at the University of California in Santa Cruz. "It's basically like putting a cancer cell in hot water and boiling it to death. The more heat the metal nanospheres generate, the better." This form of cancer therapy is actually a variation of photothermal ablation, also known as photoablation therapy (PAT), a technique in which doctors use light to burn tumors. Since the technique can destroy healthy skin cells, doctors must carefully control the duration and intensity of treatment. Researchers now know that PATs can be greatly enhanced by applying a light absorbing material, such as metal nanoparticles, to the tumor. Although researchers have developed various types of metal nanoparticles to help improve this technique, many materials show poor penetration into cancer cells and limited heat carrying-capacities. These particles include solid gold nanoparticles and nanorods that lack the desired combination of spherical shape and strong near-infrared light absorption for effective PAT, scientists say.
To develop more effective cancer-burning materials, Zhang and colleagues focused on hollow gold nanospheres — each about 1/50,000th the width of a single human hair. Previous studies by others suggest that gold "nanoshells" have the potential for strong near-infrared light absorption. However, scientists have been largely unable to produce them successfully in the lab, Zhang notes. After years of research toward this goal, Zhang announced in 2006 that he had finally developed a nanoshell or hollow nanosphere with the "right stuff" for cancer therapy: Gold spheres with an optimal light absorption capacity in the near-infrared region, small size, and spherical shape, perfect for penetrating cancer cells and burning them up.

Proteins from garden pea may help fight high blood pressure, kidney disease

Researchers in Canada are reporting that proteins found in a common garden pea show promise as a natural food additive or new dietary supplement for fighting high blood pressure and chronic kidney disease (CKD). Those potentially life-threatening conditions affect millions of people worldwide. The study, which will be presented here today at the American Chemical Society's 237th National Meeting, is the first reporting that a natural food product can relieve symptoms of CKD, the scientists say. Peas long have been recognized as nutritional superstars, with healthful amounts of protein, dietary fiber, and vitamins wrapped in a low-fat, cholesterol-free package. The new research focuses on the yellow garden pea, a mainstay pea variety enjoyed as a veggie side-dish and used as an ingredient in dozens of recipes around the world. "In people with high blood pressure, our protein could potentially delay or prevent the onset of kidney damage," says study presenter Rotimi Aluko, Ph.D., a food chemist at the University of Manitoba in Winnipeg, Canada. "In people who already have kidney disease, our protein may help them maintain normal blood pressure levels so they can live longer." High blood pressure, or hypertension, is a major risk factor for CKD, a condition that has been affecting an increasing number of people in the United States and other countries. Estimates suggest that 13 percent of American adults — about 26 million people — have chronic kidney disease, up from 10 percent, or about 20 million people, in the 1990s. CKD is difficult to treat, and may progress to end-stage kidney disease that requires kidney dialysis or a kidney transplant. That situation is fostering a search for new ways of treating CKD and preserving kidney function. Working with University of Manitoba colleague Harold Aukema, Ph.D., Aluko purified a mixture of small proteins — called pea protein hydrolysate — from the yellow garden pea. The researchers fed small daily doses of the protein mixture to laboratory rats with polycystic kidney disease, a severe form of kidney disease used as a model for research on CKD. At the end of the 8-week-long study period, the protein-fed rats with kidney disease showed a 20 percent drop in blood pressure when compared to diseased rats on a normal diet, the researchers say. "This is significant because a majority of CKD patients actually die from cardiovascular complications that arise from the high blood pressure associated with kidney malfunction," Aluko notes. In both rats and humans with polycystic kidney disease, the condition causes urine output to be severely reduced and the kidneys are unable to properly remove dangerous toxins. The researchers showed that their pea extract caused a 30 percent boost in urine production in the diseased rats, bringing their urine to within normal levels. "That's a huge improvement," says Aluko, adding that there were no obvious adverse side effects from the pea protein.

Clinical trial backs use of special yogurt to fight stomach ulcer bacteria

Results of the first human clinical studies confirm that a new yogurt fights the bacteria that cause gastritis and stomach ulcers with what researchers describe as almost vaccine-like effects, scientists in Japan will report here today at the 237th National Meeting of the American Chemical Society. Researchers have long known that yogurt, a fermented milk product containing live bacteria, is a healthy source of calcium, protein, and other nutrients. Some brands of yogurt are now made with "probiotics" — certain types of bacteria — intended to improve health. The new yogurt represents a unique approach to fighting stomach ulcers, which affect 25 million people in the United States alone, and is part of a growing "functional food" market that now generates $60 billion in sales annually. "With this new yogurt, people can now enjoy the taste of yogurt while preventing or eliminating the bacteria that cause stomach ulcers," says study coordinator Hajime Hatta, Ph.D., a chemist at Kyoto Women's University in Kyoto, Japan. The new yogurt is already on store shelves in Japan, Korea, and Taiwan. The study opens the door to possible arrival of the product in the U.S., the researchers suggest. A type of bacteria called Helicobacter pylori (H. pylori) or over-use of aspirin and or other nonsteroidal antiinflammatory drugs, causes most stomach ulcers. H. pylori ulcers can be effectively treated and eliminated with antibiotics and acid suppressants. However, that simple regimen is unavailable to millions of poverty-stricken people in developing countries who are infected with H. pylori. New research also links childhood H. pylori infection to malnutrition, growth impairment and other health problems. As a result, scientists have been seeking more economical and convenient ways of dealing with these bacteria. In the new study, Hatta and colleagues point out that H. pylori seems to rely on a protein called urease to attach to and infect the stomach lining. In an effort thwart that protein, or antigen, Hatta turned to classic vaccine-making technology. They injected chickens with urease and allowed the chickens' immune systems to produce an antibody to the protein. The researchers then harvested the antibody, called IgY-urease, from chicken eggs. Hatta and colleagues theorized that yogurt containing the antibody may help prevent the bacteria from adhering to the stomach lining.

Gulf War veterans display abnormal brain response to specific chemicals

A new study by UT Southwestern Medical Center researchers is the first to pinpoint damage inside the brains of veterans suffering from Gulf War syndrome – a finding that links the illness to chemical exposures and may lead to diagnostic tests and treatments.Dr. Robert Haley, chief of epidemiology at UT Southwestern and lead author of the study, said the research uncovers and locates areas of the brain that function abnormally. Recent studies had shown evidence of chemical abnormalities and shrinkage of white matter in the brains of veterans exposed to certain toxic chemicals, such as sarin gas during the 1991 Persian Gulf War. The research, published in the March issue of the journal Psychiatry Research: Neuroimaging,enables investigators to visualize exact brain structures affected by these chemical exposures, Dr. Haley said.
"Before this study, we didn't know exactly what parts of the brain were damaged and causing the symptoms in these veterans," he said. "We designed an experiment to test areas of the brain that would have been damaged if the illness was caused by sarin or pesticides, and the results were positive." In designing the study, Dr. Haley and his colleagues reasoned that if low-level sarin or pesticides had damaged Gulf War veterans' brains, a likely target of the damage would be cholinergic receptors on cells in certain brain structures. If that was so, administering safe levels of medicines that stimulate cholinergic receptors would elicit an abnormal response in ill veterans. In the study, 21 chronically ill Gulf War veterans and 17 well veterans were given small doses of physostigmine, a substance which briefly stimulates cholinergic receptors. Researchers then measured the study participants' brain cell response with brain scans. "What we found was that some of the brain areas we previously suspected responded abnormally to the cholinergic challenge," Dr. Haley said. "Those areas were in the basal ganglia, hippocampus, thalamus and amygdala, and the thalamus. Changes in functioning of these brain structures can certainly cause problems with concentration and memory, body pain, fatigue, abnormal emotional responses and personality changes that we commonly see in ill Gulf War veterans." A previous study funded by the U.S. Army found that repetitive exposure to low-level sarin nerve gas caused changes in cholinergic receptors in lab rats.

New study finds daily drinking is biggest risk factor in serious liver disease

Long-term daily drinking, rather than weekly binge drinking, is by far the biggest risk factor in serious liver disease, according to a new report from the University of Southampton. The study, published in Addiction journal this week, concludes that increases in UK liver deaths are a result of daily or near daily heavy drinking, not episodic or binge drinking, and this regular drinking pattern is often discernable at an early age. It also reccommends that several alcohol-free days a week is a healthier drinking pattern. In the study of drinking patterns, dependency and lifetime drinking history in 234 subjects with liver disease, 106 had ALD (Alcohol-related Liver Disease) – 80 of whom had evidence of cirrhosis or progressive fibrosis – the team found that 71 per cent of ALD patients drank on a daily basis. In contrast to the patients with alcohol-related cirrhosis or fibrosis, patients with other forms of liver disease tended to drink sparingly with only 10 subjects (8 per cent) drinking moderately on four or more days each week. The study also explored lifetime drinking histories of 105 subjects and found that ALD patients started drinking at a significantly younger age (on average at 15 years old) than other subjects and had significantly more drinking days and units than non-ALD patients from the age of 20 onwards. Lead author of the study Dr Nick Sheron, consultant hepatologist and senior lecturer at the University of Southampton, comments: "If we are to turn the tide of liver deaths, then along with an overall reduction in alcohol consumption – which means tackling cheap booze and unregulated marketing – we need to find a way to identify those people who are most likely to develop alcohol-related illnesses at a much earlier stage, and perhaps we need to pay as much attention to the frequency of drinking occasions as we do to binge drinking. "The transition from a late teenage and early 20's binge drinking pattern to a more frequent pattern of increased intake may prove to be a useful point of intervention in the future, and the importance of three alcohol-free days each week should receive more prominence."

Mayo Clinic study suggests those who have chronic pain may need to assess vitamin D status

Mayo Clinic research shows a correlation between inadequate vitamin D levels and the amount of narcotic medication taken by patients who have chronic pain. This correlation is an important finding as researchers discover new ways to treat chronic pain. According to the Centers for Disease Control and Prevention, chronic pain is the leading cause of disability in the United States. These patients often end up taking narcotic-type pain medication such as morphine, fentanyl or oxycodone. This study found that patients who required narcotic pain medication, and who also had inadequate levels of vitamin D, were taking much higher doses of pain medication — nearly twice as much — as those who had adequate levels. Similarly, these patients self-reported worse physical functioning and worse overall health perception. In addition, a correlation was noted between increasing body mass index (a measure of obesity) and decreasing levels of vitamin D. Study results were published in a recent edition of Pain Medicine. "This is an important finding as we continue to investigate the causes of chronic pain," says Michael Turner, M.D., a physical medicine and rehabilitation physician at Mayo Clinic and lead author of the study. "Vitamin D is known to promote both bone and muscle strength. Conversely, deficiency is an under-recognized source of diffuse pain and impaired neuromuscular functioning. By recognizing it, physicians can significantly improve their patients' pain, function and quality of life." Researchers retrospectively studied 267 chronic pain patients admitted to the Mayo Comprehensive Pain Rehabilitation Center in Rochester from February to December 2006. Vitamin D levels at the time of admission were compared to other parameters such as the amount and duration of narcotic pain medication usage; self-reported levels of pain, emotional distress, physical functioning and health perception; and demographic information such as gender, age, diagnosis and body mass index. Further research should document the effects of correcting deficient levels among these patients, researchers recommend. This study has important implications for both chronic pain patients and physicians. "Though preliminary, these results suggest that patients who suffer from chronic, diffuse pain and are on narcotics should consider getting their vitamin D levels checked. Inadequate levels may play a role in creating or sustaining their pain," says Dr. Turner."Physicians who care for patients with chronic, diffuse pain that seems musculoskeletal — and involves many areas of tenderness to palpation — should strongly consider checking a vitamin D level," he says. "For example, many patients who have been labeled with fibromyalgia are, in fact, suffering from symptomatic vitamin D inadequacy. Vigilance is especially required when risk factors are present such as obesity, darker pigmented skin or limited exposure to sunlight." Assessment and treatment are relatively simple and inexpensive. Levels can be assessed by a simple blood test (25-hydroxyvitamin D [25(OH)D]). Under the guidance of a physician, an appropriate repletion regimen can then be devised. Because it is a natural substance and not a drug, vitamin D is readily available and inexpensive. In addition to the benefits of strong muscles and bones, emerging research demonstrates that vitamin D plays important roles in the immune system, helps fight inflammation and helps fights certain types of cancer.

To Fight Drug Addiction, UB Researchers Target the Brain with Nanoparticles

A precise, new nanotechnology treatment for drug addiction may be on the horizon as the result of research conducted at the University at Buffalo. Scientists in UB's Institute for Lasers, Photonics and Biophotonics and UB's Department of Medicine have developed a stable nanoparticle that delivers short RNA molecules in the brain to "silence" or turn off a gene that plays a critical role in many kinds of drug addiction. The UB team's in vitro findings were published online the week of March 23 in the Proceedings of the National Academy of Sciences. "These findings mean that in the future, we might be able to add a powerful pharmaceutical agent to the current arsenal of weapons in order to more effectively fight a whole range of substance addictions," said Paras N. Prasad, Ph.D., executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine, who led the UB team.

Diabetics on high-fiber diets might need extra calcium

The amount of calcium your body absorbs might depend, in part, on the amount of dietary fiber you consume. Researchers at UT Southwestern Medical Center report that patients with noninsulin-dependent diabetes (type 2) excreted less calcium through their urine when they consumed 50 grams of fiber a day than when they ate 24 grams a day. Excreting less calcium indicates that they absorbed less of the mineral. “We already know that fiber helps improve your cholesterol and glucose control and improves your bowel regularity. Our new findings suggest that dietary fiber reduces the body’s capacity to absorb calcium,” said Dr. Abhimanyu Garg, professor of internal medicine and an investigator in the Center for Human Nutrition at UT Southwestern. He is senior author of a study appearing online in Diabetes Care. “Because more calcium equals better bone health, we recommend that people on high-fiber diets talk to their physician about increasing their dietary calcium as well, in order to get the most benefit from both.”

Researchers Studying Hearing Loss in Adult Animals Find that Auditory Regions of the Brain Convert to the Sense of Touch

Virginia Commonwealth University School of Medicine researchers have discovered that adult animals with hearing loss actually re-route the sense of touch into the hearing parts of the brain. In the study, published online in the Early Edition of the Proceedings of the National Academy of Sciences the week of March 23, the team reported a phenomenon known as cross-modal plasticity in the auditory system of adult animals. Cross-modal plasticity refers to the replacement of a damaged sensory system by one of the remaining ones. In this case, the sense of hearing is replaced with touch. About 15 percent of American adults suffer from some form of hearing impairment, which can significantly impact quality of life, especially in the elderly. “One often learns, anecdotally, that ‘grandpa’ simply turned off his hearing aid because it was confusing and no longer helped. Our study indicates that hearing deficits in adult animals result in a conversion of their brain’s sound processing centers to respond to another sensory modality, making the interpretation of residual hearing even more difficult,” said principal investigator Alex Meredith, Ph.D., a professor in the VCU Department of Anatomy and Neurobiology. “Whether this becomes a positive feedback cycle of increasing hearing difficulty is currently under investigation, but these findings raise the possibility that even mild hearing loss in adult humans can have serious and perhaps progressive consequences,” Meredith said.

Smithsonian scientist warns that palm oil development may threaten Amazon

Oil palm cultivation is a significant driver of tropical forest destruction across Southeast Asia. It could easily become a threat to the Amazon rainforest because of a proposed change in Brazil's legislation, new infrastructure and the influence of foreign agro-industrial firms in the region, according to William F. Laurance, senior scientist at the Smithsonian Tropical Research Institute in Panama. Laurance and Rhett A. Butler, founder of environmental science Web site Mongabay.com, warn in the open-access journal Tropical Conservation Science, that oil palm expansion in the Brazilian Amazon is likely to occur at the expense of natural forest as a result of a proposed revision to the forest code that requires landowners to retain 80 percent forest on lands in the Amazon. The new law would allow up to 30 percent of this reserve to consist of oil palm.
Expansion may be driven by economics. As the world's highest-yielding oil-containing seed source, oil palm is likely to offer better financial returns and to employ larger numbers of people than cattle ranching and mechanized soy farming, the dominant agricultural activities in Brazilian Amazon. Furthermore, oil palm producers will benefit from a "logging subsidy," whereby timber harvested from a tract of land helps to offset the cost of establishing a plantation. Before the recent run-up in palm oil prices, logging had been a factor in the profitability of oil palm plantations in Southeast Asia.

Long-term L-carnitine supplementation prevents development of liver cancer

A study will be published on March 21, 2009 in World Journal of Gastroenterology addresses the question. A research group in King Saud University, Kingdom of Saudi Arabia investigated, for the first time, the role of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the development of hepatocarcinogenesis. Authors of the study reported that carnitine deficiency is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that long-term L-carnitine supplementation prevents the development of liver cancer. Therefore, carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer. Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or reversed. L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production. Despite the liver being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to find any studies investigating the role of long-term endogenous carnitine depletion and/or carnitine deficiency during induction of hepatic carcinogenesis. The research team by Professor Sayed-Ahmed from College of Pharmacy, King Saud University used an experimental model of hepatocarcinogenesis under conditions of carnitine depletion and carnitine supplementation. In the carnitine-depleted rat model, there were a progressive increase in the activities of liver enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate, diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes compared to normal values, as well as normal liver histology with unremarkable central vein and no evidence of pre-neoplastic lesions in liver tissues. Due to the fact that liver cancer is one of the major health problems in the world and a large sector of patients seek medical attention at a relatively late stage which increases the cost of treatment, King Saud University granted Prof. Sayed-Ahmed and his colleagues a research project with the following specific aims: (1) to understand the possible molecular mechanisms whereby carnitine deficiency provokes hepatic carcinogenesis. (2) to understand the relationship between hepatic cancer and its resistance to cancer chemotherapy, and (3) to gain knowledge on the possible mechanisms by which carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.

tTGA - Is it more essential in diagnosis of gluten sensitive enteropathy?

CD is a highly prevalent disease (1:100 to 1:300) which fulfils most of the criteria favoring mass screening. Despite this, screening for gluten sensitive enteropathy (GSE) is still controversial due to its dubious benefits and the acceptance of a gluten-free diet (GFD). A research article to be published on March 21, 2009 in the World Journal of Gastroenterology address this question. The study shows that GSE patients in the general population may not be identified by clinical features, since a similar percentage of related CD symptoms was found in individuals with positive and negative markers. This fact explains why CD remains underdiagnosed in a high proportion of affected subjects and is an additional argument for mass-screening using other approaches. It was also demonstarted that Marsh I subjects detected by t-TGA evaluation in a non-at-risk group for CD, were as symptomathic as Marsh III patients and also responded to GFD, reinforcing the final diagnosis of GSE in mild enteropathy. GSE in the general population is frequent and is clinically relevant, irrespective of the severity of the histological lesions. Mass screening programs are useful to identify these patients in order to initiate either a GFD or close follow-up monitoring. t-TG antibody is more sensitive than EmA for the diagnosis of the whole spectrum of GSE in the general population. The authors of the paper work in a tertiary hospital and individuals were recruited from an Occupational Health Department.

Intensive insulin therapy risks

Intensive insulin therapy significantly increases the risk of hypoglycemia in critically ill patients, found a new study in CMAJ (http://www.cmaj.ca/press/cmaj.090206.pdf). Intensive insulin therapy is used in many intensive care units around the world as a means to tightly regulate blood sugar. Although labour intensive, it has been recommended as a standard of care for critically ill patients by many organizations including the American Diabetes Association and the American Association of Clinical Endocrinologists. A randomized trial in 2001 reported that intensive insulin therapy significantly reduced hospital mortality, although subsequent trials have reported inconsistent effects on mortality and higher rates of severe hypoglycemia. The CMAJ study includes data from 26 trials, including the NICE-SUGAR Study on intensive insulin therapy, an international, multicentre randomized trial that is the largest intensive insulin therapy trial to date. The NICE-SUGAR study is published online in the New England Journal of Medicine March 24, 2009 and March 26 for the print edition. "By including the largest trial on intensive insulin therapy published to date, we provide the most current and precise estimate of the effect of intensive insulin therapy on vital status and hypoglycemia in the ICU setting," write Dr. Donald Griesdale, anesthesiologist and critical care physician at Vancouver General Hospital and clinical instructor at the University of British Columbia, and coauthors.
The CMAJ study looked at 26 trials involving 13 567 patients. There was a 6-fold increased risk of hypoglycemia compared to the control treatment. The study was conducted by researchers from the University of British Columbia and Vancouver General Hospital, Vancouver, BC; Harvard School of Public Health, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Boston, Mass; Queen's University and Kingston General Hospital, Kingston, Ontario; McMaster University, Hamilton, Ontario; Royal North Shore Hospital and the University of Sydney, Australia.

Mayo researchers find link between anesthesia exposure and learning disabilities in children

Mayo Clinic researchers have found that children who require multiple surgeries under anesthesia during their first three years of life are at higher risk of developing learning disabilities later. Several studies have suggested that anesthetic drugs may cause abnormalities in the brains of young animals. This is the first study in humans to suggest that exposure of children to anesthesia may have similar consequences. The finding is reported in the current issue of the journal Anesthesiology. Using data from the long-term Rochester Epidemiology Project, researchers studied the medical records of 5,357 children from Olmsted County who were born between 1976 and 1982. The research team, led by Robert Wilder, M.D., Ph.D., a Mayo Clinic anesthesiologist, found that although one exposure to anesthesia was not harmful, more than one almost doubled the risk that a child would be identified as having a learning disability before age 19. The risk also increased with longer durations of anesthesia. "It's very important for parents and families to understand that although we see a clear difference in the frequency of learning disabilities in children exposed to anesthesia, we don't know whether these differences are actually caused by anesthesia," says Randall Flick, M.D., a Mayo Clinic anesthesiologist and co-author of the study. "The problem is that anyone who underwent an anesthetic also had surgery," says Dr. Wilder. "It's unclear whether it's the anesthetic, the physiological stress of surgery or perhaps the medical problems that made surgery necessary that are responsible for the learning disabilities." Young children's brains are more vulnerable to a variety of problems because they are undergoing dynamic growth. The brain is rapidly forming connections between cells and trimming excess cells and connections, says Dr. Wilder. The general anesthesia chemicals in use during the study period were primarily halothane and nitrous oxide (laughing gas). Although halothane is no longer used in the U.S., it has been replaced by newer agents that have similar effects on the brain. Nitrous oxide is widely used throughout the U.S. and the world.

Caltech researchers find tiny genetic change keeps nicotine from binding to muscle cells

A tiny genetic mutation is the key to understanding why nicotine--which binds to brain receptors with such addictive potency--is virtually powerless in muscle cells that are studded with the same type of receptor. That's according to California Institute of Technology (Caltech) researchers, who report their findings in the March 26 issue of the journal Nature. By all rights, nicotine ought to paralyze or even kill us, explains Dennis Dougherty, the George Grant Hoag Professor of Chemistry at Caltech and one of the leaders of the research team. After all, the receptor it binds to in the brain's neurons--a type of acetylcholine receptor, which also binds the neurotransmitter acetylcholine--is found in large numbers in muscle cells. Were nicotine to bind with those cells, it would cause muscles to contract with such force that the response would likely prove lethal. Obviously, considering the data on smoking, that is not what happens. The question has long been: Why not? "It's a chemical mystery," Dougherty admits. "We knew something subtle had to be going on here, but we didn't know exactly what." That subtlety, it turns out, lies in the slight tweaking of the structure of the acetylcholine receptor in muscle cells versus its structure in brain cells. The shape of the acetylcholine receptor, and the way the chemicals that bind with it contort themselves to fit into that receptor, is determined by a number of different weak chemical interactions. Perhaps most important is an interaction that Dougherty calls "underappreciated"--the cation-? interaction, in which a positively charged ion and an electron-rich ? system come together. Back in the late 1990s, Dougherty and colleagues had shown that the cation-? interaction is indeed a key part of acetylcholine's ability to bind to the acetylcholine receptors in muscles. "We assumed that nicotine's charge would cause it to do the same thing, to have the same sort of strong interaction that acetylcholine has," says Dougherty. "But we found that it didn't." This would explain why smoking doesn't paralyze us; if the nicotine can't get into the muscle's acetylcholine receptors, it can't cause the muscles to contract.

Columbia researchers identify early brain marker for familial form of depression

Findings from one of the largest-ever imaging studies of depression indicate that a structural difference in the brain – a thinning of the right hemisphere – appears to be linked to a higher risk for depression, according to new research at Columbia University Medical Center and the New York State Psychiatric Institute. The research was led by Myrna Weissman, Ph.D., professor of epidemiology in psychiatry, Columbia University College of Physicians and Surgeons, and director of the Division of Epidemiology at the New York State Psychiatric Institute, and co-senior author of the study, and Bradley Peterson, M.D., director of Child & Adolescent Psychiatry and director of MRI Research in the Department of Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute, and first author of the study. Published in the upcoming early online edition of the Proceedings of the National Academy of Sciences (PNAS), the researchers found that people at high risk of developing depression had a 28 percent thinning of the right cortex, the brain's outermost surface, compared to people with no known risk. The drastic reduction surprised researchers, which they say is on par with the loss of brain matter typically observed in persons with Alzheimer's disease and schizophrenia. "The difference was so great that at first we almost didn't believe it. But we checked and re-checked all of our data, and we looked for all possible alternative explanations, and still the difference was there," said Dr. Peterson. Dr. Peterson says the thinner cortex may increase the risk of developing depression by disrupting a person's ability to pay attention to, and interpret, social and emotional cues from other people. Additional tests measured each person's level of inattention to and memory for such cues. The less brain material a person had in the right cortex, the worse they performed on the attention and memory tests. The study compared the thickness of the cortex by imaging the brains of 131 subjects, aged 6 to 54 years-old, with and without a family history of depression. Structural differences were observed in the biological offspring of depressed subjects but were not found in the biological offspring of those who were not depressed. One of the goals of the study was to determine whether structural abnormalities in the brain predispose people to depression or are a cause of the illness. Dr. Peterson said, "Because previous biological studies only focused on a relatively small number of individuals who already suffered from depression, their findings were unable to tease out whether those differences represented the causes of depressive illness, or a consequence." The study found that thinning on the right side of brain did not correlate with actual depression, only an increased risk for the illness. It was subjects who exhibited an additional reduction in brain matter on the left side, who went on to develop depression or anxiety. "Our findings suggest rather strongly that if you have thinning in the right hemisphere of the brain, you may be predisposed to depression and may also have some cognitive and inattention issues. The more thinning you have, the greater the cognitive problems. If you have additional thinning in the same region of the left hemisphere, that seems to tip you over from having a vulnerability to developing symptoms of an overt illness," said Dr. Peterson.