VIT D DEFICIENCY HYPERTENSION LINKED

New genetic research provides compelling evidence that low levels of vitamin D have a causal role in the development of high blood pressure (hypertension). The findings, published in The Lancet Diabetes & Endocrinology, suggest that vitamin D supplementation could be effective in combating some cases of hypertension.

"In view of the costs and side effects associated with antihypertensive drugs, the potential to prevent or reduce blood pressure and therefore the risk of hypertension with vitamin D is very attractive," explains study leader Professor Elina Hyppönen from the University of South Australia.*

There has been considerable interest in the role of vitamin D in hypertension, but until now, a direct causal link has not been shown. Results from observational studies have suggested a strong association between low vitamin D levels and increases in blood pressure and hypertension, but randomised trials have not provided consistent evidence.

This Mendelian randomisation study used genetic data from the D-CarDia collaboration, involving over 146 500 individuals of European ancestry from across Europe and North America.

Researchers used two common genetic variants that affect circulating 25-hydroxyvitamin D or 25(OH)D concentrations (which are generally used to determine a person's vitamin D status), to measure the causal effect between vitamin D status and blood pressure and hypertension risk. They found that for each 10% increase in 25(OH)D concentration there was a drop in diastolic blood pressure (-0.29 mm Hg) and systolic blood pressure (-0.37 mm Hg), and an 8.1% decrease in the odds of developing hypertension.

According to Professor Hyppönen, "Mendelian randomisation helps to determine cause and effect because by using genetic data we can better avoid confounding, reverse causation, and bias. However, because we cannot exclude the possibility that our findings were caused by chance, they need to be replicated in an independent, similarly powered study. Further studies using randomised controlled trials are also needed to confirm causality and the potential clinical benefits of vitamin D supplementation."

Writing in a linked Comment, Dr Shoaib Afzal and Dr Børge Nordestgaard from Copenhagen University Hospital and the University of Copenhagen in Denmark say, "Although [this] study is an important step towards delineation of the role of low vitamin D concentrations in the pathogenesis of hypertension, much remains unknown. Confirmation of these results in independent, similarly powered studies will be necessary, as will evidence of a corresponding benefit for the prevention of diseases caused by hypertension such as stroke. Finally, randomised intervention trials will be needed to determine whether vitamin D supplementation can be used to prevent or treat hypertension before such a strategy can be used clinically."

New Gene Linked To Neuropathy

Today's post from newswise.com (see link below) talks about the discovery of a new gene that controls the branching of nerve fibres and enables us to better study the effects of a 'short circuit' in those so-called dendrites. Much of the article may go over most people's heads (it's pretty complex scientific terminology) but knowing what researchers are up to and aiming for, helps us better to understand why we're having so many problems and how they are working towards finding solutions.

Previously Unstudied Gene Is Essential for Normal Nerve Development
Released: 10/3/2013 10:00 AM EDT
Embargo expired: 10/10/2013 12:00 PM EDT
Source Newsroom: Albert Einstein College of Medicine of Yeshiva University
more news from this source Contact Information

Available for logged-in reporters only Citations Cell
Newswise — October 10, 2013 – (BRONX, NY) – Our ability to detect heat, touch, tickling and other sensations depends on our sensory nerves. Now, for the first time, researchers at Albert Einstein College of Medicine of Yeshiva University have identified a gene that orchestrates the crucially important branching of nerve fibers that occurs during development. The findings were published online today in the journal Cell.

The research focuses on dendrites, the string-like extensions of sensory nerves that penetrate tissues of the skin, eyes and other sensory organs. “The formation of dendritic branches—‘arbors’ as we call them—is vital for allowing sensory nerves to collect information and sample the environment appropriately,” said Hannes Buelow,Ph.D., senior author of the Cell paper and associate professor of genetics at Einstein. “These arbors vary greatly in shape and complexity, reflecting the different types of sensory input they receive. The loss of dendritic complexity has been linked to a range of neurological problems including Alzheimer’s disease, schizophrenia and autism spectrum disorders.” Dr. Buelow is also associate professor in the Dominick P. Purpura Department of Neuroscience.

The Human Genome Project, completed in 2003, revealed that humans possess some 20,500 genes and determined the DNA sequence of each. But for many of those genes, their function in the body has remained unknown. The newly identified gene falls into this “previously unknown function” category. In fact, the gene belongs to an entire class of genes that had no known function in any organism.

One way to learn what genes do is to study a model organism like the roundworm, which possesses a similar number of genes as people but only 956 cells, of which 302 are nerve cells (neurons). By knocking out or mutating roundworm genes and observing the effects, researchers can obtain insight into how genes influence the animal’s structure or physiology.

The Einstein scientists were looking for genes that organize the structure of the developing nervous system. They focused on a pair of roundworm sensory neurons, known as PVD neurons, which together produce the largest web of dendrites of any neurons in the roundworm—a sensory web that covers almost the entire skin surface of the worm and detects pain and extreme temperatures.

Suspecting that a gene acts in the skin to “instruct” nearby dendrites to branch, the researchers set out to identify the one responsible. To find it, they induced random mutations in the worms, singled out those worms displaying defects in PVD dendrite branching, and then identified the gene mutations that caused the defective branching.

This lengthy procedure, known as a genetic screen, was carried out by Yehuda Salzberg, Ph.D., the study’s lead author and a postdoctoral fellow in Dr. Buelow’s lab. The screen revealed that four mutations in the same gene caused defective branching of PVD dendrites. The researchers showed that this gene’s expression in the skin produces an extracellular protein that triggers normal branching of PVD dendrites during development. The dendritic branches of PVD neurons had previously been described as resembling menorahs, so the Einstein scientists named this gene mnr-1 and dubbed its protein menorin, or MNR-1.

The mnr-1 gene’s newly identified function in orchestrating dendrite branching is presumably not limited to roundworms. Versions of this gene are present in multicellular animals from the simplest to the most complex, including humans. Genes conserved in this way, through millions of years of evolution, tend to be genes that are absolutely necessary for maintaining life.

Further study revealed that menorin synthesized in the skin was necessary but not sufficient to prompt PVD dendrite branching. The menorin protein appears to form a complex with SAX-7/L1CAM, a well-known cell-adhesion protein found in the skin and elsewhere in the roundworm. The researchers found evidence that dendrite branching ensues when this two-protein complex is sensed by DMA-1, a receptor molecule found on growing sensory dendrites.

“A fair amount was already known about factors within sensory neurons that regulate dendrite branching,” said Dr. Buelow. “But until now, we knew next to nothing about external cues that pattern the sensory dendrites crucial to the functioning of any of our five senses. Hopefully, our success in finding two skin-derived cues that orchestrate dendrite branching will help in identifying cues involved in other sensory organs and possibly in the brain. Finding such cues could conceivably lead to therapies for replacing dendrite arbors depleted by injury or disease.”

The paper is titled “Skin-derived cues control arborization of sensory dendrites in Caenorhabditis elegans.” Other Einstein scientists involved in the research were Zaven Kaprielian, Ph.D., and graduate students Carlos A. Díaz-Balzac, Nelson Ramirez, Matthew Attreed, Eillen Tecle, and Muriel Desbois.

The work was funded in part by grants from the National Institute of General Medical Sciences (T32GM007288, T32GM007491), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD055380, P30HD071593, F31HD066967), the National Cancer Institute (P30CA013330) and the National Institute of Neurological Disorders and Stroke (F31 NS076243), all parts of the National Institutes of Health.

The authors report no conflicts of interest.

About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2012-2013 academic year, Einstein is home to 742 M.D. students, 245 Ph.D. students, 116 students in the combined M.D./Ph.D. program, and 360 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2012, Einstein received over $160 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center –Einstein’s founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube.

http://www.newswise.com/articles/view/608492/?sc=c145&utm_source=twitterfeed&utm_medium=twitter

ESTIMATED I 65 MILLION GLOBAL CARDIOVASCULAR DEATHS EACH LINKED TO HIGH SODIUM CONSUMPTION

More than 1.6 million cardiovascular-related deaths per year can be attributed to sodium consumption above the World Health Organization's recommendation of 2.0g (2,000mg) per day, researchers have found in a new analysis evaluating populations across 187 countries. The findings were published in the August 14 issue of The New England Journal of Medicine

"High sodium intake is known to increase blood pressure, a major risk factor for cardiovascular diseases including heart disease and stroke," said first and corresponding author Dariush Mozaffarian, M.D., Dr.P.H., dean of the Friedman School of Nutrition Science and Policy at Tufts University, who led the research while at the Harvard School of Public Health. "However, the effects of excess sodium intake on cardiovascular diseases globally by age, sex, and nation had not been well established."

The researchers collected and analyzed existing data from 205 surveys of sodium intake in countries representing nearly three-quarters of the world's adult population, in combination with other global nutrition data, to calculate sodium intakes worldwide by country, age, and sex. Effects of sodium on blood pressure and of blood pressure on cardiovascular diseases were determined separately in new pooled meta-analyses, including differences by age and race. These findings were combined with current rates of cardiovascular diseases around the world to estimate the numbers of cardiovascular deaths attributable to sodium consumption above 2.0g per day.

The researchers found the average level of global sodium consumption in 2010 to be 3.95g per day, nearly double the 2.0g recommended by the World Health Organization. All regions of the world were above recommended levels, with regional averages ranging from 2.18g per day in sub-Saharan Africa to 5.51g per day in Central Asia. In their meta-analysis of controlled intervention studies, the researchers found that reduced sodium intake lowered blood pressure in all adults, with the largest effects identified among older individuals, blacks, and those with pre-existing high blood pressure.

"These 1.65 million deaths represent nearly one in 10 of all deaths from cardiovascular causes worldwide. No world region and few countries were spared," added Mozaffarian, who chairs the Global Burden of Diseases, Nutrition, and Chronic Disease Expert Group, an international team of more than 100 scientists studying the effects of nutrition on health and who contributed to this effort. "These new findings inform the need for strong policies to reduce dietary sodium in the United States and across the world."

In the United States, average daily sodium intake was 3.6g, 80 percent higher than the amount recommended by the World Health Organization. [The federal government's Dietary Guidelines for Americans recommend limiting intake of sodium to no more than 2,300mg (2.3g) per day.] The researchers found that nearly 58,000 cardiovascular deaths each year in the United States could be attributed to daily sodium consumption greater than 2.0g. Sodium intake and corresponding health burdens were even higher in many developing countries.

"We found that four out of five global deaths attributable to higher than recommended sodium intakes occurred in middle- and low-income countries," added John Powles, M.B., B.S., last author and honorary senior visiting fellow in the department of public health and primary care at the University of Cambridge. "Programs to reduce sodium intake could provide a practical and cost effective means for reducing premature deaths in adults around the world."

The authors acknowledge that their results utilize estimates based on urine samples, which may underestimate true sodium intakes. Additionally, some countries lacked data on sodium consumption, which was estimated based on other nutritional information; and, because the study focuses on cardiovascular deaths, the findings may not reflect the full health impact of sodium intake, which is also linked to higher risk of nonfatal cardiovascular diseases, kidney disease and stomach cancer, the second most-deadly cancer worldwide.