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Mar 30
Bad News For Insomniacs: 'Hunger Hormones' Affected By Poor Sleep
Insomnia has long been associated with poor health, including weight gain and even obesity. Now researchers at UCLA have found out why.

In a study to be published in the May issue of the journal Psychoneuroendocrinology and currently available online by subscription, Sarosh Motivala, an assistant professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, and colleagues looked at two hormones that are primarily responsible for regulating the body's energy balance, telling the body when it is hungry and when it is full. The study found that chronic insomnia disrupts one of these two hormones.

To date, no study has evaluated nocturnal levels of the two hormones, ghrelin and leptin, in primary insomnia patients. Ghrelin, a peptide secreted by the stomach, stimulates appetite and increases before meals. Leptin, which affects body weight and is secreted primarily by fat cells, signals the hypothalamus regarding the degree of fat storage in the body; decreased leptin tells the body there is a calorie shortage and promotes hunger, while increased levels promote energy expenditure.

In the study, researchers compared healthy sleepers with those suffering from chronic insomnia and measured the levels of the two hormones at various times throughout the night. They found that while leptin levels averaged out over the night to be roughly the same between the two groups, levels of ghrelin were 30 percent lower in insomnia sufferers.

On the face of it, a decreased level of ghrelin would seem to inhibit weight gain; it is an increase in ghrelin, after all, that stimulates appetite. But Motivala compared his findings with other, earlier studies on sleep deprivation and speculates that a switch may occur during the day: Sleep loss leads to increased ghrelin and decreased leptin, a "double whammy" that stimulates appetite. Motivala is currently working on a study to examine this switch.

"The current study shows that insomnia patients have a dysregulation in energy balance that could explain why these patients gain weight over time," said Motivala, who is also a member of the Cousins Center for Psychoneuroimmunology at UCLA. "This is an exciting finding because it highlights how diverse behaviors like sleep and eating are connected. We are just beginning to explore the possible consequences of these connections, but it is another example of the importance of a good night's sleep for the body."

For the study, 38 male participants were divided into two groups 14 insomnia sufferers and 24 healthy subjects. Both groups had similar ages and body weight. Both groups underwent polysomnography sleep studies that monitor brain waves. Circulating levels of ghrelin and leptin were measured at 11 p.m., 2 a.m. and 6 a.m. Ghrelin levels across the night were significantly lower in insomnia patients, while leptin were not significantly different between the two groups.

Mar 30
High Prevalence Of Infection With Three Recently Discovered Human Polyomaviruses
A majority of the human population has been exposed to newly discovered KI (KIV), WU (WUV), and Merkel cell (MCV) human polyomaviruses, according to a new study by researchers at the University of Colorado. Published March 27 in the open-access journal PLoS Pathogens, the results, based on antibody measurements in serum samples, also suggest that infection with these viruses occurs early in childhood.

For over 30 years, scientists have known about two human polyomaviruses, BKV and JCV. Within the past two years, however, three new viruses have been described that belong to this same virus family. KIV and WUV were detected in nasal secretions, and may be respiratory viruses. MCV was discovered in Merkel Cell carcinomas, a rare skin cancer. Further studies are needed to determine what fraction of the human population has been infected with these viruses and when initial exposure occurs.

In this study, Kean and colleagues tested over 2220 anonymous donor blood samples (more than1500 adult and more than 700 pediatric [< 21 years of age]) They measured antibodies that reacted with specific viral proteins. In addition to KIV, WUV, MCV, BKV, and JCV, two monkey polyomaviruses, SV40 and lymphotropic polyomavirus (LPV), were also studied. Antibodies to LPV were detected in a fraction of people (15%), confirming previous studies suggesting that a relative of this virus may infect humans. The majority of antibodies against SV40 proteins may be attributed to the immune response to BKV. The diseases caused by these viruses remain to be fully described.

The samples and results reported are likely representative of infection in the Denver metropolitan area where they were collected. Future studies will be important to help determine differences in the prevalence of these infections in other geographic areas.

Mar 30
Stopping Autoimmunity Before It Strikes
Current research describes a new method to track the development of autoimmune diseases before the onset of symptoms. The related report by Zangani et al, "Tracking early autoimmune disease by bioluminescent imaging of NF-κB activation reveals pathology in multiple organ systems," appears in the April 2009 issue of The American Journal of Pathology.

Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and diabetes are caused when the immune system attacks the body's own cells. Normally, immune cells are prevented from attacking normal cells; however, in patients with autoimmune disease, this "tolerance" is lost. The immediate causes of autoimmune diseases remain unknown, partially due to the inability to detect disease before the onset of symptoms. Early detection of autoimmune disease is critical for assessing new treatments.

The molecule NF-κB is activated by inflammation, which plays a key role in autoimmune disease development, making NF-κB a prime candidate to track autoimmune activity. Researchers at the University of Oslo led by Drs. Ludvig Munthe and Bjarne Bogen in collaboration with Rune Blomhoff engineered NF-κB such that it would emit light when activated. Using a mouse model of systemic autoimmunity with features of lupus, they found that NF-κB activation signals were present in affected organs several weeks before the clinical manifestations of disease. The light signal intensity correlated with disease progression. NF-κB tracking may therefore provide a new tool in the evaluation of early autoimmune therapies.

Mar 30
Possible Adverse Environmental Effects Caused By Nanoparticles In Cosmetics/Personal Care Products
Using aquatic microbes as their "canary-in-a-cage," scientists from Ohio have reported that nanoparticles now being added to cosmetics, sunscreens, and hundreds of other personal care products may be harmful to the environment.

Their report was part of symposia that included almost two dozen papers at the 237th National Meeting of the American Chemical Society where scientists grappled to understand the environmental and human health effects of nanotechnology. Hundreds of products utilizing these microscopic particles - 1/5,000th the diameter of a human hair - already are on the market. With many more poised for debut, scientists are seeking to avoid unwanted health and environmental effects in advance.

The study by Cyndee Gruden, Ph.D. and Olga Mileyeva-Biebesheimer focused on nano-titanium dioxide (nano-TiO2) particles found in cosmetics, sunscreens, and other personal care products. The particles are added to those products for their highly beneficial effects in blocking ultraviolet light in sunlight. Excess exposure can cause premature aging of the skin and skin cancer.

Gruden, who is with the University of Toledo, explained that the particles are washed down the drain in homes as people bathe and end up in municipal sewage treatment plants. From there, they can enter lakes, rivers, and other water sources where microorganisms serve essential roles in maintaining a healthy environment.

"When they enter a lake, what happens?" Gruden asked. "Would they enter an organism or bind to it? Maybe they kill it - or have nothing to do with it at all. These are important questions for determining the effects that nanoparticles may have on the environment. Right now, we're not really sure of the answers."

Gruden studied survival of Escherichia coli (E. coli) bacteria when exposed in laboratory cultures to various amounts of nano-TiO2. She found surprisingly large reductions in survival in samples exposed to small concentrations of the nanoparticles for less than an hour. "How fast the impact was surprised me," she said. The findings open the door to future research, including studies to determine whether the same effects occur in the natural environment.

Gruden's method for pinpointing damage from nanoparticles uses fluorescence to identify when the cell membrane in microbes undergo damage. When membranes - a crucial part of the microbe - are damaged, the cells emit a faint red glow. "Methods based upon fluorescence allow us to obtain results faster, maybe with greater sensitivity," she said, adding that this approach could speed scientific efforts to understand the threshold at which nanoparticles become toxic to microbes.

In a second study on nanotoxicity at the ACS National Meeting, scientists from Utah described development of a new biosensor that flashes like a beacon upon detecting nanoparticles in the environment.

Anne Anderson and colleagues at Utah State University and the University of Utah have inserted genes into a strain of Pseudomonas putida (P. putida) - a beneficial soil microbe - so that it emits light upon contact with nanoparticles of heavy metals. They are with Utah State University. The bacteria glow brightly when it is in its normal healthy state. The glow dims upon exposure to toxic substances.

"The novelty of the biosensor is we're able to get responses very, very quickly," she said, "and we can get those answers in the absence of other factors that could bind the challenging compounds." Anderson noted that traditional approaches in measuring bacterial cell growth may take two days. "At the snap of your finger you can see some of these things take place."

Anderson's group discovered that P. putida cannot tolerate silver, copper oxide and zinc oxide nanoparticles. Toxicity occurred at levels as low as micrograms per liter. That's equivalent to two or three drops of water in an Olympic-sized swimming pool. Anderson warns it could spell danger for aquatic life. "If you look up the Environmental Protection Agency's risk level of Copper to fish and other aquatic organisms, you are at that point of toxicity."

There's much debate in the science community about nanoparticle toxicity, Anderson said. Some scientists believe that nanoparticles in nature will aggregate together or bind onto silt and/or other organic matter, greatly reducing their toxicity. "We don't know if that's true or not," she said. So other members of this Utah research group currently are investigating that aspect of the issue.

Although the public is ultimately responsible for understanding the risks of consumer products, Gruden said, science plays a large role in highlighting possible hazards. "It is the scientist's job to perform good research and let the findings speak for themselves," she said. And so far the promises of nanotechnology need more evaluation. "To date, it's unclear whether the benefits of nanotech outweigh the risks associated with environmental release and exposure to nanoparticles."

Mar 30
ADA Convenes Major Summit On Improving Access To Dental Care
Nearly 150 stakeholders from non-profit groups, government agencies and private industry met March 23-25 at a summit on access to dental care convened by the American Dental Association (ADA) to create a common vision toward improving the oral health of underserved populations.

"Both the private and public sectors are challenged to meet the needs of an ever-growing number of U.S. residents who cannot regularly access oral health care," said John S. Findley, D.D.S., ADA president. "In many ways, this is a societal issue.

"We are very pleased with the success of the summit, which will serve as a milestone toward our common goal of improving access to dental care. The ADA firmly believes that practical solutions must come from a broad spectrum of stakeholders and then be implemented first among those populations at highest risk for oral disease and with the least ability to access care. We are committed to finding common ground and shared solutions to address the oral health needs of the most vulnerable among us."

Participants included dental special interest groups, federal agencies, health care policymakers, advocacy groups, dental industry, dental education and research communities, financing communities, including third-party payers and philanthropic organizations, safety net providers, non-dental health care providers, ADA leadership, dental volunteer leaders and state dental society executive directors.

The participants shared their knowledge and experience and discussed new and existing approaches to reducing disparities and securing optimal oral health for all. Among the major topics discussed were increasing collaboration between the dental and medical communities; workforce development strategies; strengthening dental delivery systems, the dental public health infrastructure, and population-based prevention strategies; improving oral health literacy through social marketing; and finding better ways to define and measure the access issue.

The organizers' intention is that the summit's success will strengthen existing relationships among dental professionals and other stakeholders and encourage a continuing dialogue.

Mar 30
Gene Variants May Determine Lung Function And Susceptibility To Maternal Smoking
A tiny variation within a single gene can determine not only how quickly and well lungs grow and function in children and adolescents, but how susceptible those children will be to exposure to second-hand tobacco smoke, even in utero, according to researchers from the University of Southern California.

"Many factors can affect lung function and growth, including genetic variation and environmental exposures such as tobacco smoke and air pollutants," said Carrie Breton, Sc.D., lead author of the study conducted at the University of Southern California. "We wanted to determine whether specific gene variations would have measurable and predictable effects on lung function growth and susceptibility to environmental insults. We looked at a class of genes known to be involved in antioxidant defense, the glutathione-s transferase (GST) genes. Overall, we found that variation in several of the GST genes was important. This was particularly true for children of mothers who had smoked during pregnancy."

The researchers analyzed eight years' worth of lung function metrics and genotyping data from more than 2,100 children from two cohorts of fourth-graders. The lung function measurements used were maximal mid expiratory flow rate (MMEF), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).

"FEV1 is a measure of large airways, FVC of total lung volume and MMEF of smaller airways, so they measure slightly different things and we wouldn't necessarily expect to see all outcomes behaving the same," said Dr. Breton.

They found that for three of the specific haplotypes (patterns of genetic variation within genes) they investigated, each had a significant effect on lung function.

For one gene, GSTM2, two variant patterns were analyzed. These patterns occurred in 30-35 percent of the white population. One was found to promote stronger lung function, while the other variant was correlated with poorer lung function and greater susceptibility to damage caused by maternal cigarette smoking during pregnancy. Moreover, the reduction in lung function was greater in children who had two copies of the variant pattern that reduced lung function, compared to children with only one copy.

For a relatively rarer haplotype in GSTM3, occurring in only 6-8 percent of the white population, they found a strong negative effect on MMEF.

Finally, another haplotype in GSTM4, occurring in 16-22% of the population, showed significantly decreased rates of growth for FEV1, FVC and MMEF. Like GSTM2, the reduction in lung function was greatest in children who had two copies of the variant pattern that reduced lung function.

The researchers suggest that the gene variants may not alter the development of the lung, but its ability to defend itself against damage caused by free radicals. "The GST genes are important to the detoxification of reactive oxygen species, including carcinogens and environmental exposures, such as cigarette smoke. We speculate that the patterns of genetic variation we investigated may alter this process, thereby reducing the lung's ability to detoxify harmful agents and causing a cascade of other events that promote inflammation, bronchial constriction, airway hyperresponsiveness and asthma-like symptoms," said Dr. Breton.

"The next step would be to investigate how these genes interact with one another to jointly effect lung development. Future studies should also investigate the timing and quantity of tobacco smoke exposure during pregnancy in combination with variation in these genes to further understand how they jointly affect fetal lung development," said Dr. Breton.

Mar 27
New Measurement Standard For Vitamin D May Lead To Better Bone Health
In a development that could help improve the prevention and treatment of osteoporosis, rickets, and other bone diseases, government chemists are reporting an advance in developing an accurate, reliable set of standards for measuring vitamin D levels in blood. Their findings could affect the health of millions of people worldwide, particularly children, women, and the elderly, who suffer from or are at risk of these debilitating diseases. The study will be presented here at the American Chemical Society's 237th National Meeting.

The advance comes in the midst of a growing awareness that many children and adults are not getting enough vitamin D. New studies also link vitamin D deficiency to a higher risk of diseases ranging from cancer to cognitive impairment in the elderly. Everyone needs ample vitamin D not just to absorb calcium and maintain bone strength but to promote good overall health.

People produce the vitamin naturally when sunlight shines on their skin. Concerns about skin cancer, however, have reduced exposure to sunlight. Likewise, declines in consumption of certain dairy products have reduced intake of another natural source of vitamin D. The vitamin also is available as a dietary supplement.

Despite concerns about adequate vitamin D intake, there is no standard laboratory test for measuring vitamin D levels in humans, and no universal agreement on what are considered "normal" or "optimal" vitamin D levels. To understand vitamin D's role in health and disease, and use that knowledge in everyday medicine, laboratories need better measurement standards, the scientists say.

"No one really knows what methods or assays are correct at this point," says Mary Bedner, Ph.D., an analytical chemist with the National Institute of Standards and Technology (NIST) in Gaithersburg, Md. "Right now, you can send a blood sample to two different labs and get completely different results for vitamin D."

About three years ago, NIST, the Federal Government agency that sets measurement standards, began efforts to develop a standard for measuring vitamin D in collaboration with the National Institutes of Health's (NIH's) Office of Dietary Supplements. Later this year, after much consultation with experts and extensive laboratory testing, NIST scientists plan to unveil their standard to the public in a development that promises to lead to a better understanding of vitamin D in health and disease.

The most commonly used indicator of a person's vitamin D status is the measurement of 25-hydroxyvitamin D in the blood. But several different forms of this vitamin exist in the blood including 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 that are of clinical significance and would be overlooked by scientists focusing on total 25-hydroxyvitamin D alone.

To account for these other forms of vitamin D, NIST developed Standard Reference Material 972 (SRM 972). The material is composed of four different pools of human blood serum obtained from a wide cross-section of blood donors. Each of the four pools contains different amounts of 25-hydroxyvitamin D2 and D3 to represent vitamin D profiles normally seen in a clinical setting. All were carefully measured using a combination of state-of-the-art liquid chromatography and mass spectroscopy highly sensitive analytical chemistry tools.

One pool represents "normal" serum, which contains mostly 25-hydroxyvitamin D3. The second pool, which represents vitamin D deficient individuals, contains about half as much 25-hydroxyvitamin D3 as the "normal" pool. The third represents the blood profile of someone taking vitamin D supplements and contains elevated levels of 25-hydroxyvitamin D2. Finally, the fourth pool contains high levels of 3-epi-25-hydroxyvitamin D3, or the "epi" form of vitamin D, which is typically found in the blood of small children.

By using these four blood samples as reference points, clinical laboratories can calibrate their instruments and measurement techniques to assure more accurate and reliable vitamin D measurements for blood samples so doctors can make the right treatment decisions. As a result, testing based on this standard can more reliably tell patients whether they're getting enough vitamin D and provide information about what forms of vitamin D they need to take to stay healthy, the researchers say.

Mar 27
Super Micro-Surgery Offers New Hope For Breast Cancer Patients With Lymphedema
Breast cancer patients with lymphedema in their upper arm experienced reduced fluid in the swollen arm by up to 39 percent after undergoing a super-microsurgical technique known as lymphaticovenular bypass, report researchers at The University of Texas M. D. Anderson Cancer Center.

The results from the prospective analysis, presented at the 88th Annual Meeting of the American Association of Plastic Surgeons, suggest another option for breast cancer patients considering ways to manage lymphedema, a common and debilitating condition following surgery and/or radiation therapy for breast cancer.

Lymphedema results when the lymph nodes are removed or blocked due to treatment and lymph fluid accumulates causing chronic swelling in the upper arm. Currently, there is no cure or preventive measure for lymphedema and it is difficult to manage; the use of compression bandages, massage and other forms of lymphatic therapy are commonly recommended options for patients. According to the National Cancer Institute, 25 to 30 percent of women who have breast cancer surgery with lymph node removal and radiation therapy develop lymphedema.

Researchers evaluated 20 breast cancer patients with stage II and III treatment-related lymphedema of the upper arm who underwent a lymphaticovenular bypass at M. D. Anderson from December 2005 to September 2008. Due to lymphedema, the patients' affected arm was an average of 34 percent larger compared to the unaffected arm prior to the surgery. Of these 20 patients, 19 reported initial significant clinical improvement following the procedure. In those patients with postoperative volumetric analysis measurements, total mean reduction in the volume differential at one month was 29 percent, at three months 33 percent, at six months 39 percent and 25 percent at one year.

"Patients often resort to lymphatic therapy because other options brought forward to reduce lymphedema haven't proved effective," said lead author on the study David W. Chang, M.D., professor in the Department of Plastic Surgery and Director of the Plastic Surgery Clinic at M. D. Anderson. "Surgical techniques, in particular, have been limited and therefore have been met with skepticism by surgeons, making it extremely important to determine which new techniques promise to bring real benefits to patients."

In lymphaticovenular bypass surgery, surgeons use tiny microsurgical tools to make two to three small incisions measuring an inch or less in the patient's arm. Lymphatic fluid is then redirected to microscopic vessels - approximately 0.3 - 0.8 millimeters in diameter - to promote drainage and alleviate lymphedema. The procedure is minimally invasive and is generally completed in less than four hours under general anesthesia, allowing patients to return home from the hospital within 24 hours. M. D. Anderson is among a few institutions in the United States to offer this technically complex surgery.

"Lymphedema is like a massive traffic jam with no exit," Chang said. "This procedure does a lot to help relieve lymphedema by giving the fluid a way out. While it does not totally eliminate the condition, there is very little downside for the patient and we may see significant improvement in its severity."

Chang notes that while most effective when completed in earlier stages before the affected arm is fibrotic, almost any breast cancer patient suffering from lymphedema stage I, II or III is a candidate. Though breast cancer was the focus of this study, the surgery can also be performed on patients who have lymphedema in the leg resulting from cancers involving pelvic regions.

Cancer treatment is not the only cause of lymphedema. Primary lymphedema can develop from developmental causes at birth, the onset of puberty or in adulthood. Secondary lymphedema can develop as a result of surgery, radiation, infection or trauma. In developing countries, a form of lymphedema caused by a parasite called Filariasis affects as many as 200 million people worldwide. "As we begin to refine our technique and learn more about the efficacy of this surgery, we have the potential to impact a large number of people," Chang said.

Long-term follow-up with patients who have received lymphaticovenular bypass surgery is necessary to determine if the procedure continues to promote drainage after one year. Chang and his team of surgeons at M. D. Anderson believe that the fluid volume will keep decreasing over time and suggest that the surgery could possibly be used as a preventive measure for lymphedema in the future. "Working toward a definitive technique to cure this encumbering side effect of cancer and improve a patient's quality of life as a cancer survivor is a priority for those of us in this field."

Mar 27
Researchers Uncover Mechanism That Regulates Movement Of Blood-Forming Stem Cells In The Body
Researchers at the Keck School of Medicine of the University of Southern California (USC) have identified a signaling pathway that helps regulate the movement of blood-forming stem cells in the body a finding that provides important new insight into how stem cells move around the body and which may lead to improvements in the efficiency of bone marrow transplants.

The study will appear in the journal Nature, and is available online March 25th.

"By identifying the key mechanism by which these stem cells home and engraft to the bone marrow, it may be possible to pharmacologically treat the cells to activate this pathway and thus increase the effectiveness of bone marrow transplants," says lead author Gregor Adams, Ph.D., assistant professor of cell and neurobiology at the Keck School and a researcher at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

Hematopoietic stem cells are blood-forming cells that circulate through the body shifting back and forth between the bloodstream and bone marrow, Adams explains. When patients receive a bone marrow transplant, healthy blood stem cells are injected into their veins. Unless those stem cells can find their way into a specific site known as the stem cell niche, they cannot develop properly to replenish the white cells, red cells and platelets in the patient's blood.

The mechanisms that guide the cells during this migration have not been well understood. However, in this study the researchers found that blood-forming stem cells that lacked a specific signaling molecule, called GalphaS, did not home to or engraft in the bone marrow of adult mice, Adams says.

"Here we show that the GalphaS pathway is a critical intracellular pathway involved in this process," he says. "Currently, large numbers of blood-forming stem cells are required in bone marrow transplantation due to the limited efficiency of the homing process. This study opens up the possibility of treating bone marrow cells with GalphaS pathway activators as a means to increase the effectiveness of bone marrow transplants."

Improving the efficiency with which stem cells colonize the bone marrow following transplantation could have far-reaching implications for disease treatment, says Martin Pera, Ph.D., director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

"For example, such a discovery might enhance the utility of umbilical cord blood, which contains only limited numbers of stem cells, for the treatment of cancer and blood disorders in children and adults," Pera says.

Mar 27
Before Starting Dialysis, Patients Need Nephrologist Care
For patients with end-stage renal disease (ESRD), receiving care from a nephrologist in the months before starting dialysis reduces the risk of death during the first year on dialysis, reports a study in the May 2009 issue of the Journal of the American Society of Nephrology (JASN). The study also shows geographic "clusters" where pre-dialysis care for patients with advanced chronic kidney disease (CKD) is not optimal. "Assistance to improve pre-dialysis care might be profitably targeted to specific treatment centers and the health care systems they serve," comments William McClellan, MD (Emory University School of Medicine, Atlanta, GA).

Dr. McClellan and colleagues analyzed data on more than 30,000 patients starting dialysis in five of the 18 US ESRD Network regions. The researchers evaluated the quality of the patients' medical care in the months before their CKD progressed to ESRD, and how that affected the patients' outcomes on dialysis.

Just over half of the patients received at least six months of pre-dialysis care from a nephrologist, as recommended by current guidelines. For these patients, the chances of surviving the first year on dialysis were about 50 percent higher than for patients who did not receive at least six months of nephrologist care. Survival rates were higher at dialysis centers where more patients received recommended care.

The researchers also unexpectedly discovered that dialysis centers with the lowest rates of recommended pre-dialysis care tended to be "clustered geographically." For example, there was a "significant circular cluster" of low pre-dialysis care centers located in Alabama and Mississippi.

Although the reasons for the geographic variations in care are unclear, the results identify specific regions that might benefit from efforts to improve care for advanced CKD patients. "The Centers for Medicare & Medicaid Services are currently conducting a pilot quality improvement initiative in ten states to determine the feasibility of such efforts," says Dr. McClellan.