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Obstructive sleep apnea is associated with an increased risk of stroke in middle-aged and older adults, especially men, according to new results from a landmark study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Overall, sleep apnea more than doubles the risk of stroke in men. Obstructive sleep apnea is a common disorder in which the upper airway is intermittently narrowed or blocked, disrupting sleep and breathing during sleep.

Researchers from the Sleep Heart Health Study (SHHS) report that the risk of stroke appears in men with mild sleep apnea and rises with the severity of sleep apnea. Men with moderate to severe sleep apnea were nearly three times more likely to have a stroke than men without sleep apnea or with mild sleep apnea. The risk from sleep apnea is independent of other risk factors such as weight, high blood pressure, race, smoking, and diabetes.

They also report for the first time a link between sleep apnea and increased risk of stroke in women. Obstructive Sleep Apnea Hypopnea and Incident Stroke: The Sleep Heart Health Study, was published online March 25 ahead of print in the American Journal of Respiratory and Critical Care Medicine.

Stroke is the second leading cause of death worldwide. “Although scientists have uncovered several risk factors for stroke — such as age, high blood pressure and atrial fibrillation, and diabetes — there are still many cases in which the cause or contributing factors are unknown, ” noted NHLBI Acting Director Susan B. Shurin, M.D. “This is the largest study to date to link sleep apnea with an increased risk of stroke. The time is right for researchers to study whether treating sleep apnea could prevent or delay stroke in some individuals. ”

Conducted in nine medical centers across the United States, the SHHS is the largest and most comprehensive prospective, multi-center study on the risk of cardiovascular disease and other conditions related to sleep apnea. In the latest report, researchers studied stroke risk in 5,422 participants aged 40 years and older without a history of stroke. At the start of the study, participants performed a standard at-home sleep test, which determined whether they had sleep apnea and, if so, the severity of the sleep apnea.

Researchers followed the participants for an average of about nine years. They report that during the study, 193 participants had a stroke — 85 men (of 2,462 men enrolled) and 108 women (out of 2,960 enrolled).

After adjusting for several cardiovascular risk factors, the researchers found that the effect of sleep apnea on stroke risk was stronger in men than in women. In men, a progressive increase in stroke risk was observed as sleep apnea severity increased from mild levels to moderate to severe levels. In women, however, the increased risk of stroke was significant only with severe levels of sleep apnea.

The researchers suggest that the differences between men and women might be because men are more likely to develop sleep apnea at younger ages. Therefore, they tend to have untreated sleep apnea for longer periods of time than women. “It’s possible that the stroke risk is related to cumulative effects of sleep apnea adversely influencing health over many years, ” said Susan Redline, M.D., MPH, professor of medicine, pediatrics, and epidemiology and biostatistics, at Case Western Reserve University in Cleveland and lead author of the paper.

“Our findings provide compelling evidence that obstructive sleep apnea is a risk factor for stroke, especially in men, ” noted Redline. “Overall, the increased risk of stroke in men with sleep apnea is comparable to adding 10 years to a man’s age. Importantly, we found that increased stroke risk in men occurs even with relatively mild levels of sleep apnea. ”

“Research on the effects of sleep apnea not only increases our understanding of how lapses of breathing during sleep affects our health and well being, but it can also provide important insight into how cardiovascular problems such as stroke and high blood pressure develop,” noted Michael J. Twery, Ph.D., director of the NIH National Center on Sleep Disorders Research, an office administered by the NHLBI.

The new results support earlier findings that have linked sleep apnea to stroke risk. SHHS researchers have also reported that untreated sleep apnea is associated with an increased risk of high blood pressure, heart attack, irregular heartbeats, heart failure, and death from any cause. Other studies have also linked untreated sleep apnea with overweight and obesity and diabetes. It is also linked to excessive daytime sleepiness, which lowers performance in the workplace and at school, and increases the risk of injuries and death from drowsy driving and other accidents.

More than 12 million American adults are believed to have sleep apnea, and most are not diagnosed or treated. Treatments to restore regular breathing during sleep include mouthpieces, surgery, and breathing devices, such as continuous positive airway pressure, or CPAP. In people who are overweight or obese, weight loss can also help.

These treatments can help improve breathing and reduce the severity of symptoms such as loud snoring and excessive daytime sleepiness, thereby improving sleep-related quality of life and performance at work or in school. Randomized clinical trials to test whether treating sleep apnea lowers the risk of stroke, other cardiovascular diseases, or death are needed.

“We now have abundant evidence that sleep apnea is associated with cardiovascular risk factors and diseases. The next logical step is to determine if treating sleep apnea can lower a person’s risk of these leading killers, ” said Redline. “With stimulus funds, our research group is now developing the additional research and resources to begin answering this important question. ”

Through funding from the American Recovery and Reinvestment Act, the NHLBI is awarding approximately $4.4 million to Redline to conduct the first NIH-funded comparative effectiveness study of treatments for sleep apnea. In the two-year multi-center pilot study, SHHS researchers and others will compare the cardiovascular effects of adding either CPAP or supplemental oxygen during sleep to standard care in patients with moderate to severe sleep apnea who are at high risk for cardiovascular disease events such as heart attack or stroke.

The SHHS draws on a resource of existing, well-characterized and established cohort studies of cardiovascular and lung diseases supported by the NHLBI. A cohort is a well-defined group of participants who share a common background or characteristic and are being followed for an extended length of time. For this study, SHHS researchers add assessment of sleep to data collection in ongoing studies including the Atherosclerosis Risk in Communities (ARIC) Study sites in Washington County, Md., and Minneapolis; the Cardiovascular Health Study (CHS) sites in Sacramento, Calif., Washington County, Md., and Pittsburgh; the Framingham Offspring and Omni cohorts in Framingham, Mass.; the Health and Environment and Tucson Epidemiologic Study cohorts in Tucson, Ariz.; the Strong Heart Study sites in Arizona, Oklahoma, and South Dakota; a Reading Center at Case Western Reserve University in Cleveland, Ohio; and the University of Washington in Seattle (Coordinating Center 1994-1999). The Johns Hopkins University Bloomberg School of Public Health serves as the Coordinating Center.

Canadian researchers have successfully reversed type 1 diabetes in mice using a new vaccine technology that appears to solely target the immune system cells responsible for the disease.

“The body has built-in mechanisms that try to counter disease progression, and we now have a mechanism that can be [used] to selectively blunt an immune response without causing a systemic response,” said the study’s senior author, Dr. Pere Santamaria, a professor at the Julia McFarlane Diabetes Research Centre at the University of Calgary in Alberta.

What’s more, Santamaria said, the technique developed for the diabetes vaccine may be applicable to other autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis.

So far, the research has only been conducted in mice. “We don’t yet know if it will work in humans, but we’re very excited and think this offers hope,” said Santamaria.

Type 1 diabetes is an autoimmune disease. That means that the body’s immune system, which usually targets invading unwanted cells, such as bacteria, mistakenly destroys healthy cells. In the case of type 1 diabetes, the immune system destroys the insulin-producing beta cells in the pancreas. This knocks out the body’s ability to produce insulin, the hormone that helps convert blood sugar to energy for cells in the body. So, people with type 1 diabetes must inject insulin multiple times a day, every day, to stay alive.

“Autoimmune diseases, like type 1 diabetes, multiple sclerosis and rheumatoid arthritis, are caused by an overactive immune system. Normally, the immune system helps us fend off cancer and infection, but in some people, it becomes overaggressive,” Santamaria explained.

Although there are medications available that can dampen the entire immune response, these medications can create additional problems, such as an increased risk of cancer and serious infection.

However, the Canadian researchers discovered that the body doesn’t just allow the autoimmune aggression to go unchecked. There is a counter-mechanism that produces immune system cells to try to fight the rogue immune cells that are creating the damage in type 1 diabetes.

But these cells — know as memory-like autoregulatory T cells — aren’t as strong as the rogue cells and so they quickly become overwhelmed.

Using a “nanotechnology-based” vaccine, the researchers were able to boost the effects of the weaker immune cells, which allowed them to stop the damaging immune cells from attacking. The vaccine consists of nanoparticles — spheres thousands of times smaller than a single cell of the body — “coated” with antigens that bind to molecules used to stimulate certain T cells.

“With this nanovaccine, we engage the weak immune cells and make them multiply and divide, and then they can counter the autoimmune response without impairing systemic immunity,” said Santamaria.

Instead of directly attacking the stronger cells, the autoregulatory T cells turn off the signal that tells the stronger immune cells to attack, effectively stopping the destruction of the beta cells.

Santamaria said it’s not clear yet if this vaccine would be a one-time treatment, or would need to be administered periodically. He said it’s likely additional treatment might be necessary.

Santamaria said the next step in his work is to produce the drug in a version that can be used in clinical trials on humans.

Teodora Staeva, director of Immune Therapies for the Juvenile Diabetes Research Foundation International, called the new research “a very novel therapeutic approach that seems to have great potential.”

“A lot of work remains to be done. This therapy has the promise of being safer — although that has to be proven in toxicology studies — because it specifically targets the cells that are causing the problems,” Staeva said.

Staeva said that if this vaccine proves itself in human studies, it has the potential to help both newly diagnosed type 1 diabetics and those who’ve had the disease for years. But, she said, in people who’ve had type 1 for a long time, beta cell transplantation might be necessary.

Results of the study were published online April 8 and are to appear in the April 23 print version of the journal Immunity.

The U.S. Environmental Protection Agency is requiring new restrictions on aluminum and magnesium phosphide products to better protect people, especially children, from dangerous exposures. The new restrictions prohibit all uses of the products around residential areas, increase buffer zones for treatment around non-residential buildings that could be occupied by people or animals, and create more protective product labeling. These actions are part of Administrator Lisa P. Jackson’s comprehensive effort to strengthen the agency’s chemical management program and assure the safety of chemicals.

“Phosphine fumigants are poisons and must be kept away from where our children live,” said Steve Owens, assistant administrator of EPA’s Office of Prevention, Pesticides and Toxic Substances. “These new safeguards prohibit the use of these toxic pesticides near homes and impose restrictions to protect our families from exposure to them.”

Aluminum and magnesium phosphide fumigants are used primarily to control insects in stored grain and other agricultural commodities. They also are used to control burrowing rodents in outdoor agricultural and other non-domestic areas. The fumigants are restricted to use by specially trained pesticide applicators and in only narrow circumstances.

EPA is expediting approval of the new labels to reduce the potential for accidental poisonings. The primary manufacturer is voluntarily implementing the changes. EPA will apply these changes to all aluminum and magnesium phosphide products.

More information about aluminum and magnesium phosphide: http://www.epa.gov/oppsrrd1/reregistration/alphosphide/.