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A new study provides tantalizing clues about how exercise helps ward off heart disease and other ills: Fit people have more fat-burning molecules in their blood than less fit people after exercise.

And the very fittest are even more efficient, on a biochemical level, at generating fat-burning molecules that break down and burn up fats and sugars, the study reports.

A better understanding of these fat-burning molecules, called metabolites, may not only boost athletic performance, but help prevent or treat chronic illnesses such as type 2 diabetes and heart disease by correcting metabolite deficiencies, the researchers said.

The study, apparently the first of its kind, takes a look at how regular exercise — that is, fitness — alters metabolism right down to the level of chemical changes in the blood.

“Every metabolic activity in the body results in the product of [fat-burning] metabolites,” said senior study author Dr. Robert Gerszten, director of clinical and translational research at Massachusetts General Hospital Heart Center. “A blood sample contains hundreds of these metabolites and can provide a snapshot of any individual’s health status.”

Previous studies had investigated changes in metabolites generated by exercise, but researchers were limited to viewing a few molecules at a time in hospital laboratories.

But in the new study, a technique developed by the MGH Heart Center in collaboration with MIT and Harvard allowed researchers to see the full spectrum of the fat-burning molecules in action. They used mass spectrometry — which can analyze blood samples in minute detail — to develop a “chemical snapshot” of the metabolic effects of exercise.

To trace the fat-burning molecules, the researchers took blood samples from healthy participants before, just following, and after an exercise stress test that was about 10 minutes long. Then they measured the blood levels of 200 different metabolites, which are released into the blood in tiny quantities.

Exercise resulted in changes to levels of more than 20 metabolites that were involved with the metabolism of sugar, fats, amino acids, along with the use of ATP, the primary source of cellular energy, according to the study.

After running on a treadmill for 10 minutes, people who were relatively more fit had a 98 percent increase in the breakdown of stored fat, sugar, and amino acids, while less-fit people had only a 48 percent increase.

The very fit had the biggest difference of all. Blood samples taken from 25 people before and after they ran the 2006 Boston Marathon found a 1,128 percent increase in some key metabolites.

It’s unknown whether training boosts the ability of people to burn fat more efficiently, or if more fit people were genetically able to burn fat more efficiently, though it’s likely some combination of the two, Gerszten said.

The researchers also found that exercise boosted levels of niacinamide, a vitamin derivative that enhances insulin release.

To investigate what biological mechanisms may be occurring, the researchers applied different combinations of metabolites to muscle cells in a lab. They found that a combination of five molecules shown to be elevated by exercise increased expression of “nur77″ — a gene that research has shown is involved with regulating blood sugar levels and lipid metabolism. The production of the nur77 gene also increased fivefold in the muscles of mice that had exercised for 30 minutes, according to the study.

The gene and its associated metabolites hint at new treatments for metabolic syndrome, a precursor to diabetes, the researchers said.

Abundant research has shown that exercise is beneficial to health, from reducing the risk of heart disease, stroke and type 2 diabetes, to prolonging life, said Emmanuel Skordalakes, an assistant professor in the Gene Expression and Regulation Program at the Wistar Institute in Philadelphia.

Yet researchers are still trying to understand the biological reasons that explain why exercise is good. Studies such as this provide “emerging evidence that begins to explain some of the biological processes and pathways that are regulated during exercise and which have a beneficial effect for us,” Skordalakes said.

Even so, far more research has to be done before the research could have a practical application for human performance or illness, Skordalakes said.

“We can’t just make these metabolites and gobble them down,” Skordalakes said. “It’s not as simple as that. These are very complex pathways and that has to be done very carefully.”

The study was published in the issue of Science Translational Medicine.

“Medicated” oil claiming to treat multitude of ailments is potentially toxic

The U.S. Food and Drug Administration today warned consumers not to purchase or use a product called “Arrow Brand Medicated Oil & Embrocation,” also labeled as “Aceite Medicinal La Flecha (Spanish) or “箭嘜驅風油 (Chinese).” The product is potentially toxic and contains two substances, methyl salicylate and camphor, which are poisonous when ingested.

Methyl salicylate and camphor also may be poisonous when applied to a large area of the skin, or when combined with heat to increase absorption of the active ingredients. Children are particularly susceptible to poisoning from these ingredients.

Symptoms of poisoning from these ingredients could include: abdominal pain, nausea, vomiting, diarrhea, headache, visual changes, dizziness and mental confusion. Some cases of accidental overdose of methyl salicylate and camphor have been fatal.

FDA preliminary testing on product samples also revealed a compound that appears to be diethylene glycol (DEG), an ingredient used in antifreeze, which may be toxic if ingested. Further testing is needed to confirm the presence of DEG.

The product is sold primarily on the Internet and in specialty stores that serve Asian and Latino communities. The FDA is asking retailers to remove the product from store shelves.

Three major medical groups have pushed upwards the recommended age at which diabetics should start taking low-dose aspirin to prevent a first heart attack or stroke.

According to a joint statement by the American Heart Association, the American Diabetes Association and the American College of Cardiology, only male diabetics over 50 and female diabetics over 60 who are at risk for a heart attack or stroke should be taking aspirin as a preventive.

“Previously, the American Diabetes Association (ADA) recommended aspirin to prevent heart attacks and stroke in most people with diabetes over the age of 40,” noted statement co-author Dr. M. Sue Kirkman, senior vice president for medical affairs and community information at the ADA. However, “more recent studies suggest that the benefits of aspirin are modest, and that aspirin likely would be best for people at very high risk of cardiovascular disease,” she said.

The experts defined an “increased risk of cardiovascular disease” in this case as a 10 percent risk of experiencing a heart attack and/or stroke over the next 10 years.

That means that, “those adults with diabetes at increased risk include most men over age 50, and women over age 60, who have one or more of the following additional major risk factors: smoking, hypertension, high cholesterol or a family history of premature cardiovascular diseases,” Kirkman explained.

According to the U.S. Centers for Disease Control and Prevention, people with diabetes are at three times the increased risk of cardiovascular events compared with people without diabetes. Among diabetics over 65, it’s estimated that 68 percent will die from heart disease and 16 percent from stroke.

On the other side of the equation, the major adverse effects of long-term aspirin use include intracranial bleeding, which can lead to hemorrhagic stroke, and gastrointestinal bleeding.

Still, daily low-dose aspirin — the study authors suggest 75 to 162 milligrams — can have real benefits in preventing cardiovascular events, another expert said.

“Taking low-dose aspirin to prevent heart disease is reasonable for adults with diabetes who are at increased risk of cardiovascular disease and not at increased risk for bleeding,” said the statement’s senior author, Dr. Michael Pignone, chief of the general medicine division and professor of medicine at the University of North Carolina.

“Aspirin should not be recommended for heart disease prevention in men and women at very low cardiovascular risk — under 5 percent over 10 years,” he added.

“People with diabetes should talk to their physicians about their cardiovascular risk and what they should be doing to try to reduce it to a manageable level,” Pignone said. “This includes the decision about aspirin, but also blood pressure control, [cholesterol-lowering] statins, and smoking cessation.”

The clarification of aspirin use among diabetics is being made because the evidence regarding the benefit of aspirin in preventing a first heart attack or stroke has been mixed, the experts said.

Most important, health care professionals should consider diabetic patients’ absolute level of risk before recommending aspirin, Kirkman said.

“For those at relatively low risk, the risks of aspirin probably outweigh the potential benefits. For those at high risk, aspirin should be encouraged. The strong recommendation to use aspirin in patients with a history of cardiovascular events still stands,” she said.

Dr. Gregg C. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center at the University of California, Los Angeles, agreed that aspirin has a place in diabetes care.

“Low-dose aspirin is reasonable for patients with diabetes at higher cardiovascular risk, optional for those at intermediate risk, and generally not recommended in those patients at low cardiovascular risk,” he said.

Fonarow noted that even with these more limited recommendations, “there are many patients with diabetes who are high risk for cardiovascular events who are not receiving aspirin and other cardiovascular protective medications, such as statins, who could benefit from doing so, and who should consult with their physician.”

Another expert, Dr. Joel Zonszein, from the Clinical Diabetes Center, Montefiore Medical Center in New York City, said there’s still a need for much stronger data on the issue.

For now, Zonszein recommends giving patients at risk 325 milligrams of aspirin, “even though we have no [good] data,” he said. “For patients who may have more of a bleeding problem, I give them the baby aspirin, but this is very biased, because we don’t have good data.”

The statement is being published in three journals, Circulation, the Journal of the American College of Cardiology and Diabetes Care.

SOURCES: Michael Pignone, M.D., chief, general medicine division and professor of medicine, University of North Carolina, Chapel Hill; M. Sue Kirkman, M.D., senior vice president, medical affairs and community information, American Diabetes Association; Gregg C. Fonarow, M.D., professor, medicine, and director, Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles; Joel Zonszein, M.D., co-director Clinical Diabetes Center, Montefiore Medical Center, New York City;

Infants born with a severely underdeveloped heart who undergo a newer surgical procedure are more likely to survive their first year and not require a heart transplant than those who have a more traditional surgical procedure, according to a report by researchers supported by the National Heart, Lung, and Blood Institute (NHLBI), which is part of the National Institutes of Health. The study of 549 newborns, however, suggests that after the first year, the two surgical procedures for the relatively rare condition yield similar results.

The Single Ventricle Reconstruction (SVR) Trial is the largest clinical trial to compare treatments for congenital heart disease, and the first North American, multi-center, randomized trial of surgical therapy for congenital heart disease patients. Results are published in the May 27, 2010, issue of the New England Journal of Medicine. An editorial accompanies the article.

Congenital heart disease is the most common birth defect. Every year, about 1 percent of babies are born with abnormally formed hearts. The normal heart has two pumping chambers called ventricles. The right ventricle pumps blood to the lungs, and the left ventricle pumps blood to the body. This trial studied babies born with a severe form of congenital heart disease in which babies are born with a functioning right ventricle and a small, underdeveloped, nonfunctioning left ventricle. The condition is sometimes referred to as hypoplastic left heart syndrome. Without treatment, these babies usually die shortly after birth.

The SVR Trial compared for the first time two surgical procedures that are commonly used to treat babies born with only the functioning right ventricle to determine whether one procedure improves outcomes more than the other. The SVR Trial was conducted at 15 North American clinical sites that are part of the NHLBI’s Pediatric Heart Network.

“Rigorous comparison of patient outcomes is critical to fully understanding the risks and benefits of different interventions,” said NHLBI Acting Director Susan B. Shurin, M.D., a board-certified pediatrician. “To conduct meaningful clinical research on rare conditions, however, we need collaboration among multiple study sites. This study demonstrates that through consortia such as the NHLBI’s Pediatric Heart Network, we can accelerate our ability to provide needed evidence on the best ways to care for some of our most vulnerable patients.”

In general, three surgeries are needed to treat a single right ventricle. The first procedure, called the Norwood procedure, is usually performed within the first two weeks of life and is one of the highest risk procedures in congenital heart surgery. A shunt, or small tube, is implanted to provide a connection for blood to flow from the heart to the blood vessels in the lungs, or pulmonary arteries, so that blood can pick up oxygen and release carbon dioxide. Children later undergo a second surgery at 4 to 6 months of age, and a third procedure, known as the Fontan procedure, at 18 to 36 months. The operations are staged to allow the child to grow large enough that the corrective procedures can be performed. Heart transplantation may be required for children with single ventricles when surgery and other treatments fail.

In the SVR trial, participants were randomly assigned shortly after birth to receive one of two types of shunts for their initial surgery, as part of the Norwood procedure. About half of the newborn participants received a modified Blalock-Taussig (MBT) shunt, the traditional approach, which places the shunt from a branch off of the aorta, the major blood vessel that takes blood from the heart to the rest of the body, to the pulmonary artery. The other participants received a newer type of shunt, called an RVPA shunt, which is placed between the right ventricle and the pulmonary arteries.

Each type of shunt has advantages and disadvantages. A few small studies of the RVPA shunt have suggested that it provides better survival and other outcomes than the MBT shunt. However, randomized clinical trials have not been conducted to demonstrate whether one procedure is better than the other.

Researchers followed all study patients for at least 14 months. They evaluated the number of deaths and heart transplantations in each group at one year, as well as the number of complications linked to each type of shunt.

“We found that the right ventricle-to-pulmonary artery shunt improved the chances of being alive without a heart transplant one year after surgery. However, the benefit appears to be limited to the first 12 months, as the two shunts showed similar results after about two years,” said Richard G. Ohye, M.D., head, Pediatric Cardiovascular Surgery Division, University of Michigan, Ann Arbor, and lead author of the study.

“We are continuing to follow these children, and this longer follow-up will be important to determine which shunt is truly superior in the long run,” Ohye added. A follow-up study is analyzing the effects of the procedures in children 2 to 6 years of age.

The researchers report that after 12 months, 74 percent of infants with the RVPA shunt survived and didn’t need a heart transplant, compared to 64 percent of infants with the MBT shunt. The newborns with the RVPA shunt, however, had significantly more complications requiring additional interventions, for example, insertions of stents or balloons to keep the shunt open. Other outcomes, such as the size and pumping ability of the right ventricle at 14 months, were similar in the two groups of participants.

In a preliminary analysis of participants after an average follow up of 32 months, researchers found similar outcomes in the group of participants with the RVPA shunt compared to the MBT shunt.

“This study shows great promise for helping not only this high-risk group of patients, but also for improving the health and well being of many more babies and children with heart problems,” noted Gail D. Pearson, M.D., Sc.D., a pediatric cardiologist, director of the NHLBI Adult and Pediatric Cardiac Research Program, and a coauthor of the paper.

The Pediatric Heart Network (PHN) is a multi-center clinical research consortium supported by the NHLBI since 2001 to study congenital and acquired heart diseases that occur in childhood. The PHN also provides training in clinical research to young investigators, and is the clinical cornerstone of the NHLBI’s comprehensive Bench to Bassinet program in translational pediatric cardiovascular research.

To interview Dr. Gail Pearson, the NHLBI SVR spokesperson, please contact the NHLBI Communications Office at (301) 496-4236 or e-mail nhlbi_news@nhlbi.nih.gov. To speak with Dr. Ohye, please contact Dr. Ohye’s assistant, Sandy Hall at (734) 936-4978 or e-mail ohye@umich.edu. To speak with Dr. Lynn Mahony, the chair of the PHN, professor of pediatrics, University of Texas Southwestern Medical Center, and a coauthor of the paper, please call (214) 456-2325

Researchers at the National Institutes of Health and other institutions have discovered the third in a sequence of genes that accounts for previously unexplained forms of osteogenesis imperfecta (OI), a genetic condition that weakens bones, results in frequent fractures and is sometimes fatal.

The newly identified gene contains the information needed to make the protein Cyclophilin B. This protein is part of a complex of three proteins that modifies collagen, folding it into a precise molecular configuration, before it is secreted from cells. Collagen functions as molecular scaffolding that holds together bone, tendons, skin and other tissues.

Most types of osteogenesis imperfecta result from a dominant mutation in collagen itself, requiring only one copy of the mutated gene to bring about the disorder. Osteogenesis imperfecta involving the Cyclophilin B gene is a recessive trait, requiring two defective copies of the gene to cause the disorder.

“The discovery provides insight into a previously undescribed form of osteogenesis imperfecta,” said Alan E. Guttmacher, M.D., acting director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “The advance also provides new information on how collagen folds during normal bone formation, which may also lead to greater understanding of other bone disorders.”

The finding was published online Jan. 20 in the New England Journal of Medicine. The investigation involved a collaboration between researchers at the NICHD, led by Dr. Joan Marini, and the Hospital for Special Surgery in New York City. There, Dr. Cathleen Raggio diagnosed the children in the study as having a novel form of OI. In addition, researchers at the University of Washington in Seattle and the NIH’s National Human Genome Research Institute also took part in the study.

The NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases estimates that in the United States a minimum of 20,000 and possibly as many as 50,000 people are affected by osteogenesis imperfecta (http://www.niams.nih.gov/Health_Info/Bone/Osteogenesis_Imperfecta/default.asp). About 85 percent of all OI cases are caused by mutations in the genes that contain the information needed to make collagen.

Researchers at the NICHD and other institutions had earlier learned that osteogenesis imperfecta could also be caused by defects in the protein complex that modifies collagen into its final form. Joan Marini, M.D., Ph.D., chief of NICHD’s Bone and Extracellular Matrix Branch and colleagues had discovered that recessive mutations in the genes for two proteins in the complex, cartilage associated protein, or CRTAP (http://www.nichd.nih.gov/news/releases/brittle_bone_disease.cfm) , and prolyl 3-hydroxylase 1 ( P3H1) (http://www.nichd.nih.gov/news/releases/gene_recessive_bone_disease.cfm), could result in severe forms of osteogenesis imperfecta. Individuals with mutations in CRTAP have all died in childhood. Mutations in P3H1 are sometimes fatal in early life.

A new gene involved in a recessive form of brittle bone disease has been pinpointed by researchers.

The gene is the third to be identified in a sequence of genes involved in previously unexplained forms of osteogenesis imperfecta, a sometimes fatal genetic condition that weakens bones, resulting in frequent fractures.

The new gene, discovered by U.S. National Institutes of Health researchers and their colleagues, is involved in the production of Cyclophilin B, which is part of a complex of three proteins that folds collagen into a precise molecular configuration before it’s secreted from cells.

Collagen acts as the molecular scaffolding that holds together bone, tendons, skin and other tissues.

Most types of osteogenesis imperfecta are the result of a dominant mutation in collagen itself, requiring only one copy of the mutated gene to cause the condition, the researchers explained in an NIH news release. Osteogenesis imperfecta involving the Cyclophilin B gene is a recessive trait, requiring two defective copies of the gene to cause the disorder.

Identification of this new gene “provides insight into a previously undescribed form of osteogenesis imperfecta. The advance also provides new information on how collagen folds during normal bone formation, which may also lead to greater understanding of other bone disorders,” Dr. Alan E. Guttmacher, acting director of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, said in the news release.

The study is published in the Jan. 20 issue of the New England Journal of Medicine.

Plasma jets could offer a painless alternative to dentists’ drills, say German researchers.

They found that firing low temperature plasma beams at dentin — the fibrous tooth structure beneath the enamel coating — reduced the amount of dental bacteria by up to 10,000-fold. The results suggest that plasma jets could be used to remove infected tissue in tooth cavities, a procedure that currently requires a drill.

For the study, the researchers infected dentin from extracted human molars with four strains of bacteria and then exposed the dentin to plasma jets for 6, 12 or 18 seconds. The amount of bacteria that was eliminated increased the longer the dentin was exposed to the plasma jets.

The study is in the February issue of the Journal of Medical Microbiology.

“Drilling is a very uncomfortable and sometimes painful experience,” the study’s leader, Dr. Stefan Rupf, of Saarland University in Homburg, said in a news release from the journal’s publisher. “Cold plasma, in contrast, is a completely contact-free method that is highly effective.”

Rupf said that “huge progress” is being made in the field of plasma medicine and that “a clinical treatment for dental cavities can be expected within three to five years.”

SOURCE: Society for General Microbiology