Imbalanced diet, a cause of asthma?

Challenging the widespread assumption that obesity itself is a risk factor for asthma, a new study has revealed that even children of a healthy weight who have an imbalanced metabolism due to poor diet or exercise may be at increased risk of the disease. 

"Our research showed that early abnormalities in lipid and/or glucose metabolism may be associated to the development of asthma in childhood," said lead author Giovanni Piedimonte, who is professor and chairman of the Department of Pediatrics at West Virginia University School of Medicine, physician-in-chief at WVU Children's Hospital and director of WVU's Pediatric Research Institute. 

"Our findings also imply a strong and direct influence of metabolic pathways on the immune mechanisms, both innate and adaptive, involved in the pathogenesis of asthma in children" Piedimonte added. 

The research implicates metabolic disorders directly in the development of asthma, and points to a new way of viewing diet and lifestyle as risk factors for asthma, even in children who are not obviously obese or overweight. 

The researchers gathered demographic data, estimates of body mass index (BMI), and asthma prevalence on a sample of nearly 18,000 children from West Virginia who were four to 12 years old and were participating in the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project. Metabolic data was available for all children in the study, and the researchers investigated a suite of markers for early metabolic dysfunction, including triglyceride levels and evidence of acanthosis nigricans (AN), a brown to black hyperpigmented skin rash that is a biomarker for developing insulin resistance and hyperinsulinemia. 

They found that while asthma prevalence generally increased with BMI, it was significantly higher in obese and morbidly obese children than in children with healthy BMI, but that simple overweight status did not appear to be linked to increased asthma prevalence. 

However, after controlling for BMI and other confounding variables, asthma prevalence was significantly associated with triglyceride levels and the presence of AN independently of BMI. 

"The metabolic problems we investigated may have confounded the widely publicized epidemiologic link between obesity and asthma, because high triglyceride levels (dyslipidemia) and AN (hyperinsulinemia) are very common in obesity and metabolic syndrome," said Dr. Piedimonte. 

The results suggest that only above a certain threshold metabolic factors participate in the disease process of airway inflammation and hyperreactivity, which ultimately leads to asthma. 

More importantly, the association between asthma, triglyceride levels and the presence of AN exists regardless of body weight, suggesting that children who are a healthy weight, and even those who are underweight, may be at risk for developing asthma because of a subtle metabolic dysfunction leading to increased triglyceride levels and the presence of AN. 

"Both imbalanced nutrition and inadequate exercise may play a role in metabolic syndrome, and our experience suggests that degree of physical activity may be as important as nutrition," said Dr Piedimonte. 

The study was published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine. 

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Chili peppers may help fight fat

Chili peppers contain an ingredient that may cause weight loss and fight fat, scientists have reported.

According to boffins, capsaicin, the stuff that gives chili peppers their kick, may cause weight loss and fight fat buildup by triggering certain beneficial protein changes in the body.

The study, which could lead to new treatments for obesity, appears in ACS' monthly Journal ofProteome Research .

Jong Won Yun and colleagues point out that obesity is a major public health threat worldwide, linked to diabetes, high blood pressure, heart disease, and other health problems. Laboratory studies have hinted that capsaicin may help fight obesity by decreasing calorie intake, shrinking fat tissue, and lowering fat levels in the blood. Nobody, however, knows exactly how capsaicin might trigger such beneficial effects.

In an effort to find out, the scientists fed high-fat diets with or without capsaicin to lab rats used to study obesity. The capsaicin-treated rats lost 8 percent of their body weight and showed changes in levels of at least 20 key proteins found in fat. The altered proteins work to break down fats.

"These changes provide valuable new molecular insights into the mechanism of the antiobesity effects of capsaicin," the scientists say.

How sugar 'feeds'cancer

Gaining fresh insights into the notion that sugar "feeds" cancer, researchers at Huntsman Cancer Institute at the University of Utah may have moved a step closer to realising potential treatments to stop tumour growth.

"It's been known since 1923 that tumour cells use a lot more glucose than normal cells. Our research helps show how this process takes place, and how it might be stopped to control tumour growth," says Dr. Don Ayer, a Huntsman Cancer Institute investigator and professor in the Department of Oncological Sciences at the University of Utah.

The researchers point out that during both normal and cancerous cell growth, a cellular process takes place that involves both glucose (sugar) and glutamine (an amino acid).

Glucose and glutamine are both essential for cell growth, they say.

While it was long assumed they operated independently, Ayer's research shows they are inter-dependent.

He has found that glucose utilization is stopped when glutamine availability is restricted.

"Essentially, if you don't have glutamine, the cell is short circuited due to a lack of glucose, which halts the growth of the tumour cell" he says.

Dr. Mohan Kaadige, a postdoctoral fellow in Ayer's lab, focused on a protein called MondoA, responsible for turning genes on and off, during the study.

In the presence of glutamine, MondoA blocks the expression of a gene called TXNIP. TXNIP is thought to be a tumour suppressor, but when it's blocked by MondoA , it allows cells to take up glucose, which in turn drives tumor growth.

Ayer believes that his team's work may lead to new drugs that would target glutamine utilization, or target MondoA or TXNIP.

He says that the next step in his research is to develop animal models to test his ideas about how MondoA and TXNIP control cell growth.

"If we can understand that, we can break the cycle of glucose utilization which could be beneficial in the treatment of cancer," he says.

A research article describing the study has been published in the journal Proceedings of the National Academy of Sciences.

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Weight loss pill reduces 25% fat in a week

Scientists in the U.S. have created an anti-obesity pill that could dramatically reduce weight in a week. Tests on mice have shown that the drug could decreasebody weight by a quarter and their fat content by 42% after seven days. After a month, the weight of the mice had been reduced by 28% and their fat mass by 63%. The researchers say further research is needed before the drug is tested on humans. However, they say the results point to a new approach for the treatment of obesity and adult-onset diabetes.

The drug is an artificial hormone made out of glucagon and glucagon-like peptide-1 (GLP-1) - natural hormones that regulate glucose metabolism. These two hormones are similar in structure but they differ in their chemical structure and biological function. Previous studies have shown they can suppress appetite or cause weight loss by increasing the body's calorie usage.

Dr Richard DiMarchi and colleagues at Indiana University in the US created the synthetic hormone and carried out the trials on mice. "Obesity and its associated consequences, including adult-onset diabetes, remain a primary health and economic threat for modern societies," the Telegraph quoted DiMarchi as saying. At the moment, surgical interventions such as gastric bypass remain the only therapeutic options with the potential for a cure.

Dr DiMarchi said acute glucagon administration reduces food intake in animals and in humans, and some reports indicate that sustained glucagon receptor activation not only decreases food intake but also promotes weight loss.

"Pharmacological treatment of obesity using single agents has limited efficacy or presents risk for serious adverse effects," he said.

"No single agent has proven to be capable of reducing body weight more than 5 to 10% in the obese population. Combination therapies using multiple drugs simultaneously may represent the preferredpharmaceutical approach to treat obesity, and there is ample precedent for combination therapy in treatment of chronic diseases. "Here we present results that prove the principle that single molecules can be designed that are capable of simultaneously activating more than one mechanism to safely normalize body weight.

"The present results trigger an array of new questions and the opportunity for further enhancement of the pharmacology.

"First, there is no reason to assume that the fine-tuned combination of these two particular gut hormones in a single molecule represents the only or optimal pharmacological approach to prevent or treat obesity.

"Second, it seems at least theoretically possible to include circulating factors other than gut hormones in an analogous single-molecule co-agonist," he added.

Dr DiMarchi said that a combination of more than two metabolic control peptides into a single molecule may "provide an even more potent" weapon against obesity.

The findings have been published online in Nature Chemical Biology.

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New drug to treat arthritis patients

A drug in development for the treatment of rheumatoid arthritis has been found to be well tolerated and effective in a clinical trial, say researchers.

The trial of the drug called masitinib was carried out by researchers from several French hospitals. It involved 43 patients with arthritis resistant to current treatments. Reporting their findings in BioMed Central's open access journal Arthritis Research and Therapy, the researchers have revealed that treatment with masitinib significantly reduced the severity of active arthritis. "In choosing which interventions to use for the management of rheumatoid arthritis, it is important to recognise that treatment should aim to keep the disease in remission and not be used intermittently to manage exacerbations. We are encouraged from this study that masitinib not only appears to be effective, but that within the first 3 months of treatment the worst of its side-effects were over, possibly making it suitable for long-term treatment regimens," said Olivier Hermine, one of the researchers. "The results of this study also help establish the critical role of mast cells in the pathogenesis of rheumatoid arthritis and demonstrate their viability as a therapeutic target. There is sufficient compelling evidence to warrant further placebo-controlled investigation," he added.

The researchers have revealed that masitinib inhibits the activity of mast cells, a component of the immune system thought to be involved in the pathogenesis of rheumatoid arthritis. The clinical improvement described in the study was supported by laboratory evidence of reduced inflammation. The authors found that adverse effects of the treatment were mainly mild to moderate. Alain Moussy from AB Science, a pharmaceutical company who are developing masitinib for multiple indications in human and animal medicine, said: "This is a milestone article for us, being the first publication of masitinib in a human study." Moussy added: "Our preclinical studies have shown that masitinib selectively targets cell receptors known to be involved in various disease processes but does not affect those associated with toxicity, particularly cardiotoxicity."

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HIV-positive above 50s high: WHO

The rate of HIV infection is "surprisingly high" among people aged over 50 years, the World Health Organization said \, warning that cases among older people may be growing worldwide. "The scant data that exist suggest a surprisingly high prevalence and incidence of HIV among individuals 50 years of age and over," said the WHO in its March bulletin. According to authors of the study, in the United States, the proportion of people aged over 50 with HIV soared to 25 percent in 2006 from 20 percent in 2003. In Europe, only eight percent of reported cases arise from older people. In Brazil, the number of people over 50 with HIV doubled between 1996 and 2006 -- from 7.5 to 15.7 cases per 100,000 inhabitants. "The frequency of infection with HIV in older people is worrying. We need to understand why and when these people are becoming infected so that public health campaigns can be better targeted to prevent such infections,"

George Schmid, a WHO scientist said. Public perception of the disease may be part of the reason, with AIDS still being viewed as a "disease of young people." As a result, screening is less common among older people, leading to delayed diagnosis, said the WHO. "The number of older people with HIV may be increasing worldwide, but doctors seldom consider screening them for HIV so diagnosis is often delayed," added the WHO. At the same time, older people have lower immunity, which could have led to more rapid deterioration from HIV infection to AIDS, said the study.

The life expectancy of those infected at age 65 or older is just four years, while people who are infected at age five to 14 have life expectancies of over 13 years. The authors noted that sexual activity remains the most likely mode of transmission for older people. Potency drugs such as Viagra emerging in the 1990s have extended the sex life of older people, who are also less likely than younger people to practise safer sex, said the WHO.
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Stress can make you look 2 years older

Wrinkles are not due to genetics alone but also to stressful environmental factors, such as a divorce, abnormal weight loss and use of antidepressants, according to a new study. “A person’s heritage may initially dictate how they age - but if you introduce certain factors into your life, you will certainly age faster. Likewise, if you avoid those factors, you can slow down the hands of time,” said the lead author of the study, Bahaman Guyuron, an American Society of Plastic Surgeons (ASPS) member. Researchers examined 186 pairs of identical twins because “they are genetically programmed to age exactly the same”, explained Guyuron, chairman of the department of plastic surgery at the University Hospitals Case Medical Center, in Cleveland, Ohio. The study found that twins who had been divorced looked nearly two years older than their identical siblings who were married, widowed or single. Researchers found that anti-depressant use and weight gain were also factors in perceived age difference. In sets of twins younger than 40, the heavier twin seemed older, while in sets of twins more than 40 years old, the heavier twin seemed younger. “The presence of stress could be one of the common denominators in those twins who appeared older,” said Guyuron. Continued relaxation of the facial muscles due to antidepressant use could explain sagging, and losing abnormal amounts of weight has harmful effects on health and appearance, the rexperts found.
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