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Scientists at UT Southwestern Medical Center are trying to understand how Fen-phen, once hailed as a miracle weight-loss drug, behaves in the brain, in order to develop safer anti-obesity drugs with fewer side effects.

Fen-phen was removed from the market more than a decade ago for inducing life-threatening side effects, including heart valve lesions.

Now, the researchers have defined a circuit in the brain that explains the ways fenfluramine, a component of Fen-phen, suppresses appetite.

“Our findings provide evidence that the neural circuit we’ve proposed is sufficient for the neurotransmitter serotonin to regulate food intake and body weight. Fen-phen works directly on this pathway. Unfortunately, that drug also adversely affects peripheral tissue such as the heart,” said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study.

For the study, the researchers engineered mice in which the expression of a serotonin receptor called 5-hydroxytryptamine 2C was blocked throughout the entire body.

This was previously known to produce obese mice resistant to the anorexic actions of fenfluramine. However, when activated by serotonin, this receptor is also known to suppress appetite.

Using this mouse model, the authors engineered another set of mice in which the same serotonin receptor was blocked everywhere in the body except within a group of brain cells called pro-opiomelanocortin, or POMC, neurons.

The POMC neurons, which are found in the hypothalamus, are also known to play an important role in suppressing appetite and inducing weight loss.

The researchers found that the animals with no serotonin 2c receptors expectedly developed obesity as well as other metabolism disorders such as increased food intake, hyperactivity and leptin insensitivity. They also were prone to spontaneous seizures, said Dr. Elmquist.

On contrary, the mice in which the serotonin receptor was re-expressed and functioning only in the POMC neurons stayed slim and responded to fenfluramine.

“The POMC-specific reactivation of the receptor only in POMC neurons normalizes the abnormal metabolism in these mice. The animals don’t eat excessively. Their hyperactivity is also gone,” Dr. Elmquist said.

“Conventional wisdom is that fenfluramine increases serotonin release that then activates serotonin receptors in the brain to regulate food intake and body weight, but unfortunately, this drug also causes lesions in heart valves,” he said.

“If you could develop a drug that would travel to both the brain and the peripheral tissues, and then give a blocker to protect the heart, it’s possible that you could prevent the harmful side effects and still aid weight loss. Admittedly, that’s a bit farfetched, but this mouse model could be used to test that theory,” he added.

The team’s next step is to determine whether they’ve identified the sole circuit required to suppress appetite and induce weight loss.

The study is appearing in the Nov. 25 issue of Neuron.

Researchers at the University of Utah have created a synthetic version of the superglue that sandcastle worms combine with sand and shell to build their sturdy tube-shaped homes, and believe that it may one day be used to repair shattered bones in knees, other joints and the face.

“You would glue some of the small pieces together,” says Russell Stewart, associate professor of bioengineering, and senior author of the study to be published online within a week in the journal Macromolecular Biosciences.

“When you break the top of a bone in a joint, those fractures are difficult to repair because if they are not aligned precisely, you end up with arthritis and the joint won”t work anyway. So it’’s very important to get those pieces aligned as well as possible,” he adds.

The researcher has revealed that the synthetic sea-worm glue performed 37 percent as well as commercial superglue during lab tests using cow bone pieces from groceries.

He says that this glue may be tested on animals within a year or two, and on humans in five to 10 years.

Stewart has made it clear that the synthetic sandcastle worm glue will not be suitable for repairing large fractures such as major leg and arm bones, for which rods, pins and screws are used.

He, however, envisions that it may be used for gluing together small bone fragments in fractured knees, wrists, elbows, ankles, other joints, and the face and skull.

“If a doctor rebuilds a joint with pins and screws, generally weight is kept off that joint until it’’s healed. So our goal isn”t to rebuild a weight-bearing joint with glue. It is to hold the pieces together in proper alignment until they heal. … We see gluing the small fragments back into the joint,” Stewart says.

In their study report, the researchers wrote: “It is especially difficult to maintain alignment of small bone fragments by drilling them with screws and wires. An adjunctive adhesive could reduce the number or volume of metal fixators while helping maintain accurate alignment of small bone fragments to improve clinical outcomes.”

Bioengineer Patrick Tresco, associate dean for research at the University of Utah’’s College of Engineering, says: “Most current adhesives do not work when surfaces are wet so they are no good for holding together bone, which is wet and bloody. There is nothing like it (the synthetic worm glue) on the market today.”

The researchers also say that the synthetic glue can deliver pain killers, growth factors, antibiotics, anti-inflammatory medicines or even stem cells to sites where bone fragments are glued, “simultaneously fixing the bone and delivering potent drugs or even genes to the spots where they are needed.”

According to them, it may also be used to firmly attach “tissue scaffolds” where pieces of bone are cut out due to cancer, in order to encourage regrowth of the missing bone.

Stewart hopes to make better versions that have more bonding power, are biocompatible in the human body and biodegradable.

“Ultimately, we intend to make it so it is replaced by natural bone over time. We don”t want to have the glue permanently in the fracture.” Stewart says some synthetic superglues or “instant glues” are used instead of sutures for superficial skin wounds. But because of toxicity or toxic byproducts, “they are not suitable for deep tissue use,” including bone repair, he says.

Medicaid spent $200 million on unapproved drugs. This amount was paid from 2004 to 2007 for more than 100 unapproved drugs.

An investigation done by a news agency found that Medicaid paid nearly $198 million.

The remedies were mostly for common ailments like colds and pain, and they date all the way back to before Congress decided in 1962 that the FDA had to review all new drugs.

Sometimes, safety issues have come up. For instance, the FDA banned injectable versions of a go

You might not just realize this while downing a mug of chilled beer on a summer afternoon, but a new study has revealed that knocking back four beers a day can damage your eyesight.

According to a Melbourne research, men in their 60s who drink alcohol heavily are about six times more likely to develop the most debilitating form of age-related macular degeneration (AMD).

Although smoking and genetics have been linked to the condition, but Dr Elaine Chong from the Royal Victorian Eye and Ear Hospital decided to study the diet and eye health of almost 7,000 people over a period of time to determine the contribution of alcohol.

“We found that higher levels of alcohol, more than four standard drinks a day, was associated with a three-fold increase in end-stage AMD in men,” theage.com.au quoted Chong, as saying.

The study found that beer drinking, in particular, carried a six-fold increased risk. Quantities of wine and spirits drunk were too low to evaluate their risk.

The same link was not see in women, possibly because they were less likely to drink heavily, she said.

Explaining the trigger, Dr Chong said it was possible alcohol could increase oxidative stress to the retina.

“Alcohol is a neurotoxin so it is thought that high levels can actually cause retinal damage that might lead to the disease,” she said.

The findings have been presented at an ophthalmology conference in Melbourne.

Melatonin therapy, generally used for regulating sleeping patterns and reducing jet lag, can effectively treat a common inflammatory eye disease, according to researchers.

The common inflammatory eye disease called uveitis is often accompanied by sudden redness and pain in eyes. It untreated, it can lead to permanent vision loss.

A team of researchers from the University of Buenos Aires and The National Research Council (CONICET) has found that melatonin treatment significantly reduced the levels of TNFa and NF?B, the factors that contribute to inflammation.

The treatment also decreased the appearance of clinical symptoms of uveitis such as inflammation, blood vessel expansion and cataract, and protected the blood-ocular barrier integrity.

The researchers suggest that either alone or combined with corticosteroid therapy, the anti-inflammatory effects of melatonin may benefit patients with chronic uveitis and decrease the rate and degree of corticosteroid-induced complications.

Their next step will be to find out the mechanisms governing melatonin protection in the eye.

The study “Therapeutic Effect of Melatonin in Experimental Uveitis” appears in the December issue of The American Journal of Pathology.

Infants born in the autumn season are at a greater risk of developing childhood asthma, according to a new study.

The new research from Vanderbilt University has found that while having clinically significant bronchiolitis at any age during infancy was associated with an increased risk of childhood asthma, for autumn babies, that risk was the greatest.

“Infant age at the winter virus peak following birth independently predicts asthma development, with the highest risk being for infants born approximately four months prior to the peak, which is represented by birth in the fall months in the Northern hemisphere,” said Tina V Hartert, M.D., M.P.H., associate professor of medicine and director of the center for Asthma Research at Vanderbilt University, and principal investigator of the study.

“Birth during this time conferred a nearly 30 percent increase in odds of developing asthma,” she added.

The study analysed the birth and medical records of more than 95,000 children and their mothers in Tennessee to determine whether date of birth in relationship to the peak in winter respiratory viruses posed a higher risk for developing early childhood asthma.

The researchers suggest two non-mutually exclusive possible reasons for the link, one, that there is a genetic susceptibility common to both bronchiolitis and the development of asthma and the other that an environmental exposure such as winter viral infection causes asthma.

“The risk of progressing from bronchiolitis to asthma is almost certainly influenced by genetic factors,” wrote Dr. Hartert.

“However, if this association were due only to genetic factors, there would be a seasonal effect on infection but not on asthma…Instead we have shown that there is variation in the risk of developing asthma by the timing of birth in relationship to the winter virus peak for each year studied.

“This supports a causal relationship of childhood asthma with the winter virus peak after birth,” she added.