May 1, 2003 THE REALLY NATURAL PAINKILLER By Ruth Winter, MS Soldiers seriously injured by a bullet or shrapnel, may not at first feel any pain. It was once believed that this was because they were so happy to be alive. Modern pain specialists, however, now recognize that "stress relief" under such circumstances is due to the brain's ability at times to manufacture its own opiates called endorphins and enkephalins. Some scientists have also attributed the euphoria experienced by many long distance runners to the release of brain endorphins. In addition, there are theories that acupuncture, hypnosis, meditation and a variety of other techniques used to relieve pain may also cause the brain's release of its own painkillers. The trouble is that not everyone can produce enough of their self-made medications and if they can, the chemicals may not last very long. Many varieties of pain medications based on morphine-like narcotics have been developed in the laboratory or derived from biologicals. The problem is that most such narcotics have potential side effects, including severe constipation, reduced blood pressure and breathing difficulties, and addiction. Now, researchers at the University of Arizona and the University of New England have developed a new narcotic based on a natural painkiller found in the body that appears in animal studies to be more potent but less addictive. "This represents one of the most promising morphine-like painkillers to date in terms of avoiding side effects, particularly addiction," says Robin Polt, Ph.D., professor of chemistry at the University of Arizona in Tucson and a chief researcher on the project. He presented details of the investigation at a recent meeting of the American Chemical Society in New Orleans. Called a glycosylated enkephalin, the compound appears promising in studies using mice. If it works in humans, it could be a safer alternative for people who are allergic to morphine or cannot take the drug because of its side effects, the researchers say. These improved features make glycosylated enkephalin particularly appealing to the military, which hopes that the safer, less-addictive drugs can be self-administered by soldiers severely wounded during battle without depending on the assistance of a medic. These compounds have two main advantages, Polt says. First, they are easily degraded into amino acids and sugars in the body, which reduces their risk of toxicity. In addition, they are more specific in their action with the brain's receptors, which means fewer side effects. More work is needed before the medications can be used in humans; additional animal studies are now planned. If all goes well, an actual pharmaceutical could be available in five to 10 years, says Polt. Although it will likely be initially administered by injection, developing the compound as an oral pill is now under consideration, he says. .The Office of Naval Research and the National Science Foundation funded this study. HEALING BANDAGE A healing bandage is another development based--- like the glycosylated enkephalins--- on increased knowledge of body chemistry. Professor John Kao's bandage is sort of like a Jell-O salad: It's made from gelatin, turns into a solid and has stuff suspended in it. Instead of containing marshmallows and chunks of fruit, however, it has substances that can help repair damaged tissue. "The technology attempts to mimic the natural cellular environment, That's important because it enhances our ability to repair and regenerate damaged tissue.", he explains.
"The product initially takes a liquid form and then solidifies. Unlike bandages that have to be cut to shape, doctors can pour this solution over an area--- even something like a damaged internal organ--- and it will set in place,"
"The product is highly versatile depending on the application," Kao adds. He thinks it might even provide a method for transplanting stem cells to regenerate damaged or diseased tissue.
Kao's bandage is patented by the Wisconsin Research Alumni Foundation, a nonprofit organization that manages the intellectual property in the interest of UW-Madison
DHEA DOESN'T DO IT FOR ALZHEIMER'S
The supplement, dehydroepiandrosterone, or DHEA, which has been touted by some as an anti-aging hormone and a treatment for diseases such as cancer, AIDS, diabetes and Alzheimer's disease, showed no effect for Alzheimer's disease patients who took the supplement for six months, according to a study published in a recent issue of Neurology, the scientific journal of the American Academy of Neurology.
DHEA is a hormone produced naturally in the adrenal glands. The body then converts it into the hormones estrogen and testosterone. DHEA as a supplement is made from plant chemicals. In the first randomized, double-blind trial of DHEA for Alzheimer's disease, researchers gave 58 Alzheimer's patients either 100 mg per day of DHEA or a placebo. Before the study began and at three and six months, the patients were tested for cognitive functioning and rated by physicians and caregivers on any changes in the severity of the disease.
DHEA did not significantly improve cognitive performance or ratings of disease severity. A transient benefit on cognitive performance may have been seen on the tests at three months, but the benefit narrowly missed statistical significance, according to study author Owen Wolkowitz, MD, of the University of California at San Francisco. Of the 58 people who started the study, 46 completed three months of treatment and 33 completed six months of treatment.
According to neurologist David Knopman, MD, of the Mayo Clinic in Rochester, Minn., who wrote an editorial accompanying the study, the small size of the study and the high number of people who dropped out may limit the results. He said that larger studies are needed to test these findings.
NEW ANTIWRINKLE CANDIDATES
In the never-ending search to combat wrinkles---those outward signs of aging---there are two new candidates based on a once discredited one. If approved by the U.S. Food and Drug Administration (FDA), dermatologists may be injecting silicone and hyaluronic acid gel as the soft tissue fillers of choice among aging men and women looking for a natural-looking, long-lasting fix.
Dermatologist Rhoda S. Narins, MD, Clinical Professor, Department of Dermatology, New York University Medical Center, New Orkney, discussed these two substances and their advantages over the fillers currently available in this country at a recent meeting of the American Academy of Dermatology' in San Francisco.
Silicone---until the FDA banned it in 1992---was used in the United States for many years with to treat wrinkles and acne scars as well as to enhance areas such as the lips, cheekbones and the chin. For these types of procedures, the safety and efficacy was compromised when silicone was diluted with foreign substances, such as mineral oil, or when it was injected in large volumes in an area during one treatment session. In the late 1990s, a form of silicone known as liquid injectable silicone was developed and approved by the FDA for use in the eye to treat chronic retinal detachment. This new, medical grade silicone is now being studied in the U.S. to determine its safety and efficacy as a permanent filler for aging skin.
"What makes silicone unique from other fillers is that the results are permanent," explained Dr. Narins. "With other fillers, patients have to routinely come back to the office to maintain their results. but studies are showing that once the results are achieved with injectable silicone, there is no need for further treatments unless it becomes necessary as the patient ages."
Using the micro-droplet technique to ensure the best and safest results, tiny amounts of silicone are injected at four to eight week intervals until the desired result is achieved. Depending on the depth of the wrinkle or scar, no difference may be seen for one to three treatments.
"When the microdroplet technique is used with a purified silicone product by a dermatologic surgeon experienced in the technique, side effects are rare," explained Dr. Narins. "However, the decision to use silicone must be between the patient and the dermatologic surgeon after any potential complications have been weighed based on the patient's medical history."
"We're extremely hopeful that once the FDA-monitored studies are complete, liquid injectable silicone will be readily available for patients here in the U.S.," added Dr. Narins.
Hyaluronic Acid Gel is the other new soft tissue filler on the horizon that is not yet FDA approved but is being studied in the U.S. It is a non-animal form of hyaluronic acid gel. Hyaluronic acid is a naturally occurring component of the skin that is the framework or medium in which cells live. In gel form, hyaluronic acid binds to water and provides volume to easily fill in wrinkles caused by tissue loss, making it suitable for larger folds of skin around the mouth and cheeks. This highly purified, non-animal form of hyaluronic acid has already been approved for use as a filling agent in Canada, Europe and Australia.
A new multi-center clinical trial has shown this non-animal form of hyaluronic acid gel to be a superior filler to bovine collagen for the improvement of the deep lines visible from the nostrils to the corners of the mouth. Six months after treatment was completed, study findings indicated that less volume of hyaluronic acid was needed to achieve optimal cosmetic results, and patients overwhelmingly preferred the gel substance to collagen because it lasts longer, has not caused allergic reactions and has no potential for transmission of disease. One hundred and thirty-four patients were treated every two weeks until treatment was complete at six medical centers nationwide.
Dr. Narins is confident that once FDA-approved, hyaluronic acid can be Used effectively to augment and contour acne scars, enhance lips, fill in hollow areas such as the cheeks and under the eyes, and improve a receding chin. For more information, contact the AAD at 1-888-462-DERM or www.aad.org. Also check A Consumer's Dictionary of Cosmetic Ingredients.
Kao, a University of Wisconsin-Madison pharmaceutical science and biomedical engineering professor, says his bandage might contain new cells, molecules and even drug compounds needed to heal an injury.
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