Herbal Medicine

Europe's "Jules Verne" freighter edges to just 12m from the space station to show its readiness to dock.

The first dig inside the ring at Stonehenge in more than four decades hopes finally to resolve its mysteries.

Researchers reveal how pairs of rooks are able to co-operate to solve difficult problems.

HOUSTON -- (March 31, 2008) -- When it comes to the latest celebrity blunder, parents should tune in rather than tune out.

It could give parents an opportunity to talk with their children about making good decisions, said an expert at Baylor College of Medicine in Houston.

Youngsters can be exposed to drugs, alcohol and other unhealthy activities simply by reading about their favorite celebrity.

Start a conversation

"Rather than avoiding the topic, parents should do their research and be sure they have their facts straight about the situation," said Dr. John Sargent, professor of psychiatry and behavioral sciences and pediatrics at BCM and director of child and adolescent psychiatry at Ben Taub General Hospital. "It's important to know what your kids are being exposed to."

Since children may already be talking about the issues with friends, the first step is to talk with them about what they've heard and what they think about the situation.

"Be sure to make it an open conversation," said Sargent.

Choices, behaviors

Parents should discuss their own feelings about the situation and remind their youngsters that privacy is difficult to maintain as a celebrity. There are always two sides to a story, and this can relate back to a situation the youngsters might face with gossip in their own lives.

Another important point to make is that there are a number of successful celebrities who live physically and emotionally healthy lives, and that there are various ways for celebrities and others to get help when facing situations such as drug and alcohol abuse.

"Use these opportunities to talk about choices, behaviors and friends," said Sargent.

Just as any other type of news, parents should do their research about celebrity news and be prepared for an open conversation. Parents can use these same tips to talk to their children about world news, politics and other topics.

HOUSTON -- (March 31, 2008) -- A mutation in a gene controlling calcium flux in skeletal muscle cells links the rare condition malignant hyperthermia to enhanced susceptibility to heat stroke and sudden death, said a consortium of researchers led by Baylor College of Medicine in a report in the current issue of the journal Cell.

"We created our mouse to be a model for malignant hyperthermia," said Dr. Susan Hamilton, chair of molecular physiology and biophysics at BCM and senior author of the report. Coincidentally, they found that the mouse model demonstrated a link to a condition similar to heat stroke – when the mice were exposed to warm conditions and stressed.

Rare but deadly

Malignant hyperthermia occurs because a gene mutation – often in a gene called RyR1 (http://ghr.nlm.nih.gov/gene=ryr1) – causes the body to react violently to certain drugs used as anesthetics or paralytics during surgery. The drugs trigger a chain reaction affecting the skeletal muscles. The heart beats too fast, the metabolism speeds up, muscle contracts violently and temperatures exceed 110 degrees F. Without prompt treatment, patients can die. Malignant hyperthermia is rare, but no one knows how often it occurs.

RyR1 refers to ryanodine receptor (the channel through which skeletal muscle releases calcium ions when contracting). The RyR1 mutation Hamilton and her colleagues engineered in the mice makes the channel leaky. As the calcium leaks out, it activates an enzyme called nitric oxide synthase, which stimulates production of nitric oxide. The nitric oxide then interacts with cysteines (amino acids) in RyR1, making it more temperature sensitive and starting a vicious cycle in which the response just gets worse.

Vulnerabilities exposed

When they initially tested the mouse, they found that the animal did not respond negatively to the anesthetics, probably because the body temperatures of mice regularly drop when they are under anesthesia. However, if they tried to control the animal's temperature to more normal levels under the anesthesia, its muscles contracted and it had malignant hyperthermic episodes. Later, they found that if the animal was frightened or stressed in a warm room, it had the same response.

"One day, we were in a closed off room that was really warm. All of the animals seized while running on the treadmill," she said. "We found that they were vulnerable to increased temperature. After careful analysis, we realized that the muscle was contracting at temperatures that are normally well tolerated."

The situation was similar to a marathon where the temperature is not unduly warm but 1 in 1,000 people might have heat stroke.

"This is likely to be a similar thing," she said. "They are stressed, warm and exercising."

She found that under very warm conditions, the mice die of something similar to classic heat stroke.
"The important next step is to determine if this underlies enhanced susceptibility to heat stroke in humans," she said.

Triggers

In addition, she said, they found that the leaky calcium channels in the muscles of the mice led to weakening as the animals aged.

"With these mutations, the muscles get weaker," she said. "In mice, you can prevent this with low doses of a weak antioxidant called n-acetylcysteine given over a long term."

Hamilton said there are human medical implications from the study. "There are documented cases of temperature sensitivity in some families with histories of malignant hyperthermia. I think this is telling us something really important."

"Malignant hyperthermia syndrome a potentially fatal inherited disorder is most often 'triggered' by certain gas anesthetics and the paralyzing drug succinylcholine. In the naturally occurring animal model, certain breeds of swine, the syndrome is also precipitated by environmental conditions, said Dr. Henry Rosenberg, president of the Malignant Hyperthermia Association of the United States (http://www.mhaus.org/) and professor of anesthesiology at Mount Sinai School of Medicine, N.Y. "It has long been debated as to whether some cases of heat stroke and exercise-induced muscle breakdown in humans are related to malignant hyperthermia as well. This study defines a biochemical pathway that might very well clarify the relationship between anesthesia-induced malignant hyperthermia and heat stroke. This elegant study, using modern molecular techniques, opens new avenues for the study of the not-uncommon problem of heat stroke and exercise-induced muscle breakdown and the risk for malignant hyperthermia."

"Given the frequency of the mutations in the ryanodine receptor, I suspect that malignant hyperthermia is underdiagnosed or diagnosed as something else," Hamilton said. "Some people receive the volatile anesthetics, and can die on the operating table or even die a day or so later."

Their muscles undergo sustained contractions causing them to deteriorate, releasing potassium and proteins that are toxic to the heart and kidneys.

More knowledge, better treatment

Sudden death in young athletes and soldiers is frequently associated with cardiac defects, but Hamilton and her colleagues propose that some cases of sudden death at elevated environmental temperatures are secondary to the abnormal skeletal muscle response associated with RyR1 mutations. Some people may never have the classic malignant hyperthermia response but develop a disorder of the muscles when they get too hot.

"Along with cardiac abnormalities, heat stroke is a major culprit in unexpected sudden deaths of otherwise fit, young athletes and soldiers," said Robert T. Dirksen, Ph.D., associate professor of pharmacology and physiology at the University of Rochester Medical Center. "With a better knowledge of these mechanisms, we can begin to better diagnose and treat both disorders, and hopefully, save some lives," said Dirksen, a co-author on the study.

Another factor is the muscle weakness and abnormal temperature sensitivity associated with these mutations.

"An affected individual may never have a diagnosed malignant hyperthermia episode but could have quality of life issues such as muscle weakness or poor ability to tolerate warmer temperatures," Hamilton said. "No one has looked at the myopathy (muscle deterioration) component of them because it is subtle. But by the time our mice were a year old, their muscle strength had decreased by half."

This research was performed by an interdisciplinary team including William J. Durham, Paula Aracena Parks, Cheng Long, Daniel L. Galvan, Charles P. Gilman and Mariah Baker, all of BCM; Ann E. Rossi, Sanjeewa A. Goonasekera and Robert Dirksen of the University of Rochester Medical Center in New York and Simona Boncompagni and and Feliciano Protasi of Università degli Studi G. d'Annunzio in Chieti, Italy and Natalia Shirokova of the New Jersey Medical School in Newark.

Funding for this work came from National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health, the Muscular Dystrophy Association to the Italian Telethon Foundation and a NIH Dental and Craniofacial training grant.

The paper can be found at www.cell.com.