Scientists study how HIV hides in body
Fri, 01 Feb 2008 02:57:32 GMTBy LAURAN NEERGAARD, AP Medical Writer
WASHINGTON - The AIDS virus has hideouts deep in the immune system that today's drugs can't reach. Now scientists finally have discovered how HIV builds one of those fortresses — and they're exploring whether a drug already used to fight a parasite in developing countries just might hold a key to break in.
Researchers have long struggled unsuccessfully to attack what they call reservoirs of dormant HIV, and the new work is in very early stages.
But University of Rochester scientists say it may be fairly straightforward to attack one of these reservoirs, blood cells called macrophages that HIV hijacks and turns into viral hideaways.
The new discovery shows the exact steps that HIV takes to do that — and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, can block the main step and thus cause these cells to self-destruct.
"It's a very smart virus," said lead researcher Dr. Baek Kim. "They have to have a very good fence to protect their house for a long time. ... Get rid of the fence, and now their house is gone."
Today's drugs have turned HIV from a quick death sentence into, for many, a chronic infection. Yet those drugs don't eliminate HIV because they can't reach the two known pools of cells where the virus can lie dormant, ever ready to resurface.
So-called memory T cells form one such pool. As the name implies, these are the cells that ensure if you get, say, measles as a child, you're forever immune. They live for years, even decades, making them a logical HIV hideout, and one that scientists have repeatedly sought to dismantle to no avail.
Macrophages, another type of immune cell, form the second pool. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they're supposed to commit suicide. But HIV instead keeps them alive long past their normal lifespan.
"Up to now, nobody has really thought about how to eliminate the macrophage reservoir," said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. "The imagination now has turned toward, 'How do we eliminate reservoirs?' ... The best way to address our problem is to simply kill those cells."
The Rochester team found that HIV produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt that in turn prevents cell suicide, the researchers reported Thursday online in the journal Retrovirology.
That was good news, Kim said, because the Akt pathway is a culprit in certain cancers — meaning oncologists have been trying to target it for some time. So Kim put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any killed the cells.
He had luck: Miltefosine and a cousin named perifosine both rapidly killed the macrophages, thus depriving HIV of this hideout.
Perifosine is currently being studied as a possible cancer drug. But miltefosine is known to be safe through its use in leishmaniasis patients. So Kim's goal is to rapidly study the already available miltefosine in animals, to see if it truly targets infected macrophages well enough to then test in HIV patients.
"The evidence they show is in fact pretty good," said NIH's Jeang, who says the next step should be a test of miltefosine in monkeys infected with SIV, the monkey version of the AIDS virus.
Compound cuts cerebral palsy in preemies
Fri, 01 Feb 2008 01:10:12 GMTBy STEPHANIE NANO, Associated Press Writer
NEW YORK - Doctors can cut the risk of cerebral palsy in half for very premature babies by giving their mothers magnesium sulfate just before they give birth, new research shows.
The mineral compound, also known as Epsom salts, is already used to treat preganancy-related high blood pressure and to stop early labor. Doctors should consider giving it to women about to deliver an extremely preterm infant, said one of the researchers, Dr. John Thorp of the University of North Carolina.
"It's cheap. It's readily available. It doesn't harm anybody. I think it will be widely adopted," said Thorp.
The research was led by Dr. Dwight Rouse at the University of Alabama at Birmingham and was presented Thursday at a meeting of the Society for Maternal-Fetal Medicine in Dallas.
Cerebral palsy is a serious complication of premature birth. It's caused by damage to the part of the brain that controls movement and results in poor muscle control and coordination.
Thorp said it isn't clear how magnesium sulfate works, but it is thought to open up blood vessels in the newborn's brain.
In the government-funded study, researchers gave an infusion of magnesium sulfate to women about to give birth to a premature baby to see if it would reduce the risk of cerebral palsy. Enrolled in the study were 2,241 women who were 24 to 31 weeks pregnant. Infants born before 37 weeks are considered premature.
Most of the women were in early labor because their water broke. They were given either the compound or a fake solution. The infants were examined for signs of cerebral palsy at birth and over the next two years.
Of the babies who survived, moderate or severe cerebral palsy occurred in about 2 percent of those in the treatment group compared to about 4 percent of those whose mothers didn't get the compound.
The number of infants who died was about the same in both groups.
"Cerebral palsy is not a terribly common outcome in preterm infants but when it does happen, it's devastating," said Dr. Judy Aschner, chief of neonatology at Vanderbilt Children's Hospital, who was not involved in the study.
She said doctors will want to see the details on side effects when the study is published before making any changes in the care of mothers in preterm labor. Magnesium sulfate acts like a sedative and can make moms and infants groggy and sleepy, she said.
"This is a really important study and potentially one that could change general practice," Aschner said.
In another study presented at the conference, researchers found that women who take folic acid for at least a year before they become pregnant may reduce their chances of early premature birth by 50 to 70 percent. Taking folic acid is already recommended for women of childbearing age to prevent birth defects to the brain and spinal cord, such as spina bifada.
"Here we have an added reason to motivate women to take it and to take it early in their lives," said Dr. Alan Fleischman, medical director of the March of Dimes. The group was giving the research an award at the Dallas meeting.
___
On the Net:
March of Dimes: http://www.marchofdimes.com
Swiss change safe sex message on HIV
Fri, 01 Feb 2008 01:10:01 GMTBy FRANK JORDANS, Associated Press Writer
GENEVA - Swiss AIDS experts said Thursday that some people with HIV who meet strict conditions and are under treatment can safely have unprotected sex with non-infected partners.
The proposal astonished AIDS researchers in Europe and North America who have long argued that safe sex with a condom is the single most effective way of preventing the spread of the disease — apart from abstinence.
"Not only is dangerous, it's misleading and it is not considering the implications of the biological facts involved with HIV transmission," said Jay Levy, director of the Laboratory for Tumor and AIDS Virus Research at the University of California in San Francisco.
The Swiss National AIDS Commission said patients who can satisfy strict conditions, including successful antiretroviral treatment to suppress the virus and who do not have any other sexually transmitted diseases, do not pose a danger to others. The proposal was published this week in the Bulletin of Swiss Medicine.
The Swiss scientists took as their starting point a 1999 study by the U.S. Centers for Disease Control and Prevention, which showed that transmission depends strongly on the viral load in the blood.
The other studies had also found that patients on regular AIDS treatment did not pass on the virus, and that HIV could not be detected in their genital fluids.
"Let's be clear, the decision has to remain with the HIV-negative partner," said Pietro Vernazza, head of infectious diseases at the cantonal hospital of St. Gallen in Switzerland and an author of the report.
The studies cited by the Swiss commission did not themselves definitively conclude whether people with HIV and on antiretroviral treatment could safely have unprotected sex without passing on the virus.
The World Health Organization said Switzerland would be the first country in the world to try this approach.
"There is still some concern that you can never guarantee that somebody will not be infectious, and the evidence I have to say is not conclusive," said Charlie Gilks, director of AIDS treatment and prevention at WHO.
"We are not going to be changing in any way our very clear recommendations that people on treatment continue to practice safer sex, including protected sex with a condom, in any relationship," he added.
In any case, of the 2 million people worldwide now receiving HIV treatment, only a very small number receive medical care comparable to that in Switzerland, Gilks said.
Super Bowl could be heart health hazard
Fri, 01 Feb 2008 01:09:44 GMTBy MALCOLM RITTER, AP Science Writer
NEW YORK - For rabid fans of the New York Giants and New England Patriots, this Sunday's Super Bowl won't be just a game. It may be a health hazard. Heart attacks and other cardiac emergencies doubled in Munich, Germany, when that nation's soccer team played in World Cup matches, a new study reports.
While history suggests European soccer fans can get a bit more worked up than the average American football fan, doctors think there are some valid warnings to be shared.
"I know a little bit about the Super Bowl," study author Dr. Gerhard Steinbeck of Ludwig Maximilians University in Munich said in a telephone interview. "It's reasonable to think that something quite similar might happen."
He and his colleagues present their results in Thursday's New England Journal of Medicine. They blamed emotional stress for the heart problems, but they note that lack of sleep, overeating, wolfing down junk food, boozing and smoking might have played a role too.
Previous studies suggest that events like earthquakes and war can boost the risk of heart problems. Findings for soccer have been inconsistent.
The new work "confirms something people have been highly skeptical about ... that soccer produce that kind of emotional investment that might trigger a heart attack," said psychologist Douglas Carroll of the University of Birmingham in England.
"People who are not interested in sport find it very difficult to comprehend this," said Carroll, who in 2002 reported a link between World Cup soccer and heart attacks in England.
The new paper included heart attacks, cardiac arrests, episodes of irregular heartbeat and activations of automatic implanted defibrillators. The researchers noted the number of cases reported in the greater Munich area during World Cup competition in Germany in the summer of 2006. They compared that to the totals for similar periods in 2003 and 2005, and for several weeks before and after the tournament.
In all, the study included 4,279 patients. Analysis showed that on the seven days when the German team played, the overall number of cardiac emergencies was more than double the norm. For men, it tripled.
The effect was strongest in people with known heart disease. So on Super Bowl Sunday, such people and others with known risks for heart disease — like high blood pressure or diabetes — should take extra care of themselves, said Dr. Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital.
She said that means:
• Take medications as prescribed.
• Avoid tobacco smoke and fatty meals.
• Get plenty of sleep the night before.
• Don't over-exert yourself physically.
• If you drink alcohol, limit yourself to one drink for a woman and two for a man.
• Try "not to get too angry with the refs."
People with known heart conditions should also keep their nitroglycerin and aspirin handy, she said.
And if heart symptoms appear, she said, call emergency services right away. "Don't just chew that aspirin and think it'll go away."
In fact, research by Dr. David Jerrard, an associate professor of emergency medicine at the University of Maryland, indicates that some men do put off seeking emergency treatment if they're watching a game.
On a typical Super Bowl Sunday, "the number of patients waiting to be seen dries up dramatically," Jerrard said. But delaying that visit to stick with a sportscast is a bad idea, especially for people with a history of heart trouble, he says.
"Much of the chest pain or upper abdominal pain that people might be experiencing is mostly likely related to the food they're eating, the alcohol they're ingesting," he said. "But of course, you never know."
___
On the Net:
New England Journal of Medicine: http://www.nejm.org
American Heart Association: http://www.heart.org
AtkinsLike Diet Cuts Epileptic Seizures
Fri, 01 Feb 2008 00:02:52 GMTBy Steven Reinberg
HealthDay Reporter
THURSDAY, Jan. 31 -- Adults with epilepsy who have failed other treatments may be able to dramatically reduce their number of seizures by following a modified Atkins-like diet, Johns Hopkins researchers report.
The high-protein, low-carbohydrate diet has already been shown to be valuable in controlling seizures in children, and now results from a small study suggest that the diet also works for adults.
"There are a lot of adults with very bad seizures. There are a lot of adults who have failed medicines and are not candidates for other treatments," said lead researcher Dr. Eric H. Kossoff, an assistant professor of neurology and pediatrics at Johns Hopkins School of Medicine.
For the study, Kossoff's team gave the diet to 30 adults who had unsuccessfully tried at least two anti-convulsant drugs and had an average of 10 seizures a week. The eating plan restricts patients to 15 grams of carbohydrates a day. Most of the calories come from fats such as eggs, meats, oils and heavy cream. In addition, patients are free to eat as much protein and no-carb drinks as they want.
"There was good news and bad news," Kossoff said. "The good news was it worked. The bad news it was tough. About 30 percent of the patients stopped the diet. This happened even in patients who had good seizure control who thought the diet was still too tough to do."
After a month on the diet, half the patients reported suffering 50 percent fewer seizures. At three months, about one-third of the patients cut the frequency of seizures by half.
However, by three months, one-third of the patients had dropped out of the study because they found the diet too restrictive, Kossoff said.
The diet's side effects, such as increases in cholesterol or triglycerides, were mild, Kossoff noted.
After six months on the diet, 14 patients continued with it, even though the study was over, he said.
The findings are published in the February issue of the journal Epilepsia.
No one knows how the diet works to reduce seizures, Kossoff said. And, most people find it too hard to follow, so it's probably not a long-term solution for most people with epilepsy, he added.
He also noted that patients who go on the diet need to continue with it, perhaps for years to keep seizures under control.
But Kossoff thinks the diet can be simplified to make it easier to follow. "We are looking at less time in the clinic and fewer restrictions and without a dietitian," he said.
Dr. Gholam Motamedi, director of the epilepsy service at Georgetown University Hospital, thinks the diet can be useful for patients who have no other options.
"The study is promising, especially given that patients with refractory epilepsy in particular -- those who are not surgical candidates -- are left with not much hope," he said.
Normally, the plan for these patients is to try a combination of different drugs or to use vagus nerve stimulation, but none of these options offers much hope of seizure control, Motamedi said.
"Therefore, having another modality available is always welcomed by the neurologists," he said. "It also encourages basic research looking for insight to the underlying reasons for epilepsy."
More information
For more on epilepsy, visit the Epilepsy Foundation.
