Study Finds Possible Targets for H.I.V. Drugs

Using a new type of genetic screen, researchers at Harvard Medical School have identified 273 proteins that the AIDS virus needs to survive in human cells, opening up new potential targets for drugs.

Their work, published online on Thursday by Science magazine, used RNA interference to screen thousands of protein-making genes; previously, scientists had identified only 36 human proteins that the virus uses to break into cells, hijack their machinery and start reproducing.

“This is just terrific work,” said Dr. Robert C. Gallo, director of the Institute of Human Virology at the University of Maryland and a co-discoverer of the virus. “I think it’s destined to be one of the top papers in this field for the decade.”

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and the government’s top AIDS expert, called the Harvard team’s work “elegant science,” but added a caution.

“It remains to be seen if any of these proteins they identified are useful clinically,” Dr. Fauci said. “This is hypothesis-generating, not hypothesis-solving. It creates a lot of work — someone has to go down each of these pathways.”

The lead author on the paper, Dr. Stephen J. Elledge, is a geneticist, and this is his first work on the human immunodeficiency virus, which causes AIDS. His previous work has been on cancer, Dr. Elledge said, trying to figure out how cells sense when their chromosomes are broken, and this paper was a collaborative effort.

“I can’t even grow H.I.V. in my lab,” Dr. Elledge said, so he had to use virus grown by Dr. Judy Lieberman, director of the medical school’s AIDS division and one of the co-authors.

Dr. Elledge’s team used a library of tens of thousands of different short interfering RNAs, bits of genetic code — each of which, when introduced into a cell, knocks out the cell’s ability to make a single protein.

Next, about 21,000 samples of cells, each crippled in its ability to produce one protein, were placed in separate wells on laboratory plates and dosed with the virus.

If the virus could not reproduce normally in a given well, it suggested that the missing protein was one of those it needed.

Of the 273 human proteins identified, only 36 had been previously found by other methods.

The virus, which is itself only a short string of genetic material inside a protective capsule, can make only 15 proteins, so it has to adopt human proteins to its own use.

The advantage of targeting human proteins is that the virus would presumably not be able to mutate to avoid drugs that block them, Dr. Elledge said. Right now, virus strains evolve resistance to antiretroviral drugs, which attack the 15 proteins made by the virus itself, like reverse transcriptase and protease. The mutations force AIDS patients to switch drug regimens — not always successfully.

The disadvantage is that blocking human proteins can, obviously, be fatal to humans. But, as Dr. Gallo pointed out, cancer therapy works that way — doctors try to block proteins that feed fast-growing tumor cells without killing too many other fast-growing cells, like those in the bone marrow.

Right now, Dr. Elledge said, only one drug that targets one of the known human proteins, a receptor called CCR5, has been developed, and it has just won approval.

The new screening technology, known as siRNA, is now used in many laboratories, so this work could theoretically have been done elsewhere, or by using older, more laborious methods.

Dr. Elledge said he benefited from working at Harvard, which could afford the expensive robotics and imaging technology needed.

“And I had lots of collaborators and very dedicated people,” he said.

To confirm that the newly identified proteins were important to the life cycle of the virus — which Dr. Elledge described as “opaque” — the team ran further tests on three of them.

Many of the proteins identified by the screen are already known to be important to cells in the immune system, which is the port of entry for H.I.V.

Dr. Abraham L. Brass, a co-author, said the screening method undoubtedly missed other proteins the virus needs, “but the majority of the ones we found are highly likely to play a role in H.I.V. propagation.”

Source: www.nytimes.com

Sweetener in Chewing Gum Can Damage Your Health

A sweetener used in sugar-free chewing gum, some toothpastes and thousands of other products could be a severe health risk, doctors warned.

Sorbitol, also known as E 420, can trigger severe weight loss, abdominal pain and diarrhoea.

A report in the British Medical Journal today highlights the cases of patients who lost up to a fifth of their bodyweight.

The cause was eventually traced to excess intake of sorbitol - one was eating 14-20 sticks of gum a day.

Dentists recommend chewing sugarfree gum to increase saliva production, which reduces cavities and strengthens teeth.

Wrigley, which owns many of the brands sold in the UK, has seen its sales in Europe grow by a third since Sorbitol is also used in sugar-free sweets, some cereals and foods aimed at diabetics.

But gastroenterology experts in Germany say many consumers - and even some doctors - are unaware of the laxative side-effects of sorbitol, which can also hinder the absorption of nutrients into the small intestine.

Professor Herbert Lochs and Dr Juergen Bauditz, from the University of Berlin studied two patients with chronic diarrhoea, abdominal pain and substantial weight loss.

They underwent extensive investigation before a detailed analysis of their eating was undertaken. It found both had been consuming large amounts of sugarfree gum and sweets.

The first, a 21-year-old woman, chewed around 15 sticks of gum a day. Her weight plunged by almost 2st to just 6st 6lb.

The second patient, a 46-year-old man, chewed 20 sticks of gum and ate up to 200g of sweets each day. He lost more than 3st in a year.

After they started a sorbitol-free diet, their diarrhoea stopped and they gained weight.

Professor Lochs said the cases were unusual because the consumption of sorbitol was not enormously high yet the effects had been serious. He said the public, particularly diabetics who buy low- sugar or sugar-free foods, should be warned that too much sorbitol may be "dangerous".

The professor said warnings about possible side-effects were usually "in the small print" of packaging and people who suffered gastrointestinal problems might not make the connection. Doctors also needed to be alert to the possibility.

Professor Lochs said men and women should not try to lose weight using sugarfree gum because their intake of nutrients would be affected..

Wrigley said last night: "It is well documented in medical literature, with studies going back more than 20 years, that excessive consumption of polyols such as sorbitol can have a laxative effect in some individuals.

"Those studies generally indicate that people can consume up to 40g of sorbitol without experiencing a laxative effect - subject to the individual and other diet components - a level not even approached by normal consumption of sugar-free chewing gum."

The company said its labelling carried warnings required by EU regulations.

Jemma Edwards, Care Advisor and registered dietician at Diabetes UK, said "We already know that many sweeteners have a laxative effect.

"Diabetes UK does not recommend 'diabetic' food because there are no added nutritional benefits and it is often more expensive. People with diabetes can eat normal food as long as they have a healthy, balanced diet."

Source: www.dailymail.co.uk

Research Offers Promise for Cirrhosis Treatment

New findings about the inner workings of cells may be bringing scientists one step closer to reversing the scarring of the liver known as cirrhosis.

Currently, the best treatment for advanced cirrhosis is a liver transplant, an option that's often not available. But newly released research with mice suggests that a drug-based strategy could reprogram cells and make it "feasible to treat it [cirrhosis] and prevent it without a transplant," said study lead author Martina Buck, an assistant professor of medicine at the University of California, San Diego.

There's no guarantee, however, that the treatment will work in humans. And Buck said it could take at least five to 10 years for a drug to reach the market if a pharmaceutical company became interested in pursuing it.

But the research might also lead to new treatments for other conditions that lead to excess tissue scarring, such as viral hepatitis, fatty liver disease, pulmonary fibrosis, scleroderma and burns, the study authors said.

At issue is scarring in the liver, an organ that filters out toxins and breaks down medications. The scarring is a "natural healing process," Buck said, but overuse of alcohol and diseases like hepatitis can make the scarring become chronic and lead to major health problems like cancer.

In the new study, Buck and her colleagues focused on liver cells that transform into scar tissue when activated. They used mice with severe liver fibrosis that was brought about by chronic exposure to a toxin known to cause liver damage. Next, they genetically engineered mice to activate a protein that provides protection against scarring.

The researchers found that the protein seemed to protect the mice from scarring, and "if you wait until [a mouse] has cirrhosis before you treat him, he will actually regress. It's not just a preventive thing. It's an actual treatment," Buck said.

The study was published Dec. 26 in the journalPublic Library of Science Online.

Research into the workings of liver cells in people suggests that the treatment might also work in humans, Buck said. Potentially, the treatment could be converted into a drug that could be given orally or intravenously, she said.

Dr. Scott Friedman, chief of the Division of Liver Diseases at Mount Sinai School of Medicine in New York City, said that while the study is useful, it's "not a major breakthrough" considering the many research projects in a similar stage of development.

Still, he said, it "builds on 20 years of very exciting research" that looks at how cells create scarring in the liver.

Source: www.washingtonpost.com

University of Minnesota Developing Cyanide Antidote

University of Minnesota researchers are developing a fast-acting antidote to the deadly poison cyanide.

The scientists say their treatment is effective on mice. They hope to start human trials within three years.

The body already is able to detoxify the small amounts of cyanide that occur naturally in pitted fruits and other foods. Researcher Steven Patterson says the new antidote works with the body's natural protections.

Concerns over the potential use of cyanide as a chemical weapon by terrorists led to the federal funding of the research. But firefighters might benefit most of all from the antidote because building fires produce large amount of the poison.

Researchers hope their antidote becomes part of a standard kit given to first responders.

Source: http://wkbt.com/