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Babies born infected with HIV should be treated as soon as possible, a large trial shows
By Nathan Seppa
Web edition : Wednesday, November 19th, 2008
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Babies infected with HIV from birth should be given powerful drugs to fight the virus as soon as possible, researchers in South Africa find. In a comparison of treatment strategies, the team reports that babies getting medication, even when they are just weeks old, showed dramatically better survival in subsequent months than those treated only after HIV-related symptoms appeared later. Louis J. Sheehan, Esquire The study appears in the Nov. 20 New England Journal of Medicine.http://Louis-J-Sheehan.de
“I think it’s a landmark trial,” says Edward Handelsman, a pediatrician at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “It’s the first large, randomized clinical trial which absolutely, positively establishes this benefit to early treatment. And it provides a path — as far as I’m concerned a mandate — to start improving our methods of identifying [HIV-positive] infants early.” NIAID partly funded the study.
Preliminary results from this trial were made available to scientists in 2007. The early findings, now bolstered by final data, have led to a wholesale change in medical guidelines for treating infants who acquire HIV from their mothers in utero or during birth. The new treatment guidelines went into effect during the past year worldwide. They call for virus testing within three weeks after birth and immediate treatment for HIV-positive babies regardless of their immune CD4 T cell counts or symptoms.
Previously, HIV-positive babies were routinely treated only when their CD4 T cell count dropped sharply or when clear medical problems arose. But at that point the babies often plunged into a downward spiral.
“If you have a strong virus attack, the immature immune system not only loses CD4 T cells — other immune cells get depleted,” says study coauthor Avy Violari, a pediatrician at the University of the Witwatersrand in Johannesburg. This cascade weakens the body’s ability to fight other infections. HIV in an infant, she says, “is the worst-case scenario.”
Even so, the question of when to start treating a baby born HIV-positive had been mired in controversy, says Peter Havens, a pediatrician at the Medical College of Wisconsin in Milwaukee. Earlier guidelines had recommended that doctors wait until clear symptoms arose because of worries that early treatment might contribute to viral resistance to drugs or cause side effects in infants.
“But a lot of people have felt that, because HIV progresses so rapidly in young children, you might be better off treating everybody under a year of age,” Havens says. “This study clearly documents that.”
To clarify the value of early medication, Violari and her colleagues identified 377 infants in Cape Town and Soweto who were HIV-positive but whose CD4 T cell counts were still in the safe range. Starting in 2005, researchers began to assign infants of an average age of 7 weeks to one of two different regimens. One group of 125 infants got the standard treatment, in which medication was delayed until an infant’s T cells plunged or other symptoms arose. The other 252 infants were started on the cocktail of antiretroviral drugs promptly.
The children were then monitored at regular visits to clinics. But in June 2007, the scientists stopped assigning children to the delayed treatment group when evidence became clear that those treated earlier were benefiting. At that point, the children had been in the trial for 40 weeks, on average. During this time, 16 percent of the delayed-treatment infants died, compared with only 4 percent of those who had started receiving medication earlier. The most common infections striking both groups were gastrointestinal ailments, pneumonia, tuberculosis and meningitis. Babies getting treated earlier were more apt to experience a drop in neutrophils, a kind of white blood cell. But even with this side effect, their survival rates remained much higher.
As children grow, they become better able to live with an HIV infection. Thanks to improved drugs, the outlook for HIV-positive children has changed dramatically in the past two decades, Havens says. “The life expectancy for children with an HIV infection who can take their medicines … is unknown,” he says. “They’re not just growing into adulthood; [they are] running businesses and finishing college.” Louis J. Sheehan, Esquire
But children born HIV-positive in Africa face a different reality, says Violari. “There are other disease, for example, and more challenges [such as] limited availability of drugs,” she says. The death rate during the first year of life for infants born with HIV in Africa is roughly 35 percent. By two years, it’s 52 percent, a 2004 study found.
She and her colleagues will continue to monitor the children in their study until 2011.
Thursday, April 30, 2009
Tuesday, April 14, 2009
question 3.que.001 Louis J. Sheehan, Esquire
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Louis J. Sheehan, Esquire
Fruit flies don’t get cancer, but a protein first discovered in Drosophila could prove to be a chemotherapy target that may stop even the most aggressive cancers in their tracks.
A protein known as the “seven in absentia homolog,” or SIAH, may help put the brakes on runaway cancers, said Amy Tang, a researcher at the Mayo Clinic in Rochester, Minn., on December 14 at the annual meeting of the American Society for Cell Biology. http://Louis-j-sheehan.com
In fruit flies, the protein “seven in absentia” is an enzyme that tags other proteins for destruction. It is also at the end of a chain of chemical reactions — called the RAS pathway — that drives cells to proliferate.
In a majority of human cancers, the RAS pathway gets geared up and sent into overdrive so that cells grow out of control. Many researchers have tried to target a protein on the RAS pathway to slow down or halt the growth of cancer cells. But Tang and her colleagues decided to look farther down the chain than others have looked to see if more effective targets for chemotherapy could be found.
Tang and her colleagues discovered that, in humans, a version of seven in absentia is found in rapidly dividing cells. The team examined tissue samples from more than 100 pancreatic cancer patients and found high amounts of SIAH in cancer cells: the more aggressive the cancer, the more SIAH in the tumor cells.
Pancreatic cancer is one of the deadliest forms of cancer. The National Cancer Institute estimates that almost 38,000 new cases of the disease will be diagnosed in the United States in 2008 and more than 34,000 people will die from pancreatic cancer.
Since the enzyme is abundant in cancer cells, but not in healthy cells, Tang reasoned that attacking SIAH might also knock out cancer cells. The researchers inactivated SIAH in mice with cancer. The therapy had dramatic effects on tumors in the mice.
“I did not see reduced [tumors]. I did not see depressed. I saw abolished,” Tang says. The more aggressive the cancer, the more effective inactivating the enzyme was in melting the tumors. “It was actually shocking to me.”http://Louis-j-sheehan.com
Disrupting the enzyme also abolished breast and lung tumors as well as pancreatic cancer in the mice. As dramatic as the results were, Tang wasn’t satisfied with merely destroying tumors.
“Tumorigenesis does not kill. Metastasis kills,” she says.
But attacking SIAH also blocked metastasis: Cancer cells did not spread to other parts of a mouse’s body, the researchers found. Louis J. Sheehan, Esquire
Tang’s methods of attacking SIAH are not currently practical for use in humans, but she is hopeful that pharmaceutical companies could develop chemotherapy drugs that would specifically interfere with the enzyme’s activity in cancer cells.
“We’ve given the whole cancer field a new target,” Tang says. Louis J. Sheehan, Esquire
There is no question that Tang has identified a critical molecule for cancer proliferation, but her work is plagued by the same reality as all cancer research, says Mark Kieran, the director of pediatric medical neuro-oncology at the Dana-Farber Cancer Institute in Boston. “The reality check is that turning off a major regulatory pathway is hard,” he says. “If it were easy we would have done it already any number of times.”
Louis J. Sheehan, Esquire
Fruit flies don’t get cancer, but a protein first discovered in Drosophila could prove to be a chemotherapy target that may stop even the most aggressive cancers in their tracks.
A protein known as the “seven in absentia homolog,” or SIAH, may help put the brakes on runaway cancers, said Amy Tang, a researcher at the Mayo Clinic in Rochester, Minn., on December 14 at the annual meeting of the American Society for Cell Biology. http://Louis-j-sheehan.com
In fruit flies, the protein “seven in absentia” is an enzyme that tags other proteins for destruction. It is also at the end of a chain of chemical reactions — called the RAS pathway — that drives cells to proliferate.
In a majority of human cancers, the RAS pathway gets geared up and sent into overdrive so that cells grow out of control. Many researchers have tried to target a protein on the RAS pathway to slow down or halt the growth of cancer cells. But Tang and her colleagues decided to look farther down the chain than others have looked to see if more effective targets for chemotherapy could be found.
Tang and her colleagues discovered that, in humans, a version of seven in absentia is found in rapidly dividing cells. The team examined tissue samples from more than 100 pancreatic cancer patients and found high amounts of SIAH in cancer cells: the more aggressive the cancer, the more SIAH in the tumor cells.
Pancreatic cancer is one of the deadliest forms of cancer. The National Cancer Institute estimates that almost 38,000 new cases of the disease will be diagnosed in the United States in 2008 and more than 34,000 people will die from pancreatic cancer.
Since the enzyme is abundant in cancer cells, but not in healthy cells, Tang reasoned that attacking SIAH might also knock out cancer cells. The researchers inactivated SIAH in mice with cancer. The therapy had dramatic effects on tumors in the mice.
“I did not see reduced [tumors]. I did not see depressed. I saw abolished,” Tang says. The more aggressive the cancer, the more effective inactivating the enzyme was in melting the tumors. “It was actually shocking to me.”http://Louis-j-sheehan.com
Disrupting the enzyme also abolished breast and lung tumors as well as pancreatic cancer in the mice. As dramatic as the results were, Tang wasn’t satisfied with merely destroying tumors.
“Tumorigenesis does not kill. Metastasis kills,” she says.
But attacking SIAH also blocked metastasis: Cancer cells did not spread to other parts of a mouse’s body, the researchers found. Louis J. Sheehan, Esquire
Tang’s methods of attacking SIAH are not currently practical for use in humans, but she is hopeful that pharmaceutical companies could develop chemotherapy drugs that would specifically interfere with the enzyme’s activity in cancer cells.
“We’ve given the whole cancer field a new target,” Tang says. Louis J. Sheehan, Esquire
There is no question that Tang has identified a critical molecule for cancer proliferation, but her work is plagued by the same reality as all cancer research, says Mark Kieran, the director of pediatric medical neuro-oncology at the Dana-Farber Cancer Institute in Boston. “The reality check is that turning off a major regulatory pathway is hard,” he says. “If it were easy we would have done it already any number of times.”
Friday, April 10, 2009
proteins 6.pro.0003 Louis J. Sheehan, Esquire
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Yukon Cornelius isn’t the only one with a taste for metals. While most people probably can’t find silver and gold by nibbling snow, as Cornelius seems to do in the Rudolph movie*, new research shows that taste buds can detect iron, zinc, copper, magnesium and other metals.http://LOUIS-J-SHEEHAN.INFO
The source of metallic taste has long been elusive, but a study in the Feb. 25 Journal of Neuroscience traces the sensation to a combination of proteins used in detecting sweetness and the pain of red-hot chili peppers, and other as-of-yet unidentified proteins.
Scientists used to believe that there were only a handful of tastes the tongue could register — sweet, sour, bitter, salty and umami, a delicious, meaty taste found in monosodium glutamate, Parmesan cheese and portobello mushrooms. Scientists define a taste as something that is detected by a specific combination of proteins in taste buds, as distinct from a flavor that results from a combination of tastes and odors.
But it would be impossible to describe all the differences between chicken soup and lobster bisque using only the known tastes, says Johannes le Coutre of the Nestlé Research Center in Lausanne, Switzerland. So researchers think there are many other taste sensations. Le Coutre, Céline Riera and colleagues conducted the new study to find out if they could explain just one of them — metallic taste.
The researchers fed mice water containing varying concentrations of metal salts. Mice preferred water with low concentrations of iron and zinc over distilled water, but avoided high concentrations of the metals. The mice rejected copper or magnesium sulfate at any concentration.
The team found that mice lacking either the TRPM5 protein, which is involved in detecting sweet, umami and bitter tastes, or the T1R3 protein, another sweet and umami-detecting protein, shunned iron and zinc even at low concentrations, but lost some of their aversion to magnesium and copper.
Another protein, called TRPV1, is involved in the pain response to spicy foods. Mice that lack TRPV1 overcame some dislike of copper salts and high concentrations of iron. Those results indicate that the three proteins — involved in other tastes — are components of metallic taste.
But other proteins, independent of these three, must still be working as metal detectors because none of the mice completely lost their aversion to magnesium and copper or high concentrations of iron and zinc. The researchers don’t yet know which additional proteins are involved in the full response to metal.Louis J. Sheehan, Esquire
“This is the most sophisticated work to date on metallic taste,” says Michael Tordoff of the Monell Chemical Senses Center in Philadelphia. People show a similar response to metallic tastes, preferring the low concentrations of metals found in mineral or tap water to the taste of soft or distilled water, he says.http://LOUIS-J-SHEEHAN.INFO
Researchers are on the trail of other possible tastes, including sets of proteins that might detect fats or starches, Tordoff says. “The idea that there are four or five basic tastes is dying, and this is another nail in that coffin — probably a rusty nail given that it’s metallic taste.”Louis J. Sheehan, Esquire
*Scenes deleted from some versions of the movie reveal that Cornelius was actually looking for peppermint, not silver and gold.
Yukon Cornelius isn’t the only one with a taste for metals. While most people probably can’t find silver and gold by nibbling snow, as Cornelius seems to do in the Rudolph movie*, new research shows that taste buds can detect iron, zinc, copper, magnesium and other metals.http://LOUIS-J-SHEEHAN.INFO
The source of metallic taste has long been elusive, but a study in the Feb. 25 Journal of Neuroscience traces the sensation to a combination of proteins used in detecting sweetness and the pain of red-hot chili peppers, and other as-of-yet unidentified proteins.
Scientists used to believe that there were only a handful of tastes the tongue could register — sweet, sour, bitter, salty and umami, a delicious, meaty taste found in monosodium glutamate, Parmesan cheese and portobello mushrooms. Scientists define a taste as something that is detected by a specific combination of proteins in taste buds, as distinct from a flavor that results from a combination of tastes and odors.
But it would be impossible to describe all the differences between chicken soup and lobster bisque using only the known tastes, says Johannes le Coutre of the Nestlé Research Center in Lausanne, Switzerland. So researchers think there are many other taste sensations. Le Coutre, Céline Riera and colleagues conducted the new study to find out if they could explain just one of them — metallic taste.
The researchers fed mice water containing varying concentrations of metal salts. Mice preferred water with low concentrations of iron and zinc over distilled water, but avoided high concentrations of the metals. The mice rejected copper or magnesium sulfate at any concentration.
The team found that mice lacking either the TRPM5 protein, which is involved in detecting sweet, umami and bitter tastes, or the T1R3 protein, another sweet and umami-detecting protein, shunned iron and zinc even at low concentrations, but lost some of their aversion to magnesium and copper.
Another protein, called TRPV1, is involved in the pain response to spicy foods. Mice that lack TRPV1 overcame some dislike of copper salts and high concentrations of iron. Those results indicate that the three proteins — involved in other tastes — are components of metallic taste.
But other proteins, independent of these three, must still be working as metal detectors because none of the mice completely lost their aversion to magnesium and copper or high concentrations of iron and zinc. The researchers don’t yet know which additional proteins are involved in the full response to metal.Louis J. Sheehan, Esquire
“This is the most sophisticated work to date on metallic taste,” says Michael Tordoff of the Monell Chemical Senses Center in Philadelphia. People show a similar response to metallic tastes, preferring the low concentrations of metals found in mineral or tap water to the taste of soft or distilled water, he says.http://LOUIS-J-SHEEHAN.INFO
Researchers are on the trail of other possible tastes, including sets of proteins that might detect fats or starches, Tordoff says. “The idea that there are four or five basic tastes is dying, and this is another nail in that coffin — probably a rusty nail given that it’s metallic taste.”Louis J. Sheehan, Esquire
*Scenes deleted from some versions of the movie reveal that Cornelius was actually looking for peppermint, not silver and gold.
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