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Waking up Dormant HIV

World HIV/AIDS Awareness Day
Image by reflexblue via Flickr

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to ‘turn on’ latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.
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Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

Sources
:http://www.asbmb.org/News.aspx?id=2286

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Health Quaries

Some Health Quaries & Answers

Q: I like to avoid breakfast as I feel it is unnecessary. I also think I am more likely to lose weight in this way.

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A: Many studies have shown that 40 minutes of exercise followed by a healthy breakfast is the best way to kickstart your day. It prevents “mid morning blues” and reduces the craving for food and hence the total consumption of calories during the day.

Dog bite bother

Q: I got bitten on the cheek by my neighbour’s dog. They say that they were unable to complete the schedule of immunising the dog.

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A: Dog bites are dangerous as they can transmit rabies. The safest course of action is to clean the wound thoroughly with soap and water and then leave it open. Take a single injection of tetanus toxoid and then proceed to take the anti-rabies injections as per schedule of the injection package. The newer vaccines are given in the arm. They are safe and produce fewer side effects than the older vaccine which was given around the umbilicus. The vaccine is freely available. You need not go to a government hospital for treatment as earlier.

Better safe than sorry

Q: I was told that only the semen contains disease causing organisms, and so using a condom just before ejaculation is enough to prevent diseases like AIDS.

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A: During sex the skin of the vagina is in close contact with that of the penis even before ejaculation. Small abrasions are enough to transmit infection. Be safe. Use a condom from the beginning of the intercourse. You have only one life. Why endanger yourself?

i-pill?

Q: My wife has just had a baby. How soon can we have intercourse? I don’t want another child before 3-4 years. Can we use the i-pill?

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A: Intercourse can be resumed six weeks after childbirth, provided the attending physician hasn’t advised otherwise. You need to use contraception even if your wife doesn’t begin menstruating after six weeks or if she is breast feeding. You can use condoms, or opt for the insertion of an IUCD (intrauterine contraceptive device), also called a “loop”, or take regular injections (every 12 weeks) of a long acting progesterone or take “progesterone only” pills daily. Combined (estrogen-progesterone) pills are not advisable for breast feeding mothers.

The i-pill is intended only for emergency contraception. It is not meant for use on a regular basis.

Rash riddle

Q: My one-year-old son developed rashes on both his cheeks. The doctor said it is allergy to cow milk. Although I’ve stopped giving him milk, the rash has not improved. How is that possible?

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A: What you are describing is eczema, an allergic skin reaction. You may have stopped giving him milk but he may be receiving milk indirectly in biscuits or pre-packaged ready to eat weaning cereals. This may perpetuate the problem.

Help, I’m fat

Q: I am 32 years old and weigh 97kg. I calculated my BMI and it is 37. I read recently that if the cholesterol values are high, it is not possible to lose weight no matter what you do. This is very discouraging.

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A: You do urgently need to lose weight and this cannot be achieved by diet alone. You need a sensible low fat 1,500-calorie diet and at least an hour of exercise. Brisk walking is probably sufficient. Consult your physician for your cholesterol values and appropriate treatment. Safe medications are now available to lower cholesterol and also to control appetite.

Twin trouble

Q: What are the chances of having twins? The number of twins seems to be increasing in general and I am worried.

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A: Twins occur in around 30 out of 1,000 pregnancies. The percentage may seem to be high. In fact, pregnancies after fertility medication or in vitro fertilisation (test tube babies) are more likely to be multiple.

Your chance of having twins is greater if there is a family history of twins.

Sources:
The Telegraph (Kolkata, India)

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AIDS Can be Eliminated in 10 Years

The virus that causes AIDS could theoretically be eliminated in a decade if all people living in countries with high infection rates are regularly tested and treated, according to a new mathematical model………..CLICK & SEE

It is an intriguing solution to end the AIDS epidemic. But it is based on assumptions rather than data, and is riddled with logistical problems. The research was published online on Tuesday in the medical journal, the Lancet.

“It’s quite a startling result,” said Charlie Gilks, an AIDS treatment expert at the World Health Organization and one of the paper’s authors. “In a relatively short amount of time, we could potentially knock the epidemic on its head.”

Gilks and colleagues used data from South Africa and Malawi. In their model, people were voluntarily tested each year and immediately given drugs if they tested positive for HIV, regardless of whether they were sick. Within 10 years, HIV infections dropped by 95%. Other initiatives like safe sex education and male circumcision were also used.

The strategy would cut the estimated number of AIDS deaths between 2008 and 2050 by about half, from about 8.7 million to 3.9 million, leaving only sporadic HIV cases. Experts think the strategy’s cost would peak at about $3.4 billion a year, though expenses would fall after an initial investment.

“This is certainly beyond the bounds of the current infrastructure for many countries, but that is not a reason not to think big,” said Myron Cohen, of the University of North Carolina, who has done similar research.

Only 3 million people are currently on AIDS drugs. Nearly 7 million people are still awaiting treatment, and about 3 million more people were infected last year. Worldwide, WHO guesses that about 33 million people have HIV. Increasing access to testing and drugs would stretch already weak health systems in Africa, which has most of the world’s HIV cases.

WHO emphasized that the study findings do not signal a policy change. “This is only a theoretical exercise,” said Kevin De Cock, director of WHO’s HIV/AIDS department. He said WHO would hold a meeting next year to study the idea more closely.

Sources: The Times Of India

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Bone Marrow ‘Cures AIDS Patient’

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A bone marrow transplant using stem cells from a donor with natural genetic resistance to the AIDS virus has left an HIV patient free of infection for nearly two years, German researchers.

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The patient, an American living in Berlin, was infected with the human immunodeficiency virus that causes AIDS and also had leukemia.

The best treatment for the leukemia was a bone marrow transplant, which takes the stem cells from a healthy donor’s immune system to replace the patient’s cancer-ridden cells.

Dr Gero Hutter and Thomas Schneider of the Clinic for Gastroenterology, Infections and Rheumatology of the Berlin Charite hospital said on Wednesday the team sought a bone marrow donor who had a genetic mutation known to help the body resist AIDS infection.

The mutation affects a receptor, a cellular doorway, called CCR5 that the AIDS virus uses to get into the cells it infects.

When they found a donor with the mutation, they used that bone marrow to treat the patient. Not only did the leukemia disappear, but so did the HIV.

“As of today, more than 20 months after the successful transplant, no HIV can be detected in the patient,” the clinic said in a statement. “We performed all tests, not only with blood but also with other reservoirs,” Schneider told a news conference. “But we cannot exclude the possibility that it’s still there.”

The researchers stressed that this would never become a standard treatment for HIV. Bone marrow stem cell transplants are rigorous and dangerous and require the patient to first have his or her own bone marrow completely destroyed.

Patients risk death from even the most minor infections because they have no immune system until the stem cells can grow and replace their own.

HIV has no cure and is always fatal. Cocktails of drugs can keep the virus suppressed, sometimes to undetectable levels. But research shows the virus never disappears — it lurks in so-called reservoirs throughout the body.

Hutter’s team said they have been unable to find any trace of the virus in their 42-year-old patient, who remains unnamed, but that does not mean it is not there. “The virus is tricky. It can always return,” Hutter said.

The CCR5 mutation is found in about 3% of Europeans, the researchers said. They said the study suggests that gene therapy, a highly experimental technology, might someday be used to help treat patients with HIV.

Sources: The Times Of India

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Of Glowing Proteins and Killer Viruses

This year’s Nobel prizes in physics, chemistry and medicine have a strong Japanese flavour.

As is the case with most great scientific discoveries, it all started with a bit of curiosity. In the 1960s, Osamu Shimomura wondered why crystal jellyfish gave off green pinpricks of light. Now, half a century later, Shimomura has been awarded for his curiosity with the Nobel prize in chemistry.

Shimomura was fascinated by the chemistry involved in bioluminescence and collected more than one million jellyfish from Friday Harbor in Washington State in the US in the 1960s and early 1970s. He spent the next 40 years meticulously examining the proteins that made them glow. In a crystal jellyfish’s approximately 300 photo-organs, Shimomura found a protein he named aequorin that produces blue light, which subsequently is converted to green light by green fluorescent protein, or GFP.

In the decades since Shimomura isolated it, GFP has revolutionised stem cell research, cloning, organ transplants, neuroscience — and everything in between. That’s because GFP can be attached biochemically to proteins within a cell, making a formerly invisible protein fluoresce beneath blue light. Proteins are extremely small and cannot be seen, even under an electron microscope. But attaching GFP makes a protein fluoresce: it’s like seeing headlights from the window of a plane even if you’re too high to make out the cars.

Proteins in human cancer cells have been tagged with GFP, and the resulting fluorescent tumours have been implanted in mice. As cancer cells break from the tumour and begin to metastasise, or move about the body, they continue to fluoresce, and scientists can watch the cancer spread.

Four other scientists are largely responsible for making this curious glowing protein into the most useful modern imaging technique available. Douglas Prasher cloned the GFP gene and was the first to think about using GFP as a fluorescent protein tag. Sergey Lukyanov won the race to find the first red fluorescent proteins, which he found in corals in a Moscow aquarium, and his research led to the discovery of fluorescent proteins in many other marine organisms.

Unfortunately, the Nobel can be shared among only three people, and these two worthy scientists were denied a slice of the $1.4 million prize.

Two others, however, join Shimomura as the new chemistry laureates: Marty Chalfie, who was the first to use GFP to light up bacteria and worms, and Roger Tsien, who has been in the forefront of fluorescent protein research since 1994 and has created a series of fluorescent proteins whose colours span the spectrum.

Many more continue to contribute to GFP research. GFP has been used to show how HIV travels from infected to non-infected cells. In another study, scientists created a mouse with fluorescent neurons that connect its whiskers with its cortex. By replacing part of its skull with a glass window, they have been able to observe how the mouse rewires its brain to cope when half of its whiskers are removed. This fluorescent window into the brain is being used to study the effects of ageing and neuro-degenerative diseases.

GFP is the microscope of the 21st century. It lets us see things we have never been able to see before. And, like the microscope, it has completely changed the way we think about science.

Green fluorescent protein has been floating in the ocean for more than 160 million years, but it took an inquisitive scientist, fascinated by bits of green light, to begin unlocking its potential.

Two French researchers were awarded the Nobel prize for medicine last week for discovering the AIDS virus, bypassing an American researcher who played a key role in the discovery.

Luc Montagnier of the World Foundation for AIDS Research and Prevention and Francoise Barre-Sinoussi of the Pasteur Institute, both in Paris, were awarded the Nobel prize in physiology and medicine by the Karolinska Institute in Stockholm for their 1983 identification of what was later named the human immunodeficiency virus (HIV).

The pair split the $1.4 million prize with Harald zur Hausen of the University of Heidelberg in Germany, who discovered that another virus, the human papilloma virus (HPV), causes cervical cancer.

Excluded from the prize was Robert C. Gallo, who for years was locked in a bitter dispute with Montagnier over credit for the discovery of HIV from work he did while at the National Cancer Institute in the US. Gallo is now at the University of Maryland.

Although the prize’s rules limit the number of scientists who can win the award to three, Jans Jornvall, scientific secretary to the assembly, made it clear the committee felt that Montagnier and Barre-Sinoussi deserved sole credit because in 1983 they published the first papers identifying the virus in the journal Science.

“We think the two that we named are the discoverers of the virus,” Jornvall said in a telephone interview. “If you look at the initial papers on the publication of the discovery you will find those who discovered it.”

Jornvall praised Gallo’s work but said the committee based its decision on the French researchers publishing their work first.

“Dr Gallo is an excellent person and has meant very much for science, but there are many people who are excellent and do very much for science,” Jornvall said. “We named the three people we consider to be the discoverers of the viruses we named.”

Other researchers said Montagnier and Barre-Sinoussi clearly deserved the prize, but that it was disappointing that Gallo was excluded.

“Gallo deserves enormous credit,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “It’s a shame you can’t give it to four people because Gallo’s contributions were enormous.”

In a written statement, Gallo congratulated the winners, adding that he was “gratified” by Montagnier’s “kind statement” that he was “equally deserving.”

“I am pleased that the Nobel Committee chose to recognise the importance of AIDS with these awards and I am proud that my colleagues and I continue to search for an AIDS vaccine,” he said.

Montagnier and Gallo were locked in a bitter dispute in the 1980s over the discovery of the virus. Beyond who should get the credit, millions of dollars were also at stake from fees for blood tests. President Ronald Reagan and French Prime Minister Jacques Chirac eventually signed an agreement in 1987 that divided the royalties equally, and Gallo and Montagnier published a paper together in The New England Journal of Medicine in 2003 acknowledging each other’s work.

In announcing the award, the Nobel Committee said Montagnier and Barre-Sinoussi’s initial discovery led to a series of crucial advances, including deciphering how the virus reproduces and infects cells and the development of the blood test and powerful antiviral drugs that have helped contain the spread of the virus and reduce the death toll.

The committee also praised zur Hausen’s work, saying he “went against current dogma” when he proposed that HPV caused cervical cancer, the second most common cancer among women and the most common sexually transmitted agent. Among other things, the work led to the development of vaccines against strains of the virus.

“The global public health burden attributable to human papilloma viruses is considerable,” the committee said.

“I’m of course totally surprised. It’s of course a great pleasure for me,” said zur Hausen, 72, said during an interview posted on the Nobel Committee’s website.

An American and two Japanese physicists won the 2008 Nobel prize in physics for their discovery of tiny asymmetries in nature’s fundamental particles that help explain why our universe exists.

Yoichiro Nambu, of the Enrico Fermi Institute at the University of Chicago, will receive half of the $1.4 million prize. The other half will be split between Makoto Kobayashi, of the High Energy Accelerator Research Organization in Tsukuba, Japan, and Toshihide Maskawa, of the Yukawa Institute for Theoretical Physics at Kyoto University.

The three physicists were pioneers in understanding “broken symmetry,” which explains why the universe can contain life as we know it. When matter and antimatter collide, they annihilate one another, leaving only radiation. In a symmetric universe with an equal amount of matter and antimatter, life — if any could exist — would be nasty, brutish and short.

That doesn’t happen because there is a tiny imbalance of one extra particle of matter for every 10 billion antimatter particles, resulting in the matter-dominated universe we live in today.

How exactly this happened is still a mystery. But Nambu, 87, born in Tokyo, was among those who opened up the field to further questions with the discovery of “spontaneous symmetry breaking”.

Nambu’s work, done in the 1960s and 1970s, predicted the behaviour of the tiny particles known as quarks and underlies the Standard Model of the universe, which unites three of the four fundamental forces of nature: the strong nuclear force, weak nuclear force and electromagnetic force. The working of gravity, and how it relates to the other three forces, is still a mystery.

Kobayashi and Maskawa predicted there were three families of quarks, instead of the two then known. Their calculations were confirmed by experiments in high-energy physics, leading to the discovery of the six quarks known today. Quarks and leptons are considered to be the two basic components of all matter, which make up atomic particles like protons and neutrons.

“It is my great honour and I can’t believe this,” Kobayashi told Reuters news service.

Physicists are now searching for spontaneous broken symmetry in the Higgs mechanism, which threw the universe into imbalance at the time of the Big Bang 13.7 billion years ago.

Scientists at the Large Hadron Collider at the European Organization for Nuclear Research, or CERN, in Switzerland will be looking for the Higgs particle when they restart the collider in spring 2009.

Sources:
The Telegraph (Kolkata, India)

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