HIV inner shell structure revealed

Researchers have for the first time unravelled the complex structure of the inner protein shell of HIV.

The US team, reporting in Nature, also worked out exactly how all the components of the shell or 'capsid' fit together at the atomic level.

Until now the exact structure had proved elusive because of the capsid's large size and irregular shape.

The finding opens the way for new types of drugs, the researchers from the University of Pittsburgh said.

It was already known that the capsid, which sits inside the outer membrane of the virus, was a cone-shaped shell made up of protein sub-units in a lattice formation.

But because it is huge, asymmetrical and non-uniform, standard techniques for working out the structure had proved ineffective.

Computer model of HIV capsid structure

The team used advanced imaging techniques and a supercomputer to calculate how the 1,300 proteins which make up the cone-shaped capsid fit together.

Critical interactions

The process revealed critical interactions between molecules in areas that are necessary for the shell's assembly and stability.

These potential vulnerabilities in the protective coat of the viral genome could be exploited by scientists designing new drugs to tackle the problem of HIV resistance, the researchers explained.

Study leader Dr Peijun Zhang, associate professor in structural biology at the University of Pittsburgh School of Medicine said: "The capsid is critically important for HIV replication, so knowing its structure in detail could lead us to new drugs that can treat or prevent the infection.

"The capsid has to remain intact to protect the HIV genome and get it into the human cell, but once inside, it has to come apart to release its content so that the virus can replicate.

"Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing."

She added that the fast mutation rate of HIV made drug resistance a big problem.

"This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes."

Prof Simon Lovell, a structural biologist at the University of Manchester, said not only had the researchers managed to achieve something that was very difficult, they had also found some really interesting results.

"The big problem with HIV is that it evolves so quickly that any drug you use you get drug resistance which is why we use a multi-drug cocktail.

"This is another target, another thing we can go after to develop a new class of drugs to work alongside the existing class.

READMORE:http://www.bbc.co.uk/news/health-22708437

Common painkillers 'pose heart risk

Two common painkillers, ibuprofen and diclofenac, can slightly increase the risk of heart problems if taken in high doses for a long time, data suggests.

People with severe arthritis often take the drugs, which also calm inflammation, to go about daily life.

The researchers said some patients would deem the risk acceptable, but they should be given the choice.

A study, published in the Lancet, showed the drugs posed even greater risks for smokers and the overweight.

The risks have been reported before, but a team of researchers at the University of Oxford analysed the issue in unprecedented detail in order to help patients make an informed choice.

The group investigated more than 353,000 patient records from 639 separate clinical trials to assess the impact of non-steroidal anti-inflammatory drugs.

They looked at high-dose prescriptions levels, rather than over-the-counter pain relief, of 150mg diclofenac or 2,400mg ibuprofen each day.

They showed that for every 1,000 people taking the drugs there would be three additional heart attacks, four more cases of heart failure and one death as well cases of stomach bleeding - every year as a result of taking the drugs.

So the number of heart attacks would increase from eight per 1,000 people per year normally, to 11 per 1,000 people per year with the drugs.

"Three per thousand per year sounds like it is quite a low risk, but the judgement has to be made by patients," said lead researcher Prof Colin Baigent.

He added: "So if you're a patient and you go and sit in front of your doctor and discuss it, you are the one who should be making the judgement about whether three per thousand per year is worth it to allow you, potentially, to go about your daily life."

He said this should not concern people taking a short course of these drugs, for example for headaches.

However, he did warn that those already at risk of heart problems would be at even greater risk as a result of the high-dose drugs.

High blood pressure, cholesterol and smoking all increase the risk of heart problems.

Prof Baigent said: "The higher your risk of heart disease, the higher your risk of a complication. Roughly speaking, if you've got double the risk of heart disease, then the risk of having a heart attack is roughly doubled."

He said patients should consider ways to reduce their risk, which could include statins for some patients.

Alternative

A similar drug called rofecoxib (known as Vioxx), was voluntarily taken off the market by its manufacturer in 2004 after similar concerns were raised.

There are more than 17 million prescriptions of non-steroidal anti-inflammatory drugs in the UK each year. Two thirds are either ibuprofen or diclofenac.

A third drug, naproxen, had lower risks of heart complications in the study and some doctors are prescribing this to higher-risk patients.

The drug does a similar job to aspirin by stopping the blood from clotting although this also increases the odds of a stomach bleed.

Prof Alan Silman, medical director of Arthritis Research UK, said the drugs were a "lifeline" for millions of people with arthritis and were "extremely effective in relieving pain".

He added: "However, because of their potential side-effects, in particular the increased risk of cardiovascular complications which has been known for a number of years, there is an urgent need to find alternatives that are as effective, but safer."

Prof Donald Singer, member of the British Pharmacological Society and from the University of Warwick, said: "The findings underscore a key point for patients and prescribers - powerful drugs may have serious harmful effects.

"It is therefore important for prescribers to take into account these risks and ensure patients are fully informed about the medicines they are taking."

READMORE:http://www.bbc.co.uk/news/health-22694858

Gene clues for testicular cancer, heart defect

PARIS: Separate studies of the human genome have found tantalising clues to the inherited causes of testicular cancer and non-inherited causes of congenital heart disease, journals reported on Sunday.

University of Pennsylvania researchers looked at the DNA of more than 13,000 men, comparing the DNA code of those with testicular cancer -- the commonest form of cancer diagnosed among young men today -- against men who were otherwise healthy.

They found four new variants that increase the risk of this disease, bringing the tally of known mutations to 17, according to research reported in Nature Genetics.

Meanwhile, investigators at the Yale School of Medicine found a clutch of gene mutations, absent in parents but found in their offspring, which account for at least 10 percent of cases of severe congenital heart disease, a birth defect that afflicts nearly one percent of babies.

"Most interestingly, the set of genes mutated in congenital heart disease unexpectedly overlapped with genes and pathways mutated in autism," said Richard Lifton, a professor of genetics.

"These findings suggest there may be common pathways that underlie a wide range of common congenital diseases."

The study appears in the journal Nature.

Genomics is one of the fastest-moving areas of medical research.

Identifying genetic signatures associated with disease opens up the prospect of DNA tests to identify people most at risk. They also throw open avenues of research to block or reverse the disease. (AFP)

 READMORE:http://www.thenews.com.pk/article-100719-Gene-clues-for-testicular-cancer,-heart-defect

Embryonic stem cells: Advance in medical human cloning

Human cloning has been used to produce early embryos, marking a "significant step" for medicine, say US scientists.

The cloned embryos were used as a source of stem cells, which can make new heart muscle, bone, brain tissue or any other type of cell in the body.

The study, published in the journal Cell, used methods like those that produced Dolly the sheep in the UK.

However, researchers say other sources of stem cells may be easier, cheaper and less controversial.

Stem cells are one of the great hopes for medicine. Being able to create new tissue might be able to heal the damage caused by a heart attack or repair a severed spinal cord.

There are already trials taking place using stem cells taken from donated embryos to restore people's sight.

However, these donated cells do not match the patient so they would be rejected by the body. Cloning bypasses this problem.

The technique used - somatic cell nuclear transfer - has been well-known since Dolly the sheep became the first mammal to be cloned, in 1996.

However, researchers have struggled to reproduce the feat in people. The egg does start dividing, but never goes past the 6-12 cell stage.Skin cells were taken from an adult and the genetic information was placed inside a donor egg which had been stripped of its own DNA. Electricity was used to encourage the egg to develop into an embryo.

'Real deal'

A South Korean scientist, Hwang Woo-suk, did claim to have created stem cells from cloned human embryos, but was found to have faked the evidence.

Now a team at the Oregon Health and Science University have developed the embryo to the blastocyst stage - around 150 cells - which is enough to provide a source of embryonic stem cells.

Continue reading the main story

Cloned babies?

Could scientists fully clone a person? It's an interesting question that emerges from this research.

These researchers have certainly developed a cloned embryo further than anyone else.

But producing a five-day-old embryo is a world away from a woman giving birth to the first human clone.

The embryo would need to be implanted as per IVF, but primate research shows that things often go wrong before the clone is born.

Prof Robin Lovell-Badge of the UK National Institute for Medical Research said: "It is an unsafe procedure in animals and it will similarly be an unsafe procedure in humans. For this reason alone it should not be attempted."

It would also be illegal is some countries, such as the UK, which differentiate between "therapeutic" and "reproductive" cloning.

Dr Shoukhrat Mitalipov said: "A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells.

"While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine."

Chris Mason, a professor of regenerative medicine at University College London, said this looked like "the real deal".

"They've done the same as the Wright brothers really. They've looked around at where are all the best bits of how to do this from different groups all over the place and basically amalgamated it.

"The Wright brothers took off and this has actually managed to make embryonic stem cells."

The ethical rival

Embryonic stem cell research has repeatedly raised ethical concerns and human eggs are a scarce resource. This has led researchers to an alternative route to stem cells.

The technique takes the same sample of skin cells but converts them using proteins to "induced pluripotent" stem cells.

However, there are still questions about the quality of stem cells produced using this method compared with embryonic stem cells.

Prof Mason said the field was leaning towards induced pluripotent stem cells: "It has got a lot of momentum behind it, a lot of funding and a lot of powerful people now."

Dr Lyle Armstrong at Newcastle University said that the study "without doubt" marked an advance for the field.

But he warned: "Ultimately, the costs of somatic cell nuclear transfer-based methods for making stem cells could be prohibitive."

Dr David King, from the campaign group Human Genetics Alert, warned that: "Scientists have finally delivered the baby that would-be human cloners have been waiting for: a method for reliably creating cloned human embryos.

"This makes it imperative that we create an international legal ban on human cloning before any more research like this takes place. It is irresponsible in the extreme to have published this research."

READMORE:http://www.bbc.co.uk/news/health-22540374