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Apr 04
Promising target for AIDS vaccine identified
A new research by Dana-Farber Cancer Institute scientists have indicated that a section of the AIDS virus's protein envelope once considered an improbable target for a vaccine now appears to be one of the most promising.

The section, a twisting strand of protein known as the V3 loop, is an attractive vaccine target because immune system antibodies aimed at the loop may offer protection against multiple genetic subtypes of HIV-1, the virus that causes AIDS.

This is a key prerequisite of any AIDS vaccine because the viruses mutate rapidly and by now comprise millions of different strains that are grouped into different genetic subtypes, or "clades."

In the study, the investigators injected a monoclonal antibody -- a preparation of millions of identical antibodies that fight viral infection -- into Asian monkeys known as macaques.

The antibody came from a person infected with a specific clade of HIV-1. The macaques were then exposed to virus of a different clade.

The investigators knew that the antibody would latch onto a portion of the virus's V3 loop, potentially barring the virus from invading nearby cells, but they did not know whether it would prevent infection from a separate subtype of the virus.

The results were striking: All the treated monkeys were protected from infection by the monkey form of HIV-1, known as SHIV.

Monkeys exposed to the virus without receiving the monoclonal antibody, by contrast, became heavily infected.

"This is the first time a monoclonal antibody made against an AIDS virus of one clade has provided complete protection against an AIDS virus of a different clade in animal models," said senior author Ruth Ruprecht, of Dana-Farber.

"Previous studies have shown that such neutralizing antibodies can protect macaques from infection within one clade; but as more clades of the AIDS virus evolve, it has been unclear whether such antibodies could shield across different clades and prevent infection. Now we have an answer," she added.

The antibody treatment technique used in the study is unlikely to confer long-term protection against HIV-1 because the infected antibodies do not remain active in the body for very long.

The value of the study is that it demonstrates that antibodies directed against the V3 loop of one clade of HIV-1 can create an immune system shield against another clade.

Apr 04
Antidepressant use linked to thicker arteries
In a study of twin veterans, antidepressant use has been linked to thicker arteries, possibly contributing to the risk of heart disease and stroke.

Depression can heighten the risk for heart disease, but the effect of antidepressant use revealed by the study is separate and independent from depression itself, says first author Amit Shah, a cardiology fellow at Emory University School of Medicine.

The data suggest that antidepressants may combine with depression for a negative effect on blood vessels, he says. Shah is a researcher working with Viola Vaccarino, chair of the Department of Epidemiology at Emory's Rollins School of Public Health.

The study included 513 middle-aged male twins who both served in the U.S. military during the Vietnam War.

Twins are genetically the same but may be different when it comes to other risk factors such as diet, smoking and exercise, so studying them is a good way to distill out the effects of genetics, Shah says.

Researchers measured carotid intima-media thickness - the thickness of the lining of the main arteries in the neck -- by ultrasound. Among the 59 pairs of twins where only one brother took antidepressants, the one taking the drugs tended to have higher carotid intima-media thickness (IMT), even when standard heart disease risk factors were taken into account.

The effect was seen both in twins with or without a previous heart attack or stroke. A higher level of depressive symptoms was associated with higher IMT only in those taking antidepressants.

"One of the strongest and best-studied factors that thickens someone's arteries is age, and that happens at around 10 microns per year," Shah says. "In our study, users of antidepressants see an average 40 micron increase in IMT, so their carotid arteries are in effect four years older."

Antidepressants' effects on blood vessels may come from changes in serotonin, a chemical that helps some brain cells communicate but also functions outside the brain, Shah says.

The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), which increase the level of serotonin in the brain. Other types of antidepressants also affect serotonin levels, and antidepressants can act on other multi-functional brain chemicals such as norepinephrine.

In the study, researchers saw higher carotid IMT in both participants who used SSRIs (60 per cent of those who took antidepressants) and those who used other types of antidepressants.

Most of the serotonin in the body is found outside the brain, especially in the intestines, Shah notes. In addition, serotonin is stored by platelets, the cells that promote blood clotting, and is released when they bind to a clot. However, serotonin's effects on blood vessels are complex and act in multiple ways. It can either constrict or relax blood vessels, depending on whether the vessels are damaged or not.

"I think we have to keep an open mind about the effects of antidepressants on neurochemicals like serotonin in places outside the brain, such as the vasculature. The body often compensates over time for drugs'' immediate effects," Shah says.

"Antidepressants have a clinical benefit that has been established, so nobody taking these medications should stop based only on these results. This isn't the kind of study where we can know cause and effect, let alone mechanism, and we need to see whether this holds up in other population groups."

Apr 02
Expanding Waistlines Increase AMD Risk
Age-related macular degeneration (AMD) leading to vision loss is linked with increasing girth in men, report researchers at the University of Melbourne.

The researchers tracked changes in the waistlines of more than 21,000 men and women, aged between 40 and 69, over several years and observed how many developed AMD later on. They found that abdominal fat releases the female hormone oestrogen into the body. Using animals in their studies they discovered that the hormone can cause inflammation in blood vessels at the back of the eyes. This is why women, having had higher levels of oestrogen throughout their lives, are not similarly affected.

'There is evidence that chronic inflammation is involved in AMD and obesity is a pro-inflammatory state,' said the scientists.

Small changes in a man's waist/hip ratio lead to a sharp increase in risk. A healthy score is usually anything below a ratio of around 0.95. But if it rises above that, the risk of diabetes and heart disease looms up. With each increase of 0.1 in the waist/hip ratio, a man's chances of developing AMD goes up by 75 per cent.

Most develop 'dry AMD', which develops over several years. 'Wet AMD', which can cause blindness in just three months, happens when new blood vessels develop over the macula in the eye and then start to leak fluid, causing scar tissue to form and destroying vision in the centre of the eye. This makes it difficult to recognize faces, read or watch TV.

Apr 01
Migraine headaches in kids linked to common heart defect
A new study has suggested a connection between migraine headaches in children and a heart defect called patent foramen ovale.

Roughly 15% of children suffer from migraines, and approximately one-third of these affected children have migraines with aura, a collection of symptoms that can include weakness, blind spots, and even hallucinations.

Rachel McCandless and colleagues from the Primary Children's Medical Center and the University of Utah studied children 6-18 years old who were diagnosed with migraines between 2008 and 2009. The 109 children enrolled in the study were treated at the Primary Children's Medical Center, which serves kids from Utah, Idaho, Montana, Nevada, Colorado, and parts of Wyoming.

The researchers took two-dimensional echocardiograms of each child's heart, looking for a patent foramen ovale (PFO), a common defect in the wall between the two upper chambers of the heart. Although a PFO is not necessarily dangerous, it can allow unfiltered blood to bypass the lungs and circulate throughout the body.

McCandless explained, "Some adult studies have suggested a link between having a PFO and migraine headaches."

Of the studied children who had migraines with aura, 50% also had a PFO; this is nearly double the PFO rate of the general population. However, only 25 pc of children who had migraines without aura had a PFO.

McCandless and colleagues hypothesize that if a causal relationship can be established, closure of a PFO with a catheter device may help in the treatment of certain kinds of migraines, specifically migraines with aura. It is her hope that "our study will help guide future research about this difficult problem."

The study will be published in The Journal of Paediatrics.

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