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November 4, 2016

NIH Scientists Uncover Genetic Explanation for Vexing Syndrome

Scientists at NIH have identified a genetic explanation for a syndrome characterized by multiple vexing and difficult-to-treat symptoms, including dizziness and lightheadedness, skin flushing and itching, gastrointestinal complaints, chronic pain and bone and joint problems. Some people who experience these diverse symptoms have elevated levels of tryptase—a protein in the blood often associated with allergic reactions. Multiple copies of the alpha tryptase gene drive these tryptase elevations and may contribute to the symptoms, according to a new study led by investigators at NIAID.

Other studies have indicated that 4 to 6 percent of the general public has high tryptase levels. While not all of these people experience symptoms, many do, raising the possibility that this mildly prevalent trait in some cases drives the symptoms, although how it does so remains unclear.

“This work suggests that multiple alpha tryptase gene copies might underlie health issues that affect a substantial number of people,” said NIAID director Dr. Anthony Fauci. “Identifying one genetic cause for high tryptase opens the door for us to develop strategies for diagnosing and treating people carrying this genetic change.”

The study appeared online in Nature Genetics Oct. 17.

Women Report Vaginal Ring for Preventing HIV Had Little Effect On Sexual Intercourse

Most women who used an experimental vaginal ring for HIV prevention report that the physical act of sex was largely unaffected by using the product, which is inserted monthly for continuous wear. This finding is among several insights gleaned about experiences of women who used the ring during the ASPIRE study, announced Oct. 18 at the HIV Research for Prevention meeting in Chicago.

image of a Vaginal Ring

ASPIRE evaluated whether the ring, which continuously releases the anti-HIV drug dapivirine, could safely reduce HIV infection among 2,629 women ages 18-45 years in Malawi, South Africa, Uganda and Zimbabwe. Among participants randomized to receive the ring, risk of HIV infection fell by 27 percent. A further analysis found that the ring reduced the risk of HIV infection by at least 56 percent among women who used it with greater frequency, and up to 75 percent or higher among those who used it consistently. Further exploration of the ring’s clinical potential began in July 2016 through the large-scale HOPE study. ASPIRE, HOPE and their ancillary studies were primarily funded by NIAID. The nonprofit International Partnership for Microbicides developed the dapivirine ring and supplied it for the studies.

“Women need an HIV prevention modality that offers safe, effective protection and is practical for use in their daily lives,” said NIAID director Dr. Anthony Fauci. “Women enrolled in the ASPIRE study reported that the experimental vaginal ring generally did not interfere with sexual intercourse, which is an encouraging sign that this product could appeal to a larger group of women at risk for HIV infection.”

The potential for women to suffer social harm and violence by sexual partners, along with other qualitative data from HIV prevention studies, suggest that some women may prefer methods of HIV protection undetectable by sexual partners.

Weight Loss Leads to Strong Increase in Appetite

Study provided clues of how strongly appetite counters weight loss.
Study provided clues of how strongly appetite counters weight loss.

Analysis of a trial that used the drug canagliflozin found that as people lost weight, their appetite increased proportionately, leading to consumption of more calories and weight loss plateau (leveling off). The findings provide the first measurement in people of how strongly appetite counters weight loss as part of the body’s feedback control system regulating weight. Results were published in Obesity during Obesity Week 2016 (Oct. 31-Nov. 4).

A team led by NIDDK analyzed data from a year-long, placebo-controlled, double-blind trial in people with type 2 diabetes who could eat and drink without restriction. Of the 242 participants, 153 received canagliflozin, a drug that caused a substantial increase in the amount of glucose excreted in their urine. Those people were not directly aware of that calorie loss, which caused a gradual decrease in weight averaging about 8 pounds.

The team used a validated math model to calculate the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people who got a placebo. However, for every pound of lost weight, the people treated with canagliflozin consumed about 50 calories per day more than they were eating before the study. This increase in appetite and calorie intake led to slowing of weight loss after about 6 months.

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