Popular HIV drug may cause memory declines

Johns Hopkins study suggests the commonly prescribed anti-retroviral drug efavirenz attacks brain cells

2012-09-27

(Press-News.org) The way the body metabolizes a commonly prescribed anti-retroviral drug that is used long term by patients infected with HIV may contribute to cognitive impairment by damaging nerve cells, a new Johns Hopkins research suggests.

Nearly 50 percent of people infected with HIV will eventually develop some form of brain damage that, while mild, can affect the ability to drive, work or participate in many daily activities. It has long been assumed that the disease was causing the damage, but Hopkins researchers say the drug efavirenz may play a key role.

People infected with HIV typically take a cocktail of medications to suppress the virus, and many will take the drugs for decades. Efavirenz is known to be very good at controlling the virus and is one of the few that crosses the blood-brain barrier and can target potential reservoirs of virus in the brain. Doctors have long believed that it might be possible to alleviate cognitive impairment associated with HIV by getting more drugs into the brain, but researchers say more caution is needed because there may be long-term effects of these drugs on the brain.

"People with HIV infections can't stop taking anti-retroviral drugs. We know what happens then and it's not good," says Norman J. Haughey, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine. "But we need to be very careful about the types of anti-retrovirals we prescribe, and take a closer look at their long-term effects. Drug toxicities could be a major contributing factor to cognitive impairment in patients with HIV."

For the study led by Haughey and described online in the Journal of Pharmacology and Experimental Therapeutics, researchers obtained samples of blood and cerebrospinal fluid from HIV-infected subjects enrolled in the NorthEastern AIDS Dementia study who were taking efavirenz. Researchers looked for levels of the drug and its various metabolites, which are substances created when efavirenz is broken down by the liver. Performing experiments on neurons cultured in the lab, the investigators examined the effects of 8-hydroxyefavirenz and other metabolites and found major structural changes when using low levels of 8-hydroxyefavirenz, including the loss of the important spines of the cells.

Haughey and his colleagues found that 8-hydroxyefavirenz is 10 times more toxic to brain cells than the drug itself and, even in low concentrations, causes damage to the dendritic spines of neurons. The dendritic spine is the information processing point of a neuron, where synapses — the structures that allow communication among brain cells — are located.

In the case of efavirenz, a minor modification in the drug's structure may be able block its toxic effects but not alter its ability to suppress the virus. Namandje N. Bumpus, Ph.D., one of the study's other authors, has found a way to modify the drug to prevent it from metabolizing into 8-hydroxyefavirenz while maintaining its effectiveness as a tool to suppress the HIV virus.

"Finding and stating a problem is one thing, but it's another to be able to say we have found this problem and here is an easy fix," Haughey says.

Haughey says studies like his serve as a reminder that while people infected with HIV are living longer than they were 20 years ago, there are significant problems associated with the drugs used to treat the infection.

"Some people do seem to have this attitude that HIV is no longer a death sentence," he says. "But even with anti-retroviral treatments, people infected with HIV have shortened lifespans and the chance of cognitive decline is high. It's nothing you should treat lightly."

###The study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (AA0017408), the National Institute of Mental Health (MH077543, MH075673 and MH71150), the National Institute on Aging (AG034849) and the National Institute of Neurological Disorders and Stroke (NS049465).

Other Hopkins researchers involved in the study include Luis B. Tovar y Romo, Ph.D.; Lindsay B. Avery, Ph.D.; Ned Sacktor, M.D.; and Justin McArthur, M.B.B.S., M.P.H.

For more information: http://www.hopkinsmedicine.org/neurology_neurosurgery/research/jhu_nimh/researchers/nhaughey.html

ELSE PRESS RELEASES FROM THIS DATE:

Retiring during economic booms could cause financial hardships for retirees, MU researcher finds

2012-09-27

COLUMBIA, Mo. -- The recent economic downturn and volatile financial markets have drastically reduced the retirement accounts of many current and future retirees. In a new study, a University of Missouri financial expert has found that many Americans choose to retire when the economic markets are peaking, an action that can, ironically, cause major problems for the long-term financial stability of retirees. "Potential retirees often will first meet their targeted retirement savings goals during an up market and will be tempted to retire at that point," said Rui Yao, an ...

African-American youth exposed to more alcohol advertising than youth in general

2012-09-27

African-American youth ages 12-20 are seeing more advertisements for alcohol in magazines and on TV compared with all youth ages 12-20, according to a new report from the Center on Alcohol Marketing and Youth (CAMY) at the Johns Hopkins Bloomberg School of Public Health. The report is available on CAMY's website, www.camy.org. The report analyzes alcohol exposure by type and brand among African-American youth in comparison to all youth. It also assesses exposure of African-American youth to alcohol advertising relative to African-American adults across various media ...

BMI and shuttle run among techniques IOM Report recommends for youth fitness testing

2012-09-27

WASHINGTON — Techniques ranging from running to push-ups to sit-and-reach tests have been used to measure various aspects of fitness in children and adults. However, evidence is sparse on how well some of these techniques correspond to desired health outcomes in children, fueling debate about the best fitness measures for youth. Fitness testing has traditionally focused on four aspects: heart and lung function, body composition, muscular and skeletal fitness, and flexibility. A committee convened by the Institute of Medicine undertook a comprehensive review of the ...

Contrast-enhanced ultrasound better detects high-grade prostate cancers with less biopsies

2012-09-27

PHILADELPHIA— Contrast-enhanced ultrasound was found to better detect high-grade prostate cancer than conventional methods, making it a more appropriate approach for screening clinically important cancers and monitoring low-risk ones with less biopsies, researchers from Thomas Jefferson University and Hospitals conclude in a phase III study published online in September in the Journal of Urology. Findings from the randomized, double-blind trial revealed the technique, which uses microbubbles to measure change in blood flow, found almost three times as many higher grade ...

Researchers examine bias among sports journalists on Twitter

2012-09-27

CLEMSON — Sports journalists covering the Penn State sex abuse scandal posted commentary on Twitter that was inherently biased, Clemson University and University of Louisville researchers say. Their study explored how sports journalists used Twitter to develop and promote their stories during the scandal. Their research findings were published Thursday in the International Journal of Sport Communication. While sports journalists used Twitter in ways that were similar to traditional media channels, a key finding was that they posted commentary that reflected a personal ...

Cogmed Working Memory Training: Does it actually work? The debate continues…

2012-09-27

San Diego, CA, September 27, 2012 – Helping children achieve their full potential in school is of great concern to everyone, and a number of commercial products have been developed to try and achieve this goal. The Cogmed Working Memory Training program (http://www.cogmed.com/) is such an example and is marketed to schools and parents of children with attention problems caused by poor working memory. But, does the program actually work? The target article in the September issue of Journal of Applied Research in Memory and Cognition (JARMAC) calls into question Cogmed's ...

New efficiency record for photovoltaic cells - thanks to heterojunction

2012-09-27

In the medium term, an investment of only $2500 in photovoltaic cells would suffice to provide more than enough electricity for the consumption of a four people household. This promising scenario has been made possible by the innovations accomplished by EPFL's Institute of Microengineering in Neuchatel. The team of prof. Christophe Ballif, director of the Photovoltaics Laboratory (PVlab), presented their work at the European Photovoltaic Solar Energy Conference and Exhibition that just took place in Frankfurt. The PVlab specializes in thin film solar cells and has been ...

Single-site laparoscopic surgery reduces pain of tumor removal

2012-09-27

Researchers at the University of California, San Diego School of Medicine have found that recovery from an emerging, minimally invasive surgical technique called Laparo-Endoscopic Single-Site Surgery (LESS) was less painful for kidney cancer patients than traditional laparoscopic surgery. Study results were published in the September online edition of Urology. "In the largest prospective study of kidney cancer patients to date, the UC San Diego study showed less use of narcotic pain medication and lower pain scores upon hospital discharge," said Ithaar Derweesh, MD, senior ...

Cyborg surgeon: Hand and technology combine in new surgical tool that enables superhuman precision

2012-09-27

VIDEO: This video shows how the SMART surgical tool is able to “hold still” by responding to unexpected movement from a surgical target (in this case, a chicken embryo). In the... Click here for more information. WASHINGTON, Sept. 27, 2012—Even the most skilled and steady surgeons experience minute, almost imperceptible hand tremors when performing delicate tasks. Normally, these tiny motions are inconsequential, but for doctors specializing in fine-scale surgery, such as ...

Learning to overcome fear is difficult for teens

2012-09-27

NEW YORK (Sept. 27, 2012) -- A new study by Weill Cornell Medical College researchers shows that adolescents' reactions to threat remain high even when the danger is no longer present. According to researchers, once a teenager's brain is triggered by a threat, the ability to suppress an emotional response to the threat is diminished which may explain the peak in anxiety and stress-related disorders during this developmental period. The study, published Sept. 17 in the early online edition of the Proceedings of the National Academy of Sciences (PNAS), is the first to decode ...

LAST 30 PRESS RELEASES:

Study unexpectedly finds living in rural, rather than urban environments in first five years of life could be a risk factor for developing type 1 diabetes