University Times

Blood pressure regulators found

School of Medicine researchers have identified key players in a little-known biochemical pathway that appears to regulate blood pressure. The findings, reported in the online version of Cardiovascular Research, have evolved from studies conducted by Jeffrey S. Isenberg, Eileen M. Bauer and colleagues at Pitt’s Vascular Medicine Institute.

Isenberg said: “Identifying and unraveling this important pathway for blood pressure regulation could lead to a better understanding of who will get high blood pressure and why, as well as allow us to develop better drugs to treat these patients. Poorly controlled hypertension is a major risk factor for heart attacks and heart failure, stroke and kidney failure.”

The pathway he and collaborator David D. Roberts of the National Cancer Institute have been exploring involves nitric oxide (NO) signaling.

The cells that line blood vessels, called the endothelium, produce NO in a few biochemical steps. NO promotes blood vessel dilation and increases blood flow. Conversely, endothelial dysfunction, along with loss of NO production, is known to be involved in the development of many forms of cardiovascular disease, including hypertension.

Through cell culture and mouse experiments, the researchers found that a protein called thrombospondin-1 (TSP1) and its receptor, CD47, inhibit activation of the endothelial-based enzyme called endothelial nitric oxide synthase (eNOS), which in turn limits the production of NO and thus prevents blood vessels from relaxing and blood pressure from dropping. Circulating TSP1, at levels consistent with those found in the blood stream, is capable of inhibiting activation of endothelial-based eNOS and thus blocking NO production.

“For some time now, it has not been clear what role TSP1 served in the blood. Experiments in cells told us TSP1 could alter NO signaling. But TSP1 is a protein too large to cross through the endothelial layer and into the blood vessel wall, so it was not obvious how it could alter the muscle tone of the arteries,” Isenberg said. “We also knew that mice genetically engineered to not produce TSP1 or CD47 showed more NO-based blood flow and blood vessel dilation. This suggested to us that perhaps circulating TSP1 was altering the ability of the endothelium to make NO by acting on eNOS.”

He and his team now are developing agents that can alter the activity of eNOS by “blocking” the inhibitory signal mediated by TSP1 and CD47, which have the potential to be novel blood pressure-regulating drugs. Some cases of hypertension may arise from gene-based differences in these proteins, Isenberg noted.

“This work has identified a key pathway that effectively puts the brakes on nitric oxide production, which slows down blood flow,” said Mark T. Gladwin, director of the Vascular Medicine Institute. “Furthermore, drugs that block this pathway have the potential to restore nitric oxide levels and may be useful for the treatment of high blood pressure and other vascular diseases.”

Infrared pics predict dust, sandstorms

Pitt researchers have developed a way to use infrared satellite images to predict dust storms and sandstorms. The technique, used to forecast a 2008 New Mexico dust storm, could be implemented globally.

Thermal and visible images of New Mexico’s White Sands Dune Field captured by NASA’s Earth-orbiting ASTER (Advanced Spaceborne Thermal Emission and Reflectance Radiometer) instrument reliably indicated when soil moisture levels were low enough to result in a dust storm, the team recently reported in the Journal of Geophysical Research Earth Surface.

Lead author Stephen Scheidt, a research associate in the Department of Geology and Planetary Science; Michael Ramsey, a faculty member in geology and planetary science and member of NASA’s ASTER science team, and Nicholas Lancaster of Nevada’s Desert Research Institute further determined that this approach could be expanded into a worldwide system to monitor areas prone to dust storms or to track drought in regions threatened by desertification.

The group analyzed daytime and nighttime images of White Sands ASTER captured between May 2000 and March 2008. By studying thermal infrared images of moisture content and albedo — or sunlight reflected by the ground — at White Sands, the team found that the sand became drier and more reflective until it was a mass of loose sediment susceptible to strong winds.

ASTER images from the project available on Pitt’s Web site at www.pitt.edu/news2010/White_Sands_slides.pdf illustrate the increase in albedo and decrease in soil moisture preceding the 2008 White Sands dust storm. In the March 14, 2008, storm, the dust plume emanated from a darkened area that corresponds with the driest areas indicated by ASTER.

The paper is available at www.pitt.edu/news2010/White_Sands_paper.pdf.

Researchers to explore key component of ‘smart grid’

Researchers in the Swanson School of Engineering have received a $200,000 grant from Westinghouse Electric.

A team led by Gregory Reed, a faculty member in electrical and computer engineering and director of the Swanson School’s Power and Energy Initiative, will design an interface to integrate nuclear power and other low-emissions energy resources more efficiently into the nation’s larger power grid.  Their work will contribute to better management of the electric power infrastructure as part of the development of the “smart grid” network that can monitor power generation and delivery and respond to customer demand in real time.

A key feature of the smart grid is the integration and automated flow of electricity from a variety of energy resources, including nuclear, wind, solar and fossil-fuel power, Reed said.

The interface to be developed at Pitt will let consumers access information directly from the energy supplier and allow them to control and manage how much electricity is flowing in and out of a facility.

The intent is to improve overall energy management, which would save energy and reduce costs. As it applies to nuclear power, the new interface would balance nuclear power with renewable energy resources and eventually could influence future nuclear reactor designs by managing electrical output more efficiently.

Artificial cells developed

Inspired by the social interactions of ants and slime molds, Pitt engineers have designed artificial cells capable of self-organizing into independent groups that can communicate and cooperate. Recently reported in the Proceedings of the National Academy of Sciences (PNAS), the research is a step toward producing synthetic cells that behave like natural organisms and could perform important, micro-scale functions in fields ranging from the chemical industry to medicine.

The team presents in the PNAS paper computational models that provide a blueprint for developing artificial cells — or microcapsules — that can communicate, move independently and transport “cargo” such as chemicals needed for reactions. Corresponding author Anna Balazs, Distinguished Professor of Chemical Engineering in the Swanson School of Engineering, said the “biologically inspired” devices function entirely through simple physical and chemical processes, behaving like complex natural organisms but without the complicated internal biochemistry.

The microcapsules interact by secreting nanoparticles in a way similar to that used by biological cells  to  communicate  and  assemble into groups. And with a nod to ants, the cells leave chemical trails as they travel, prompting fellow microcapsules to follow. Balazs worked with lead author German Kolmakov and Victor Yashin, both postdoctoral researchers in Pitt’s Department of Chemical and Petroleum Engineering, who produced the cell models; and with Pitt professor of electrical and computer engineering Steven Levitan, who devised the ant-like trailing ability.

The researchers write that communication hinges on the interaction between microcapsules exchanging two different types of nanoparticles. The “signaling” cell secretes nanoparticles known as agonists that prompt the second “target” microcapsule to emit nanoparticles known as antagonists.

Once the signaling cell goes dormant, the target cell likewise stops releasing antagonists, making the signaling cell start up again. The microcapsules get locked into a cycle that equates to an intercellular conversation, a dialogue humans could control by adjusting the capsules’ permeability and the quantity of nanoparticles they contain.

Video simulation of this interaction is available at www.pitt.edu/news2010/CellTalk.wmv.

Locomotion results as the released nanoparticles alter the surface underneath the microcapsules. The cell’s polymer-based walls begin to push on the fluid surrounding the capsule and the fluid pushes back even harder, moving the capsule. At the same time, the nanoparticles from the signaling cell pull it toward the target cells. Groups of capsules begin to form as the signaling cell rolls along, picking up target cells.

In practical use, Balazs said, the signaling cell could transport target cells loaded with cargo; the team’s next step is to control the order in which target cells are collected and dropped off.

The researchers adjusted the particle output of the signaling cell to create various cell formations. A clip at www.pitt.edu/news2010/CellAntTrail.wmv shows the trailing “ants,” wherein the particle secretions of one microcapsule group are delayed until another group passes by and activates it. The newly awakened cluster then follows the chemical residue left behind by the lead group.

Another clip, at www.pitt.edu/news2010/CellDragon.wmv depicts a “dragon” formation comprising two cooperating signaling cells leading a large group of targets. Similar to these are “snakes” made up of competing signaling capsules pulling respective lines of target cells.

SCARED tool found valid in rural teens

A member of the Pitt-Bradford nursing faculty has found a tool that detects anxiety in adolescents to be equally valid in rural populations and in urban ones. Tammy Haley, coordinator of UPB’s bachelor of science in nursing program, presented her research at the National Conference for Nurse Practitioners and at the Pitt School of Nursing PhD program second annual Research Day.

Haley examined rural data for results of the Screen for Child Anxiety Related to Emotional Disorders (SCARED) to see if it was a valid tool in detecting anxiety in rural adolescent populations. SCARED was developed at Western Pennsylvania Psychiatric Institute and Clinic and had been tested primarily with urban populations. The screening tool evaluates different types of anxiety common among young people: panic, separation anxiety, school anxiety, general anxiety and social anxiety.

While the prevalence of anxiety disorders is not greater in a rural population, there is less access to mental health care, Haley said, adding that nearly three-fourths of federally designated mental health professional shortage areas are in rural communities.

“When we don’t have great resources, it’s really important to screen well so that we can refer those who need it,” she said.

HIV research presented

Graduate School of Public Health (GSPH) researchers presented findings at the XVIII International AIDS Conference. Among the work presented:

Low drug use among older gay men

Most older gay and bisexual men enrolled in a long-term study of HIV used recreational drugs infrequently over a 10-year period, Pitt researchers have found. Their study explored the drug use of 1,378 HIV-positive and negative gay and bisexual men, ages 44-63, enrolled in the Pitt Men’s Study.

Researchers surveyed participants about use of recreational drugs (poppers, crack, cocaine, methamphetamine and ecstasy) between 1998 and 2008. Among participants, 79 percent reported infrequent drug use, but three subgroups emerged: Nearly 6 percent reported consistently high drug use; more than 7 percent increased their drug use, and 7 percent decreased their use.

Jessica G. Burke, study author and faculty member in the Department of Behavioral and Community Health Sciences, said, “Previous studies have linked drug use in gay men to risky sexual behaviors and to higher rates of HIV infection, but most of these studies have focused primarily on specific time-points and on younger men.”

According to Burke, the data will provide insights to develop interventions for preventing and treating drug use among gay and bisexual men as they age.

Pitt co-authors included Sin How Lim, Michael Marshal, Steven Albert and Ronald Stall of behavioral and community health sciences, and Anthony Silvestre of infectious diseases/microbiology.

Few men would be circumcised to prevent HIV

Adult circumcision has been proposed as a possible HIV prevention strategy for gay men, but a new GSPH study conducted in conjunction with the San Francisco Department of Health suggests it would have a very small effect on reducing HIV incidence in the United States.

Circumcision is thought to reduce the risk of HIV transmission by removing cells in the foreskin that are most susceptible to infection by the virus. Clinical trials in Africa have found it reduces the risk of HIV in heterosexual men, yet there is little evidence that it can reduce transmission among gay American men.

The study was based on surveys of 521 gay and bisexual men in San Francisco: 115 men (21 percent) were HIV-positive and 327 (63 percent) had been circumcised. Of the remaining 69 men (13 percent), only three (0.5 percent) said they would be willing to participate in a clinical trial of circumcision and HIV prevention, and only four (0.7 percent) were willing to get circumcised if it were proven safe and effective in preventing HIV.

The researchers extrapolated these findings to the entire gay and bisexual male population of San Francisco, an estimated 65,700 people, and determined that only 500 men potentially would benefit from circumcision.

Study author Chongyi Wei, a post-doctoral associate in behavioral and community health sciences, said, “Any potential benefit may likely be too small to justify implementing circumcision programs as an intervention for HIV prevention.”

Abuse, shame in gay boys linked to later HIV risk

Gay and bisexual men who reported sexual abuse and social shaming in childhood experience psychosocial health problems later in life that could put them at greater risk for HIV, according to a study of more than 1,000 HIV-positive and negative men.

Almost 10 percent of the participants reported that they had been victims of childhood sexual abuse and nearly 30 percent had experienced gay-related victimization between the ages of 12 and 14, including verbal insults, bullying, threats of physical violence and physical assaults. Men who experienced childhood sexual abuse and a sense of masculinity failure were more likely to use illicit drugsand to engage in risky sexual behavior in adulthood.

According to study authors, these health issues combine to create a “syndemic,” or linked epidemic, that together may be driving the AIDS epidemic in gay men.

“Our study shows that the early socialization experiences of gay men can be deeply stigmatizing and increase their risks for these syndemic conditions in adulthood,” said study author Sin How Lim, a post-doctoral associate in behavioral and community health sciences.

Co-authors included Amy Herrick, Thomas Guadamuz, Mark Friedman, Michael Marshal and Ronald Stall, all of behavioral and community health sciences.

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