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April 15, 2010

Research Notes

Research grants announced

The Schools of the Health Sciences recently announced the following government and private grant funding for new or continuing research:

• The School of Health and Rehabilitation Sciences (SHRS) has received a five-year, $4.75 million grant from the National Institute on Disability and Rehabilitation Research to continue its Rehabilitation Engineering Research Center on Telerehabilitation.

The main emphasis of the center is to investigate the value and effectiveness of rehabilitation services delivered in consumers’ homes, workplaces and communities.

• Leming Zhou, a faculty member in SHRS’s Department of Health Information Management, received a two-year, $283,640 grant from the National Science Foundation for his project, “Health Computing: Integrating Computational Thinking Into Health Science Education.”

The project’s aim is to teach undergraduate students in health information management and other health science students to grasp the skills of extracting information from large data sets using computing concepts, technologies, tools and methods that are referred to as “computational thinking.”

• Samuel Poloyac, a faculty member in the Department of Pharmaceutical Sciences, and Paula Sherwood, a faculty member in the School of Nursing’s Department of Acute and Tertiary Care, are co-principal investigators on a five-year, $3.5 million grant from the National Institute for Nursing Research.

This research project will help to identify key factors that predict complications and outcomes in patients who have had a subarachnoid hemorrhage in the brain in order to develop early intervention strategies.

• Thomas Krivak, director of the gynecologic oncology fellowship program in the Department of Obstetrics, Gynecology and Reproductive Sciences, received the 2009-2010 GCF/Caring Together NY Ovarian Cancer Research Grant from the Gynecologic Cancer Foundation. The $50,000  grant will fund research on gene alterations to help identify patients who are most likely to respond to different therapies.

• Gretchen M. Ahrendt of surgery and Jules Sumkin of radiology, both of the Magee-Womens Hospital breast cancer program, received one-year grants totaling $133,000 from the Pittsburgh affiliate of Susan G. Komen for the Cure to support an interdisciplinary breast surgery and a breast imaging fellowship.

The local Komen affiliate also awarded Magee Womancare International $17,100 to develop and facilitate Mujeres Educando Mujeres: Breast Health in the Latina Community. The grant will facilitate training of Spanish-speaking “promotores,” breast self-examination community educators, and promotion of breast health awareness education and outreach activities to Latinas, in collaboration with organizations serving the Latino community.

Enzyme attacks nanotubes

An international study based at Pitt has identified a human enzyme that can biodegrade carbon nanotubes, according to findings published online in Nature Nanotechnology.

The researchers found that carbon nanotubes degraded with the human enzyme myeloperoxidase (hMPO) did not produce the lung inflammation that intact nanotubes have been shown to cause.

Furthermore, neutrophils, the white blood cells that contain and emit hMPO to kill invading microorganisms, can be directed to attack carbon nanotubes specifically.

The results could open the door to the use of carbon nanotubes as a safe drug-delivery tool and also could lead to the development of a natural treatment for people exposed to nanotubes, either in the environment or the workplace, the team reported.

Carbon nanotubes are one-atom thick rolls of graphite 100,000 times smaller than a human hair yet stronger than steel. They are used to reinforce plastics, ceramics or concrete; are excellent conductors of electricity and heat, and are sensitive chemical sensors.

However, a nanotube’s surface also contains thousands of atoms that could react with the human body in unknown ways. Tests on mice have shown that nanotube inhalation results in severe lung inflammation coupled with an early onset of fibrosis. The tubes’ durability raises additional concern about proper disposal and cleanup.

According to lead researcher Valerian Kagan, a vice chair in the Department of Environmental and Occupational Health in the Graduate School of Public Health, “The successful medical application of carbon nanotubes relies on their effective breakdown in the body, but carbon nanotubes also are notoriously durable. The ability of hMPO to biodegrade carbon nanotubes reveals that this breakdown is part of a natural inflammatory response. The next step is to develop methods for stimulating that inflammatory response and reproducing the biodegradation process inside a living organism.”

Kagan and his research group led the team of more than 20 researchers from four universities along with faculty members Yulia Tyurina of environmental and occupational health, Donna Stolz of cell biology and physiology, and the laboratory groups of Alexander Star of chemistry and Judith Klein-Seethharaman of structural biology.

Other researchers were from Sweden’s Karolinska Institute, Trinity College in Ireland, the National Institute for Occupational Safety and Health and West Virginia University.

Low EPCs, pre-eclampsia linked

Compared to women with uncomplicated pregnancies, women with pre-eclampsia have reduced numbers of special cells that are thought to help grow and maintain blood vessels, according to a study by researchers at the Magee-Womens Research Institute (MWRI) and the School of Medicine. The findings are available online in Reproductive Sciences.

As a healthy pregnancy progresses, two types of endothelial progenitor cells (EPCs) increase in number, possibly indicating the augmentation of the mother’s cardiovascular system to meet the need of the growing fetus, explained senior author Carl A. Hubel, MWRI associate investigator and faculty member in obstetrics, gynecology and reproductive sciences.

This adaptation doesn’t happen in patients with pre-eclampsia, a pregnancy disorder characterized by high blood pressure and protein overload in the third trimester. Pre-eclampsia is the leading cause of preterm labor.

“When we examined blood samples from these women, we found they had far fewer EPCs,” Hubel said. “We wouldn’t have been able to tell them apart from women who weren’t pregnant or men.”

The researchers drew blood samples during the first, second or third trimester from 52 healthy women expecting their first child; 14 with pre-eclampsia expecting their first child; and 13 women who had never been pregnant.

In addition to the reduced numbers of EPCs, pre-eclampsia samples showed alterations in key signaling molecules that may contribute to the mobilization of precursor cells into the circulation.

The researchers also collected third-trimester blood samples from other groups of 11 women with pre-eclampsia and 12 healthy pregnant women. From those samples, they cultured cells known as circulating angiogenic cells (CACs), which are a type of progenitor cell thought to secrete growth factors to support cells that regenerate the vascular endothelium, or blood vessel lining. Cultures from pre-eclampsia samples grew fewer CACs.

“Still, it’s not clear to us whether these differences are the cause of pre-eclampsia or are a consequence of it,” Hubel noted. “We need to monitor women throughout pregnancy to see if we can figure out what came first, as well as get a better understanding of how all these cells work.”

He added that studying women with pre-eclampsia after pregnancy also would be valuable because of the relationship between low numbers of EPCs and the development of cardiovascular disease.

The research team included lead author Patrizia Luppi of pediatrics; Vivek Verma, Lia Edmunds and Daniel Plymire of MWRI, and Robert W. Powers, of MWRI, the Department of Obstetrics, Gynecology and Reproductive Sciences and the Center for Vascular Remodeling and Regeneration.

The project was funded by the National Institutes of Health and the Pennsylvania Department of Health.

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