University Times

Pharmacy prof receives grant

Bonnie Falcione of pharmacy and therapeutics has received a $1,000 incentive grant from the American Pharmacists Association Foundation for her proposal, “Improving Prescribing and Documentation of Immunization and Education for Vaccines Administered as Prevention for Overwhelming Post-Splenectomy Infection in Patients Who Undergo Emergency Splenectomy.”

Falcione will study the impact on required medical record documentation and patient education for vaccines for patients who undergo emergency splenectomy after implementing a pre-printed physician order set and corresponding pharmacy dispensing procedure for this patient population.

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Patent awarded

Electrical and computer engineering professor Peng Chen has been awarded a patent for “Active in-fiber optic components powered by in-fiber light, No. 7,349,600.” The components are used in fiber optic communications and sensing applications.

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Immune system trigger found

School of Medicine researchers have identified genetic components of dendritic cells that are key to asthma and allergy-related immune response malfunction. Targeting these elements could result in more effective drugs to treat allergic disorders and asthma, according to a study reported in the May edition of the journal Nature Medicine.

“We now have identified a molecule, c-Kit, that is central to the process of allergic response,” said Anuradha Ray, co-corresponding author and professor of medicine and immunology in the Division of Pulmonary, Allergy and Critical Care Medicine. “We show that genes encoding for c-Kit and the cytokine interleukin 6 (IL-6) are significantly activated when allergens are present, but c-Kit is the very first molecule that gets triggered.”

Interactions between viruses and bacteria and molecular steps that initiate the immune defense have remained largely unknown.

The Pittsburgh team incubated dendritic cells with cholera toxin and house dust mite allergens, finding that both substances induced significant secretion of c-Kit and IL-6, initial steps in a cascade resulting in the activation of T helper cells.

Co-author Prabir Ray, professor of medicine and immunology, said, “Therapy directed against c-Kit specifically on dendritic cells using compounds coupled to c-Kit inhibitors such as Gleevec, a drug that is already FDA-approved and used in cancer treatment, may alleviate allergic diseases and, potentially, inflammatory bowel disease.”

Anuradha Ray said, “Dual upregulation of c-Kit and stem cell factor has been noted in some cancers, such as small cell lung cancer. IL-6 has been associated with cancers such as multiple myeloma. Collectively, similar approaches to inhibit c-Kit, in addition to Gleevec or other inhibiting compounds, could alleviate multiple cancers.”

This study is the foundation for the doctoral dissertation of first author Nandini Krishnamoorthy, a student in the immunology graduate program.

Other Pitt authors are Timothy Oriss, Division of Pulmonary, Allergy and Critical Care Medicine; Mingjian Fei, interdisciplinary biomedical graduate program, and Melissa Paglia and Manohar Yarlagadda, research specialists in Prabir Ray’s lab.

The study was funded by the National Heart, Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

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Program seeks cancers’ genetic links

The University of Pittsburgh Cancer Institute has established the Frieda G. and Saul F. Shapira BRCA Cancer Research Program. BRCA 1 and 2 are two genes that, when mutated, dramatically increase the risk of breast, prostate, ovarian and pancreatic cancers.

Women who possess either mutation have a 50-80 percent lifetime risk of developing breast cancer, and the disease progresses more quickly than in individuals without the mutations. Experts estimate that as many as one out of every 345 people in the U.S. carries a BRCA mutation, but for individuals of Ashkenazi (Eastern European) Jewish descent, the number is approximately one in 40.

While these mutations are linked primarily with an increased risk of breast cancer in women, they also increase the risk for other cancers. Both men and women can carry the genetic mutations, which means they can be passed to children from either parent.

The David S. and Karen A. Shapira Foundation committed an initial $1 million to the program, structuring the gift as a matching grant to raise an additional $1.5 million from individuals and foundations. UPMC is matching these gifts on a dollar-for-dollar basis, for an overall goal of $5 million.

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Impact of parent’s sudden death studied

The children of parents who die suddenly are three times more likely to develop depression and are at higher risk for post-traumatic stress disorder (PTSD) than children who don’t face such a difficult life event, according to a School of Medicine study published in the Archives of Pediatric Adolescent Medicine.

In the first study of its kind, Pitt and UPMC researchers also found that, as expected, parents who died of suicide had higher rates of bipolar disorder, alcohol and substance abuse disorders and personality disorders.

However, those who died accidentally or from sudden natural death also had higher rates of psychiatric disorders, specifically alcohol and substance abuse and personality disorders, and showed a trend toward higher rates of bipolar disorder.

While the death of a parent consistently is rated as one of the most stressful events that a child can experience, little has been known about the psychiatric outcomes in bereaved children until now. “Our study shows that when premature parental death occurs, physicians should be alert to the increased risk for depression and post-traumatic stress disorder in bereaved offspring and in their surviving caregivers,” said David A. Brent, academic chief of child and adolescent psychiatry at Western Psychiatric Institute and Clinic and professor of psychiatry, pediatrics and epidemiology at the School of Medicine. “Not surprisingly, we found that bereaved offspring are at increased risk for adverse outcomes in part because of factors that may have contributed to the parent’s death.”

The study involved 140 families in which one parent had died of either suicide, accidental death — such as drug overdoses and car accidents — or sudden natural death, while a control group consisted of 99 families with two living biological parents who were matched to the deceased parents in the study group based on sex, age and neighborhood. Ages of the children at their parents’ deaths ranged from 7 to 25.

Other factors that affected outcomes included the nature of the last conversation with the deceased. Researchers found that a surviving caregiver’s recollection of a supportive conversation led to a higher risk of depression. “Understanding the effects of bereavement is essential to identifying those at highest risk who should be targeted for future prevention and intervention efforts,” noted psychiatry professor and first author Nadine Melhem.

These findings point out the importance of improving the detection and treatment of bipolar illness, substance and alcohol abuse, and personality disorders, as well as the significance of addressing the lifestyle associations of these illnesses that lead to premature deaths, according to Brent.

“The [surviving] caregivers should be monitored for depression and PTSD because restoring their normal mental functioning could lead to more positive outcomes for the children,” said Brent. “However, given the increased risk of depression and PTSD, the bereaved children also should be monitored.”

Co-authors of the study include Monica Walker, psychiatry and WPIC, and Grace Moritz, UPMC’s Division of Collaborative Care Medicine.

Brent and Melhem were supported by funding from the National Institute of Mental Health and the American Foundation for Suicide Prevention.

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Geriatrics research presented

Pitt researchers presented their work recently at the annual meeting of the American Geriatric Society in Washington, D.C.

* DDR hooks more than teens

Interactive video dance (IVD) has been found to encourage physical activity in postmenopausal women, reports Stephanie Studenski, professor of medicine in the Division of Geriatric Medicine. The most recognized form of IVD is the popular teen video game Dance, Dance Revolution (DDR), in which players compete to best-imitate the dance moves displayed on-screen while standing on platforms that measure their performance. This six-week pilot study followed 31 sedentary women, ages 48-70, who played DDR for 30 minutes twice weekly in individually coached sessions.

All but two of the women progressed to a higher level of difficulty and two-thirds of the women who completed the sessions voluntarily exceeded the required duration of exercise.

Most women reported high rates of satisfaction and continued interest. Thus, IVD could serve as a tool to encourage postmenopausal women to perform the recommended amount of daily physical activity.

* Exercise program aids energy-efficient walking

In older adults, walking can demand increasing amounts of energy, which may have an impact on mobility disabilities. This is because as adults age, they undergo changes in gait and begin to walk at a slower, less even pace.

While traditional exercise was found to further increase the energy used to walk, a new motor-learning exercise program helped make walking more energy-efficient, according to a randomized, controlled trial conducted by Jessie Van Swearingen, professor of medicine at the School of Health and Rehabilitation Sciences and physical therapist at the University of Pittsburgh Institute on Aging.

The motor-learning program also improved gait abnormalities and physical function, more so than the traditional program. This 12-week trial monitored adults with significant declines in gait to compare the two programs, including the traditional exercise program of endurance, strength and balance training, and the motor-learning program, which enforced smooth automatic movement and movement adaptations to altered conditions.

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Eclampsia may signal heart disease risk

C-reactive protein (CRP), an inflammatory marker associated with a higher risk of cardiovascular disease, was found to be elevated even 30 years after a pregnancy affected by eclampsia, according to a Magee-Womens Research Institute (MWRI) study in the journal Hypertension.

The finding indicates that pregnancy outcome can be viewed as “a natural early stress test” for future risk of cardiovascular disease, the leading cause of death for women.

Lead author Carl Hubel, a faculty member in obstetrics, gynecology and reproductive sciences at the School of Medicine and an MWRI assistant investigator, said: “Levels of CRP were doubled in postmenopausal women who had a prior episode of eclampsia compared to those who had a history of normal pregnancies. This difference remained after adjusting for other, potentially confounding risk factors.”

Eclampsia can involve coma, convulsions and organ failure. About two women in 100 will develop preeclampsia during pregnancy. About seven in 10,000 will develop eclampsia.

“We propose that prior preeclampsia — particularly severe preeclampsia — be considered as a red flag to identify women of reproductive age who stand to benefit from cardiovascular risk factor modification,” said Hubel.

Additional Pitt authors were Robert Powers, Hilary Gammill and James Roberts of obstetrics, gynecology and reproductive sciences, and Roberta Ness, epidemiology.

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Psychological research presented

Pitt-Bradford psychology professor Greg Page presented research in which he and two colleagues evaluated the reliability of a psychological assessment that could one day provide meaningful information about juvenile sex offenders.

Page presented “Assessing Cognitive Distortions Associated With Sexual Offending: Reliability of the Adolescent Bumby Scales” at the 2008 Psychology-Law Society conference.

Page, along with associate professor of psychology Warren Fass and Stephanie L. Pascarella, who is pursuing degrees in psychology and sociology, reviewed modified scales intended to evaluate juvenile sex offenders. According to Page, psychological assessment tools are used to evaluate the attitudes of adult sex offenders regarding molestation and rape.

Before the scales for juvenile offenders can be used, Page said they first needed to be found reliable and consistent. The researchers tested college students enrolled in several psychology classes to see if their scores on the scales were consistent when they were tested at different times. Page said the students’ test results were consistent, which indicates that the scales are reliable.

The next step, he said, is to coordinate with researchers at other universities to see if the scales accurately and reliably assess the attitudes of juvenile sex offenders.

The scales, he said, may one day be used to determine appropriate treatment for the juvenile offenders and assess their progress and success as they are treated.

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IPF biomarkers found

School of Medicine researchers have found a combination of blood proteins that appear to distinguish patients with idiopathic pulmonary fibrosis (IPF).

Their work, reported in PLoS Medicine, an open-access journal of the Public Library of Science, could help improve diagnosis and monitoring of the lung disease.

Senior author is Naftali Kaminski, director of the Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease in the Division of Pulmonary, Allergy and Critical Medicine and associate professor of medicine.

IPF is a degenerative illness distinguished by progressive lung scarring and diminished breathing capacity, typically leading to death within five years of diagnosis.

Researchers analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and 53 normal controls. A combination of five proteins related to normal tissue breakdown and remodeling and certain disease processes, including arthritis and cancer, was found to be highly indicative of IPF. Increases in matrix metalloproteinases (MMP) 7 and 1 were observed in tissue and fluid taken from the lungs of IPF patients. Other proteins in the IPF signature are matrix metalloproteinase 8, insulin-like growth factor binding protein 1 and tumor necrosis factor receptor superfamily member 1A.

“These proteins were increased in IPF patients, but not in patients with lung illnesses such as chronic obstructive pulmonary disease,” said Ivan O. Rosas, first author on the study and assistant professor of medicine.

Other Pitt authors were Thomas J. Richards, Yingze Zhang, Kevin Gibson, Frank C. Sciurba. James Dauber, Kazuhisa Konishi, Anna E. Lokshin and Kathleen O. Lindell of the Department of Medicine.

The study was funded by the National Heart, Lung and Blood Institute, the Simmons family and the National University Autonoma de Mexico.

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Weiland earns NSF award

Lisa Weiland of mechanical engineering and materials science in the Swanson School of Engineering has been awarded a 2008 National Science Foundation CAREER Award. The one-year continuing grant of $64,458 provides funding for her project, “High Performance, Mechanical Robust Ionomeric Sensors.”

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DOD funds pharmacy study

Miranda Sarachine, a School of Pharmacy graduate student in Billy Day’s lab, has been awarded $97,200 by the Department of Defense for her project, “The Nuclear Matrix and Its Interactions With the Estrogen Receptors: A Role in the Development and Progression of Breast Cancer.”

This three-year study will use ductal carcinoma in situ (DCIS) and breast reduction mammoplasty derived cell lines generated through a tissue engineering system.

The goal of this project is to identify the nuclear matrix proteins and determine how estrogen receptor alpha and estrogen receptor beta and validation of nuclear matrix proteins are differentially expressed between invasive DCIS, non-invasive DCIS and breast reduction cell lines.

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