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May 3, 2007

RESEARCH NOTES

IPT prevents depression relapse in women

Most women with recurrent depression may be able to prevent subsequent depressive episodes with monthly maintenance interpersonal psychotherapy (IPT), say researchers from the Pitt School of Medicine in a study published in the May issue of the American Journal of Psychiatry.

Researchers found that once-per-month maintenance IPT, a form of therapy that focuses on relationships and interpersonal events that tend to trigger depression, was effective in preventing recurrence of depression in women who achieved remission through IPT alone.

Ellen Frank, professor of psychiatry, “Studies have shown that when a person recovers from depression by using medication, the best way for them to stay well is to continue on the same dosage of medication.

“However, many people, especially women of childbearing age or those taking medications for other conditions, may not feel comfortable taking antidepressants for long periods of time. We found that interpersonal psychotherapy is a valid alternative to help women with recurrent depression remain symptom-free, especially women who were able to recover from a depressive episode using therapy alone.”

The Pittsburgh study looked at 99 women whose depressive episodes remitted after outpatient treatment with IPT alone and 32 women who achieved remission with outpatient IPT and medication.

The women were randomly assigned to receive maintenance IPT at intervals of once per week, twice per month or once per month over the course of two years, or until they had a subsequent depressive episode.

Of those who initially remitted with IPT alone, 74 completed the two-year maintenance phase. Only 19, or 26 percent, had a recurrence of depression. Of those who remitted with IPT and medication, 26 completed the maintenance phase. Half had a recurrence of depression. In both groups there was no significant difference in recurrence rates between those who received maintenance IPT weekly, bi-monthly or monthly.

“Our study indicates, as many prior studies have, that not every person’s depression is the same, nor should each person be treated the same way,” said Frank. “Some people respond best to therapy, others to medication and others to a combination of the two. It’s important that clinicians evaluate their patients carefully to determine the best treatment for each individual.”

Other Pitt authors were David J. Kupfer, Daniel J. Buysse, Holly A. Swartz, Paul A. Pilkonis, Patricia R. Houck, Paola Rucci, Danielle M. Novick, Victoria J. Grochocinski and Deborah M. Stapf.

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Engineering faculty receive grants

Electrical and computer engineering professors Kevin Chen and Joel Falk have received a $167,000 U.S. Department of Energy research program award as part of the National Energy Technology Laboratory (NETL) -University Collaboration for their project “Raman Spectroscopy for Monitoring of Natural Gas Composition.”

Chen also has been awarded a three-year $342,000 National Science Foundation grant for research into three-dimensional photonic devices and a $250,000 U.S. Department of Defense contract for research and development of nuclear batteries. In addition, Chen has received a $93,000 contract from Sabeus Photonics for research on advanced fiber optical component fabrication.

Steven Levitan, John A. Jurenko Professor in Computer Engineering, and Donald Chiarulli, professor of computer science, have received a three-year NSF grant of $200,000 for “Nonlinear Model Order Reduction for Behavioral Models of Emerging Technologies.”

A NETL grant also is funding a collaboration between mechanical engineering and materials science faculty members Jeffrey S. Vipperman and William Clark and researchers at Carnegie Mellon and West Virginia University to develop active combustion throttles for gas turbine engines.

Qing-Ming Wang received a three-year grant from the Army Research Office to develop new approaches for on-chip integration of thin film bulk acoustic wave resonators used in radio frequency and microwave frequency control applications.

Sung Kwon Cho received a three-year, $234,000 NSF grant to develop micro bubble tweezers for individual cell manipulation and ultrasonic cell therapy and a 21-month, $150,000 grant from the U.S. Homeland Security Advanced Research Project Agency to develop channel-to-droplet sample extraction and purification.

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New HIV research funded

The National Institutes of Health has awarded a $4.6 million five-year grant to Michael A. Parniak, professor of molecular genetics and biochemistry at the School of Medicine.

Parniak heads a multi-team effort to identify and develop new drugs for the treatment of HIV. The research focuses on ribonuclease H, an HIV enzyme that is not targeted by any of the current HIV therapeutics. The research program will optimize anti-HIV agents identified from a library of more than 160,000 natural products derived from a unique plant cell culture technology developed by company partner Millenia Hope.

Parniak stated, “While natural products have traditionally been a major source for anti-infective agents, they have not been widely tapped as a source for anti-HIV drugs. This award allows us to evaluate a consistent and importantly renewable plant cell culture technology as a source for novel anti-HIV agents.”

HIV encodes four enzymes essential for virus replication: protease, integrase, reverse transcriptase and ribonuclease H. Almost all of the current HIV therapeutics target protease and reverse transcriptase, and drugs against HIV integrase are in late-stage clinical trials. Few if any drugs against ribonuclease H are even in early stages of development.

“HIV resistance to current drugs is an increasingly serious problem, and some virus strains, the so-called ‘superbugs,’ are resistant to most if not all of the currently available drugs,” said Parniak. Drugs directed against new HIV targets such as ribonuclease H are likely to be effective against resistant HIV strains.

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Group calls for new critical care system

The nation’s critical care medical services system needs to be reorganized, says a group led by Pitt School of Medicine researchers.

Its report appears in the April issue of the journal Critical Care Medicine.

Amber E. Barnato, an assistant professor in the medical school’s Department of Medicine, said, “The number of Americans over the age of 65 is expected to double by 2030. In addition to non-elective medical admissions for critical illness among chronically ill elders, the growth rate in elective surgical procedures requiring intensive care unit admission, such as bypass surgery, is growing fastest among this age group. All of this means more and more people will demand already strained intensive care services. This anticipated mismatch between supply and demand is perhaps no different for critical care services than for other medical care disproportionately serving elders — ranging from emergency services to long-term care services — but the opportunities for improving the efficiency of the existing system to meet demand are probably greater.”

The report, developed following a September 2005 meeting of critical care stakeholders called the Prioritizing the Organization and Management of Intensive care Services (PrOMIS) conference, calls for creation of a tiered, regionalized system for critical care services in an effort to centralize expertise, equipment and facilities. This would make the necessary critical care services readily available to the patients who are most in need.

“Prior conferences aimed at addressing this problem sought input only from critical care professionals, who are a fraction of all the stakeholders,” said Barnato, lead author of the report. “These groups often stated the need for more trained providers. Surveying a wider group of interested parties, we found that this isn’t necessarily the best or only solution.”

PrOMIS conference organizers attempted to identify problems in the current U.S. critical care system as seen by those from professional organizations, critical care and non-critical care physicians, federal and private health insurers, federal and private funding organizations and the general public.

Prior to the conference, attendees selected from each of the groups were asked to fill out a survey aimed at identifying problems in the organization and delivery of critical care services. Attendees then participated in breakout groups where they discussed the themes and issues identified by the pre-conference survey.

In the paper, researchers say the primary concern voiced by participants was that the “utilization, organization and management of intensive care services in the United States was not optimal.” They broadly agreed that there was a need to regionalize and tier the critical care system, similar to what previously had been done by the U.S. trauma system. Such a system would require the most critically ill patients to be seen in top-level critical care centers. Lower-level centers would not provide ongoing critical care services, but would need to transfer critically ill patients to higher-level centers.

Participants also cited the need to acknowledge that some critical care services should be provided by physicians, such as hospitalists and emergency physicians, who currently are not certified by the existing critical care boards.

Conference organizers seek support for a second stakeholder meeting, PrOMIS II, to develop accreditation criteria for the proposed regionalized tiered system, define explicit triage and quality surveillance criteria for each tier, develop a comprehensive set of core competencies for critical care providers and endorse a way to train and certify critical care providers in these competencies.

Derek C. Angus of the School of Medicine was among the co-authors of the paper.

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Less toxic leukemia killer found

A naturally occurring compound found in many fruits and vegetables as well as red wine, selectively kills leukemia cells in culture while showing no discernible toxicity against healthy cells, according to a study by researchers at Pitt’s School of Medicine.

These findings, published online and in the May 4 Journal of Biological Chemistry, offer hope for a more selective, less toxic therapy for leukemia.

Corresponding author Xiao-Ming Yin, associate professor of pathology, said, “Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide.”

Leukemia occurs when there is an excess of abnormal white blood cells. It is not a single disease but a number of related cancers that start in the blood-forming cells of the bone marrow.

Based on previous reports that anthocyanidins, a group of naturally occurring compounds widely available in fruits and vegetables as well as in red wine, have chemopreventive properties, Yin and his collaborators studied the effects and the mechanisms of the most common type of a naturally modified anthocyanidin, cyanidin-3-rutinoside (C-3-R), in several leukemia and lymphoma cell lines.

They found that C-3-R, which was extracted and purified from black raspberries, caused about 50 percent of a human leukemia cell line known as HL-60 to undergo programmed cell death, or apoptosis, within about 18 hours of treatment at low doses. When they more than doubled the concentration of C-3-R, virtually all of the leukemia cells became apoptotic and died. C-3-R also induced apoptosis in other human leukemia and lymphoma cell lines.

When the investigators studied the mechanism of cell death in the leukemia cells, they found that C-3-R induced the accumulation of peroxides, a highly reactive form of oxygen, which, in turn, activated a mitochondria-mediated apoptotic pathway. In contrast, when the researchers treated normal human blood cells with C-3-R, they did not find any increased accumulation of reactive oxygen species and there were no apparent toxic effects on these cells.

Previous studies have shown that C-3-R possesses strong antioxidant properties, a characteristic shared by other polyphenols, such as those found in green tea, which could be responsible for their chemoprevention effects.

Yin’s work suggests that although C-3-R demonstrates antioxidant effects in the normal cells, paradoxically it induces an oxidative “stress” in the tumor cells. It is possible that this differential effect of C-3-R may account for its selective toxicity in the tumor cells.

Other University researchers involved in the study were Rentian Feng, Hong-Min Ni, Irina L. Tourkova and Michael R. Shurin, all of pathology.


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