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September 13, 2012

Research Notes

How older women can control weight

Older women who increased their consumption of fruits and vegetables and decreased consumption of desserts, sugar-sweetened beverages, meat and cheese were the most likely to control their weight over time, according to a study by researchers at the School of Education and GSPH.

Lead author Bethany Barone Gibbs, who is a faculty member in the education school’s Department of Health and Physical Activity, said: “With more than one-third of all Americans considered obese, it’s clear that standard behavioral obesity treatment is producing poor long-term results. We found that some important behaviors differ for long-term versus short-term weight control among women in their 50s and 60s, who are already at higher risk for weight gain.”

The study, which was published in the September issue of the Journal of the Academy of Nutrition and Dietetics, is available online at www.andjrnl.org/webfiles/images/journals/jand/jand_pc_112_9.pdf.

Researchers studied 465 overweight and obese postmenopausal women previously enrolled in GSPH’s Women on the Move through Activity and Nutrition (WOMAN) study and analyzed changes in eating habits and weight loss.

The women were assigned randomly to either a lifestyle-change intervention group or a control group. The women in the intervention group regularly met with nutritionists, exercise physiologists and psychologists, while women in the control group were offered occasional seminars focusing on general women’s health. Participants in both groups reported their eating habits using a detailed questionnaire. At the end of four years, 57 percent of the intervention participants and 29 percent of controls had maintained at least a five-pound weight loss.

Women in both groups who decreased their consumption of desserts and sugar-sweetened beverages experienced a greater weight loss than those who did not in both the short- and long-term. However, participants who decreased fried foods and eating out, and increased fish consumption, had greater weight loss at six months; those who increased their fruit and vegetable intake and decreased intake of meats and cheeses were more likely to be successful at long-term weight loss. Eating out and eating fried food had no apparent effect on long-term weight change.

“Behaviors like cutting out fried foods may work in the short-term, but may be too restrictive to continue for a long period of time. On the other hand, adding fruits and vegetables may be a small change that makes a difference over a period of many months or years,” said Barone Gibbs.

Researchers at GSPH conducted the WOMAN study from 2002 to 2008 to investigate whether a change in diet and lifestyle, along with a 10 percent reduction in body weight, could lower low density lipoprotein (LDL) cholesterol and triglycerides and decrease cardiovascular disease.

Lewis Kuller, professor emeritus in GSPH’s Department of Epidemiology, was the study co-author.

Other Pitt collaborators included Laura S. Kinzel, also of epidemiology and Yuefang Chang of neurological surgery in the School of Medicine.

The research was funded by the National Heart, Lung and Blood Institute.

fruits

NSF funds biodiversity study

Although polyploids, which are plants with more than two sets of chromosomes, are common, how they contribute to the biodiversity has remained a mystery.

But that mystery may be solved with the help of a $2 million grant from the National Science Foundation. Researchers at Pitt and Oregon State University will use wild strawberry plants (Fragaria) to identify what role genetic diversity plays in polyploids, which make up 30-80 percent of all living plants. This will help scientists predict the ecological responses plants may have to environmental change.

Tia-Lynn Ashman, principal investigator of the study and associate chair of Pitt’s Department of Biological Sciences, said: “This deeply integrated comparative study of the wild relatives of the cultivated strawberry — a species of world-wide economic importance — will provide foundational knowledge and contribute unparalleled resources that may be harnessed in efforts to ensure the sustainability of the strawberry and related crops such as the cherry, peach or apple, in the face of stress from non-living factors.”

The strawberry, a plant with 20 species (nearly half of which are polyploids), has centers of diversity in China and America and possesses numerous features that make it the perfect plant to examine.

For example, Fragaria is susceptible to climate change, due to its early spring flowering and northern latitude or high-elevation distribution. Ashman said the wild strawberry will be the key to helping biologists resolve uncertainties about polyploidization’s impact on the biodiversity.

“We will use common garden studies of natural and synthetic polyploids in the greenhouse and at climatically diverse sites to quickly identify the factors that underlie its functional traits and gene expression diversity,” she said.

This will allow her team to forge links between gene expression and functional variation, said Ashman, allowing them to determine where in the lineage the majority of genetic/functional diversity resides.

In addition to solving the mysteries of multi-chromosome plants, the project also facilitates training by broad participation and international collaboration, including middle school science curriculum, involvement of high school teachers, next-generation sequencing workshops, cross-cutting training and communication of research through journals.

Ashman’s project falls under “Dimensions of Biodiversity” in NSF’s investment in Science, Engineering and Education for Sustainability program (SEES). The goal of the Dimensions of Biodiversity campaign is to transform, by 2020, how the scope and role of life on Earth is described.

The SEES program addresses challenges in climate and energy research and education using a systems-based approach to understanding, predicting and reacting to change in the natural, social and built environments. Initial SEES efforts focused on coordination of a suite of research and education programs at the intersection of climate and environment, including specific attention to incorporating human dimensions.

Lab-produced cells could be answer to male infertility

Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can be coaxed into becoming precursor sperm cells, suggesting that it might be possible one day to restore fertility for sterile males with an easily obtained skin sample, according to researchers at the  School of Medicine. Their findings were published online in Cell Reports.

Infertility can be a side effect of some cancer treatments because the drugs work by destroying rapidly-dividing cells, which includes sperm precursor cells, explained the study’s lead author Charles Easley, formerly a post-doctoral fellow in the Department of Obstetrics, Gynecology and Reproductive Sciences, and now a faculty member at Emory University.

There is evidence that adult somatic cells, such as those of the skin, can be induced or biologically prodded to return to a more primitive state and then redirected to become different cell types. To see if it was possible to derive sperm cells, Easley and his colleagues cultured lab-grade hiPSCs from commercially available skin samples, as well as hESCs from established cell lines, in conditions typically used to sustain spermatogonial stem cells.

They found that both kinds of stem cells were able to generate key cells, including the spermatogonial stem cells, spermatocytes containing a full complement of chromosomes prior to cell division known as meiosis, then post-meiotic spermatocytes with half the chromosome number, and round spermatids, which are precursors to sperm. Testing of certain chromosome sites showed correct parent-of-origin genomic imprints in these haploid cells as well, the researchers noted.

“No one has been able to make human sperm from pluripotent stem cells in the lab, but this research indicates it might be possible,” Easley said.

Other Pitt co-authors of the paper included Bart T. Phillips, Hanna Valli, Calvin R. Simerly, Aleksander Rajkovic, Kyle E. Orwig and senior author Gerald P. Schatten, all of the Department of Obstetrics, Gynecology and Reproductive Sciences and the Magee-Womens Research Institute (MWRI), and Megan M. McGuire and Jennifer M. Barringer of MWRI.

The research was funded by the National Institutes of Health (NIH) and MWRI.

Disability, race predict Rx adherence after heart attack

Patients’ race and disability status make a significant difference in their compliance with a life-prolonging medication regimen in the year following a heart attack, according to research led by Yuting Zhang, faculty member in health economics at the Graduate School of Public Health (GSPH).

The findings were published in the September issue of the American Heart Journal.

African Americans, followed by Native Americans, had the worst adherence to essential medications, including beta-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARB) one year after a heart attack. The racial difference in medication adherence is more pronounced among individuals with a disability. Even after adjusting for age, gender, income, drug coverage, location and health status, the racial difference in adherence persisted.

“Even among individuals with nearly full drug coverage, the difference in adherence rates between racial groups remains,” said Zhang. “This suggests that policies simply relying on cost reduction cannot eliminate racial disparities in medication adherence.”

Approximately 7.9 million Americans have had heart attacks, according to the American Heart Association. Clinical guidelines set by an American College of Cardiology and American Heart Association task force recommend that all heart attack patients take a beta-blocker, a statin, aspirin, and either an ACE inhibitor or ARB for the remainder of their lives.

Zhang and her team analyzed 2008-09 Medicare Part D data for all Medicare fee-for-service beneficiaries discharged from the hospital after suffering a heart attack in 2008. They found that one-year medication adherence to beta-blockers in the United States was 68 percent for whites, 66 percent for Asians, 61 percent for Hispanics, 58 percent for Native Americans and 57 percent for African Americans.

Among individuals with a disability, adherence rates were 59 percent for whites, 54 percent for Asians, 52 percent for Hispanics, 47 percent for Native Americans and 43 percent for African Americans.

“Physicians should be aware of these differences in adherence as they treat patients,” Zhang said. “Long-term follow-up may be necessary to ensure that patients continue to use these important medications over time.”

In 1996, the National Committee for Quality Assurance  began requiring health plans to provide performance measures of the drugs given after heart attacks. Following that requirement, the six-month adherence rate improved by more than 34 percent, indicating that such policies could be beneficial in improving long-term adherence rates, Zhang said.

Co-authors on the study included Seo Hyon Baik, Cameron M. Kaplan and Judith R. Lave, all of GSPH’s Department of Health Policy and Management, and Chung-Chou H. Chang of the medical school’s Department of Medicine.

Targeted oxidation blocker prevents secondary damage after TBI

Treatment with an agent that blocks the oxidation of an important component of the mitochondrial membrane prevented the secondary damage of severe traumatic brain injury (TBI) and preserved function that otherwise would have been impaired, according to a research team from the School of Medicine, GSPH and the Dietrich School of Arts and Sciences’ chemistry department. The report was published online in Nature Neuroscience.

An estimated 1.7 million Americans sustain a TBI due to traffic accidents, falls, assaults and sports participation, said the study’s senior author Hülya Bayir, faculty member in the Department of Critical Care Medicine. She added that 52,000 of those injured die, and 85,000 are left with significant disability.

“We don’t yet have a specific therapy for TBI, but can provide only supportive care to try to ease symptoms,” Bayir said. “Our study drug shows promise as a neuroprotective agent that might help address this important public health problem.”

For the study, the research team conducted a global assessment of all the phospholipids in rat brain cells. This revealed that damage from TBI was nonrandom and mostly involved cardiolipin, a phospholipid that is found in the membranes that form mitochondria, the cell’s powerhouse. They noted that in the healthy animal, only 10 of the 190 cardiolipin species were modified by oxygen, but after a brain injury the number of oxidized species rose many-fold.

The researchers then developed an agent, called XJB-5-131, which can cross the blood-brain barrier and prevent the oxidation of cardiolipin. Using an established research model of severe TBI, the agent or a placebo was injected into the bloodstream of rats five minutes and again 24 hours after head injury.

In the weeks that followed, treated animals performed akin to normal on tests of balance, agility and motor coordination, learning and object recognition, while placebo-treated animals showed significant impairment. The results indicate that blocking cardiolipin oxidation by XJB-5-131 protected the brain from cell death.

“The primary head injury might not be that serious,” Bayir noted. “But that initial injury can set into motion secondary cellular and molecular events that cause more damage to the brain and that ultimately determine the outcome for the patient.”

She added that a targeted oxidation-blocker also might be beneficial in the treatment of other neurological disorders, such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and stroke.

Also contributing to the research were lead author Jing Ji of critical care medicine, environmental and occupational health, the Center for Free Radical and Anti-oxidant Health and the Safar Center for Resuscitation Research; Patrick M. Kochanek of critical care medicine and the Safar center; Peter Wipf of chemistry; Valerian E. Kagan of environmental and occupational health and the Center for Free Radical and Anti-oxidant Health; Anthony E. Kline of the Department of Physical Medicine and Rehabilitation, as well as Pitt researchers from pediatrics and neurological surgery and of the Center for Neuroscience, as well as Noxygen Science Transfer and Diagnostics GmbH in Elzach, Germany.

The study was funded by NIH, the National Institute for Occupational Safety and Health and the U.S. Army.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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