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June 28, 2012

Research Notes

Startup grant awarded

Chemistry faculty member Sean Garrett-Roe was awarded a $40,000 Spectroscopy Society of Pittsburgh startup grant to develop new spectroscopic methods to investigate how next-generation solar cells will work. The project aims to result in a spectroscopy system that can measure the energy and charge transfer that occurs after a solar cell has absorbed a photon under conditions relevant to working devices.

The starter grant awards are given to chemistry professors early in their career to encourage high-quality, innovative research. The goal of the grants is to promote the training and development of graduate students in the fields of spectroscopy and analytical chemistry.

STDs are understood but prevention is not so good

While adolescents understand how sexually transmitted diseases (STD) occur, their risk-reduction strategies often are not the most effective, report Pitt researchers in a study published online in Perspectives on Sexual and Reproductive Health.

Co-author Aletha Y. Akers, a faculty member in obstetrics, gynecology and reproductive sciences, said, “In 2006, we recruited 37 black adolescents from two rural North Carolina counties to participate in focus groups exploring adolescent understanding of how primary prevention strategies reduce STD transmission, described common barriers to the adoption of prevention strategies, and identified risk reduction strategies adolescents commonly employ.

“What we found is adolescents understand how STDs are transmitted but consider primary prevention strategies like abstinence and consistent condom use unlikely or difficult to implement.”

According to Akers, the adolescents interviewed reported developing their own strategies to reduce their STD risk, which included indirect partner assessments like evaluating a person’s physical appearance, eye contact and body language. The girls who were interviewed often used regular STD testing as a way to fact-check their partners’ faithfulness. As long as they remained STD-free, they felt they could trust their partners’ commitment.

“This study is incredibly important because it shows us a disconnect between adolescents and the public health messages put forth,” said Akers. “We need to identify whatever misconceptions about STD transmission they may have and correct them. The adolescents we spoke with consider having sex at their age normal and abstinence unlikely for teenagers. With this information in mind, we need to change our messaging and provide tools that can be implemented to help adolescents think more critically about their choices.”

Akers and her colleagues focused on rural African-American adolescents for this study because their rates of early sexual activity and STDs are among the highest in the country. Each year, approximately 9.1 million new cases of STDs are diagnosed among 15- to 24-year-olds.

Melanie A. Gold, a staff physician in Pitt’s Student Health Services, was among the study’s co-authors.

The study was sponsored by the Robert Wood Johnson Foundation.

Protein key in aging

Pitt researchers report that blocking a protein that regulates the activity of certain genes slowed the aging process in a mouse model of premature aging as well as in healthy mice. Their findings, published online ahead of print in the Journal of Clinical Investigation, could lead to drugs that prevent cellular damage due not only to growing old, but also to cancer and diseases caused by abnormal DNA repair activity.

Aging is thought to be the result of accumulated cellular damage, including DNA damage, but the biological mechanisms that drive aging in response to damage are not understood, said senior author Paul Robbins, a faculty member in the Department of Microbiology and Molecular Genetics. His team studied NF-kappa B, a protein involved in turning certain gene activity on and off in response to inflammation, stress and cellular damage.

“Other studies have shown that NF-kappa B activity is elevated in aging tissues,” Robbins said. “We examined whether this held true for mice with progeria, a disease of accelerated aging, and what would happen if we blocked NF-kappa B activation.”

The researchers found that a higher percentage of cells contained activated NF-kappa B in old and progeroid mice than in healthy adult mice. Age-related activation of NF-kappa B happens in some but not all cells, they said.

Altering expression of NF-kappa B slightly or blocking its activation with chemicals led to a delay in the onset and reduction in severity of age-related changes in tissues, including in muscle, liver, kidney and the nervous system. Researchers also found that inhibiting the protein reduced free radical-induced oxidative damage.

“It’s possible that as we age, NF-kappa B becomes activated by accumulation of cellular damage, and that in turn increases the production of free radicals, resulting in more cell damage,” Robbins said. “An agent that blocks this protein could be used to slow down aging and also to treat certain cancers and diseases, such as xeroderma pigmentosum, which are characterized by altered DNA repair activity.”

Pitt co-authors included Cheryl L. Clauson, Laura J. Niedernhofer and Jeremy S. Tilstra of microbiology and molecular genetics; Andria R. Robinson of human genetics; Siobhán Q. Gregg of cell biology; Daniel P. Reay and Paula R. Clemens of neurology; Johnny Huard, Luigi A. Nasto, Arvydas Usas and Nam Vo of orthopaedic surgery; Claudette M. St Croix of environmental and occupational health, and Donna B. Stolz and Simon C. Watkins of cell biology.

The research was funded by the National Institutes of Health, the Ruth L. Kirschstein National Research Service Award, the Ellison Medical Foundation and the Hartwell Foundation.

Gastric bypass, alcohol disorders linked

Pitt researchers have found that people who receive the most popular weight-loss surgical procedure are at increased risk of developing symptoms of alcohol use disorders.

The findings, published in the Journal of the American Medical Association, draw a clear link between Roux-en-Y gastric bypass (RYGB) surgery and symptoms of alcohol use disorders and could have implications for patient screening before surgery, as well as clinical care after surgery. Alcohol use disorders include alcohol abuse and dependence, popularly known as alcoholism.

Lead author Wendy King, a faculty member in epidemiology, said, “Patients should be educated about the potential effect of bariatric surgery, in particular RYGB surgery, to increase the risk of alcohol use disorders. Alcohol screening should be included in routine pre- and post-operative care.”

King and her colleagues investigated alcohol consumption and alcohol use disorder symptoms in the longitudinal assessment of bariatric surgery study, a prospective study of patients undergoing weight-loss surgery at one of 10 different hospitals across the United States. Within 30 days before surgery and again one and two years after surgery, 1,945 study participants completed the Alcohol Use Disorders Identification Test, developed by the World Health Organization, to identify symptoms of alcohol use disorders.

Nearly 70 percent of study participants underwent the RYGB surgery, which reduces the size of the stomach and shortens the intestine, limiting food intake and the body’s ability to absorb calories. Another 25 percent of patients had laparoscopic adjustable gastric banding, where the surgeon inserts an adjustable band around the patient’s stomach, lessening the amount of food the stomach can hold. The remaining 5 percent of patients had one of three less-popular weight-loss surgeries.

Among participants who had the RYGB procedure, 7 percent reported symptoms of alcohol use disorders prior to surgery.  One year after surgery, there was not a significant increase in alcohol use disorders. However, by the second post-operative year, there was greater than a 50 percent relative increase, with 10.7 percent of patients reporting symptoms of alcohol use disorders. In contrast, there was not a significant increase in alcohol use disorders following laparoscopic adjustable gastric banding.

“Among RYGB patients, there was a significant decrease in alcohol consumption in the first year after surgery, compared to the year before surgery, but not in the second year. Thus, the increase in alcohol use disorder symptoms following RYGB surgery was likely a result of an increase in alcohol sensitivity following surgery combined with resumption of higher levels of alcohol consumption in the second post-operative year,” King said.

Safe levels of alcohol consumption have yet to be established for the post-operative patient. Previous studies on the effect of alcohol following bariatric surgery suggest that, after having RYGB, patients feel intoxicated more rapidly and for longer after drinking less.

King’s study found that one in eight participants reported consuming at least three drinks per typical drinking day by the second post-operative year.

King’s study also found several patient characteristics that could help predict whether a patient is more likely to develop alcohol use disorders following surgery, including a lower sense of interpersonal support (i.e., having people to do things with), smoking, recreational drug use, consumption of alcohol at least two times per week and prior alcohol use disorders. However, more than half of patients with post-operative alcohol use disorders did not report the illness in the year prior to surgery. Men and younger adults also were more likely to develop alcohol use disorders.

Depressive symptoms, mental health, binge eating and having received treatment for psychiatric issues prior to surgery were not related independently to an increased likelihood of alcohol use disorders following surgery.

Bariatric surgery is the most effective treatment for substantial weight loss in adults with severe obesity. King said, “While this study highlights a potential risk, it is important that it is considered in conjunction with the benefits of bariatric surgery.”

Pitt collaborators included Jia-Yuh Chen of biostatistics, Anita P. Courcoulas of surgery and Melissa A. Kalarchian of psychiatry.

The study was funded by the National Institutes of Health.

Weight-loss plans compared

Although a standard behavioral weight loss intervention among overweight and obese adults resulted in greater average weight loss over 18 months, a stepped-care intervention resulted in clinically meaningful weight loss that cost less to implement, according to a study in the June 27 issue of JAMA.

John Jakicic, chair of the School of Education’s Department of Health and Physical Activity and director of the Physical Activity and Weight Management Research Center, and his colleagues enrolled 363 overweight and obese adults ages 18-55 years. Participants were placed on a low-calorie diet, prescribed increases in physical activity and attended group-counseling sessions ranging from weekly to monthly during an 18-month period.

Participants were placed in either a fixed program or a stepped-care group in which counseling and weight loss strategies could be modified every three months in response to observed weight loss as it related to weight loss goals.

Of the 363 study participants, 260 weighed in at the 18-month assessment. The researchers found that weight loss at 18 months was 16.8 pounds in the fixed program group compared with 13.7 pounds in the stepped-care group.

The fixed program participants lost an average of 8.1 percent of their body weight, compared with 6.9 percent for the stepped-care group. Both groups had significant and comparable improvements in resting heart rate, blood pressure level and fitness. However, the average cost for the stepped-care program was $785, significantly less expensive than the average cost for the fixed program’s $1,357.

The authors wrote: “Most weight loss programs are intensive during the initial weeks of treatment, become less intensive over time and maintain a fixed contact schedule for participants irrespective of treatment success or failure. Intensive weight loss programs are costly and require substantial time commitments from the participants, making them impractical in many circumstances.

“An alternative is a stepped-care approach. It involves an initially low-intensity intervention that is increased if weight loss milestones are not achieved at fixed time points. Stepped care has been effective for treatment of other health conditions. In theory, stepped care could result in better weight loss than conventional therapy because treatment intensity is escalated if weight loss goals are not met during the treatment period.

“A stepped-care approach could prove to be a cost-effective means for obesity treatment.”

Other Pitt authors were Kelli K. Davis and Amy D. Rickman of the Department of Health and Physical Activity and the Physical Activity and Weight Management Research Center.

Biodegradable artery developed

Research published online June 24 in Nature Medicine highlighted a cell-free biodegradable artery graft that harnesses the body’s regenerative capacity.

The work was led by Yadong Wang, a faculty member in the Swanson School of Engineering and the School of Medicine’s Department of Surgery, in conjunction with fellow researchers Wei Wu, a former Pitt postdoctoral associate (now a postdoctoral associate at Yale University), and Robert Allen, a Pitt PhD student in bioengineering.

Wang’s approach is a philosophical shift from the predominant cell-centered approaches in tissue engineering of blood vessels.

“The host site, the artery in this case, is an excellent source of cells and provides a very efficient growth environment,” said Wang. “This is what inspired us to skip the cell culture altogether and create these cell-free synthetic grafts.”

Wang said, “This report is the first that shows a nearly complete transformation of a synthetic plastic tube to a new host artery with excellent integration within three months. Most likely, the amount of time it takes to regenerate an artery can be further shortened as we refine the system.” Current approaches toward tissue-engineered arteries require a long production cycle because of the required cell culture steps. The newly developed graft is made in a few days, stores in a dry pouch at ambient temperature and is readily available off the shelf.

The graft is made of an elastic polymer called PGS that is resorbed quickly by the body and is wrapped with a fibrous sheath to trap the cells. It is coated with heparin to reduce blood clotting and bind many growth factors.

The researchers made grafts as small as 1 millimeter in diameter and monitored the graft’s transformation in vivo for three months. Because the graft was highly porous, cells were able to penetrate the graft wall easily, and mononuclear cells occupied many of the pores within three days. Within 14 days, smooth muscle cells — an important blood vessel builder — appeared. At 28 days, cells were distributed more evenly throughout the graft. At 90 days, most inflammatory cells were gone, which correlated with the disappearance of the graft materials. The artery was regenerated in situ and pulsed in sync with the host. Furthermore, the composition and properties of the new arteries are nearly the same as native arteries.

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


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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