University Times

Potential of regenerative medicine explored

Clinical and basic science research findings were presented by researchers from the University's McGowan Institute for Regenerative Medicine at the annual meeting of the American Society for Artificial Internal Organs.

Highlights of the findings include: Filtering antibodies from blood may decrease the risk of organ rejection, William Federspiel, associate professor of chemical engineering and surgery and bioengineering at the School of Medicine, graduate student Mariah Hout and their colleagues report. Federspiel, who also is director of the artificial lung lab at the McGowan Institute, said that experiments using a hollow fiber material similar to that contained in a typical dialysis filter showed that between 40 percent and 60 percent of targeted rejection antibodies were removed when the fibers were coated with specific antigens. These "specific antibody filters" are showing promise in initial lab tests and may eliminate the need for time-intensive plasma replacement therapy in immunologically sensitive patients prior to transplantation.

An injected solution of blood-soluble drag-reducing polymers (DRPs) improved survival rates in a low-oxygen environment, according to work done in animal models by Marina Kameneva, research associate professor of surgery, and her colleagues. Kameneva's research group injected a solution of such polymers at minute concentrations into the tail veins of experimental rats, which were then subjected to atmospheric pressure corresponding to an altitude of more than 25,000 feet. Control animals that had been injected with the same volume of saline solution were observed for comparison. While 40 percent of control animals died due to extremely low oxygen concentrations, all animals injected with the polymer solution survived.

Other McGowan Institute faculty presented work that touches on decreasing the risk for blood clotting with artificial respiratory support and easing the physical burden of implantable left-ventricular assist devices.

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PET/CT found effective in detecting cancer

If more doctors had access to a combined PET/CT scanner to examine patients with ovarian or cervical carcinomas, they would likely catch cancerous lesions that would not be found by CT (computed tomography) or ultrasound, according to research done at the School of Medicine.

In two studies presented before the Society of Nuclear Medicine, Todd Blodgett, a fellow in radiology in the School of Medicine, found the advanced scanners identified additional lesions in 80 percent of a group of patients with ovarian carcinoma and in 45 percent of a group of patients with cervical carcinoma. Those lesions did not show on scans of the same patients taken with conventional CT or ultrasound.

CT and ultrasound are the most frequently used imaging methods for these cancers, but do not provide images with the necessary combination of clear structural definition and metabolic activity that is achieved with the PET/CT, said Blodgett.

The PET/CT, developed by David Townsend, senior PET physicist, and professor of radiology at the School of Medicine, and Ronald Nutt, of CPS Innovations, works by combining PET (positron emission tomography) technology, in which the scanner maps cellular metabolism of glucose, and CT, which builds a clear cross section of tissue structures using X-rays.

In areas where tissue is dense, organs and bone make it difficult to separate cancerous tissue from normal. Images from the combined PET/CT scanner are particularly useful in allowing a radiologist to see cancerous activity at a metabolic level and pinpoint its exact location in the tissue so a biopsy can be performed and proper treatment begun.

In the first study, Blodgett and his colleagues examined 15 women with ovarian carcinoma using both CT and PET/CT. In 12 of 15 cases, or 80 percent, PET/CT identified lesions that CT did not. In 11 of the 12 cases where additional lesions were uncovered, the revelation changed the way doctors managed the illness.

In the second study, Blodgett and his colleagues studied 11 patients with cervical carcinoma. Of those 11, five had additional lesions identified by PET/CT and all five had their treatment changed to reflect the new information.

The results, though a very promising development for those with difficult-to-track cancers, most likely will not lead to an immediate change in current diagnostic standards because the scanners are not as widely available as CT or ultrasound equipment. Combined PET/CT scanners have been available commercially for just over a year, and are located in about 70 hospitals in the United States, Europe and Asia.

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Researchers present results at Diabetes Assn. meeting

At the American Diabetes Association's annual scientific sessions held this month, Pitt researchers presented findings from two studies.

Significant weight loss, metabolic control possible for some with diabetes

People with type 2 diabetes who have the freedom to choose their own diets within certain guidelines, follow an aggressive exercise regimen and are monitored by a registered dietitian, can achieve and maintain significant weight loss and maintain metabolic control, according to a study by School of Medicine researchers.

The one-year intervention study enrolled 52 overweight adults with type 2 diabetes who were not taking insulin. During the study they were taken off all of their diabetes medicines. Their goal was to lose 7 percent of their baseline weight during the study period.

"The diet focused on reducing fat and calories. The exercise program consisted of walking, which gradually increased to 45 minutes a day for five to six days each week," said Pat Harper, principal investigator of the study, who is from the School of Medicine's division of endocrinology.

Participants made weekly visits to a dietitian. In a random double-blind method, participants also took either Orlistat or a placebo. Orlistat is an FDA approved drug to help people lose weight.

After six months, the participants lost an average of 10 percent of their baseline weight and their blood sugar levels went down an average of 45 milligrams. At the end of one year, the 39 participants who completed the program still maintained an average loss of 8.5 percent of their baseline weight.

Researchers find high mortality among blacks with diabetes

While the rate of deaths related to type 1 diabetes is declining in the overall population, mortality among African Americans with the disease remains higher than in whites, and acute complications such as diabetic coma are to blame, according to a study being conducted in Pittsburgh.

Preliminary results of the study were presented at the American Diabetes Association's scientific sessions by Zsolt Bosnyak, a research fellow at the Graduate School of Public Health (GSPH).

Investigators are examining cause of death for 200 type 1 diabetic patients among a cohort of 1,261 patients diagnosed with type 1 diabetes between 1965 and 1979. At 20 years' follow-up, 15 percent of the African American patients had died, compared with 6 percent of the white patients, with mortality from acute complications seven times higher in African Americans.

"These results, while preliminary, suggest an inadequacy in care for African Americans with type 1 diabetes," said Trevor Orchard, professor of epidemiology and senior researcher on the study. "This could be a result of issues such as access to care, or the availability of monitoring supplies and appropriate education about diabetes. It is critical that further studies are undertaken to identify the reasons for this disparity."

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Pitt shares biotech grant aimed at aiding antibioterrorism efforts

Researchers at Pitt and the University of Cincinnati have been awarded a $5 million grant from the United States Department of Defense's Multidisciplinary University Research Initiative program to study ion transport through proteins in synthetic membranes, a process that could assist fields as diverse as developing sensors to detect dangerous chemicals, fuel cell technology, drug discovery and drug delivery.

Rob Coalson, Pitt professor of chemistry and physics, is working with a team at the University of Cincinnati.

Coalson said the technology has ramifications in biotechnology, for example, in creating molecular-level chemical sensors that could be used to fight bioterrorism or monitor blood glucose levels. "If we could harness the extraordinary efficiency of ion channels — carriers and ion pumps that transport substances across cell membranes — they can be used to develop these new devices."

The research will explore how native and engineered channel proteins pass such substances as ions like sodium and chloride through cell membranes; create proteins that will transport new substances, such as polypeptides, and develop new materials and devices containing biological proteins.

Coalson's expertise in chemical dynamics theory — particularly in molecular level modeling of the transport of ions and biopolymers like polypeptides and DNA through protein channels — will help the team. Coalson's group will use supercomputers and mathematical modeling to study transport and structural changes in the protein that occur over short- and long-time intervals.

The five-year grant will help pay for several postdoctoral fellows or graduate student researchers, and Coalson believes the impact could spur growth in the field at Pitt and in the region.

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Magee gets women's health grant

Physician research groups at Magee-Womens Hospital received a $594,000 grant from Pfizer Inc. to study the effects of hormone-replacement therapy and oral contraceptives on women's health.

Grant recipients are Sarah Berga, director of the Division of Reproductive Endocrinology and Endocrinology and professor in the departments of Obstetrics, Gynecology and Reproductive Sciences and psychiatry at the School of Medicine, and Joseph Sanfilippo, vice chairman of reproductive sciences and professor of obstetrics, gynecology and reproductive sciences.

Berga received $376,000 to study the effects of hormone-replacement therapy on serotonin levels in the brains of post-menopausal women. The focus of the study is to determine whether hormone replacement therapy can benefit central nervous system function in a way similar to natural sex hormones, which become severely depleted at menopause.

Working with Berga are Eydie Moses-Kolko, assistant professor of psychiatry; Carolyn Cidis Meltzer, associate professor of radiology and psychiatry and medical director of the PET facility; Julie Price, associate professor of radiology and a physicist at the PET facility; Chester Mathis, professor of radiology and pharmaceutical science and acting co-director of the PET facility; Kathleen L. Laychack, clinical research coordinator, and Tammy L. Loucks, research manager.

Sanfilippo's group received $218,000 from Pfizer, which is being shared with investigators from the Woman's Health Research Institute in Baton Rouge, La. The object of his study is to compare the effect of continuous oral contraceptive use to cyclic use in adolescents who suffer from polycystic ovary syndrome, one of the most common endocrine disorders that affects some 6 percent of women of reproductive age. Along with reproductive problems, women who have polycystic ovary syndrome tend to have other metabolic abnormalities, including high levels of insulin, obesity, LDL or "bad cholesterol," and high blood pressure.

Sanfilippo's group will examine the effect that differing oral contraceptive treatments may have on young women through detailed endocrinological surveys and psychological inventories.

Working with Sanfilippo are faculty members in the adolescent medicine division at Children's Hospital of Pittsburgh and Andrew Sword, a resident in obstetrics, gynecology and reproductive sciences at Magee-Womens Hospital.

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Chronic stress found to affect more than fertility

Increased levels of the stress hormone cortisol are clearly elevated in child-bearing-age women who have stopped menstruating, a senior researcher at the Magee-Womens Research Institute has found. The study is significant because it shows a definitive link between cortisol levels in circulating blood and those in the fluid that surrounds and bathes the brain and spinal cord.

"In fact, cortisol levels in the cerebrospinal fluid are even higher than in the circulating bloodstream," said Sarah Berga, a professor in the departments of obstetrics, gynecology and reproductive sciences and psychiatry at the School of Medicine and a senior investigator at Magee-Womens Research Institute. "This is really important because cortisol is neurotoxic."

Benedetta Brundu, an obstetrics and gynecology resident in Padua, Italy, who participated in a research exchange program in Berga's Pittsburgh laboratory, presented the study findings at the annual Meeting of the Endocrine Society, an organization made up of endocrine specialists in internal medicine, pediatrics and gynecology.

"This is one of these 'Why treat stress?' stories," said Berga, senior study author, who is also director of the Division of Reproductive Endocrinology and Infertility at Magee-Womens Hospital.

For more than 15 years, she has been studying functional hypothalamic amenorrhea (FHA), a condition that affects some 5 percent of women in their reproductive years. It is characterized by wildly irregular or absent periods — often for as long as two years or more.

What the researchers found was that women with FHA exhibited free cortisol concentrations in cerebrospinal fluid that were 30 percent greater than those among women with normal periods. Serum cortisol levels were 23 percent higher in women with FHA.

"What this means is that stress in women with FHA affects more than fertility," said Berga.

Study authors also included Tammy L. Loucks and Judy L. Cameron.