University Times

Grants awarded to researchers

Deborah L. Chapman of the biological sciences department has received a grant of $259,200 from the National Institute of Child Health and Human Development for a study, “Molecular Mechanism of Paraxial Mesoderm Formation.”

The National Institute on Deafness and Other Communication Disorders has granted $1.3 million to Joseph Furman of the medical school’s otolaryngology department for research examining whether the neurotransmitter norepinephrine, which is involved in psychiatric diseases, also affects vestibular reflexes.

Walter Kaye of the medical school’s psychiatry department has received a $583,996 grant from the National Institute of Mental Health for research on the genetics of anorexia nervosa.

The Graduate School of Public Health’s Douglas Perkins has been awarded $377,452 by the National Institute of Allergy and Infectious Diseases for a study, “Genetic Basis of Severe Malarial Anemia.”

David G. Roodman of the medicine department has received a $325,788 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for his study, “Pathobiology of the Osteoclast in Paget’s Disease.”

The Freeman Foundation has granted $339,400 to Diana Wood of the University Center for International Studies to fund UCIS’s participation in the National Consortium for Teaching About Asia, a multi-year initiative to encourage and facilitate teaching and learning about Asia in world history, geography, social studies and literature courses.

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St. John’s wort, citalopram compared for depression

Researchers at Western Psychiatric Institute and Clinic (WPIC) are participating in a $4 million collaborative study to determine the effectiveness of St. John’s wort, a common herbal supplement, and citalopram, a standard antidepressant, in treating minor depression.

The grant from the National Institutes of Health will be divided between WPIC and two other institutions and will enroll a total of 300 study participants with minor depression. Participants will be randomly assigned to receive a standardized extract of St. John’s wort, citalopram or placebo in a 12-week double-blind trial.

“Minor depression is a common disorder that may impair a person’s functioning and quality of life and is a serious risk factor for major depression, yet it is often under-diagnosed and under-treated,” said Robert Howland, associate professor of psychiatry at Pitt’s School of Medicine and principal investigator at the Pittsburgh site. “Patients with minor depression who seek treatment from a family doctor are often treated with prescription antidepressants, if their disorder is diagnosed at all, and many use St. John’s wort without consulting a physician.”

“If the trial demonstrates that citalopram or St. John’s wort benefits patients with minor depression, it will expand our understanding of this under-recognized mood disorder and offer new evidence-based treatment recommendations for either primary care or mental health clinicians,” said Matthew Rudorfer, associate director of treatment research, division of services and intervention research, National Institute of Mental Health (NIMH).

Minor depression affects about 7.5 percent of Americans during their lifetime.

Its symptoms are the same as those of major depression, though fewer in number and causing less impairment. They include either a depressed mood most of the day, nearly every day, or a markedly diminished interest or pleasure in daily activities, plus two to four of the following symptoms:

• Significant weight loss or gain, or decrease or increase in appetite.

• Disturbance in sleep pattern.

• Noticeable agitation or slowness.

• Fatigue or loss of energy.

• Inappropriate feelings of worthlessness or guilt.

• Diminished ability to concentrate, indecisiveness.

• Recurrent thoughts of death or suicide.

The study is funded by the NIMH, NCCAM and the Office of Dietary Supplements. The other two study sites are Massachusetts General Hospital, Boston, and Cedars-Sinai Medical Center, Los Angeles.

For more information about the study or how to participate, call 412/624-5035. Calls are confidential.

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Grant awarded for study of pediatric brain tumors

Marie E. Beckner, research assistant professor in the pathology department at Pitt’s School of Medicine, has been awarded a $40,000 grant from the Nick Eric Wichman Foundation (NEWF) to study pediatric brain tumors.

Beckner is collaborating with Ian F. Pollack, a professor in Pitt’s Department of Neurosurgery, in ongoing studies of brain tumors. Last year, the NEWF supported studies in Pollack’s laboratory of a number of promising agents that are now undergoing pilot testing in phase I clinical trials.

Nick Eric Wichman, from Ellicott City, Maryland, died at the age of 8, only a few weeks after becoming ill from an untreatable brain tumor.

His parents established the foundation to fund specific medical research for and increase public awareness of pediatric brain tumors in order to make a difference in the lives of afflicted children and their families.

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Noninvasive glucose sensor developed

Millions of people suffering from diabetes mellitus may be spared the ordeal of pricking their fingers several times a day to test blood sugar levels, thanks to a breakthrough by University researchers who have developed a noninvasive method to measure the glucose level in body fluids.

Chemistry professor Sanford A. Asher and David Finegold, a professor of pediatrics in the School of Medicine, created a thin plastic sensor that changes color based on the concentrations of glucose.

The sensor material, which would be worn like a contact lens, was described in a paper published in the online version of Analytical Chemistry.

The paper was published in the print version of Analytical Chemistry, a publication of the American Chemical Society, on May 1.

“There has been an increasing demand for continuous, noninvasive glucose monitoring due to the increasing number of people diagnosed with diabetes mellitus and the recognition that the long-term outcome of these patients can be dramatically improved by careful glucose monitoring and control,” Asher said.

The researchers plan to embed the sensing material into contact lenses worn by patients. Patients will determine their glucose levels by looking into a mirror — similar to women’s makeup compact mirrors, but with a color chart to indicate glucose concentrations — to compare the color of the sensing material with the chart.The sensor will change from red, which indicates dangerously low glucose concentrations, to violet, which will indicate dangerously high glucose concentrations. When the glucose level is normal, the sensor will be green.

The researchers are still determining the number of detectable gradations, but expect that it may be as high as the finger stick meters currently provide.

Pitt, which owns this patented technology, has licensed the technology to a new startup company, which will engineer the material and commercialize it. Researchers believe the product is at least a year from being tested in humans.

The researchers also expect that their technology could be incorporated into available commercial contact lenses, which would be replaced weekly.

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Changes in timing, dosage of drug improves life, survival in transplant patients

Measurable improvements in quality of life and long-term survival could be achieved in organ transplant patients if clinicians were to adopt two prescriptive changes in their treatment approach, say University of Pittsburgh Medical Center (UPMC) researchers in the May 3 issue of the British medical journal The Lancet.

The authors from UPMC’s Thomas E. Starzl Transplantation Institute report initial results involving 82 patients who had kidney, liver, pancreas and small bowel transplants and were treated under a clinical protocol developed by the Pittsburgh team.

Just before transplantation, each patient received a one-time dose of a drug that depletes T cells (key immune system cells that are known to target the donor organ) and, following their transplants, patients were treated with just one anti-rejection drug that was administered at radically reduced levels and given progressively more sparingly over time. Eleven of their patients were on just one pill once a week with no signs of organ rejection or other complications, the researchers reported.

“Our findings suggest that improvements in clinical transplantation might be within easy grasp by simple modification of timing and dosage,” stated lead author and surgery professor Thomas E. Starzl.

The protocol developed by the Pittsburgh team is based on two principles: pre-treatment of the recipient and the administration of as little immunosuppression as possible after transplantation. The regimen of T-cell depletion as a pre-treatment and the use and tapering of a single drug has become the standard of care for most of UPMC’s transplant patients. Unlike their counterparts at other centers, the majority of UPMC’s liver, kidney, pancreas and small bowel transplant patients have been taking lower doses of one drug rather than the typical cocktail of two or three agents.

For example, 39 of 47 (83 percent) of the surviving kidney transplant patients were being treated with one drug, usually tacrolimus, and 25 of these were able to begin weaning of the drug to every-other-day dosage.

“The intent throughout was to find the minimum amount of immunosuppression consistent with the avoidance of irreversible graft damage,” wrote the authors.

To determine the limits of their treatment, the transplant team engaged in closer-than-usual monitoring of patients for evidence of increased activity of the recipient immune cells, but increased immune activation was not always associated with graft dysfunction or thought to be of serious consequence. In such cases, treatment was not intensified. For the patients experiencing bona fide rejection episodes, the rejections were treated with the addition of steroids, or if necessary, stronger drugs, and for as brief a period as possible. After rejection was resolved, many of the patients returned to the single-drug regimen and weaning was reconsidered.

It is widely believed that in order to protect their donor organs from rejection, transplant patients must take potent immunosuppressive drugs for the rest of their lives. While these drugs have been quite successful in addressing early acute rejection, they are not a panacea. Later-developing rejection, called chronic rejection, is difficult to treat and is the most common reason for re-transplantation. Furthermore, the drugs can make patients vulnerable to serious infections, malignancies and other complications.

According to the authors, the common practice of giving several drugs in right after transplantation may prevent acceptance of the transplanted organ by preventing a process known as immune tolerance and thereby creating a near-certain life-long dependence on anti-rejection drugs. The reason is that “over-immunosuppression” eliminates the all-important, initial immune reaction against the donor organ, which under the right circumstances proceeds to clonal deletion, or selective removal of a subset of T cells that are directed against the donor tissue. Without this activation and deletion process, T cells targeted against the graft will persist, and drugs will always be required to keep them at bay.

The study was funded in part by a grant from the National Institutes of Health.