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June 22, 2000

RESEARCH NOTES

CO2-soluble material developed by engineering researchers

Pitt researchers have developed a highly carbon dioxide (CO2)-soluble material that is much less expensive than previous versions.

This new material could be used as building blocks for products such as CO2-soluble soaps, metal-binding agents, and additives for enhanced oil recovery.

Further, researchers believe that the method they used to create the new poly(ether-carbonate) copolymers holds promise for creating similar compounds that will open the door for CO2 to be used in a variety of manufacturing processes.

"Carbon dioxide is considered an environmentally benign solvent, but it is also rather feeble," said Eric Beckman, professor of chemical engineering at Pitt. "In order to dissolve even small amounts of many compounds, such as metals and proteins, very high CO2 pressures are often needed, which makes CO2-based processing prohibitively expensive."

To capitalize on the potential of carbon dioxide as a solvent, many researchers turned to fluorocarbons, which, though highly CO2-soluble, are prohibitively expensive to use in industry if they cannot be recycled efficiently.

Using inexpensive propylene and CO2 as raw materials, Beckman and his colleagues synthesized a series of poly(ether-carbonate) copolymers and showed that these materials will dissolve in CO2 at lower pressures than a poly(perflu-oroether).

The research findings were described in a paper published last month in Nature.

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Pitt gets funds for arthritis research

Carol A. Feghali, research assistant professor at Pitt's Arthritis Institute, received a research grant from the Scleroderma Foundation for work on systemic sclerosis in a cohort of identical and fraternal twins concordant and discordant for the disease.

Feghali also received an Arthritis Investigator Award from the National Arthritis Foundation to support her research.

The research is being conducted under the sponsorship of Timothy M. Wright, chief of the Division of Rheumatology and Clinical Immunology, in collaboration with Thomas A. Medsger Jr., Gerald P. Rodnan Professor of Medicine and director of the Scleroderma Research Program.

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Researchers reveal possible screening to ID transplant patients who are "rejecters"

Patients prone to rejection could be screened and their immunosuppression tailored to prevent serious episodes that could result in graft loss, according to a Pitt study that classified pediatric heart transplant patients by their genetic profiles of certain hormones involved in the immune response.

Results were presented last month at the first combined scientific sessions of the American Society of Transplant Surgeons and the American Society of Transplantation.

"These profiles could be used by the transplant team to help determine the best immunosuppressant regimen for their patients," said Adriana Zeevi, professor of pathology and surgery at Pitt's Thomas E. Starzl Transplantation Institute.

Using a polymerase chain reaction method that detects the unique profiles of genes, 81 heart recipients, 29 organ donors and 50 control patients were cytokine-genotyped. Cytokines are hormone-like substances that cells use to communicate with each other and that modulate immune activity.

Those recipients who had multiple acute rejection episodes — referred to as rejecters — had a markedly different profile of cytokine genes (lower levels of Interleukin-10, or IL-10) than did those who experienced few episodes (higher levels of IL-10 and low levels of Tumor Necrosis Factor-alpha, or TNF-a). Donor cytokine genotype had little correlation with rates of rejection.

Because the screening may prove useful as a predictor factor for the frequency of rejection, Zeevi's colleagues plan to evaluate its value in a protocol that involves weaning patients off immunosuppression. Typically, transplant patients are required to take anti-rejection drugs for the rest of their lives. Such drugs can cause serious complications, such as tumor growth, and make patients more susceptible to infections.

In another study, George Mazariegos, assistant professor of surgery at the Starzl Transplantation Institute, reported that nearly a third of the 120 patients enrolled in the physician-controlled protocol have been completely weaned. Weaning was stopped in another third who experienced acute rejection.

"While these cases were successfully treated, usually by reinstating their previous levels of immune suppression with or without steroid therapy, and no grafts were lost, it would be extremely helpful to be able to predict in advance which patients we can successfully wean," Mazariegos said.

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Brain center gets $6 million renewal grant

The University of Pittsburgh Brain Trauma Research Center has been awarded a $6 million grant from the National Institutes of Health's National Institute of Neurological Disorders and Stroke to continue research in the treatment of traumatic brain injuries.

The five-year grant allows investigators to research the causes of brain swelling following head injury, why some head injury patients experience a poor outcome and the role that drugs play in treating brain injury.

"This renewal grant permits us to continue our investigations of basic molecular mechanisms responsible for secondary brain injury, and to identify new medications that will improve outcomes. We are focusing on the causes of brain swelling soon after injury. Brain swelling is the most important cause of death and disability following traumatic brain injury," said Donald W. Marion, professor and interim chief of the neurosurgical service in Pitt's neurological surgery department, and director and founder of the Brain Trauma Research Center.

The center is one of only three National Institutes of Health-designated head injury centers in the United States. It is closely allied with the University's Center for Injury Research and Control (CIRCL), also directed by Marion, and the Safar Center for Resuscitation Research, directed by Patrick Kochanek.

In the United States, traumatic brain injury is the most common cause of death, disability and mental impairment in people between 1 and 45, affecting an estimated two million people each year. Because trauma disproportionately affects younger individuals, it accounts for more years of potential life loss than cancer and cardiovascular disease combined.

Annually, 50,000 people suffer severe brain injuries and require long-term care at a cost of more than $20 billion, according to the National Institute of Neurological Disorders and Stroke. Motor vehicle accidents are the most common cause of such injuries.

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Early lead exposure hikes likelihood of juvenile delinquency, research shows

Children exposed to lead have significantly greater odds of developing delinquent behavior, according to a Pitt researcher.

Herbert Needleman, known for his groundbreaking studies on the effects of lead exposure on children that were instrumental in nationwide government bans on lead from paint, gasoline and food and beverage cans, examined 216 youths convicted in the Juvenile Court of Allegheny County and 201 non-delinquent controls from high schools in Pittsburgh.

Bone lead levels, measured by K X-ray fluorescence spectroscopy of the tibia, showed that the delinquent youths had significantly higher mean concentrations of lead in their bones — 13.7 parts per million (pm) — compared to the control group. Those results were true for both whites and African Americans and males and females.

"This study provides further evidence that delinquent behavior can be caused, in part, by childhood exposure to lead," Needleman said. "Of all the causes of juvenile delinquency, lead exposure is perhaps the most preventable. These results should be a call to action for legislators to protect our children by requiring landlords to not simply disclose known instances of lead paint in their properties, but to remove it."

While this study is the first to show that lead exposure is higher in arrested delinquents, it is part of a growing body of evidence linking lead to cognitive and behavioral problems in children. In 1996, Needleman published a study of 300 boys in Pittsburgh public schools and found that those with relatively high levels of lead in their bones were more likely to engage in antisocial activities like bullying, vandalism, truancy and shoplifting. In 1979, Needleman, using measurements of lead in children's teeth, concluded that children with high lead levels in their teeth, but no outward signs of lead poisoning, had lower IQ scores, shorter attention spans and poorer language skills.

The results of Needleman's latest study were presented last month.

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Bioengineering grant awarded

David A. Vorp, assistant professor of bioengineering and mechanical engineering, has been awarded a $70,000 bioengineering transitional research grant from the Whitaker Foundation for a one-year followup grant to continue studies of abdominal aortic aneurysm, previously funded by the foundation.

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Milk-white artificial blood tested at UPMC Presbyterian

UPMC Presbyterian is one of 40 sites evaluating a blood substitute product in patients undergoing cardiac bypass surgery.

The multi-center research study is a phase III trial of Oxygent, which was developed by Alliance Pharmaceutical Corp. as a means to reduce or eliminate the need for donor blood transfusions during surgery or other periods of acute oxygen deficit. UPMC was one of the first to enroll patients into the international trial, the results of which will determine possible U.S. Food and Drug Administration approval.

"We are happy to participate in this trial because clearly, an alternative source of blood is needed," said Bartley P. Griffith, Henry Bahnson Professor of Surgery and chief, division of cardiothoracic surgery at Pitt's School of Medicine, and the principal investigator for the Pittsburgh site.

Each year, more than 4 million patients in the United States require 1-4 units of donor blood during surgeries, totaling about 11 million units. Increasingly, elective surgeries are being cancelled or postponed because of shortages of donor blood. And while sophisticated screening measures are routine, they can increase the cost of obtaining donor blood and do not guarantee the safety of the supply.

A phase II trial involving more than 250 patients provided preliminary evidence of the safety of Oxygent and that it may be more effective in improving oxygenation within the body than a unit of fresh blood. The phase III trial will enroll 600 patients.

Oxygent looks like milk and contains no blood or blood products. Unlike donor blood, which has a shelf-life of about six weeks, Oxygent can be stored for about two years and can be used for patients of all blood types. Oxygent is a perflubron emulsion that picks up oxygen from the lungs and carries it through the blood stream.

An artificial blood product called HemoMax, developed by Pitt's McGowan Center for Artificial Organ Development, is undergoing animal testing.


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