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July 21, 2005


Research could aid golfers with low back pain

The findings of a Pitt research study may assist clinicians in designing appropriate back-specific exercise programs for golfers to prevent or rehabilitate low-back injury.

The research findings were reported last week at the annual meeting of the American Orthopaedic Society for Sports Medicine.

“More than 30 percent of golfers have experienced issues related to low-back pain or injury that have affected their ability to continue enjoying the game of golf,” said principal investigator Yung-Shen Tsai of the University of Pittsburgh Neuromuscular Research Laboratory (NMRL), where the study was conducted.

The results of this study are being used to develop injury prevention programs that will be offered at the UPMC Golf Fitness Laboratory in Pinehurst, N.C., which opened to the public July 18.

“It is difficult to design an appropriate back-specific swing or exercise program for low-back injury prevention and rehabilitation without knowing the differences in the kinematics and spinal loads of the golf swing and the physical characteristics of golfers with low-back pain,” Tsai explained.

So Tsai’s team set out to examine the kinematics of the trunk and spinal loads in golfers with and without low-back pain (LBP) and their trunk and hip physical characteristics. Sixteen male golfers with a history of LBP were matched by age and handicap to 16 male golfers with no history of LBP. All study participants underwent a biomechanical swing analysis and physical characteristics assessment. Researchers used a 3D motion analysis system and two force plates to assess kinematics and spinal loads of the trunk. They used a bottom-up inverse dynamics procedure to calculate spinal loads of the lower back. In addition, they measured trunk and hip strength and flexibility, back proprioception and postural stability.

“We found deficits in physical characteristics in the golfers with a history of LBP,” reported Tsai. “These differences may hinder dissipation of the tremendous spinal forces and movements generated by the golf swing over time and limit trunk rotation during the backswing. These conditions may lead to lower back muscle strain, ligament sprain or disc degeneration.

“Clinicians may be able to use our data to design appropriate back-specific exercise programs for golfers to prevent or rehabilitate low-back injury,” said Tsai.

Specifically, the LBP golfers in Tsai’s study demonstrated less trunk and hip strength and less hamstring and right torso rotation flexibility. The LBP group also demonstrated back proprioception deficits significantly in trunk flexion. No significant differences were found for postural stability. The LBP group showed less maximum angular displacement between shoulders and hips during the backswing. No significant differences were found in other trunk kinematics and spinal loads during the golf swing.

Other investigators for this study were Timothy Sell, James Smoliga, Joseph Myers, Jean McCrory, Richard Erhard and Scott Lephart.


Specific regions of brain may be implicated in anorexia

Just why those with anorexia nervosa are driven to be excessively thin and seem unaware of the seriousness of their condition could be due to over-activity of a chemical system found in a region deep inside the brain, a Pitt study suggests. Reporting in the journal Biological Psychiatry, researchers found an over-activity of dopamine receptors in the brain’s basal ganglia, an area known to play a role in how people learn from experience and make choices.

Results of the study, led by Walter Kaye of the School of Medicine, and Guido Frank, now of the University of California at San Diego, contribute to the understanding of what may cause anorexia. The disorder affects about 1 percent of American women, some of whom die from complications of the disease. The research may point to a molecular target for development of more effective treatments than those currently available.

The study is the first to use positron emission tomography (PET) imaging to assess the activity of brain dopamine receptors, a neurotransmitter system that is best known for its role in controlling movement. These receptors also are associated with weight and feeding behaviors and responses to reinforcement and reward. Researchers used a harmless molecule designed to bind to the dopamine D2 and D3 receptors that lie on the membrane surface of neurons. Ten women who had recovered from anorexia nervosa were studied, as were 12 normal female subjects.

Since other studies have found reduced binding of these dopamine receptors both in people who are obese and those who have substance abuse problems, Kaye and Frank hypothesized that they would find just the opposite in women with anorexia.

Indeed, there was increased receptor binding in the basal ganglia’s antero-ventral striatum in the women with a history of anorexia nervosa irrespective of their age, body mass index or time since recovery, but not in any of the healthy women. The antero-ventral striatum is an area known to modulate reward and reinforcement and therefore is important in learning from experience.

The researchers also found increased dopamine D2/D3 receptor activity in another part of the basal ganglia called the dorsal caudate, which is related to responses to and avoidance of harm. Such activity may help explain why women with anorexia exhibit exaggerated worry and concern about what might happen in the future.

“When they are ill, people with anorexia nervosa resist and ignore feedback that signifies their precarious state of health,” said Kaye, professor of psychiatry. “They don’t see an emaciated figure in the mirror, they ignore the most obvious warning signs and dismiss comments from loved ones that suggest they are seriously and medically ill. People with anorexia nervosa have extreme self-denial, not only of food, but often of many comforts and pleasures in life. Yet people with anorexia nervosa can be very energetic and productive.”

“Taken together, the alterations in the dopamine system may help explain the tell-tale symptoms of anorexia,” added Kaye.

Alteration in dopamine function may affect the value of perceived rewards, or perhaps make it difficult to associate good feelings with things most people find rewarding, Kaye explained. Consequently, people with anorexia nervosa may appear to be obsessive about certain stimuli that may be uniquely rewarding to them, but may not be able to respond well to stimuli related to food or pleasure.

More research is needed to address the questions that remain, including what causes the dopamine receptors to be overactive in the first place. Genetic studies could yield some answers. A study supported by the Price Foundation, which recently was published in the on-line edition of Neuropsychopharmacology, found alterations in genes for the D2 receptor in some individuals with anorexia nervosa. Kaye is a co-author of that paper.

Other authors on the study included Carolyn Meltzer, Julie Price, Chester Mathis, Jessica Hoge and Scott Ziolko, all of the School of Medicine Department of Radiology; Ursula Bailer, Shannon Henry and Angela Wagner, from Pitt’s Department of Medicine; Lisa Weissfeld of the Graduate School of Public Health Department of Biostatistics; Wayne Drevits, National Institute of Mental Health, and Nicole Barbarich-Marsteller, State University of New York at Stony Brook.

The research was supported by the National Institute of Mental Health and the Price Foundation.


NIH-funded center to create methods for assessing compounds

Pitt’s School of Medicine has received $9 million from the National Institutes of Health (NIH) to establish the University of Pittsburgh Molecular Libraries Screening Center (UP-MLSC). The center is one of nine in the nation that will create the most sophisticated methods for assessing rapidly hundreds of thousands of compounds for their biological activities and therapeutic potential — a capability that has until now been limited almost exclusively to pharmaceutical companies.

Moreover, to help speed the use of promising targets for drug development, all the information collected by the centers will be available to the entire scientific community through PubChem, a comprehensive database that has been established by NIH.

As part of NIH’s Roadmap, which has as its overarching theme “New Pathways to Discovery,” NIH has allocated $88.9 million over the next three years to create the Molecular Libraries Screening Centers Network (MLSCN). NIH selected nine outside institutions as pilot centers to be included in the network, as well as its Chemical Genomics Center.

Each center will work to develop the necessary tools for conducting so-called high throughput screenings of molecules. This will allow each center by the third year to screen up to 100,000 molecule compounds using 20 different approaches, or assays, that help determine how these compounds interact with molecular targets, within cells and in regulating events that may be the root cause of different diseases.

Pitt’s center takes advantage of close ties between the medical school’s Department of Pharmacology and the School of Arts and Sciences Department of Chemistry, along with new facilities devoted to drug discovery in the Biomedical Science Tower 3. It also represents a collaboration with Carnegie Mellon University and Sandia National Laboratories in Albuquerque, N.M., and provides the UP-MLSC unique expertise in design and development of novel probes that use fluorescence and other optical imaging techniques.

John S. Lazo, Allegheny Foundation Professor of Pharmacology at the School of Medicine and principal investigator of the UP-MLSC, said: “As a pilot center in the Molecular Libraries Screening Centers Network, we will be able to exploit and expand our existing strengths for developing and implementing methods for the detection, characterization and refinement of small molecules that have attractive biological and pharmacological properties and eventually may be developed as therapeutic approaches to treating various diseases and conditions.”

Pitt’s center was selected because of the expertise of its investigators, including Lazo, who will direct a core devoted to assay implementation. Andreas Vogt, research assistant professor of pharmacology in the medical school, will focus on high throughput screening, which will exploit Pitt’s existing expertise in screening compounds in the context of whole cells. Peter Wipf, University Professor in the Department of Chemistry and co-principal investigator, will lead the synthetic chemistry core. The focus of that core will be to further improve and refine compounds designated as being the most promising to better target the specific errors that occur on the smallest of scales yet have profound effects on the development of disease.

Mark D. Rintoul, manager of computational biology at Sandia National Laboratories, will direct the informatics core.

An NIH steering committee for the MLSCN, of which Lazo will be a member, will determine which of the methods for screening molecules will be pursued and select from among its network of funded pilot centers those that will develop and implement these particular assays.

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