April 2004

Research Capsules

Diabetes and Mental Decline

A new study has found that women with type 2 diabetes are at increased risk of cognitive decline, as measured by a series of tests assessing their verbal and memory skills. Finding a way to slow or prevent this cognitive decline can have important public health benefits. The good news is that diabetic women in the study who took glucose-lowering pills, called oral hypoglycemic agents, for their condition had a risk similar to women without diabetes.

Previous research has found links between diabetes and early cognitive decline, but few studies have followed cognitive change over time. A Harvard research team supported by NIH set out to investigate the connection in older women, an age group disproportionately affected by type 2 diabetes. The researchers gave cognitive tests by telephone to women of ages 70-81 from the nurses' health study, a long-running study of registered nurses. The women were then retested starting about two years later. Over 16,500 women completed the study.

Women with diabetes had greater cognitive declines over the two years than those without. The longer they had lived with diabetes, the greater their odds of decline. For example, the odds of poor cognitive performance of those with diabetes for 15 or more years was 50% higher than for women without diabetes. Women taking insulin for their diabetes had similar results to those not taking medication for their diabetes, but those on oral hypoglycemic treatment had cognitive declines similar to those without diabetes.

According to the National Diabetes Statistics Fact Sheet, 18.2 million people — 6.3 percent of the population — have diabetes, with type 2 diabetes accounting for up to 95 percent. Type 2 diabetes is most common in adults over the age of 40, and is strongly linked to obesity, inactivity, family history of diabetes, and racial or ethnic background. It is the main cause of kidney failure, limb amputations, and new onset blindness in adults, and is a major cause of heart disease and stroke.

This new study adds to the growing number of reasons to focus on preventing type 2 diabetes, and on controlling your blood sugar if you have it. If you have type 2 diabetes, make sure to talk to your doctor about controlling your blood sugar. And if you're in danger of developing type 2 diabetes, learn what you can do to prevent it.

— Written by Harrison Wein, Ph.D.

Source: British Medical Journal 328:548

A study of diabetes treatment and cognition is being supported by NIH's National Institute on Aging as part of the ACCORD trial, currently recruiting patients. For information, see http://clinicaltrials.gov/ct/show/NCT00000620?order=1.

Learn more about preventing and controlling diabetes at the National Diabetes Education Program's web site: http://www.ndep.nih.gov/diabetes/diabetes.htm. Materials are also available in Spanish and six Asian American and Pacific Islander languages at http://www.ndep.nih.gov/diabetes/pubs/catalog.htm#PubsAsianAm. Or contact:
National Diabetes Information Clearinghouse (NDIC)
1 Information Way
Bethesda, MD 20892-3560 (Use 9-digit ZIP code.)
Phone: 1-800-860-8747 or 301-654-3327
Fax: 301-634-0716
Email: ndic@info.niddk.nih.gov

Also see Dealing With Diabetes from NIH's National Institute on Aging at http://www.niapublications.org/engagepages/diabetes.asp; a Spanish version is available at http://www.niapublications.org/spnagepages/diabetes-sp.asp. Or contact:
National Institute on Aging (NIA) Information Center
P.O. Box 8057
Gaithersburg, MD 20898-8057
Phone: 1-800-222-2225
TTY: 1-800-222-4225

The Pain of Rejection

Physical pain exists to keep us alive. Neural circuits and chemicals tell us when something is wrong so we can take action and survive another day. Our sense of pain tells us to remove our hand from a hot stove top, cradle a broken arm, or remove an eyelash from our eye. But are these same neural circuits involved in other kinds of pain? Do they prompt us to cry when separated from our moms as infants, feel devastated after a bitter break-up, or get distressed when picked last for the company softball team? Pain is the word we use to describe what we feel in these situations, but can these social pains really come from the same region of the brain as physical pain? New research shows that they do.

A research team funded by NIH's National Institute of Mental Health (NIMH) devised a clever experiment. Participants played a virtual ball-tossing game while they lay in a functional magnetic resonance imaging (fMRI) scanner that monitored blood flow to their brains. Participants first just watched two other players toss a ball (observation). They were told that they could not join in the game of "Cyberball" because of technical difficulties. Eventually they joined in the game of catch (inclusion). However, after a few tosses, the other players stopped throwing the ball to them (exclusion). Although the participants were led to believe that the other players existed and were also in scanners, their Cyberball playmates were really created by a preset computer program. Afterwards, the participants filled out questionnaires about their level of social distress and how excluded they felt.

The researchers found that during exclusion from the game, the area of the participant's brain that became active was the anterior cingulate cortex (ACC), the same area that is active during physical pain. The greater the reported feeling of social distress, the more active this area of the brain had become. In addition, another area of the brain, the right ventral prefrontal cortex (RVPFC), also became active in an apparent attempt to lessen the distress of being shunned.

These remarkable findings reveal that feelings of social pain and physical pain arise from similar regions in the brain. This sharing of neural machinery highlights the importance of social connections. Social attachment and support are crucial to our minds, regardless of whether the inclusion consists of bonding with your newborn child or joining a game of catch.

— Written by Carol E. Torgan, Ph.D.

Source: Science 302: 290-292, JAMA 290:2389

For more information on pain, visit http://www.ninds.nih.gov/health_and_medical/pubs/pain.htm.

Visit the MEDLINE plus information page on pain at: http://www.nlm.nih.gov/medlineplus/pain.html.

Gene Therapy in Salivary Glands

Scientists at the National Institute of Dental and Craniofacial Research (NIDCR) have taken another step toward making gene transfer into salivary glands a therapeutic reality. The new results may open up possibilities for treating diseases and conditions that are resistant to conventional treatments.

Salivary glands can secrete substantial amounts of protein into saliva. The glands are easily accessible through the mouth via their excretory ducts, and infusing fluid into the ducts causes little discomfort for patients. These attributes mark salivary glands as potential 'factories' for producing secreted proteins to treat both oral and systemic disease.

Scientists can induce salivary glands to produce new proteins through gene transfer, which involves delivering a gene into a cell that then expresses the protein encoded by the gene. Therapeutic proteins have been produced by the salivary glands of many types of animals using this technique, but only in an unregulated, continuous manner that could create problems for clinical use.

The NIDCR scientists set out to adapt a method that had proven effective in other tissues, and succeeded in creating a gene expression system they could turn on and off in rat salivary glands. The system is controlled by administering the drug rapamycin, which turns the gene on and thereby induces protein production. When the drug is not given, the gene is inactive and no protein is made. The researchers demonstrated that the production of human growth hormone (hGH), used as a "model protein," and its secretion into the saliva of rats could be generated by rapamycin at least three times over a 16-day period. Rats not given rapamycin had no hGH in their saliva.

These results could potentially lead to new treatments for oral or systemic diseases. Oral fungal and bacterial infections, for instance, usually require treatment for about 10-14 days - a period the scientists showed could be achieved with their system. Therapeutic genes administered to the salivary glands can provide a higher local concentration of medications than is possible with injections into the bloodstream or muscle. The approach might also enable doctors to deliver therapeutics that cannot be given systemically.

— Written by Beatrijs Lodde, M.D.

Source: Gene Therapy 2004 Jan 22 [online publication]

For more information about gene transfer, see the Gene Transfer NIH Backgrounder at http://www.nih.gov/news/backgrounders/genetransferbackgrounder.htm.

For information about oral health, visit the Oral Health Information Index at http://www.nidcr.nih.gov/health/newsandhealth/oralDiseases.asp.

Heard It From a Fly

Think those tiny, pesky flies circling the fruit bowl in your kitchen are simply a nuisance? Think again! Scientists continue to learn secrets about human health from basic research with simple organisms such as insects, worms, mice, and rats. Fruit flies have been a particular favorite for researchers investigating the role of heredity in the formation of tissues and organs. Both insects and people develop according to a genetically determined body plan, and scientists know that many of the genes involved in this process are very similar among animals.

Using fruit flies as a model system, National Institute of General Medical Sciences (NIGMS) grantee Grace Boekhoff-Falk of the University of Wisconsin in Madison recently made a fundamental discovery about hearing. She and her coworkers discovered an insect gene nicknamed "spalt" that profoundly affects flies' ability to hear. The scientists found that experimental flies created to lack the spalt gene were deaf, as measured by direct tests of the flies' hearing organs located inside their antennae.

Boekhoff-Falk and her team also discovered that the spalt gene is nearly identical in flies and people. That means that what she learns about spalt in fruit flies may also apply to humans, and her work may help scientists find new approaches to diagnosing certain inherited hearing disorders.

— Written by Alison Davis, Ph.D.

Source: Proceedings of the National Academy of Sciences 100,18:10293-10298

Basic Studies Yield Myeloma Drug

A series of lab studies begun in the 1970s by NIGMS grantee Alfred L. Goldberg of Harvard Medical School has led to a promising new cancer drug now on pharmacy shelves. The medicine, named Velcade™, was approved by the U.S. Food and Drug Administration in May 2003 to treat a deadly type of bone marrow cancer called multiple myeloma. Velcade is now being tested in more than 30 different clinical trials to determine if it can be helpful in treating many other types of cancer.

Velcade is a brand-new kind of cancer drug that targets a molecular machine found in virtually all cells. Goldberg was a pioneer in the discovery that our cells use this machine, called the proteasome, to continually break down their own protein components in order to remove improperly made or damaged proteins and to control cell growth and other vital processes. He reasoned that small molecules that block proteasome function might be useful in treating different diseases. Goldberg and other researchers founded a small biotechnology company that went on to design and make Velcade based on detailed chemical knowledge of how the proteasome cuts up proteins.

The discovery and development of this drug differs from the traditional approach, which relies on the screening of large numbers of chemicals to find those that that can slow the growth of cancer cells. The findings also show how advances in understanding basic biology can help scientists find new and better ways to treat diseases.

— Written by Alison Davis, Ph.D.

For information about detection, symptoms, diagnosis, and treatment of multiple myeloma, see http://www.cancer.gov/cancerinfo/wyntk/myeloma or call 1-800-4-CANCER.