December 2003

Research Capsules
by Harrison Wein, Ph.D.

Physical Activity for Weight Loss
You've heard that physical activity is important for losing weight. But how much activity? According to a new study supported by NIH's National Heart, Lung, and Blood Institute (NHLBI), women trying to lose weight can benefit as much from moderate physical activity as from an intense workout.

Researchers enrolled 201 sedentary and overweight but otherwise healthy women, ages 21-45, in a trial to test different physical activity regimens. All the women received reduced-calorie meals, and each was randomly assigned to one of four physical activity regimens. The regimens involved either a moderate or vigorous physical activity for either a shorter (2½ to 3½ hours per week) or longer (3½ to 5 hours per week) time. The women were given treadmills and encouraged to walk briskly for at least 10 minutes at a time, but they were free to do other exercise if they preferred.

Women in all four of the groups lost a significant amount of weight over a period of 12 months-from eight to 10 percent of their body weight, on average. They also improved their general fitness levels. However, there were no significant differences in weight loss or fitness improvement between the four groups.

The Centers for Disease Control and Prevention (CDC), NIH's sister agency in the Department of Health and Human Services, recommends that people get a minimum of 30 minutes of moderate-intensity activity on most days, for a total of about 150 minutes per week. The authors of this study recommend that people try to get at least that amount.

This research shows that, with a diet reduced in calories and fat, physical activity of moderate intensity is enough to help overweight people lose weight. The key is not how intense your physical activity is, but how much total energy you burn in the end.

— a report from The NIH Word on Health, December 2003

Source: JAMA 290,10:1323-1330

For more information on losing and controlling your weight, visit http://www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/index.htm or contact:
NHLBI Health Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
Phone: 301-592-8573
TTY: 240-629-3255
Fax: 301-592-8563

NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) also has resources to help you lose or control your weight. Visit http://www.niddk.nih.gov/health/nutrit/nutrit.htm or contact:
Office of Communications and Public Liaison, NIDDK, NIH
Building 31, Room 9A04 Center Drive, MSC 2560
Bethesda, MD 20892-2560

Heart Stem Cells Identified
The heart has long been considered an organ that wasn't able to renew itself. But a new study shows that the adult heart may contain stem cells that have the potential to regenerate tissue when the heart is damaged, such as during a heart attack. Scientists now hope to harness these cells to develop new therapies to repair damaged hearts.

Most researchers had assumed that the heart had a relatively stable number of fully developed, specialized heart muscle cells from shortly after birth well into adulthood. But in the past few years, stem cells (cells with the potential to transform into other cells in the body and replenish them) have been found in many adult tissues, including the brain. Recent studies suggested that stem cells may also contribute to a process of cell death and renewal in the heart.

A team of researchers supported by NIH's National Heart, Lung, and Blood Institute (NHLBI) and National Institute on Aging (NIA) took heart muscle from older rats and isolated cells they believed might be stem cells. They were able to grow these cells in the laboratory for well over a year, and could also successfully freeze and thaw them, important characteristics for any cells that might be used as a therapy. When the cells were prompted to transform into heart cells, the cells displayed some of the chemical characteristics of three different types of heart cells, although they seemed to be immature forms of the cells when viewed under the microscope. The researchers next injected the cells into damaged rat hearts to see what they would do. They found that the cultured cells grew into different types of heart cells. Moreover, the cells seemed to hone in on the damaged areas of the rats' hearts. Within 20 days, the damaged areas started to function again, and the rats' overall heart function improved.

These types of cells have been found not only in rats, but also in mice, dogs, pigs and humans. In another recent study, the research team looked at people who died after aortic stenosis (the narrowing or obstruction of the heart's aortic valve) and found that new heart cells were being created by similar cardiac stem cells.

So if these stem cells are already in the heart, why don't they mobilize and repair the heart when it's damaged? That is a question the researchers hope to answer soon. If the regenerative power of these cells could be harnessed, they might form the basis for an effective therapy to treat heart damage.

— a report from The NIH Word on Health, December 2003

Source: Cell 114:763-776, Proceedings of the National Academy of Sciences 100,18:10440-10445

For more information about stem cells, see the NIH Stem Cell Backgrounder at http://www.nih.gov/news/backgrounders/index.html.

For more information on aortic stenosis, visit http://www.nlm.nih.gov/medlineplus/ency/article/000178.htm.

For general information on heart disease, visit http://www.nhlbi.nih.gov/health/public/heart/index.htm or contact:
NHLBI Health Information Center
Attention: Web Site
P.O. Box 30105
Bethesda, MD 20824-0105
Phone: 301-592-8573
TTY: 240-629-3255
Fax: 301-592-8563
E-mail: NHLBIinfo@rover.nhlbi.nih.gov (Please include a valid return e-mail address in the body of the message.)

Women's Heart Attack Signs
A new study-one of the first to look at symptoms before and during heart attacks in women-found that fewer than 30% of women reported chest pain and discomfort prior to a heart attack, and 43% didn't experience chest pain during one. Most doctors consider chest pain the most important heart attack symptom for both men and women, but the women's most frequently reported early warning symptoms were unusual fatigue (70.7%), sleep disturbance (47.8%), and shortness of breath (42.1%). This finding may help women and their doctors more accurately identify the early warning symptoms of a heart attack so that they can better forestall or prevent the attacks.

Women's Heart Attack Signs Major symptoms preceding a heart attack in order of reported frequency include: Unusual fatigue — 70% Sleep disturbance — 48% Shortness of breath — 42% Indigestion — 39% Anxiety — 35%     Major acute symptoms during a heart attack in order of reported frequency include: Shortness of breath — 58% Weakness — 55% Unusual fatigue — 43% Cold sweat — 39% Dizziness — 39%

The current description of "typical" cardiac symptoms is based primarily on the experience of white, middle-aged men. Researchers funded by NIH's National Institute of Nursing Research (NINR) set out to find if women have the same symptoms. They asked 515 women who had been diagnosed with a heart attack, called an acute myocardial infarction (AMI), within the previous 4 to 6 months about their symptoms prior to their AMI. The researchers found that 78% of the women had at least one of a number of symptoms (see box) either daily or several times a week for at least one month prior to their heart attack. The two most frequent symptoms, fatigue and sleep disturbances, were most likely to be rated as severe.

Perhaps most surprising is that 43% of the women said they didn't experience any type of chest discomfort with their AMI. A lack of major chest pain may be a major reason why women have more unrecognized heart attacks than men. The women in this study who experienced chest discomfort more often described it as aching, tightness or pressure rather than pain.

It's still not clear at what point these symptoms might help predict a heart attack, but women and their clinicians need to be sensitive to the wide range of symptoms that might signal a woman is having a heart attack. It's important not to miss the earliest possible opportunity to prevent or treat an AMI, the number one cause of death in both men and women. If you are a woman and have severe, unexplained fatigue or any of these symptoms at least several times a week, particularly if you have known risk factors for heart disease (like smoking or high blood pressure-see the links below for more information), contact a health provider immediately.

— a report from The NIH Word on Health, December 2003

Source: Circulation 108: 21:2619-2623.

For more information about heart attacks, visit http://123819272.net/Diseases/HeartAttack/HeartAttack_WhatIs.html.

For more information on women and heart disease, visit The Heart Truth, a national awareness campaign for women about heart disease, at http://www.nhlbi.nih.gov/health/hearttruth/ or contact:
NHLBI Health Information Center
Attention: The Heart Truth
P.O. Box 30105
Bethesda, MD 20824-0105
Phone: 301-592-8573, TTY: 240-629-3255
Fax: 301-592-8563
E-mail: NHLBIinfo@rover.nhlbi.nih.gov

New Drug to Suppress Immune System
Immunosuppressant drugs are designed to inhibit the body's immune system so that your body doesn't reject transplanted organs, and to treat autoimmune diseases such as lupus, rheumatoid arthritis, eczema and psoriasis-conditions in which the body's own immune system attacks healthy, normal tissue as if it were an invading microbe. Unfortunately, current immunosuppressants can cause serious side effects such as diabetes, elevated cholesterol and high blood pressure. A new drug, developed by Pfizer Global Research and Development with help from NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), has now been successfully tested in mice and monkeys, and may eventually prove to be a major help for those needing organ transplants or with autoimmune diseases.

The new drug is designed to inhibit an enzyme called JAK3, a protein discovered by the NIAMS team in 1994 that is found only in immune system cells. Current immunosuppressants target enzymes found in cells throughout the body, resulting in toxic side effects. In setting out to find a compound that selectively inhibited JAK3 so that it only affected immune cells, Pfizer researchers searched through a library of chemical compounds developed by the company. They eventually arrived at a compound they call CP-690,550.

They tested CP-690,550 in mice with heart transplants and in monkeys with kidney transplants. In both cases, the animals treated with CP-690,550 survived much longer than untreated animals. Their survival was also longer than that of animals treated with other immunosuppressant drugs in past studies, with fewer side effects.

This finding culminates a long process of research and discovery by the NIAMS team. After discovering JAK3, the team demonstrated that this protein, called a kinase, was critical for the cell signaling process, resulting in the development of infection-fighting white blood cells. They went on to show that the mutation of the gene encoding JAK3 was responsible for a form of severe combined immunodeficiency (SCID). Because JAK3 is essential for immune cell function, and because its expression is limited to blood cells, the team proposed that inhibiting JAK3 might be the basis for a new class of immunosuppressant drugs. The group then entered into a collaborative research and development agreement with Pfizer-a partnership that has facilitated Pfizer's development of this new drug.

This study shows that inhibiting JAK3 has the effect of suppressing the immune system, while not affecting other systems of the body. Further animal studies are now being done to determine if this drug could be tested safely in humans. If it proves safe and effective, it would prove a major advance in the development of immunosupressant drugs.

— a report from The NIH Word on Health, December 2003

Source: Science 302:875-878

For more information about autoimmune diseases, visit http://health.nih.gov/result.asp?disease_id=63.