Medicine Man

Utilizing a technique that combines low temperature measurements and theoretical calculations, Hebrew University of Jerusalem scientists and others have revealed for the first time the electronic structure of single DNA molecules.

The knowledge of the electronic properties of DNA is an important issue in many scientific areas from biochemistry to nanotechnology -- for example in the study of DNA damage by ultraviolet radiation that may cause the generation of free radicals and genetic mutations. In those cases, DNA repair occurs spontaneously via an electronic charge transfer along the DNA helix that restores the damaged molecular bonds.

In nano-bioelectronics, which is the advanced research field devoted to the study of biological molecules (to produce electrical nanocircuits, for example), it has been suggested that DNA, or its derivatives, may become used as possible conducting molecular wires in the realization of molecular computing networks which are smaller and more efficient than those produced today with silicon technology.

The knowledge that has been acquired in this project, say the researchers, may also be relevant for current attempts to develop new sophisticated, reliable, faster and cheaper ways to decode the sequence of human DNA.

The research, published in the prestigious journal Nature Materials, is a result of an international collaboration. The research was conducted by Errez Shapir and coordinated by Dr. Danny Porath at the Department of Physical Chemistry and Center for Nanoscience and Nanotechnology at the Hebrew University and by Dr. Rosa Di Felice at the S3 Center of INFM-CNR in Modena, Italy. Also collaborating in the project were Prof. Alexander Kotlyar at Tel Aviv University, who synthesized the molecules, the CINECA supercomputing center in Italy, and Prof. Gianaurelio Cuniberti at the University of Regensburg, Germany.

In their work, the researchers were able to decode the electronic structure of DNA and to understand how the electrons distribute into the various parts of the double helix, a result that has been pursued by scientists for many years, but was previously hindered by technical problems.

The success of this project was finally achieved thanks to collaboration between experimental and theoretical scientists who worked with long and homogeneous DNA molecules at minus 195 degrees Celsius, using a scanning tunneling microscope (STM) to measure the current that passes across a molecule deposited on a gold substrate. Then, by means of theoretical calculations based on the solution of quantum equations, the electronic structure of DNA corresponding to the measured current has been obtained. These results also suggest an identification of the parts of the double helix that contribute to the charge flow along the molecule.

http://www.huji.ac.il/

A chronic autoimmune disease, rheumatoid arthritis (RA) is characterized by persistent inflammation of the synovial membrane and progressive joint destruction.

Beyond loss of mobility, sufferers face a high risk of heart failure. An inflammatory cytokine known for contributing to the development of RA, tumor necrosis factor a (TNFa) has also been implicated in cardiovascular disorders. Inhibition of TNFa has opened promising new treatment options for RA patients. Anti-TNF drugs such as infliximab, etanercept, and adalimumab have been shown to not only diminish signs and symptoms of the disease, but also prevent joint damage. However, in cardiac trials, TNFa inhibitors have shown no more positive effects on heart failure risk -- and sometimes less -- than placebo.

Does TNFa inhibition prevent heart failure in RA patients -- or promote it? That's the critical question Dr. Joachim Listing and a team of specialists with the German Rheumatism Research Centre in Berlin set out to answer. Featured in the March 2008 issue of Arthritis & Rheumatism ( http://www.interscience.wiley.com/journal/arthritis), their study indicates that anti-TNF therapy does a patient's heart more good than harm, when it successfully reduces the inflammatory toll of RA.

To clearly assess the role of TNFa inhibitors in heart failure risk, the researchers analyzed a 3-year span of disease activity and cardiovascular incidents in 4,248 RA patients enrolled in an ongoing Germany-wide study of biologic therapy. At the time of enrollment, 2,757 of the subjects had started treatment with an anti-TNF drug -- infliximab, etanercept, or adalimumab -- and 1,491 had started a new disease-modifying antirheumatic drug (DMARD). Within the study period, several hundred of the patients were also treated with glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or COX-2 inhibitors. Over 78 percent of the patients were women. The mean age at baseline was 53.7 years for the anti-TNF group and 56 years for the DMARD controls.

Recorded at baseline and regular intervals through the 60-month follow-up, data on every patient included C-reactive protein level, duration of morning stiffness, and the number of tender and swollen joints, based on the 28-joint count Disease Activity Score (DAS). Cardiovascular events, whether acute or congestive, were also noted. Researchers used Cox proportional hazards models to investigate the impact of disease-related and treatment-specific risk factors on the development or worsening of heart failure.

At baseline, RA patients in the anti-TNF group had significantly more active disease, more physical limitations, and more heart problems than patients in the control group. Not surprisingly, the incidence rates of heart failure were significantly higher -- more than double -- for patients with a cardiovascular condition at the start of treatment than for those in good heart health. After adjusting for age, sex, body mass index, and prevalence of cardiovascular events, an increased risk of heart failure was found in patients with low functional capacity and high disease activity. Notably, a 2-point increase in the DAS28 score resulted in a 1.8-fold increase in heart failure risk.

When adjusting for functional capacity and disease activity at follow-up, along with the standard risk factors, the contribution of anti-TNF therapy to heart failure risk was insignificant. The small residual risk was balanced by the treatment's effectiveness in reducing inflammation, ultimately protecting the heart and other vital organs in addition to the joints. In contrast, COX-2 inhibitors and glucocorticoids, which tend to promote elevated blood pressure and insulin resistance, were associated with an increased risk of heart disease and heart attack.

Confirming the grave risk of heart failure for patients with severe rheumatoid arthritis, especially those with highly active disease, this study also sheds light on the benefits of treatment with TNFa inhibitors to the heart and whole body. "Our data suggests that controlling the inflammatory activity of RA not only leads to better outcome of the rheumatic disorder, but also contributes to a reduction of cardiovascular risk," Dr. Listing notes. He calls attention to the need for more research to weigh the positive effects of glucocorticoids, such as cellular proliferation, against their harmful effects to the cardiovascular system. Finally, he urges caution in prescribing any drug that may be hazardous to the heart of a vulnerable patient. "Screening for cardiac risk factors and effective treatment of both the rheumatic disorder and the cardiac disease are essential," Dr. Listing stresses.

http://www.wiley.com/wiley-blackwell

The U.S. Food and Drug Administration approved Nexium (esomeprazole magnesium) for short-term use in children ages 1-11 years for the treatment of gastroesophageal reflux disease (GERD).

The agency approved Nexium in two forms, a delayed-release capsule and liquid form. Nexium is approved in 10 milligrams (mg) or 20 mg daily for children 1-11 years old compared to 20 mg or 40 mg recommended for pediatric patients 12 to 17 years of age.

"This approval provides important information for appropriate dosing for children ages 1-11 years with GERD," said Julie Beitz, M.D., director of the FDA's Office of Drug Evaluation III in the Center for Drug Evaluation and Research. "Children prescribed this drug should be monitored by their physicians for any adverse drug reactions."

Nexium is part of a class of drugs known as proton pump inhibitors (PPIs). PPIs decrease the amount of acid produced in the stomach and help heal erosions in the lining of the esophagus known as erosive esophagitis.

FDA approved the use of Nexium in patients 1 to 11 years for short-term treatment of GERD based upon the extrapolation of data from previous study results in adults to the pediatric population, as well as safety and pharmacokinetic studies performed in pediatric patients. In one study, 109 patients 1-11 in age, diagnosed with GERD, were treated with Nexium once-a-day for up to eight weeks to evaluate its safety and tolerability. Most of these patients demonstrated healing of their esophageal erosions after eight weeks of treatment.

The most common adverse reactions in children treated with Nexium were headache, diarrhea, abdominal pain, nausea, gas, constipation, dry mouth and sleepiness. The safety and efficacy of Nexium has not been established in children less than one year of age.

http://www.fda.gov/

Many older adults have their blood cholesterol level checked regularly.

Now, easy-to-understand information about why this test is so important to heart health and what the results mean is available on NIHSeniorHealth, the National Institutes of Health (NIH) Web site designed especially for seniors. Consumers can log onto http://nihseniorhealth.gov/highbloodcholesterol/toc.html for answers to questions such as: What's the difference between LDL and HDL? Which one is the "good" cholesterol? What are triglycerides? What do the numbers mean? How is high blood cholesterol treated?

"Because high blood cholesterol does not cause symptoms, many people are unaware that their levels are elevated," says Elizabeth G. Nabel, M.D., director of the National Heart, Lung, and Blood Institute (NHLBI), a component of NIH. "Lowering cholesterol levels that are too high reduces the risk of developing heart disease. NIHSeniorHealth is a great resource for older adults who want to learn more about how to prevent, detect, and treat high blood cholesterol." 

One of the fastest growing age groups using the Internet, older Americans increasingly turn to the World Wide Web for health information.  In fact, 68 percent of online seniors surf for health and medical information when they go online.  NIHSeniorHealth is a joint effort of the National Institute on Aging (NIA) and the National Library of Medicine (NLM).  The site is based on the latest research on cognition and aging.  It features short, easy-to-read segments of information that can be accessed in a number of different formats, including various large-print type sizes, open-captioned videos, and even an audio version. 

Additional topics coming soon to the site include Parkinson's disease, leukemia, kidney failure, and eating well as you get older.   The site links to MedlinePlus, NLM's more detailed site for consumer health information. 

The NIA leads the Federal effort supporting and conducting research on aging and the health and well-being of older people.  The NLM, the world's largest library of the health sciences, creates and sponsors Web-based health information resources for the public and professionals.  The NHLBI supports research in diseases of the heart, lung, and blood, and sleep disorders.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

http://www.nih.gov/news/

Although rheumatoid arthritis (RA) is more predominant in women, the reasons for this are unclear.

Many studies have examined the effects of estrogen on the risk and severity of RA, but the results are conflicting and controversial. A new study using data from the Women's Health Initiative (WHI) clinical trials on hormone replacement therapy found that there were no significant differences in the risk of developing RA or the severity of RA between postmenopausal women who were on hormone replacement therapy and those who took placebos. The study was published in the March issue of Arthritis Care & Research (http://www.interscience.wiley.com/journal/arthritiscare).

The WHI randomized controlled trials included over 27,000 postmenopausal women between the ages of 50 and 79 who took estrogen and progestin, estrogen alone or a placebo. Led by Brian Walitt of Washington Hospital Center in Washington, DC, the current study identified women who had RA based on whether they reported having it and were taking prescription medications to treat it. Self-reported information about whether women had RA was collected annually, and they were assessed for disease severity at the beginning of the study and after one year. Measures of self-reported joint pain/stiffness were also collected at that time and participants were asked to rate the severity of their symptoms.

The study is the only placebo-controlled trial to evaluate the effect of hormone replacement therapy on developing RA and the sixth study to evaluate the effects of hormone therapy on how women perceive disease severity. The results showed that there were 105 new cases and 63 existing cases of RA. There were no statistically significant differences on either new RA cases over an average of five to six years or on the severity of RA symptoms after one year. While earlier studies had suggested that hormones had a protective effect against developing RA, they were observational. The current study found no significant protective benefit from hormones in preventing RA.

Although the prevalence of RA in the study was about half of what is found in the general population, this may be due to the tendency of clinical trials to recruit healthier patients and the exclusion of participants taking prednisone, which is used to treat arthritis. Although the WHI methodology has many advantages over prior studies, the sample size for RA was much less than what would be required to observe the effect of hormone replacement therapy on developing RA. However, it is unlikely that larger studies will be carried out, due to the health risks of hormone replacement therapy. Also, the study relied on self-reported information, and even though it tried to minimize overreporting by including only women taking medications for RA, this approach is not as effective as performing chart reviews or physical exams.

The authors conclude that "the design of the WHI provided a unique opportunity to examine the effects of PHT [postmenopausal hormone therapy] on RA. Despite the participation of 27,347 women, there was no statistically significant evidence of a difference in the hazard of RA incidence or a difference in RA symptom severity between the PHT and placebo groups."

http://www.wiley.com/wiley-blackwell