What's Hot

What's Hot

May 2001

What's Hot Archive

May 30, 2001

CNS trauma produces immune response

Central nervous system (CNS) trauma can create a cascade of events leading to delayed further degeneration of nerve cells. A study published in the June 1, 2001 issue of Journal of Neuroscience demonstrated for the first time that CNS trauma creates an immune reaction in the body against itself, helping to protect nerve cells from future damage. This contrasts with the widely held belief that CNS immune activity and autoimmune responses are always destructive.

In four experiments with mice and rats in whom central nervous system injuries were induced, researchers observed a protective T-cell immune response which reduces the loss of neurons. In one experiment, rats who received spinal cord injuries experienced greater survival of retinal nerve cells when later receiving an optic nerve injury than those who did not experience the initial CNS injury. In the second experiment, rats with spinal cord injuries were given splenocytes from another group of spinally injured rats and showed better locomotor activity of their hindlimbs than untreated rats with similar injuries or rats treated with splenocytes from animals who did not receive injuries. A further experiment showed that rats who had no mature T cells had 40% less survival of neurons after an injury to the optic nerve than normal rats.

The researchers hope that the findings may lead to the development of a vaccine to aid in the recovery of spinal cord injuries. The treatment, by boosting the natural autoimmune response or creating it in those for whom it does not exist, could inhibit the damage that occurs after the initial injury. Esther Sternberg, MD of the National Institute of Mental Health commented, "These studies provide new avenues for development of potential treatments and prevention of paralysis resulting from injury."

—D Dye


May 28,2001

Spinal muscular atrophy treatable with folic acid and B12

The May 2001 issue of the journal Molecular Cell published evidence that folic acid and vitamin B12 may lessen the symptoms of spinal muscular atrophy, or SMA, a disease caused by low levels of SMN, a housekeeping protein required by all cells. When the cells lack adequate SMN, motor neurons that control that activity of muscle groups are the first cells that degenerate, so that major muscle groups do not receive adequate stimulation. Many patients with the disease die as infants while some people are not affected until later in life, and its symptoms vary among individuals.

Researchers had believed that the variation in onset and intensity of symptoms was due to genetic modifiers, but researchers at the University of Pennsylvania School of Medicine believe that these differences may be related to vitamin B12 and folic acid intake. The researchers observed that SMN, which stands for "survival of motor neurons" will bind efficiently if the proteins it binds to are tagged by certain enzymes. The tags are composed of methyl groups attached through arginine to sites on the surface of SMN's protein targets. This process requires adequate folic acid and B12 to occur. A lack of the vitamins causes undermethylation of proteins, which are the proteins that SMN requires for its functioning.

Principle author Gideon Dreyfuss, PhD, Isaac Norris Professor of Biochemistry and Howard Hughes Medical Institute Investigator summarized, "We would like to say, very cautiously, that our work raises the possibility that folic acid, and vitamin B12 may be helpful in lessening, even if only slightly, the severity of the disease for some SMA patients-or at least ensure that their condition is not worse than their genetics dictate. Certainly, we hope clinical studies will be initiated to see whether folate and the B vitamins make a difference for SMA patients that extends beyond laboratory research."

—D Dye


May 24, 2001

Dual virus cause of MS proposed

The yearly meeting of the American Society for Microbiology held this week was the site of the announcement that multiple sclerosis may result from confusion of the nervous system caused by infection by two viruses. Multiple sclerosis is an autoimmune disease caused by the body's attack on its own myelin, the substance surrounding and protecting the nerve cells. A viral cause of the disease has been previously studied and reported. Identical twin studies have indicated that the cause may lie beyond genetics, with less than a third of twin siblings acquiring the disease when the other twin has been diagnosed.

The dual virus theory, reported in Nature Science Updates, proposes that the disease occurs when a virus that has proteins resembling myelin initially attacks the body, followed by an infection by a nonmyelin-resembling agent. The initial infection programs CD4+ immune cells to recognize myelin as a foreign tissue, while the second infection stimulates the production of interleukin-12, stimulating the primed CD4+ killer cells, which then attack the myelin, causing the disease known as multiple sclerosis. A number of viruses can stimulate nterleukin-12, including the viruses that cause respiratory infections.

The University of Utah Salt Lake City research team infected mice who were susceptible to the disease with a genetically engineered virus containing myelin-like surface proteins, and observed no damage to the nerve cells as would occur in MS. The mice were later infected with a cowpox virus with no similarity to myelin proteins, and they rapidly developed MS symptoms. Research team member Robert Fujinami summarized, "No one virus has been ascribed as a cause for MS," research team member Robert Fujinami summarized. "One virus silently primes for autoimmune disease that is then triggered by later viral infections." Researchers hope to identify the viruses involved in the disease so that antiviral therapies or a preventive vaccine can be developed.

—D Dye


May 23, 2001

Immunotherapy effective against prostate cancer

New studies are showing that cancer may not be as resistant to immunotherapy as has been believed. The May 20 issue of the journal Human Gene Therapy published the results of an early-phase study in which a gene that delivers interleukin-2 was injected into the prostate gland, resulting in fewer side effects than chemotherapy and a reduction of PSA levels in half of the participants. PSA, or prostate specific antigen, is a prostate cancer marker found in the blood.

In this study, twenty-four men whose prostate cancer was locally advanced, or spreading beyond the prostate, received ultrasound-guided injections of the gene directly into the prostate gland before removal of the prostate or following unsuccessful radiation therapy. The expression of interleukin-2 by the gene stimulates the immune system to attract lymphocytes to attack and destroy prostate cancer cells. The therapy's safety rests on the fact that it is delivered locally rather than systemically, as in the case of chemotherapy. This is the first time interleukin-2 was shown to be effective against prostate cancer.

Lead study author Arie Belldegrun, MD, chief of urologic oncology at the Jonsson Cancer Center at UCLA stated, "Based on our earlier studies in the laboratory, which were published in the journal Cancer, we suspected that this approach might work in humans. We did not know, however, that gene therapy and immunotherapy could be options for patients with locally advanced prostate cancer, a high-risk group to whom we have little to offer right now. This is the first clinical study of its kind aimed at exploring the role of immunotherapy and gene therapy in prostate cancer patients. We' re encouraged by the significant reductions of PSA levels and by the clinical outcome in this high-risk group of patients."

Study coauthor Robert Figlin, also of UCLA commented, "We anticipate that, in the near future, newer and more powerful agents will be delivered directly to the prostate via gene therapy - perhaps eliminating the need to remove the prostate. This is an important new concept and a proof of principal that the technology can work."

—D Dye


May 21, 2001

Synthetic version of vitamin D shows antitumor activity in mice

At the annual meeting of the American Association for Cancer Research held in March, UCLA researchers presented the results of a study in which mice with a mutation similar to that which causes hereditary colon cancer in humans received a synthetic analogue of vitamin D and experienced a lower tumor volume than a placebo group. Vitamin D is known to have an anticancer effect, but high levels can elevate serum calcium, leading to side effects.

In this study, partly funded by the National Institutes of Health, vitamin D as well as the synthetic version known as Ro 26-9114 were tested against a placebo in mice bred with the defect similar to that which causes familial adenomatous polyposis in humans. The disease can cause the formation of thousands of colon polyps early in life which progress to cancer, necessitating surgical removal of the colon to avoid the development of metastatic cancer. Both forms of vitamin D decreased tumor formation, with nonsythetic vitamin D reducing total tumor surface area to a greater extent. The vitamin D analogue elicited milder side effects which occurred near the end of the eighth week of the ten week study as opposed to the fourth week in which symptoms were observed with natural vitamin D.

Segio Huerta MD, postdoctoral fellow at the Center for Human Nutrition at UCLA stated, "The activated form of vitamin D has anticancer effects against many common cancers, but it produces abnormally high levels of calcium in the blood, which can lead to toxic effects such as fatigue, headache, nausea, vomiting, and loss of appetite. Our study found that Ro 26-9114 displayed the beneficial antitumor properties of vitamin D but with only modest loss of appetite and weight. . . . We hope that these studies will lead to preventive treatments for patients at risk for colon cancer, and improve our understanding of how to optimize diets to lower cancer risk for the general population."

—D Dye


May 18, 2001

N-acetylcysteine protects rat lungs from inflammatory damage

Oxidant stress has been shown to increase in lung inflammation, leading to tissue damage. Reactive oxygen species such as hydrogen peroxide, superoxide and hydroxyl radicals are produced during inflammation at the site of injury.

The May 2001 issue of the journal of the Federation of American Societies for Experimental Biology (FASEB) published the results of a study in which rats in whom lung injuries were experimentally induced were protected from inflammation damage by the administration of the antioxidant amino acid N-acetylcysteine (NAC). N-acetylcysteine exerts its antioxidant effects by several mechanisms, among them contributing to the regeneration of glutathione and upregulating superoxide dismutase. It converts to L-cysteine within the cell, acting as a precursor to glutathione peroxidase, a potent antioxidant.

Anesthetized rats received injections of carrageenan or saline into the lung cavity to induce inflammation, followed by intraperitoneal injections of N-acetylcysteine or an equal volume of normal saline three, six and twelve hours later. Twenty-four hours after receiving the carrageenan the lung cavities of the rats were examined and biopsy specimens of the lungs obtained.

The animals receiving carrageenan experienced significant injury, edema and infiltration of neutrophils, a type of white blood cell, into the lung cavity and lung compared to those who received saline. In the carrageenan injured rats who received N-acetylcysteine, less injury and infiltration occurred. The infiltration of neutrophils into the lung was associated with lipid peroxidation, as determined by the measurement of malondialdehyde levels. The NAC treated group had lower malondialdehyde levels, indicating decreased lipid peroxidation. The carrageenan-administered animals also experienced an alteration in the shape of red blood cells, which was significantly prevented in the group receiving NAC. The authors conclude that NAC exerts its protective effects by several mechanisms, among them scavenging free radicals and reducing the infiltration of neutrophils into the inflammatory site.

—D Dye


May 16, 2001

Cancer vaccine increases lifespan in poor prognosis patients

Research reported at the annual conference of the American Society of Clinical Oncology this week in San Francisco announced the ability of new therapeutic cancer vaccines to extend lifespan in patients with advanced cancers. The finding was a result of a phase I trial conducted at the Lombardi Cancer Center at Georgetown University. Two vaccines, Vaccinia-CEA and ALVAC-CEA, were administered to patients with advanced metastatic cancer of the breast, pancreas, stomach, esophagus, spleen, cervix and colon which expressed the CEA tumor antigen. One group of patients received one dose of Vaccinia-CEA followed by three of ALVAC-CEA while another group received three doses of ALVAC-CEA followed by one of Vaccinia-CEA. The group receiving the first regimen experienced a T cell immune response that led to five of the nine subjects surviving at two years, compared to zero in the other group.

Vaccinia-CEA and ALVAC-CEA are recombinant, pox virus-based vaccines that generate an immune response against carcinoembryonic antigen, or CEA, which is a protein found on the surface of some cancer cells. The vaccines generate cytotoxic T cell activity which can destroy the cancer cells. Principle investigator, John Marshall MD, Associate Professor of Medicine at Georgetown University commented, "Therapeutic cancer vaccines have long been believed to hold great promise. Our data today demonstrate the first link between the ability of vaccines to elicit a strong, specific T cell response against advanced metastatic cancers and subsequently increase patient survival.

The current life expectancy for these late-stage cancer patients is less than one year, so to see more than 50 percent of the patients treated with CEA vaccines alive two years later is striking, even in this small study population." Georgetown University will be conducting Phase II trials including more patients, based on these positive results.

—D Dye


May 14, 2001

Parathyroid hormone is powerful osteoporosis treatment

The May 10 issue of the New England Journal of Medicine reported that the administration of parathyroid hormone to postmenopausal women significantly increased bone density and lessened the incidence of fractures. Current treatments for osteoporosis involve slowing bone resorption and bone loss. Parathyroid hormone actually promotes bone formation.

In an international clinical trial involving ninety-nine investigators in seventeen countries, 1,637 postmenopausal women with osteoporosis received 20 or 40 micrograms parathyroid hormone or a placebo by subcutaneous injection. All groups received supplements containing 1000 mg calcium per day and 400 to 1200 iu vitamin D. After twenty-one months, women taking the hormone had up to 13% more bone in their spine than women taking the placebo.

Principle investigator Robert Neer, MD, director of the Osteoporosis Center at Massachusetts General Hospital summarized the results: "Parathyroid hormone reduces the percentage of women with osteoporosis who develop a new vertebral fracture by 65 and 69 percent. No other drug has reduced it more than 40 to 50 percent . . . The key to parathyroid hormone's fracture-thwarting powers is that it stimulates bone formation dramatically-it doubles the normal rate. . . . Because parathyroid hormone acts at a very fundamental level to stimulate new bone formation, it has worked on all forms of osteoporosis tested to date, including osteoporosis in men and osteoporosis induced by cortisone-like drugs. And it prevents estrogen-deficiency bone loss in women with normal bones."

The study also found that parathyroid hormone decreased the risk of multiple spinal fractures by 77 percent in the group receiving 20 mcg of the hormone and by 86 in the group receiving 40 mcg. The authors note that vitamin D has decreased the risk of nonvertebral fractures by 50 to 60 percent in two studies, but the effects in this study were in addition to those of vitamin D's, since all test subjects received vitamin D.

Parathyroid hormone, produced by four glands in the neck, has been researched since the 1920s for its role in increasing bone density. Neer cautions that the hormone is not by itself a cure for osteoporosis, but should be combined with a second drug that suppresses bone destruction.

—D Dye


May 11, 2001

Test prevents second cancer surgeries

The annual meeting of the American Association for Thoracic Surgery held in San Diego, California was the site of the announcement that a rapid test for detecting tumor cells in lymph nodes during surgery has been developed as a result of research collaboration between the University of Pittsburgh School of Medicine and Cepheid Corporation of Sunnyvale, California. The current method is to examine lymph nodes under a microscope, which can miss lymph node metastases in many cases. In melanoma and breast cancer patients, second surgeries are necessary in 10 to 20% of all cases.

The test, called the Smart Cycler, employs a method of gene amplification that enables the detection of the cancer gene CEA which signals the presence of micrometastases in lymph nodes. Test codeveloper Tony Godfrey PhD, assistant professor of surgery at the University of Pittsburgh, stated, "To properly treat cancer patients, lymph nodes need to be evaluated during surgery. Unfortunately, current intraoperative methods are not sensitive enough to detect micrometastatic disease. As a result, many patients are either under-treated or undergo a second operation, once more sensitive and time-consuming tests identify disease spread. Our goal is to avoid these limitations by providing the surgeon with accurate and sensitive information at this pivotal point in the treatment decision process."

The newer test provides results within a half hour and in some cases has proved to be more accurate than histopathology methods involving tissue stains which can take as much as several days to provide results. In an ongoing prospective study the test identified cancer in two out of twenty-three biopsies in which current methods of examining the lymph nodes during surgery failed to identify the disease.

—D Dye


May 9, 2001

Low folic acid and B12 more prevalent in Alzheimer's patients

The May 8 2001 issue of the journal Neurology featured the results of a population based longitudinal study in Sweden which sought to determine the association between the incidence of Alzheimer's disease and low levels of serum folate and vitamin B12. Three hundred seventy individuals aged 75 years and older without dementia who were not supplementing with vitamin B12 and folate were followed for a three year period in which Alzheimer's disease and other dementia were diagnosed by specialists.

When low levels of vitamin B12 were defined as 150 picomoles per liter or lower and low levels of folate defined as 10 nanomoles or lower per liter, study participants with a low level of either vitamin at baseline were found to be diagnosed with dementia at over twice the rate of subjects with normal levels. The associations were stronger in participants whose cognition was good at the beginning of the study. A similar pattern was found when a deficiency was diagnosed when serum levels of vitamin B12 were 250 picomoles per liter or lower and when folate was 12 nanomoles per liter or lower. An interaction between the two vitamins was not found.

Research coauthor Hui-XinWang commented, "In our study, we found that low levels of either of these two vitamins were related to an increased Alzheimer's disease risk. Monitoring B12 and folate levels is important in order to avoid unfavorable conditions, even for those elderly people who are quite healthy in terms of cognition." The researchers believe that the two vitamins may influence Alzheimer's risk by affecting neurotransmitters or by their homocysteine-lowering effect. Homocysteine has a toxic effect on nervous system cells that could lead to Alzheimer's disease, and elevated homocysteine levels have been linked with an increased incidence of Alzheimer's disease and dementia.

—D Dye


May 7, 2001

Quercetin reduces blood pressure in spontaneously hypertensive rats

Quercetin is a bioflavonoid with antioxidant effects that is available as a dietary supplement. In a study published in the British Journal of Pharmacology, researchers from the University of Granada and the University Complutense of Madrid, Spain, tested the effects of 10 mg per kilogram body weight of oral quercetin in spontaneously hypertensive rats and rats with normal blood pressure. After five weeks of receiving quercetin, the spontaneously hypertensive rats experienced an 18% reduction in systolic blood pressure, a 23% reduction in diastolic blood pressure and a 12% reduction in heart rate. The normotensive rats did not experience any reduction in blood pressure or heart rate.

Hypertension can lead to enlargement of the heart and kidneys, and these parameters were also studied in this experiment. The kidney weight index and the left ventricular weight index of the heart in the hypertensive rats were greater than those of the control rats, and quercetin was found to reduce these values parallel to the reduction in systolic blood pressure. In isolated aorta taken from the hearts of the rats, quercetin enhanced the relaxation of the endothelium induced by acetylcholine.

Plasma malonyldialdehyde and urinary isoprostane F(2alpha) excretion, which are measures of oxidation, were elevated in the sponatenously hypertensive rats at the beginning of the study, but normalized to the levels of the controls with quercetin treatment, due to its antioxidant properties. This study shows that quercetin can reduce hypertension as well as reduce renal and cardiac hypertrophy in hypertensive rats while not effecting normal rats.

—D Dye


May 4, 2001

DHEA replacement beneficial for Addison's disease patients

Addison's disease, or primary adrenalcortical insufficiency, is a disease caused by failure of the adrenal cortex to produce adequate corticosteroid hormones. The disease afflicts 4 out of every 100,000 individuals and can strike at any age. Symptoms include low blood pressure, fatigue, weakness, dizziness, excessive pigmentation, and eventually weight loss, muscle aches and diarrhea. Left untreated, some cases can result in death. Current treatment involves replacement of glucocorticoid and mineralcorticoid hormones. The hormone dehydroepiandrosterone, or DHEA, is also produced by the adrenal cortex, but is not part of standard treatment for Addison's disease.

In the December 2000 issue of the Journal of Clinical Endocrinology and Metabolism, researchers at Oxford University in England reported the results of a study in which twenty-four women and fifteen men with Addison's disease were randomized to receive one of two regimens: 50 mg micronized DHEA orally for twelve weeks followed by a four week period without the hormone, then twelve weeks of a placebo, or 50 mg placebo for twelve weeks, followed by a four week absence of treatment, then twelve weeks of the hormone. Following DHEA replacement, serum levels of DHEA-sulfate and delta(4)-androstenedione were found to be normalized to within the adult physiological range. Total testosterone also increased to a low normal range in females but was not affected in males.

Psychological assessment of the participants showed an improvement of self esteem, well-being, mood and fatigue associated with DHEA therapy. There were no effects observed on body composition, lipid levels, bone mineral density, sexual or cognitive function. In the absence of adverse effects, the authors suggest a role for DHEA replacement therapy in Addison's disease.

—D Dye


May 2, 2001

Hormone replacement in men could prevent Alzheimer's disease

Some research has indicated that estrogen status in women may be involved in the development of Alzheimer's disease, although a recent study showed no association between synthetic hormone replacement therapy in women and risk of developing the disease. It has been proposed that the main component of the senile plaque, the amyloid-beta peptide, may be effected by gonadal hormones, and that elevated plasma amyloid-beta levels are associated with the onset of Alzheimer's disease. Late-onset Alzheimer's disease risk also may be related to genetically linked high plasma amyloid-beta.

A letter published in the Journal of the American Medical Association reported the results of a small study of men forty-four to eighty-three years of age who, because of prostate cancer, received hormone blockade. The men received the drug flutamide three times per day and leuprorelin acetate weekly, for twelve weeks. Blood samples measuring estradiol, testosterone and amyloid-beta levels were taken one week before initiation of the drug therapies, and on the fourth, twelfth and twenty-fourth weeks. While levels of testosterone and estradiol dropped dramatically and then stabilized at low levels during the first two months in all patients, plasma amyloid-beta concentrations doubled and then stabilized for over six months.

The University of Western Australia researchers believe that these findings support the idea that circulating amyloid-beta levels may be under the control of gonadal hormones and hypothesize that replacement of these hormones in postandropausal men may help prevent or delay the onset of Alzheimer's disease. They recommend further studies.

—D Dye


May 1, 2001

Drug fights free radicals and protects heart

Research conducted at Wake Forest University Baptist Medical Center presented at the American Academy of Pediatrics meeting in Baltimore last week revealed a new drug called M40403 which removes free radicals from heart tissue when administered following a heart attack, preventing the extensive damage that they cause. During a heart attack, or myocardial infarction, blood flow to an area is prevented by blockage of an artery. When the patient's damaged blood vessels are reopened and blood flow reestablished, the fresh flow of blood causes heavy free radical activity in the affected tissue, which can cause DNA damage and scar tissue formation. If the drug is administered before reopening the blocked vessel, this damage can be prevented.

Principle investigator Mark Payne, MD, associate professor of pediatric cardiology at Wake Forest University School of Medicine stated, "The applications of this research are enormous. The early animal studies are very positive. These data support our hypothesis that tissue can be protected during a heart attack, with potentially improved cardiac functioning . . . Normally these cells have coping mechanisms to deal with free radicals that are generated within the cells in low amounts. But when the heart has suffered an attack, the cells become overwhelmed and cannot cope with the enormous burst of free radicals that are produced when blood flow is reestablished to the injured regions of the heart. This synthetic drug is much smaller in size than naturally occurring proteins that usually remove free radicals. The small size is very important because it allows the drug to penetrate into tissues, such as the brain and the heart, that larger synthetic drugs and proteins cannot easily penetrate. Many people take doses of vitamins A, C, and E, which can bind to free radicals in the body and remove them. The unique thing about this drug is that it removes the free radicals from the body, but stays behind to neutralize more.

—D Dye


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