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LE Magazine June 2002

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Studies from throughout the world that can help you live longer

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June 2002 Table of Contents

  1. Synergistic inhibition of prostate cancer
  2. Protective effect of DHEA against lipid peroxidation in human liver cells
  3. Role of oxidative stress in inflammation of pancreas
  4. Gastrectomy a risk factor for pancreatic cancer
  5. Interferon-ribavirin for chronic hepatitis C with and without cirrhosis
  6. IGF-1 blocks the aging-related loss of skeletal muscle function
  7. Osteoporosis in men - prevention and management
  8. Prevention or reversal of long-term depression by pregnenolone sulfate

1. Synergistic inhibition of prostate cancer

Retinoic acid and vitamin D3 have demonstrated significant capacity to control proliferation in vitro of many solid tumors. Cooperative synergistic effects by these two have been reported. It is, therefore, possible that greater therapeutic effects could be achieved if these compounds were administered together. The role of retinoid-dependent protein 1 in controlling cancer cell proliferation appears significant. Researchers utilized a retinoid, and a potent vitamin D3 analogue together at low, physiologically safer doses against a panel of prostate cancer cells. The cell lines were synergistically inhibited in their clonal growth by the combination, whereas retinoic acid alone was essentially inactive. Cancer cells underwent apoptosis in the presence of retinoic acid and vitamin D3. The data suggest the retinoid and the vitamin D3 analogue may naturally act synergistically to control cell proliferation, a process that is interrupted during transformation, and that this combination may form the basis for treatment of some androgen-independent prostate cancer.

BRITISH JOURNAL OF CANCER, 1999, Vol 79, Iss 1, pp 101-107


2. Protective effect of DHEA against lipid peroxidation in human liver cells

Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. This study evaluated whether DHEA's two opposed effects on lipid peroxidation reported in literature may be dependent on schedule and doses used. Chang liver cells, a line derived from normal human liver, were grown in media containing: 1) no steroids (control) or 2) DHEA at concentrations ranging from 0.1 mu mol/l to 50 mu mol/l. The results demonstrated that at concentrations ranging from 0.1 mu mol/l to 1 mu mol/l, DHEA protected Chang liver cells against lipid peroxidation and/or artificially induced death. This protective effect disappears if the concentration is increased to 10 mu mol/l. At higher concentrations (50 mu mol/l), a pro-oxidant/cytotoxic effect of DHEA appears. DHEA exhibits two opposed effects on lipid peroxidation. Depending on its concentration, it acts either to limit or to induce oxidative stress (free radicals). The point at which the pro-oxidant activity of DHEA begins to prevail is not far in excess of the amount offering an antioxidant effect.

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 1999, Vol 141, Iss 1, pp 35-39


3. Role of oxidative stress in inflammation of pancreas

In the last decade, the role of oxidative stress has been extensively evaluated in acute pancreatitis. This review shows that there is strong evidence that this stress occurs as an early phenomenon in pancreatic tissue in the course of cerulein-induced acute pancreatitis. Oxidative stress was documented in pancreatic tissue by methods showing generation of free radicals and accumulation of products of free radical-mediated lipid peroxidation, occurring together with a depletion of enzymes and antioxidants. Cell injury and inflammation show a marked improvement following treatment with a broad spectrum of antioxidants, platelet activating factor antagonists, or donors of nitric oxide (NO). Unfortunately, in most cases, these beneficial effects are temporary and generally restricted to an early phase of the disease. Results of future well-designed clinical trials should finally evaluate the importance of oxidative stress-oriented treatment in acute pancreatitis in humans.

EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, Vol 377, Iss 1, pp 1-11


4. Gastrectomy a risk factor for pancreatic cancer

Pancreatic cancer is the fifth leading cause of cancer death mainly because of an advanced disease stage at the time of diagnosis. Patients with a remote partial gastrectomy (surgical removal of a portion of the stomach) for benign ulcer disease may constitute a high-risk group for pancreatic cancer. After a follow-up time of 20 years or more since peptic ulcer surgery, the relative risk of pancreatic cancer reported in the literature varies from 1.65 to five-fold. In the Amsterdam study of 2,633 post-gastrectomy patients, an overall increased risk of 1.8 was observed. The risk gradually increases to 3.6 after a postoperative interval of 35 years or more. Thus, patients who underwent peptic ulcer surgery are at higher risk of developing subsequent pancreatic cancer, especially after a prolonged (greater than 20 years) postoperative interval. An increased index of suspicion may contribute to early detection and potential preventive strategies.

ANNALS OF ONCOLOGY, 1999, Vol 10, Suppl. 4, pp 204-207


5. Interferon-ribavirin for chronic hepatitis C with and without cirrhosis

The aim of this study was to compare interferon (IFN)-ribavirin combination therapy with IFN therapy alone in chronic hepatitis C with particular focus on its efficacy in cirrhosis. Researchers analyzed individual patient data of all randomized controlled trials that used IFN-ribavirin, which were reported between 1991 and March 1998 from one Asian and five European university-based referral centers for liver disease. A total of 197 patients with chronic hepatitis C received IFN-alpha three times weekly and ribavirin for six months, and 147 patients received only IFN-alpha three times weekly for six months. The results showed that those without cirrhosis, treated with IFN-ribavirin had a significantly higher sustained response rate (approximately three-fold) than those treated with IFN alone. In cirrhosis, sustained response rates with IFN-ribavirin were also significantly higher. The superiority of combination therapy over IFN monotherapy was also observed for relapse; the same trend was observed for nonresponders. Tolerance for IFN-ribavirin was similar for patients with or without cirrhosis. Combination with ribavirin significantly enhances the sustained response rate of IFN therapy in major patient types (cirrhosis) with chronic hepatitis C. Thus, IFN-ribavirin combination is likely to become the antiviral therapy of choice for cirrhosis caused by hepatitis C.

GASTROENTEROLOGY, 1999, Vol 117, Iss 2, pp 408-413


6. IGF-1 blocks the aging-related loss of skeletal muscle function

During the aging process, mammals lose up to a third of their skeletal muscle mass and strength. This study attempted to reduce the loss by increasing the regenerative capacity of muscle. This involved the injection of a virus causing an increase of insulin-like growth factor I (IGF-I) in muscle fibers. Results showed that the IGF-I increase promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice, and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles. Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. According to researchers, these effects are primarily due to stimulation of muscle regeneration via the activation of satellite cells by IGF-I. This supports the hypothesis that the primary cause of aging-related impairment of muscle function is a cumulative failure to repair damage sustained during muscle utilization. These results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, Vol 95, Iss 26, pp 15603-15607


7. Osteoporosis in men - prevention and management

Osteoporosis is increasingly recognized in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology, In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Conversion of androgens to estrogens occurs. Human models exist for the effects of estrogens on the male skeleton. In men over 65, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is important to exclude pathological causes of osteoporosis here because 30% to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid (steroids) excess (mostly originating outside the body) is common. Gastrointestinal disease makes patients susceptible to bone disease as a result of intestinal malabsorption of calcium and vitamin D. Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilization, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormones may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with osteoporosis of unknown origin have low circulating insulin-like growth factor-1 (IGF-1, somatomedin-l) concentrations, and IGF-1 administration. Studies of changes in BMD with IGF-I treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available.

DRUGS & AGING, 1998, Vol 13, Iss 6, pp 421-434


8. Prevention or reversal of long-term depression by pregnenolone sulfate

The present study investigated the possible relation between long-term depression and barbiturates/benzodiazepine-induced amnesia and attempted to determine the possible effect of pregnenolone sulfate on long-term depression. Results showed long-term depression was either blocked or reversed by pregnenolone sulfate at concentrations (10 mu M). The results suggest that the response of this type of long-term depression by benzodiazepines and barbiturates can explain the main adverse effect of these drugs on amnesia and cognitive impairment. Thus, the prevention or reversal of this type of long-term depression by pregnenolone sulfate, may suggest a clinical application of this agent in the management of amnesia or dementia.

PHARMACOLOGICAL RESEARCH, 1998, Vol 38, Iss 6, pp 441-448



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