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LE Magazine August 2002

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Studies from throughout the world that can help you live longer

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August 2002 Table of Contents

  1. Melatonin protects against mercury-induced mortality
  2. Gamma-tocopherol, not alpha-tocopherol, inhibits COX-2 activity
  3. Adenosine vs. colorectal cancer cells
  4. NSAIDs, telomeres and tumor growth
  5. Alternative to HRT for hot flashes
  6. Procyanidins may decrease platelet activation
  7. Life-style factors and risk of aneurysm
  8. Vitamin C supplements and BMD in postmenopausal women
  9. Antioxidant properties of carvedilol in heart failure
  10. Air pollution and emergency hospital admissions for CVD
  11. Raloxifene and estrogen reduces atherosclerosis
  12. Kidneys, homocysteine and atherosclerosis in elderly

1. Melatonin protects against mercury-induced mortality

Mice were given methyl mercury chloride (MMC) in their diet with or without melatonin for five weeks. In the group not given the melatonin, four of 10 mice began to show neurological signs (e.g., abnormal righting reflex, staggering gait, falling and posture on its side) concomitant with loss of body weight four to seven days before death. Their survival rate was 60% on the 35th day. However, the melatonin treated group, showed a 100% of survival rate on the 35th day, although one of 10 mice began to show the neurological signs on the 33rd day. The level of thiobarbituric acid reactive substance (TBARS, an indication of oxidative damage) in the brain, showed a significant decrease in the treated group compared with the control group. Thus, the 100% survival rate in the treated group may be partly due to the antioxidative effect of melatonin on induced neurotoxicity.

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2000, Vol 191, Iss 4, pp 241-246


2. Gamma-tocopherol, not alpha-tocopherol, inhibits COX-2 activity

Gamma-tocopherol is the most abundant form of vitamin E. However, research has found that much of it is excreted through urine after being metabolized by the liver. The "gamma" form has been shown to be superior to the "alpha" form for inhibiting cancer cell growth. Recent research supports the theory that gamma-tocopherol's antioxidant role goes above and beyond that of alpha-tocopherol by effectively entrapping and removing mutagenic (induces genetic mutation) oxidants. It is the gamma-form that seems to disband free radicals and force them into submission. Cyclooxygenease-2 (COX-2) is an enzyme that causes synthesis of prostaglandin El, an inflammation-causing chemical in the body, which plays a key role in inflammation, vascular heart disease and cancer. It promotes tumor growth via several mechanisms, one of which is to promote the development of blood vessels into the tumor. It is believed that blocking the action of the COX-2 enzyme is a crucial variable in cancer therapy. A study showed that gamma-tocopherol (gamma T) reduced prostaglandin synthesis in both macrophages (immune cells) and human epithelial cells with 7.5 micrometer and 4 micrometer, respectively. In addition, gamma T's major metabolite (gamma-CEHC, produced by metabolism) (30 micrometer), also showed an inhibitory effect. In contrast, the alpha-tocopherol form (50 micrometer) only slightly reduced prostaglandin formation in macrophages, and had no effect in epithelial cells. The inhibitory effects shown by gamma-tocopherol and its metabolite came from their inhibition of COX-2 activity, and appeared to be independent of antioxidant activity. The metabolite also inhibited prostaglandin synthesis to COX-2-preinduced cells after arachidonic acid was added, when exposed for only one hour. However, gamma-tocopherol required eight to 24 hours to cause the inhibition. The results indicate that gamma-tocopherol and its major metabolite both possess anti-inflammatory activity, important in human disease prevention.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, Vol 97, Iss 21, pp 11494-11499


3. Adenosine vs. colorectal cancer cells

8-Cl-adenosine represents a new nontoxic chemotherapeutic agent shown to inhibit growth of cancer cells in the colon and rectum. Adenosine inhibited growth by slowing cell growth at the G phase, which was associated with an eight-fold increase in p53 protein levels and a decrease in the phosphorylation status. (P53 is a gene that encodes a protein that regulates cell growth and can cause potentially cancerous cells to destroy themselves.) The cancer cells, however, did not undergo apoptosis (programmed cell death). Adenosine also induced some degree of differentiation (increasing structural heterogeneity of the cells). Both villin protein levels as well as alkaline phosphatase activity rose (2- and 3.5-fold, respectively) in response to treatment with adenosine. The results suggest that in colon and rectal cancer cells, adenosine not only inhibits growth, but also induces differentiation.

DIGESTIVE DISEASES AND SCIENCES, 2001, Vol 46, Iss 4, pp 757-764


4. NSAIDs, telomeres and tumor growth

Indomethacin is part of a group of NSAIDs (ibuprofen, sulindac sulfone, etc., anti-inflammatory agents that work by inhibiting the production of prostaglandins). It is well recognized that such inhibitors of the cyclooxygenase enzyme (produces prostaglandins from arachidonic acid) weaken tumor growth. A study showed that indomethacin weakens tumor growth in mice by inducing apoptosis/necrosis (cell death) and inhibiting the lengthening of telomeres (ends of chromosomes). Human colon cancer cells showed both slowed growth and slowed telomerase activity, even though there was a low level of prostaglandins present. Sulindac sulfone decreased growth and telomerase activity in colon cancer cells, without any effects on prostaglandin production. Ibuprofen reduced prostaglandin production but had no effect on growth or telomerase activity. The results demonstrate that cyclooxygenase inhibitors can slow growth in human tumor cells by inhibiting the activity of the enzyme, telomerase.

INTERNATIONAL JOURNAL OF ONCOLOGY, 2001, Vol 18, Iss 5, pp 929-937


5. Alternative to HRT for hot flashes

Hot flashes are a major problem for many postmenopausal women. Women with unrelieved hot flashes suffer negative psychosocial consequences. The relief of hot flashes may improve mood, affect daily activities such as sleep, concentration, and sexuality, and overall quality of life. Findings concerning concentration are consistent with research showing decreased cerebral blood flow during hot flashes in healthy women. In women without breast cancer, hormone replacement therapy (HRT) involving estrogen is the typical treatment prescribed to relieve the problem. However, hot flashes are a significant problem in women following treatment for breast cancer presumably because of the effects of chemotherapy and tamoxifen and the inability to take HRT. In comparison to naturally menopausal healthy women of the same age, the chemotherapy used to treat the cancer causes the woman to go into early menopause and experience hot flashes that were significantly more frequent, severe, bothersome, and of greater duration. Because of the concern that estrogen may lead to the growth of breast cancer cells, these women are often denied estrogen for hot flashes. Recent findings suggest that currently available nonhormonal hot flash treatments may be ineffective, underutilized, or not acceptable to breast cancer survivors. Although these women have tried nonhormonal prescription medications (e.g., clonidine) in the past compared to healthy women, few breast cancer survivors were using these medications at the time of the survey despite frequent, severe, and bothersome hot flashes. This implies that although women may have tried these medications in the past, they may have discontinued the medications for reasons such as failure to obtain relief, cost, or side effects. Although many prescription medications are effective in reducing hot flashes, they can be associated with significant side effects. However, in a Mayo Clinic study, long-term use of the new antidepressant drug, venlafaxine, provided women treated for breast cancer with safe and effective relief from hot flashes. This antidepressant can be an alternative to estrogen for women who want a nonhormonal treatment for their hot flashes. The study showed that 102 postmenopausal women receiving extended-release venlafaxine (75 mg/day) over eight weeks maintained approximately a 60% reduction in their hot flashes and its severity. Venlafaxine works to control various neurotransmitters in the brain. Some of those neurotransmitters are thought to trigger hot flashes. It was found that venlafaxine is a safe, effective, and well tolerated nonhormonal treatment for postmenopausal cancer patients and over a longer period. The side effects of venlafaxine include mild appetite loss, dry mouth and, in some women, nausea. Only a minority of women in this study experienced nausea from venlafaxine, and most rated their nausea as relatively mild and transitory. In about 10% of the women, nausea was a more prominent problem. Thus, the study provides the most comprehensive assessment available of the symptom experience of hot flashes in breast cancer survivors. In addition, this study is the only one to include a comparison group of healthy women.

Oncology Nursing Forum, April 2002, Volume 29, Number 3


6. Procyanidins may decrease platelet activation

Polyphenolic phytochemicals inhibit the vascular and inflammatory processes that contribute to disease. (Phytochemicals are plant chemicals such as carotenoids, which may impart health benefits such as better protection from cancer.) The positive effects of phytochemicals are thought to result from polyphenol-mediated alterations in the synthesis of eicosanoids (such as leukotrienes, prostacyclin, prostaglandins, and thromboxanes). A study determined the ability of cocoa procyanidins to alter the synthesis of eicosanoids in human and cultured human aortic endothelial cells. After an overnight fast, 10 healthy adults consumed 37 g low-procyanidin (0.09 mg/g) and high-procyanidin (4.0 mg/g) chocolate. Relative to the effects of the low-procyanidin chocolate, high-procyanidin chocolate induced increases in blood prostacyclin (32%) and decreases in blood leukotrienes (29%). After the in vitro (culture) procyanidin treatments, aortic endothelial cells synthesized twice as much prostaglandin and 16% less leukotriene as did the control group of cells. The in vitro and in vivo (body) effects of procyanidins on blood leukotriene-prostacyclin ratios in culture were also comparable: decreases of 58% and 52%, respectively. The data from this short-term investigation support the concept that certain flavonoids derived from food, can favorably alter eicosanoid synthesis in humans. This provides a plausible hypothesis for a mechanism by which flavonoids can decrease platelet activation in humans.

AMERICAN JOURNAL OF CLINICAL NUTRITION, 2001, Vol 73, Iss 1, pp 36-40


7. Life-style factors and risk of aneurysm

A study looked at the association of life-style factors with risk for aneurysm in the aortic artery (main artery that distributes blood to the whole body except the lungs) in the abdominal area among 29,133 male smokers (50 to 69 years of age). (An aneurysm is a sac formed by the dilation of the wall of an artery, vein or the heart.) During a follow-up of six years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured abdominal aortic aneurysm plus aneurysmectomy (excision of an aneurysm). The risk for abdominal aortic aneurysm was positively associated with age for smoking years, systolic blood pressure, diastolic blood pressure, and total cholesterol. High-density lipoprotein cholesterol (HDLC) was strongly oppositely associated with risk for aortic aneurysm. High-energy intake was associated with lower risk for aortic aneurysm, but there were no associations with nutrients. Thus, the classical risk factors for atherosclerotic diseases are important in development of large abdominal aortic aneurysms.

EPIDEMIOLOGY, 2001, Vol 12, Iss 1, pp 94-100


8. Vitamin C supplements and BMD in postmenopausal women

Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity (a marker for bone cell formation). A study evaluated the independent relation of daily vitamin C supplement use with bone mineral density (BMD) in 994 postmenopausal women, 277 of whom were regular vitamin C supplement users. Daily vitamin C supplement intake ranged from 100 to 5000 mg. The average daily dose was 745 mg, and the average duration of use was 12.4 years. (Eighty-five percent had taken vitamin C supplements for more than three years.) The results showed that vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip. In a fully adjusted model, significant differences remained at the femoral neck and marginal significance was observed at the total hip. Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck, total hip, ultradistal radius, and lumbar spine. Thus, vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.

JOURNAL OF BONE AND MINERAL RESEARCH, 2001, Vol 16, Iss 1, pp 135-140


9. Antioxidant properties of carvedilol in heart failure

Carvedilol, the first beta-blocker labeled in the United States for the treatment of heart failure, has been shown to improve left ventricular function and may reduce mortality. Beta-blockers work by affecting the response to some nerve impulses in certain parts of the body. As a result, they decrease the heart's need for blood and oxygen by reducing its workload. They also help the heart to beat more regularly. Carvedilol is used to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Carvedilol is also used to prevent further worsening of congestive heart failure, and for other conditions. Animal and human studies have shown that carvedilol has significant antioxidant properties compared with other beta-blockers. A 12-week study determined if these antioxidant effects were detectable in 24 individuals with heart failure. The results showed that the need for, and thus, the levels of endogenous antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GSH) in red blood cells were significantly reduced in those treated with carvedilol. Thus, in addition to improving symptoms in heart failure, carvedilol also possesses significant antioxidant properties. Whether this additional action influences long-term outcome is unknown at the present time.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2001, Vol 37, Iss 1, pp 48-54


10. Air pollution and emergency hospital admissions for CVD

A study looked at the short-term association between air pollution levels and emergency hospital admissions for cardiovascular diseases in Valencia, Spain (between 1994 to 1996). The pollutants were black smoke, sulphur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O-3). Estimations were calculated according to the hottest (May to October) and the coldest (November to April) periods. It was found that a rise in SO2 levels of 10 microgram/m3 was associated with an increment of 3% in the expected number of cardiovascular admissions. A significant association for black smoke, SO2 (24 hours), SO2 (one hour), and CO (one hour) was found in the hottest semester. NO2 was independently associated with cerebrovascular admissions. There were no significant associations between air pollution and admissions for digestive diseases. Thus, current levels of air pollution and emergency cardiovascular admissions are significantly related.

JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, 2001, Vol 55, Iss 1, pp 57-65


11. Raloxifene and estrogen reduces atherosclerosis

A study investigated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on atherosclerosis of the aorta in 80 cholesterol-fed rabbits with pre-induced atherosclerosis, and with ovaries removed. They were fed an atherogenic diet (accelerates the formation of lipid deposits in arteries) containing 240 mg cholesterol/day for 15 weeks. Thereafter, they were given oral estradiol (estrogen) 4 mg/day, raloxifene (210 mg/day) or placebo. In the treatment period of 39 weeks, the dietary cholesterol content was reduced to 80 mg cholesterol/day. There was a significant increase in uterine weight induced by estradiol treatment (10.3g), but raloxifene intervention caused a decreased uterus weight (1.21g) when compared to placebo (2.48 g). Blood lipids increased in all groups to levels seen in very high-risk humans. After 58 weeks, the cholesterol content in the aorta was reduced 38% in the estradiol group, and 29% in the raloxifene group. Thus, both estradiol and raloxifene significantly reduced the progression of atherosclerosis.

ATHEROSCLEROSIS, 2001, Vol 154, Iss 1, pp 97-102


12. Kidneys, homocysteine and atherosclerosis in elderly

Studies suggest that people with minor impairment of the kidneys are at higher risk of stroke and coronary heart disease. One explanation may lie with observations that deterioration in the kidneys is accompanied by a rise in blood homocysteine concentrations. There is evidence that moderately elevated homocysteine may cause atherosclerosis. A study investigated the relations between the kidneys, blood homocysteine and atherosclerosis of the carotid arteries in 128 men and women aged 69 to 74 years. The severity of atherosclerosis of the carotid artery was greatest in men and women with the poorest kidney function. Small decrements in kidney function were associated with increased risk. Blood homocysteine concentrations were significantly higher in people with poorer kidney function.

ATHEROSCLEROSIS, 2001, Vol 154, Iss 1, pp 141-146



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