LE Magazine, October 2002 - Medical Updates

Studies from throughout the world that can help you live longer

1. Periodontal disease and elevated cholesterol

Periodontitis is associated with increased prevalence of cardiovascular morbidity and mortality. It is thought that the presence of periodontal pockets, which can harbor pathogenic microorganisms and cause an immune response, could elicit a systemic effect. Therefore, a study examined if periodontal pockets may be associated with elevated blood lipid levels, a known risk factor for atherosclerotic disease. The periodontal health of 10,590 Israeli military service men and women was assessed using the Community Periodontal Index of Treatment Needs (CPITN). The relationship of blood lipids and periodontal disease and CPITN index was tested, controlling for factors that are related to elevated cholesterol levels, including high body mass index (BMI), age, diastolic blood pressure and smoking. The results showed that the presence of periodontal pockets was positively associated with higher cholesterol and LDL cholesterol blood levels in men. No significant association was found in women. The findings support the reports linking increased prevalence of cardiovascular mortality among those with periodontal disease.

JOURNAL OF PERIODONTOLOGY, 2002, Vol 73, Iss 5, pp 494-500

2. Cognitive performance and death in the oldest old

A study examined the cognition-survival relationship among 466 nondemented individuals (age 80 to 98). There were three examinations at two-year intervals. During the six years of follow-up, 206 individuals died. Tests of cognitive functioning encompassed crystallized knowledge, inductive reasoning, visuospatial ability, short-term memory, episodic memory and speed. There were significant associations found between cognitive performance at the start of the study, and subsequent survival. After adjusting for stroke and indicators of cardiovascular disease, only three out of six cognitive areas remained significant predictors of survival. There was limited evidence for an accelerated decline before death. The main results suggest that the level of cognitive performance in late life is associated with proximity to death, and that this relationship is longstanding, and partially influenced by compromised functioning of the heart and brain.

JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES, 2002, Vol 57, Iss 3, pp P268-P276

3. Risk and protection of physical functioning in older adults

The inevitability of declining health in older age may be exaggerated, including declines for those with chronic health conditions. Data from the MacArthur Study of Successful Aging were used to examine the impact of sociodemographic, health status, health behavior and social and psychological factors on patterns of change in physical functioning over a 2.5-year period for groups of older adults with prevalent hypertension, diabetes, cardiovascular disease (CVD), cancer, or fractures, and those with no chronic conditions at the start. The results revealed a consistently protective effect of regular physical activity with respect to patterns of change in physical functioning in nearly all groups. For those with CVD, greater emotional support was associated with higher starting functioning levels and less declines in functioning. Greater social conflict was associated with greater decline among those with high blood pressure or diabetes. For those with a history of cancer, helpful self-efficacy beliefs were protective, and lower psychological symptoms was associated with less risk of decline among those with a history of fracture. Social and psychological factors were unrelated to changes in functioning for those with no chronic conditions. The findings suggest that risks for decline in physical functioning are influenced by a number of potentially modifiable factors. These factors could be targets for intervention and treatment to promote better functioning, even among older adults with various types of chronic conditions.

JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES, 2002, Vol 57, Iss 3, pp S135-S144

4. Cardio respiratory fitness and cancer mortality in men

A study investigated the association between cardio respiratory fitness and smoking-related, nonsmoking-related, and total cancer mortality in 25,892 men (age 30 to 87), who had a preventive medical evaluation, including a maximal exercise test and self-reported health habits. There were 335 cancer deaths (133 from smoking-related cancer, 202 from nonsmoking-related cancer) during an average of a 10-year follow-up. The results showed an opposite association between cardio respiratory fitness levels and smoking-related, nonsmoking-related and total cancer mortality. Moderate and high levels of cardio respiratory fitness were associated with lower risk of smoking-related and nonsmoking-related cancer mortality when compared with low fitness in men. Smoking-related mortality rates were progressively lower across low, moderate, and high fitness groups in former and current smokers. They concluded that cardio respiratory fitness may provide protection against cancer mortality in men.

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2002, Vol 34, Iss 5, pp 735-739

5. Physical activity and stress in women

A study examined the relationship between physical activity and levels of blood lipid peroxides, superoxide dismutase (SOD, endogenous antioxidant) in erythrocytes (red blood cells), and glutathione peroxidase (GSH-Px, endogenous antioxidant) in whole blood activities of 488 Spanish women. The study defined two categories of leisure time physical activity, according to their intensity: 1) Low (less than or equal to 6 METs (Metabolic Energy Equivalent) and 2) High (greater than 6 METs). (A MET is the most precise measurement of metabolic load, and therefore cardiovascular load. Resting energy expenditure is considered 1 MET. Walking requires 2 to 4.5 METs, and running or bicycling requires 6 METs or more). The amount of leisure time physical activity was associated with high activity levels of SOD and GSH-Px. Similar results were obtained when physical activity in household activities was added to total leisure physical activity. Physical activity of low intensity was associated with high SOD levels, and physical activity of high intensity with high GSH-Px activity levels. Thus, the amount and intensity of leisure physical activity were directly related to both antioxidant enzyme activity levels. The results suggest that leisure physical activity intensity has a modulatory effect on antioxidative balance in women.

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2002, Vol 34, Iss 5, pp 814-819

6. DNA damage: a predictor of atherosclerosis

Atherosclerosis and the development of cancer may share some common mechanisms of exogenous compounds that cause disease by damaging DNA (genotoxic), such as polycyclic aromatic hydrocarbons (PAHs). A study tested whether DNA-adducts in muscle cells of the largest artery, the aorta, are associated with the stage of atherosclerosis. The data was taken at autopsy from 133 sudden and accidental male deaths, (age 30 to 60). The main group (66) had severe atherosclerotic damage. The control group had slight and moderate total atherosclerotic body damage. The results showed significantly higher DNA-adduct levels in the main group as compared with the controls (2.11 adducts vs. 1.49). Those in the main group were significantly older and had elevated heart weight and blood cholesterol levels, and a higher frequency of being overweight as compared with the control group. There were no significant differences in DNA-adduct levels between smokers and non-smokers within either group. Thus, DNA-adducts, which are most likely related to environmental exposure to genotoxic chemicals, remain a statistically significant predictor of the stage of atherosclerosis. Since DNA-adduct levels predict the progression of atherosclerosis, independently of smoking, this indicates that the formation of atherosclerotic plaques may also be caused by environmental exposures other than tobacco smoke.

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2002, Vol 501, Iss 1-2, pp 115-128

7. Effect of aloe against liver cell toxicity

Aloe is a familiar ingredient in a wide range of health care and cosmetic products and has been reported to possess various physiological effects, antioxidative, anticarcinogenic, anti-inflammatory and laxative. Aloe has been reported to have an effect on liver function. A study evaluated the cytoprotective effect of aloe extract against artificially induced liver toxicity, in cultured rat cells. After exposure to the liver toxicity inducer, there was a decrease in cell viability. Cellular glutathione (GSH) and protein-SH levels were also significantly decreased in a time-dependent manner. However, the addition of aloe extract resulted in a dose-dependent improvement of these effects. This cytoprotective effect of aloe could be attributed to its inhibition of GSH depletion. The effect of the aloe extracts were also dose-dependent. The results suggest that toxicity in liver cells may be inhibited by aloe extract.

PHARMACOLOGY & TOXICOLOGY, 2002, Vol 90, Iss 5, pp 278-284

8. Cell phones linked with cell damage

A two-year study in Finland has found that mobile phone radiation can cause changes in human cells that might affect the brain. The study found that exposure to radiation from mobile phones can cause increased activity in hundreds of proteins in human cells grown in a laboratory. It was not yet known whether the biological response that was detected could have any physiological effects on the human brain or body. The study focused on changes in cells that line blood vessels, and on whether such changes could weaken the functioning of the blood-brain barrier which prevents potentially harmful substances from entering the brain from the blood stream. Changes in the overall pattern of protein phosphorylation suggest that mobile phone radiation activates a variety of cellular signal transduction pathways, among them the hsp27 stress response pathway. They found that the hsp27 protein was linked to the functioning of the blood-brain barrier and showed increased activity due to irradiation. (Irradiation did not alter the temperature of cell cultures, which remained throughout the irradiation period at 37±0.3°C.) There is a possibility that such activity could make the shield more permeable. Increased protein activity might cause cells to shrink. Then tiny gaps could appear between those cells through which some molecules could pass. Based on the known functions of hsp27, researchers hypothesized that mobile phone radiation-induced activation of hsp27 may facilitate the development of brain cancer. These events, when occurring repeatedly over a long period, might become a health hazard because of the possible accumulation of brain tissue damage. Their hypothesis suggests that other brain damaging factors may co-participate in mobile phone radiation-induced effects. A Swedish group also suggested a possible link with Alzheimer's disease. The study raises new questions about whether mobile phone radiation can weaken the brain's protective shield against harmful substances. More research is needed to determine the seriousness of the cell changes and their impact on the brain or the body.

DIFFERENTIATION 2002 May;70 (2-3):120-9

9. Pyruvate blocks zinc-induced neurotoxicity

Zinc is an essential trace element and present at high concentrations in the central nervous system. Recent studies have revealed that excess amount of extracellular zinc is neurotoxic, and that the disruption of zinc homeostasis may be related to various neurodegenerative diseases. In a recent study, zinc (25-100 muM) caused significant death of immortalized (reproduce indefinitely) neurons in the hypothalamus of the brain in a dose and time dependent manner. (The hypothalamus regulates many metabolic processes, including body temperature and certain emotional states.) The results showed that pre-administration of sodium pyruvate (1-2 mM), however, inhibited the zinc-induced neurotoxicity. Carnosine has also been shown to protect against this type of zinc toxicity to the brain.

CELLULAR AND MOLECULAR NEUROBIOLOGY 2002;22(1):87-93.

10. CRP: an independent predictor of diabetes

Accumulating evidence implicates inflammation in the development of type 2 diabetes. Elevated CRP is a known indicator of inflammation. A study assessed the ability of C-reactive protein (CRP, a blood protein) to predict the development of diabetes in 5,245 middle-aged men. During the study, 127 transitioned from normal glucose control to overt diabetes. The results showed CRP to be an important predictor of diabetes development, independent of other predictors, including starting level, bone BMI, fasting triglycerides and glucose concentrations. In addition, there was an increase in risk across CRP measurement groups even after one year. The highest group (CRP greater than 4.18 mg/l) was associated with a greater than three-fold risk (3.07) of developing diabetes at five years. Thus, CRP predicts the development of type 2 diabetes in middle-aged men, independently of established risk factors. These results have potential in helping to better predict those destined to develop type 2 diabetes, as well as adding to the notion that low-grade inflammation is important in the development of type 2 diabetes.

DIABETES 2002;51(5):1596-1600

11. Vitamin C prevents DNA mutations

The precise role of vitamin C in the prevention of DNA mutations is controversial. Although vitamin C has strong antioxidant properties, it also has pro-oxidant effects in the presence of free transition metals. Vitamin C was recently reported to induce the decomposition of lipid hydrogen peroxides (H2O2), independent of interaction with metals, suggesting that it may cause DNA damage. To directly address the role of vitamin C in maintaining the integrity of genes, a study developed a genetic system for quantifying mutations induced in human cells under free radical stress. Cells were loaded with vitamin C by exposing them to dehydroascorbic acid (the reversibly oxidized form of vitamin C), thereby avoiding transition metal-related pro-oxidant effects of vitamin C. Vitamin C loading resulted in substantially decreased mutations induced by H2O2. Without vitamin C, the depletion of glutathione led to cell toxicity and an increase in H2O2-induced mutation frequency. However, in cells preloaded with vitamin C, glutathione depletion was substantially decreased, as was a decrease in total 8-oxo-guanine measured in the DNA of cells. This directly supports the concept that high intracellular concentrations of vitamin C can prevent oxidation-induced mutations in human cells.

JOURNAL OF BIOLOGICAL CHEMISTRY 2002;277(19):16895-9

12. Neuroprotective effects of carnosine

Carnosine, a molecule composed of amino acids, has demonstrated in numerous animal studies strong and specific antioxidant properties, protection against radiation damage, improvement in the function of the heart, and promotion of wound healing. It is found in high concentration in skeletal muscle, heart muscle and in the brain, and has been suggested to provide neuroprotection. A study exposed cell cultures to oxygen-glucose-deprivation (OGD) followed by reoxygenation (after 18 hours) under regular atmospheric oxygen level. The toxicity induced was partially caused by generation of free radicals. It was found that 5 mM carnosine provided maximal neuroprotection of about 50% against OGD trauma. This neuroprotective effect was similar to that of a known antioxidant drug and free radial scavenger, tempol. This indicates that carnosine may act as an antioxidant-neuroprotective agent in the brain.

JOURNAL OF NEUROSCIENCE RESEARCH 2002;68(4):463

13. Supplemental glutathione and diabetic nephropathy

Recently, much attention has focused on the role of free radical stress in the various forms of tissue damage in those with diabetes. A study examined the involvement of free radicals in the progression of kidney dysfunction and neuropathy in diabetes, and evaluated the potential usefulness of glutathione (GSH) in diabetes. Diabetic rats were treated with 1 g/100 g GSH as a dietary supplement. GSH significantly suppressed the diabetes-induced increase in urinary 8-hydroxy-2'-deoxyguanosine (indicator of free radical stress). It also prevented the diabetes-induced increases in albumin and creatinine in urine. The dietary GSH also normalized the rats' tail flick reaction time to thermal stimuli. Thus, GSH administration can beneficially affect diabetes in rats, while preserving in vivo kidney and neural function. This suggests a potential usefulness of supplemental glutathione to reduce diabetic complications in humans.

JOURNAL OF NUTRITION 2002;132(5):897-900.

14. Relationship between walnuts and CHD

Four independent experts evaluated the scientific evidence for a potential beneficial health relationship between the intake of walnuts (and other tree nuts and legumes) and the reduction and prevention of coronary heart disease (CHD). Compared to most other nuts, which contain monounsaturated fatty acids, walnuts are unique because they are rich in n-6 (linoleic acid) and n-3 (linolenic acid) polyunsaturated fatty acids. Walnuts contain multiple health-beneficial components, such as having a low lysine: arginine ratio and high levels of arginine, folic acid, fiber, tannins and polyphenols. Though walnuts are energy rich, clinical dietary intervention studies show that walnut consumption does not cause a net gain in body weight when eaten as a replacement food. Five controlled, peer-reviewed, human clinical walnut intervention trials, involving approximately 200 individuals representative of the 51% of the adult population in the United States at risk of CHD were reviewed. The trials consistently demonstrated that walnuts, being part of a heart-healthy diet, lower blood cholesterol concentrations. None of these studies, however, were of extended duration that would be essential for evaluation of the sustainability of the outcomes. Nevertheless, the results were supported by several large studies in humans, all demonstrating a dose response-related opposite association of the relative risk of coronary heart disease with the frequent daily consumption of small amounts of nuts, including walnuts.

JOURNAL OF NUTRITION 2002;132(5):1062S-1101S.

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