A comparison of the effects of different concentrations of fluoride in the drinking water in different parts of Port Elizabeth and Despatch: a first report.

Since April 1993 a part of Port Elizabeth and the surrounding areas have been receiving water from the Orange river, containing on average 0.62 ppm fluoride, while the rest is still receiving water which contains < 0.1 ppm. During August 1994 a survey was done to determine whether the increased levels of fluoride in the Orange river water influenced the caries experience of school children using it. Schools in high, middle and low socio-economic areas in both areas were randomly identified and a random sample of 6-, 12- and 15-year-old children from these schools were examined for caries experience, using the 1987 WHO methodology and criteria for the diagnosis. Results of the survey show that the caries experience in the permanent dentition of 12- and 15-year-old children respectively are 14.0 per cent and 7.8 per cent less in the areas receiving Orange river water, while in the primary dentition at age 6 it is 17.2 per cent higher. This study shows that after only 16 months the use of fluoride containing water may have benefitted the permanent dentition of 12- and 15-year-old children. However the primary dentition of 6-year-old children showed a negative effect.

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Augmentative inhibition of lymphocyte proliferation by cyclosporin A combined with the riminophenazine compounds clofazimine and B669.

We have investigated the effects of cyclosporin A (CsA, 3-50 ng/ml) in combination with the riminophenazine agents clofazimine and B669 (60-500 ng/ml) on the mitogen- and alloantigen-activated proliferative responses of human mononuclear leukocytes (MNL), as well as on the phospholipase A2 and Na+, K+- adenosine triphosphatase activities of these cells. When used in combination these agents caused inhibition of the proliferative responses of both mitogen- and alloantigen-activated MNL which was at least additive. Combinations of CsA with the riminophenazines also caused augmentative activation of PLA2 and inhibition of Na+, K+-ATPase. The inhibitory effects of these agents, both individually and in combination, on the Na+, K+-ATPase and proliferative responses of MNL were neutralized by the membrane-stabilizing, lysophospholipid complex-forming agent alpha-tocopherol (vitamin E, 20 microgram/ml). These observations suggest that combinations of CsA with riminophenazines cause interactive enhancement of the activity of PLA2 in MNL leading to lysophospholipid-mediated inactivation of Na+, K+-ATPase and consequent inhibition of the proliferative responses of these cells. In the therapeutic setting combinations of these agents may enable reduction in the dose of CsA required to achieve meaningful immunosuppression with a consequent decrease in the risk of chemotherapy-related organ toxicity.

Plasma levels of beta-carotene are inversely correlated with circulating neutrophil counts in young male cigarette smokers.

Relationships between plasma levels of beta-carotene (BC) and the numbers and oxidant-generating activities of circulating neutrophils have been investigated in a group of asymptomatic young male cigarette smokers (N = 40) and in a group of nonsmoking control subjects. Plasma BC levels were measured using HPLC, while oxidant generation was measured using a phorbol myristate acetate (PMA) activated whole blood luminol-enhanced chemiluminescence (LECL) method. Relative to nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were increased by 41% (p = 0.0001) and 47% (p = 0.004), respectively, while plasma BC levels were decreased by 24% (p = 0.01). In cigarette smokers, but not in nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were significantly and inversely correlated with plasma BC levels (r = -0.36, p = 0.02; and r = -0.33, P = 0.04 respectively). Diminished plasma levels of BC in cigarette smokers probably reflect the increased numbers and prooxidative activities of circulating neutrophils. Intake of this antioxidant nutrient may be a determinant of susceptibility to smoking-related pulmonary dysfunction mediated by oxidants derived from smoke-activated phagocytes.

Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers.

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.

Relationship between the plasma levels of beta-carotene and lung functions in cigarette smokers.

Relationships between the plasma levels of beta-carotene (BC) and spirometry were studied in 30 asymptomatic male cigarette smokers and 34 age-matched non-smoking control subjects. Plasma BC-levels, determined by high performance liquid chromatography (HPLC), were decreased on average by 18% (p 0.1251) in the smokers relative to the non-smokers and by 28% (p 0.015) following correction for blood cholesterol. The spirometric values, FEV1 and FEF25-75, determined from the flow-volume loops of each subject, were decreased by 5% (p 0.095) and 12% (p 0.0072) respectively in the smokers relative to the non-smokers. In the smokers, but not in the non-smokers, the plasma levels of BC correlated significantly and positively with the spirometric values, FEV1 (r 0.48, p 0.01) and FEF25-75 (r 0.58, p 0.0008). The results suggest that BC-status may determine susceptibility to oxidant-mediated pulmonary dysfunction in cigarette smokers.