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Alkalosis associated with elevated pH is characteristic of many clinical pathologies. Respiratory alkalosis is a result of hyperventilation, i.e., reduced partial CO2 pressure in alveolar air and blood. Yet another type of alkalosis, i.e., metabolic alkalosis, is associated with an absolute or relative increase in the levels of alkaline compounds in the organism. Despite high toxicity of the latter, mechanisms whereby these compounds exert their toxic effects remain obscure. In multicellular organisms, cell survival is controlled by a vast variety of factors, such as autocrine survival factors (AF) specifically targeted at cells that secrete them. Our previous studies (Lutsenko and Diachkova, 2003) demonstrated that AF control cell survival and energy metabolism in T-lymphocytes. In this study, combined effects of AF deficiency and alkalosis (pH 8.3) on cell survival, intracellular content of ATP and mitochondrial transmembrane potential of T-lymphocytes were studied using an IL-2-dependent cell line CTLL-2. It was found that in the absence of AF deficiency, alkalosis had no effect on survival of cultured CTLL-2 cells. The main mechanism of protection of CTLL-2 cells against cytotoxic effects of alkalosis was an enhanced anaerobic glycolysis and consequential increase in the lactate production. In contrast, alkalosis combined with AF deficiency caused a substantial decrease of cell survival, which lowered down to 53% after 6 h and to about 10 % after 20 h of culturing under these conditions. The ATP content dropped down sharply under the AF deficiency even at pH 7.3 but gradually restored to the initial level within the next 2-3 h; cell survival was at a high level under these conditions. Alkalosis combined with the AF deficiency notably worsened the functional state of the cells; ATP content in them remained at a low level over the whole period of the alkaline stress. After a 2-h incubation under alkalosis and AF deficiency, 23% of cells contained depolarized mitochondria; lactate production was notably suppressed. The data obtained suggest that the reduction of the intracellular ATP level in CTLL-2 cells under alkalosis and AF deficiency are due to inhibition of anaerobic glycolysis and mitochondrial dysfunction. Cell death developed predominantly via the necrotic rather than the apoptotic pathway.

The role of pyruvate and autocrine polypeptide factors (APF) secreted by cytotoxic IL-2-dependent CTLL-2 cells in cell defense from oxidative stress was investigated. The addition of a conditioned medium (CM) containing pyruvate and APF into CTLL-2 cell cultures significantly increased the cell survival under oxidative stress conditions induced by hydrogen peroxide (H2O2). The kinetics of (H2O2) removal from cell cultures with added CM has been registered. It has been shown that, at the beginning of oxidative stress (less than 15 min), H2O2 was mostly removed by means of its reaction with pyruvate contained in CM. Pyruvate content in CM was estimated as 138 ± 7 μM. Gel filtration on a column with Bio-Gel P-10 was used to eliminate pyruvate from CM. Gel filtration resulted in three CM fractions (A, B, and C) corresponding to three chromatogram peaks. Pyruvate was not detected in any fraction. The fraction A was the first to be eluted from the column and contained the largest molecules. In the cell survival test, fraction B had the highest protective ability for CTLL-2 cells under oxidative stress. Fraction A supported cell survival to a lesser degree and fraction C did not show any protective abilities. Fraction B added to cells under oxidative stress kept intracellular ATP content at a significantly higher level then in control cells. Moreover, it was found that APF from fraction B was able to react with H2O2 directly and inactivate it in the absence of cells. APF from fraction A did not have such properties.

The influence of exogenous ions Ca2+ on the autholytic alterations of lipids in the brain grey matter of rats was investigated during incubation in a sterile physiological solution in vitro. The level of phospholipids decreased with parallel accumulation of diacylglycerols and free fatty acids. The contents of cholesterol and its esters varied in reciprocal oscillatory mode with prevalence of the disintegration of cholesterol esters started after 4 hrs of autholysis and further. The most probable degradation reactions of phospholipids and also cholesterol esters were the hydrolytic reactions. Transacylation reactions of between phospholipids, cholesterol and its esters were also possible. The presence of exogenous Ca2+ ions in the incubation medium promoted decrease of the total lipid grey matter. This effect was noted 10 min after onset of autolysis and continued up to 24 h. The reduction of lipid concentration occurred due to the decrease of phospholipid level and to a lesser extent--to the cholesterol level.

The study included 43,197 men aged 40-54 years, of whom 23,378 were in the intervention group and 19,819 in the comparison group; the number of man-years of follow-up totalled for the whole group 177,703. The study proved the efficacy of active, predominantly secondary prevention of arterial hypertension (AH), carried out in men aged 40-54 years over a period of 3-5 years in 12 centres within the framework of the cooperative programme. In comparison with the control group, the following changes were registered in the intervention group: 1) overall mortality decreased by 17.3%; 2) stroke mortality decreased by 48.4%; 3) non-lethal stroke morbidity decreased by 51.4%; 4) morbidity of non-fatal myocardial infarction decreased in the course of four years by 23.8%. In contrast to this, mortality due to ischaemic heart disease was in the intervention group and in the control group practically the same.