The paper contains results of the investigation of the laser-inducedfluorescence detection method for the assessment ofbrain metabolism in situ through the dura mater. Models ofanoxia and acute brain ischemia were used for the evaluation ofreliability of the method utilizing registration of reduced tissuepyridine nucleotides fluorescence, as well as for the assessmentof the viability index, based on the conversion of oxy- anddeoxyhemoglobin. Some pathobiochemical mechanisms ofalterations in the pool ofpyridine nucleotides in anoxia and ischemia were analyzed.

The aim of this work was to evaluate contribution of released membrane particles (RMP) to the development of systemic inflammatory response (SIR) after aortocoronary bypass grafting (ACBG). The number of RMP carrying surface adhesion molecules, CD62L, CD62P, CD62E, was shown to increase in the early postoperative period in parallel with the enhancement of lymphocyte plasma membrane blebbing and elevation of cytokine levels in peripheral blood. It is concluded that (1) activation of plasma membrane blebbing in peripheral blood cells underlies the appearance of RMP in circulation; (2) increased number of RMP expressing CD62L, CD62P, CD62E is a marker of intercellular communication associated with the development of SIR and suggests new mechanisms of RMP involvement in the reaction of organism to massive surgical injury.

The pathogenesis of neuronal dysfunction was evaluated from the viewpoint of cellular disturbances in NAD(+) metabolism and changes in activity of NAD(+)-utilizing enzymes (e g., ADP-ribosyl cyclase/CD38). S-100B concentration and CD38 expression on peripheral blood lymphocytes were altered in patients after surgery for coronary heart disease with extracorporeal circulation. These changes in patients during the early postoperative period correlated with variations in CD38 expression on neuronal cells from postischemic rats with cognitive dysfunction.

The present views of the pathogenesis of neuronal dysfunction in critical conditions are analyzed, by taking into account of impairments of cellular NAD+ metabolism, the activity of NAD+-converting enzymes, including ADP-ribosyl cyclase/CD38, the possibilities of developing new neuroprotective strategies. Key words: neuronal dysfunction, ADP-rybosyl cyclase/CD38, NAD+, critical condition.

Using a model of perinatal hypoxic-ischemic injury of rat brain we have found the patterns of changes in the activity of ADP ribosyl cyclase in brain cells that determine the specific features of programmed cell death and maintenance of the intracellular NAD(+) homeostasis.

На модели перинатального гипоксически-ишемического повреждения головного мозга крыс обнаружены закономерности изменения активности АДФ-рибозилциклазы клеток коры головного мозга, определяющие особенности реализации запрограммированной клеточной гибели и поддержания внутриклеточного гомеостаза НАД+.

Mechanisms of the myelotoxic action of doxorubicin associated with changes in the expression and functional activity of P2X7 receptors have been assessed. The acute and subacute exposure of bone marrow cells to doxorubicin in vivo changed the expression of P2X7, altered the intracellular and extracellular ATP concentrations, and modulated the process of programmed cell death. These changes were associated with transformed susceptibility of hemopoietic cells to the apoptogenic action of ATP. Various possible mechanisms of realization of the apoptogenic action of ATP during acute and subacute exposure to doxorubicin are discussed.

Activation of purified glutathione transferase (CE 2.5.1.18) from the rabbit liver by cAMP-dependent protein kinase (protein kinase A) and activation of glutathione transferase from the rat liver and heart by cAMP preparations have been studied. A comparison of glutathione transferase activation on different substrates and the results of the inhibitor analysis of the activation phenomenon have shown that the second (mu) family of glutathione transferase isoenzymes (subunits, 3, 4, 6) is the most probable object of regulation. The first (alpha) family (subunits 1 and 2) and isoenzyme 5-5 are not probably regulated.

The phenobarbital and ionol administration to rats and mice increases considerably the glutathione transferase, glutathione reductase and gamma-glutamyl transferase activities in the liver. The induction of these enzymes has been observed in a number of experiments in the heart and kidney but it was less pronounced. A correlation was established between the induction of glutathione transferase, glutathione reductase and gamma-glutamyl transferase, their changes in mice and rats, phenobarbital and ionol effects. The stimulatory effect of cAMP on glutathione transferase in the liver (and in a number of experiments in the heart) increased against a background of the both agents. The cAMP-dependent activation of glutathione peroxidase was retained in the heart but in some series experiments it disappeared in the liver and kidney. Mechanisms of the long-term (induction) and short-term (cAMP) elevation of the glutathione transferase and glutathione peroxidase activities functioned independently and often in concord. It is suggested that induction of glutathione metabolism enzymes may play an important role in biological effects of ionol.

Immobilization of rats for 20 minutes and for 4 hours activates glutathione peroxidase in the heart, liver, and kidneys and glutathione transferase in the heart and liver, but inhibits gamma-glutamyl transferase in the liver and kidneys. Most of these changed values become normalized one hour after cessation of 4-hour stress. Propranolol completely prevents activation of glutathione peroxidase and glutathione transferase by stress. The changes in the activity of the glutathione metabolism enzymes are evidently of a protective character in relation to lipid peroxidation.

Emotional stress during 20 min induced the stimulation of the glutathione peroxidase activity in heart, liver and kidney tissues and the activation of glutathione-S-transferase in heart and liver tissues. gamma-Glutamyl transferase activity was inhibited in liver and kidney tissues. The alterations were gradually decreased in heart greater than or equal to liver greater than kidney. Both catecholamines (in vivo) and cAMP (in vitro) produced the same effects. Close correlation between the stress and cAMP actions on the glutathione metabolizing enzymes was found. No changes of glutathione reductase activity was observed in all the tissues studied.

In vivo exo- and endogenous catecholamines have no influence on the activities of thioredoxin reductase, glutathione reductase, thiol transferase and nonselenium-dependent glutathione peroxidase. At the same time catecholamines activate via beta-adrenoceptors glutathione S-transferase and selenium-dependent glutathione peroxidase from many tissues and inhibit gamma-glutamyl transferase from kidney. In vitro cAMP has identical effects on the activities of the above enzymes. The possible significance of regulation of glutathione metabolism enzymes is discussed.

Tumors were studied in 38 patients, tissues located far away from tumor being used as control. Breast and stomach tumors revealed relatively high levels of glutathione reductase, glutathione-S-transferase (I) and, particularly, gamma-glutamyl transferase (II). The said changes were not observed in colorectal tumors. Gamma-glutamyl transferase (II) may be used as a marker for breast and stomach malignancies in man but it is not a universal and absolutely specific marker for all tumors. The activity of glutathione peroxidase (III) either did not change or decreased. The activating effect of cAMP on III and I remained generally unchanged in all tumors studied.