Vasoplegia in septic shock (review).

Vasoplegia is considered as a key factor responsible for the death of patients with septic shock, due to persistent and irreversible hypotension. The latter associated with vascular hyporeactivity to vasoconstrictors is a significant independent prognostic factor of mortality in severe sepsis. Loss of control of the vascular tone occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators. The aim of this review is to discuss in detail the recent suggested alternative mechanisms of vasoplegia in severe sepsis: Overproduction of nitric oxide (NO) by activation of inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; significantly elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) during septic shock and their involvement in vascular dysfunction. The review also discusses some therapeutic approaches based on pathogenetic mechanisms of severe sepsis and their efficacy in treatment of patients with septic shock. The loss of vascular tone control occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators in the pathogenesis of septic shock. Overproduction of nitric oxide (NO) by the inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) and their involvement in vascular dysfunction - all these factors combined together lead to steady refractory shock with the lethal outcome in patients.

[Influence of antioxidant phenovin and immunomodulator Una de gato on free radical oxidation at parodontitis].

The aim of the research: detection of changes in free radical oxidation at treatment of parodontitis with combination of preparations - antioxidant Phenovin and immunomodulator Una de gato. Reactive compounds of nitrogen, oxygen and lipids in saliva, blood and gingival tissue of patients suffering from moderate form of parodontitis has been studied by means of the electronic paramagnetic resonance (EPR) method and spin-traps (DETC, DMPO, PBN - Sigma). In patients with parodontitis content of free NO in saliva and blood increases, while in gingival tissue - decreases. In saliva, blood and gingival tissue of patients intense EPR signals of superoxidradicals (O2(-)) and lipoperoxides (LOO(-)) has been revealed indicating intensification of processes of lipid peroxidation in oral cavity, as well as in whole organism of patient. Exaggerated synthesis of NO in saliva and blood of patient is determined by high- expression of inducible NO-synthase triggered by oxidative stress, and increased activity of neuronal NO-synthase in saliva as a result of high concentrations of metacholine and P substance intensely secreted at parodontitis. Decreased content of free NO in gingival tissue of patients with parodontitis compared to control is the result of biological degradation of nitric oxide (conversion of NO into peroxinitrite on the background of intense oxidative stress in oral cavity) and nitrosylation of mitochondrial electron transport proteins of gingival tissue (characteristic for parodontitis) with further decrease in content of free oxide, suppression of intensity of mitochondrial respiration, energogenesis, development of ischemia in oral tissue leading to further initiation of destructive processes and progression of parodontitis. Treatment with combination of preparations - Phenovin and Una de gato decreased intensity of oxidative stress in organism of patients and reduced destructive processes of tissues in oral cavity. Relative normalization of oxidative metabolism in organism, restoration of NO-synthase system activity (intensity of EPR signals of spin-trapped nitric oxide and lipoperoxide radicals approach to control data) has been observed. It is concluded that combined treatment of patients suffering from parodontitis using preparations of antioxidant and immunoregulatory activity results in long-term remission of disease.

[Cell death in Jurkat cells induced by oxygen/nitrogen stress].

The maintenance of balance between lymphocyte proliferation and lymphocyte death is extremely important for normal functioning of the immune system. Considering essential role of nitrogen and oxygen radicals in functioning of immune competent cells, we studied the mechanisms of cell death induced by nitrogen/oxygen stress on the model of Jurkat cell line. We have observed that hyperproduction of reactive oxygen in Jurkat cells incubated with hydrogen peroxide contributes to the activation of membrane peroxidation, to a decrease in the intensity of apoptosis and its replacement by more severe mechanism of cell death - necrosis, which is obviously conditioned by a dramatic decrease in the intensity of energogenesis in mitochondria. In cells incubated with sodium nitroprusside moderate NO-induced inhibition of electron transport in oxidative chain and mitochondrial energogenesis and intensification of oxidative stress in Jurkat cells is accompanied with the activation of the cell death mechanisms- both apoptosis and necrosis.

[Pharmacological activity of dihydroflavonol glycoside isolated from the plant Eupatorium micranthum Less].

The aim of the work was the investigation of pharmacological activity of unique dihydroflavonol glycoside, micranthoside, extracted from the leaves Eupatorium micranthum Less. introduced into Georgia. Mature human T-cell leukemia cell lines (Jurkat) were analyzed in the study under the modeled oxidative stress. For modelling of oxidative stress 30% hydrogen peroxide (H(2)O(2)) (Sigma) (100 microM) was added to Jurkat cell incubation suspension with subsequent incubation for 24, 48 h. Under the effect of H(2)O(2) there was significant elevation of superoxide and peroxyl radical levels, as well as free NO levels, and reduced antioxidant enzyme SOD activity. It was shown that dihydroflavonol glycoside, micranthoside, extragated from Eupatorium micranthum Less., has marked antioxidant properties, it inhibits hyperproduction of reactive oxygen species, and protects cells against oxidative damage, stimulates cell proliferation and inhibits necrosis in cell line.