Cytotoxicity to renal tubular epithelial cells (RTE) is dependent on the relative response of cell survival and cell death signals triggered by the injury. Forkhead transcription factors, Bcl-2 family member Bad, and mitogen-activated protein kinases are regulated by phosphorylation that plays crucial roles in determining cell fate. We examined the role of phosphorylation of these proteins in regulation of H2O2-induced caspase activation in RTE. The phosphorylation of FKHR, FKHRL, and Bcl-2 family member Bad was markedly increased in response to oxidant injury, and this increase was associated with elevated levels of basal phosphorylation of Akt/protein kinase B. Phosphoinositol (PI) 3-kinase inhibitors abolished this phosphorylation and also decreased expression of antiapoptotic proteins Bcl-2 and BclxL. Inhibition of phosphorylation of forkhead proteins resulted in a marked increase in the proapoptotic protein Bim. These downstream effects of PI 3-kinase inhibition promoted the oxidant-induced activation of caspase-3 and -9, but not caspase-8 and -1. The impact of enhanced activation of caspases by PI 3-kinase inhibition was reflected on accelerated oxidant-induced cell death. Oxidant stress also induced marked phosphorylation of ERK1/2, P38, and JNK kinases. Inhibition of ERK1/2 phosphorylation but not P38 and JNK kinase increased caspase-3 and -9 activation; however, this activation was far less than induced by inhibition of Akt phosphorylation. Thus the Akt-mediated phosphorylation pathway, ERK signaling, and the antiapoptotic Bcl-2 proteins distinctly regulate caspase activation during oxidant injury to RTE. These studies suggest that enhancing renalspecific survival signals may lead to preservation of renal function during oxidant injury.

Background. Earlier have been shown that the immune responses to course of drinking of Naftussya bioactive water from Truskavet's spa are ambiguous and individual. However, at Truskavets' spa water monotherapy is a rare exception for specific contingents, whereas the vast majority of patients use a balneotherapy complex: drinking of Naftussya, application of ozokerite and mineral baths. The immune responses to balneotherapeutic complex are also ambiguous which is a separate manifestation of the multivariate effects of balneological agents as well stressors on the body. Therefore, the purpose of this study is to analyze variants of immune responses to balneotherapeutic complex of Truskavets' spa. Material and methods. The object of observation were 34 men and 10 women aged 24-70 years old, who came to the Truskavets' spa for the treatment of chronic pyelonephritis combined with cholecystitis in remission. The survey was conducted twice, before and after balneotherapy (drinking Naftussya bioactive water three times a day, ozokerite applications, mineral baths every other day for 7-10 days). Immune status evaluated on a set of I and II levels recommended by the WHO. In portion of capillary blood we counted up Leukocytogram and calculated two variants of Adaptation Index as well as two variants of Strain Index by IL Popovych. We calculated also the Entropy of Immunocytogram and Leukocytogram. The condition of Microbiota is evaluated on the results of sowing of feces and urine. Results. Four variants of the immune responses to balneotherapeutic complex have been identified. In 40,9% of patients, initially normal immune status did not change significantly. In 31,8%, the lower boundary level of immunity is completely normalized. In 22,7% moderate immunosuppression is reduced, but not up to normal. However, in 4,5% of people, initially normal level of immunity are transformed into moderate immunosuppression. Discriminant analysis was conducted to identify exactly the parameters of the immunity and microbiota, in which the four immune response clusters differ significantly from each other. 24 parameters were characteristic, 12 of them related to the immune parameters of the blood, one of the saliva, 5 of the feces microbiota and 3 related to urinary syndrome as well as 4 parameters are information. The other 25 parameters were outside the discriminatory model. Conclusion.

Background. Earlier in clinical observations four variants of the immune responses to adaptogenic balneotherapy at the Truskavets' spa have been identified. In 40,9% of patients, initially normal immune status did not change significantly; in 31,8%, the lower boundary level of immunity is completely normalized; in 22,7% moderate immunosuppression is reduced, but not up to normal; however, in 4,5% of people, initially normal level of immunity are transformed into moderate immunosuppression. All four variants of immune responses are virtually unmistakably predicted by a set of 20 predictors. The purpose of this study is to analyze vegetative, endocrine and metabolic accompaniments of individual immune responses to balneofactors of Truskavets' spa. Material and methods. The object of observation were 34 men and 10 women aged 24-70 years old, who came to the Truskavets' spa for the treatment of chronic pyelonephritis combined with cholecystitis in remission. The survey was conducted twice, before and after balneotherapy (drinking bioactive water Naftussya three times a day, ozokerite applications, mineral baths every other day for 7-10 days). Immune status evaluated on a set of I and II levels recommended by the WHO. The state of the autonomic nervous system is estimated by HRV ("CardioLab+HRV"). To assess endocrine status we determined plasma levels of principal adaptation Hormones: Cortisol, Testosterone and Triiodothyronine (ELISA). We determined also the plasma and daily urine levels of the electrolytes: calcium, phosphates, sodium, potassium, magnesium and chloride as well as nitrous metabolites creatinine, urea and uric acid. According to the parameters of electrolyte exchange, parathyroid, calcitonin and mineralocorticoid hormonal activities was evaluated. We estimated also plasma lipide spectrum. Results. 13 immunosuppressive and 6 immuneenhancing neuro-endocrine and metabolic parameters identified. Discriminant analysis conducted to identify parameters, in which the four immune response clusters differ significantly from each other. 25 parameters are characteristic, 12 of them related to the HRV, 5 to endocrine, 5 to electrolytes and 3 to nitrous metabolites exchange. Conclusion. 208 Individual immune responses to adaptogenic balneofactors are accompanied by characteristic changes in the parameters of the autonomic nervous and endocrine systems, as well as the exchange of electrolytes, nitrogen metabolites and lipids.

Hyperproduction of reactive oxygen species can damage sperm cells and is considered to be one of the mechanisms of male infertility. Cell protection from the damaging effects of free radicals and lipid peroxidation products is generally determined by the degree of antioxidant protection. Glutathione is non-enzymatic antioxidant which plays an important protective role against oxidative damages and lipid peroxidation. The aim of the present work is to determine the content of reduced and oxidized glutathione in sperm cells of infertile men. Semen samples from 20 fertile men (normozoospermics) and 72 infertile patients (12 oligozoospermics, 17 asthenozoospermics, 10 oligoasthenozoosper­mics and 33 leucocytospermic) were used. The total, oxidized (GSSG) and reduced (GSH) glutathione levels were measured spectrophotometrically. The levels of total glutathione were significantly lower in the spermatozoa of patients with oligozoo-, asthenozoo- and oligoasthenozoospermia than in the control. Infertile groups showed significantly decreased values of reduced glutathione in sperm cells vs. fertile men, indicating an alteration of oxidative status. The oxidized glutathione levels in sperm cells of infertile men did not differ from those of normozoospermic men with proven fertility. The GSH/GSSG ratio was significantly decreased in the oligo-, astheno- and oligoasthenozoospermic groups compared to the normozoospermic group. In patients with leucocytospermia the GSH/GSSG ratio was lower but these changes were not significant. In addition, glutathione peroxidase activity in sperm cells was decreased in patients with oligozoo-, astenozoo-, oligoastenozoospermia and with leucocytospermia. The most significant changes in glutathione peroxidase activity were observed in infertile men with leucocytospermia. Decreased GSH/GSSG ratio indicates a decline in redox-potential of the glutathione system in sperm cells of men with decreased fertilizing potential. Redistribution between oxidized and reduced forms of glutathione can be caused by depletion of intracellular stores of glutathione and intensification of lipid peroxidation processes. This leads to increased production of reactive oxygen species, further depletion of antioxidant pools and disturbances of structure and function of spermatozoa. Our results indicate that the evaluation of reduced glutathione level and GSH/GSSG ratio in sperm cells of infertile men can be helpful in fertility assessment.

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