The association of systemic inflammatory markers with indicators of stress and cardiac necrosis in patients undergoing aortic valve replacement and revascularization surgeries.

The aim was to investigate: changes of inflammatory, stress and cardiac response in patients undergoing open heart surgeries up to five days after the procedure; the association between inflammatory, stress and cardiac response and whether changes in a certain marker can predict short-term patient outcome. Ninety patients were divided into three groups, 30 participants each (on-pump,off-pump revascularization and valve replacement group). The following markers were measured:complete blood count, CRP, IL-6, IL-10, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1), cortisol, CK and hsTnT in 5 points. Resistin increased in all three groups. Lower IL-10 levels were found after the surgery and higher levels of leptin and MCP-1 in the off-pump than in the on-pump group. Off-pump group had higher values of IL-6, IL-10, leptin, resistin and MCP-1 and lower levels of CK and hsTnT 24 after surgery than the on-pump group. We found significant correlation between MCP-1 and resistin. The difference between resistin at time points 2 and 3 significantly predicted transfusion needs; while the difference between CRP and resistin before and at the end of the surgery together with the difference between leukocytes at the end and 24 hours after the surgery predicted the use of inotropic agents/vasopressors. Cardiac surgeries cause an increase of inflammatory, stress and cardiac markers. Only resistin correlated with MCP-1 which confirms the link between resistin secreted form infiltrated macrophages and enhanced release of MCP-1.

Growth of mountain belts in central Asia triggers a new collision zone in central India.

Several unusual strong earthquakes occurred in central India along the Narmada-Son Lineament (NSL) zone, far from active plate boundaries. To understand the role of collisional processes in the origin of this seismicity, we develop a numerical thermomechanical model of shortening between the Indian Plate and Asia. We show that at the final stage of collision, the shortening rate of the high mountain areas slows. The continuing convergence of India and Asia triggers the initiation of a new collision zone in continental part of India. Various geological and geophysical observations indicate that the NSL is a weakest zone with northward thrusting of the thinner central Indian lithosphere underneath the thicker northern part of the Indian Plate. We hypothesize that the NSL was reactivated during the final stage of the India Asia convergence and it will possibly form a new mountain belt within the Indian continent.

Mitral regurgitation and coronary artery bypass surgery: comparison of mitral valve repair and replacement.

BACKGROUND: The aim of this retrospective study was to determine if there is a statistically significant difference (p < or = 0.05) between mitral valve repair (MVRp) with concomitant surgical revascularization of the myocardium (CABG) and mitral valve replacement (MVR) with concomitant CABG, considering the duration of surgery, early postoperative morbidity, in-hospital mortality, length of stay in the Intensive Care Unit (ICU) and overall in-hospital stay. METHODS: Between January 1st 2006 and December 31st 2008, 75 patients underwent surgery for mitral regurgitation and ischemic heart disease. Patients were divided in two groups determined by the procedure that was performed on the mitral valve (MVRp + CABG group had 34 patients, MVR + CABG group had 41 patients). All the patients were operated by the same surgical team and received the usual anaesthesia protocol. RESULTS: Patients in the MVR + CABG group had statistically significant higher EuroSCORE risk levels, higher NYHA status and higher incidence of postoperative low cardiac output syndrome (LCOS). Neurological complications showed statistically significant higher incidence in the MVRp + CABG group. There was no statistically significant difference in regard to in-hospital mortality between these two groups. Patients in the MVR + CABG group had statistically significant longer in-hospital stay. CONCLUSIONS: Mitral valve repair and mitral valve replacement are complementary methods considering early postoperative morbidity and mortality. Higher incidence of LCOS and in-hospital stay in the MVR + CABG group was to be expected on behalf of poorer preoperative status.

Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle.

AIM: Production of reactive oxygen species (ROS) in skeletal muscle is markedly increased during exercise and may be essential for exercise adaptation. We, therefore, investigated the effects of infusion with the antioxidant N-acetylcysteine (NAC) on exercise-induced activation of signalling pathways and genes involved in exercise adaptation in human skeletal muscle. METHODS: Subjects completed two exercise tests, 7 days apart, with saline (control, CON) or NAC infusion before and during exercise. Exercise tests comprised of cycling at 71% VO(2peak) for 45 min, and then 92% VO(2peak) to fatigue, with vastus lateralis biopsies at pre-infusion, after 45-min cycling and at fatigue. RESULTS: Analysis was conducted on the mitogen-activated protein kinase signalling pathways, demonstrating that NAC infusion blocked the exercise-induced increase in JNK phosphorylation, but not ERK1/2, or p38 MAPK. Nuclear factor-κB p65 phosphorylation was unaffected by exercise; however, it was reduced in NAC at fatigue by 14% (P < 0.05) compared with pre-infusion. Analysis of exercise and/or ROS-sensitive genes demonstrated that exercise-induced mRNA expression is ROS dependent of MnSOD, but not PGC-1α, interleukin-6, monocyte chemotactic protein-1, or heat-shock protein 70. CONCLUSION: These results suggest that inhibition of ROS attenuates some skeletal muscle cell signalling pathways and gene expression involved in adaptations to exercise.

A formula for the profile of voltammogram spikes in the quasistatic regime.

A phase transition occurring at electrode-electrolyte interfaces is reflected in voltammograms (the current versus voltage plots) as a sharp spike. We derive a general formula fitting the profile of the spikes due to the first-order phase transitions that can be microscopically modeled by classical two-dimensional lattice gases. The quasistatic (near equilibrium) regime is required. The profile is especially essential when interpreting generic voltammograms, where two or more close or overlapping spikes usually appear. Simple direct links between the microscopics of a phase transition and the macroscopic properties of the associated spike are explicitly given. We demonstrate our results on the voltammograms for the underpotential deposition of copper on platinum (111) and (100) and on gold (111) and achieve very good agreement with experiment.

Antioxidant treatment with N-acetylcysteine regulates mammalian skeletal muscle Na+-K+-ATPase alpha gene expression during repeated contractions.

Exercise increases Na(+)-K(+) pump isoform gene expression and elevates muscle reactive oxygen species (ROS). We investigated whether enhanced ROS scavenging induced with the antioxidant N-acetylcysteine (NAC) blunted the increase in Na(+)-K(+) pump mRNA during repeated contractions in human and rat muscle. In experiment 1, well-trained subjects received saline or NAC intravenously prior to and during 45 min cycling. Vastus lateralis muscle biopsies were taken pre-infusion and following exercise. In experiment 2, isolated rat extensor digitorum longus muscles were pre-incubated without or with 10 mm NAC and then rested or stimulated electrically at 60 Hz for 90 s. After 3 h recovery, muscles were frozen. In both experiments, the muscles were analysed for Na(+)-K(+) pump alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) mRNA. In experiment 1, exercise increased alpha(2) mRNA by 1.0-fold (P = 0.03), but alpha(2) mRNA was reduced by 0.40-fold with NAC (P = 0.03). Exercise increased alpha(3), beta(1) and beta(2) mRNA by 2.0- to 3.4-fold (P < 0.05), but these were not affected by NAC (P > 0.32). Neither exercise nor NAC altered alpha(1) or beta(3) mRNA (P > 0.31). In experiment 2, electrical stimulation increased alpha(1), alpha(2) and alpha(3) mRNA by 2.3- to 17.4-fold (P < 0.05), but these changes were abolished by NAC (P > 0.07). Electrical stimulation almost completely reduced beta(1) mRNA but only in the presence of NAC (P < 0.01). Neither electrical stimulation nor NAC altered beta(2) or beta(3) mRNA (P > 0.09). In conclusion, NAC attenuated the increase in Na(+)-K(+) pump alpha(2) mRNA with exercise in human muscle and all alpha isoforms with electrical stimulation in rat muscle. This indicates a regulatory role for ROS in Na(+)-K(+) pump alpha isoform mRNA in mammalian muscle during repeated contractions.

N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.

Intense exercise up-regulates Na+,K+-ATPase isoform mRNA, but not protein expression in human skeletal muscle.

Characterization of expression of, and consequently also the acute exercise effects on, Na(+),K(+)-ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at approximately 40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na(+),K(+)-ATPase alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) mRNA and crude homogenate protein expression, using Real-Time RT-PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na(+),K(+)-ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 +/- 69 s; mean +/-s.e.m.) immediately increased alpha(3) and beta(2) mRNA by 2.4- and 1.7-fold, respectively (P < 0.05), whilst alpha(1) and alpha(2) mRNA were increased by 2.5- and 3.5-fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for beta(1) and beta(3) mRNA, reflecting variable time-dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) isoforms, by 1.4-, 2.2-, 1.4-, 1.1-, 1.0- and 1.0-fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the alpha(1)-alpha(3) and beta(1)-beta(3) isoforms. Thus, human skeletal muscle expresses each of the Na(+),K(+)-ATPase alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na(+),K(+)-ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na(+),K(+)-ATPase up-regulation.

N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans.

Infusion of the antioxidant N-acetylcysteine (NAC) reduces fatigability in electrically evoked human muscle contraction, but due to reported adverse reactions, no studies have investigated NAC infusion effects during voluntary exercise in humans. We investigated whether a modified NAC-infusion protocol (125 mg. kg(-1). h(-1) for 15 min, then 25 mg. kg(-1). h(-1)) altered blood redox status and enhanced performance during intense, intermittent exercise. Eight untrained men participated in a counterbalanced, double-blind, crossover study in which they received NAC or saline (control) before and during cycling exercise, which comprised three 45-s bouts and a fourth bout that continued to fatigue, at 130% peak oxygen consumption. Arterialized venous blood was analyzed for glutathione status, hematology, and plasma electrolytes. NAC infusion induced no severe adverse reactions. Exercise decreased the reduced glutathione (P < 0.005) and increased oxidized glutathione concentrations (P < 0.005); NAC attenuated both effects (P < 0.05). NAC increased the rise in plasma K(+) concentration-to-work ratio (P < 0.05), indicating impaired K(+) regulation, although time to fatigue was unchanged (NAC 102 +/- 45 s; saline 107 +/- 53 s). Thus NAC infusion altered blood redox status during intense, intermittent exercise but did not attenuate fatigue.

[The potential hazard of the late toxic effects of the new Soviet herbicide levanil and of the semiproducts of its industrial manufacture]. / O potentsial'noi opasnosti otdalennykh toksicheskikh éffektov novogo otechestvennogo gerbitsida levanila i poluproduktov ego promyshlennogo proizvodstva.

Results of experimental studies in the gonado- and embryotoxicity and teratogenicity of the herbicide levanil (a chlorine derivative of phenoxipropion acid) and its synthetic semiproducts (AXBT, DXBT, OFPK) proved potential embryotoxicity and teratogenic hazards of the AXBT and DXBT semiproducts. The gonadotoxic effects of levanil and its semiproducts were also established. The compounds were characterized by a considerable degree of tropism to gonads. The revealed effects necessitate preventive measures in levanil processing and usage.

[Structural properties of leukemic and normal lymphoid cells]. / Strukturnye svoistva leikoznykh i normal'nykh limfoidnykh kletok.

DNA synthesis intensity and spectral and fluorescent properties of leucemic, PHA-induced and intact normal mouse spleen cells and of nuclei isolated from these cells were investigated. The cell electrophoretic mobility and DNA-protein interaction in the nuclei were studied. Similarity in cell and nuclei fluorescence, fluorescence of the probe ANS conjugated with the cells, the electrophoretic mobility and tightness of DNA--protein interaction for leucemic and PHA--induced cells and also the similarity of the tightness of DNA--protein interaction for leucemic and normal intact cells were found inspite of the differences in DNA synthesis intensity and cell functional peculiarities.