Effects of Zoniporide and BMA-1321 Compound on the Rate of Oxygen Absorption by Cardiomyocyte Mitochondria in Rats with Experimental Chronic Heart Failure.

Uncoupling of respiration and ATP production by myocardial mitochondria was observed in rats with chronic isoproterenol intoxication (L-isoproterenol subcutaneously, 1 mg/kg, for 10 days) in comparison with controls (injected with the solvent). Inhibitors of NHE-1 zoniporide (1 mg/kg intraperitoneally, 13 days) and BMA-1321 compound (0.92 mg/kg intraperitoneally, 13 days) improved the mitochondrial function in rats with isoproterenol-induced cardiac failure: respiratory control coefficients increased, more so for the respiratory chain complex II, the main source of ROS in heart failure. The effect of BMA-1321 was more manifest (53%; p<0.05) in comparison with zoniporide (35%; p<0.05).

Correction of Alcohol-Induced Damage to Mitochondria in Cardiac and Cerebral Cells by Derivatives of Neuroactive Amino Acids.

We studied LPO intensity and respiration of mitochondria in brain and heart cells of rats receiving 5% ethanol for 20 weeks and treated with derivatives of neuroactive amino acids. Chronic semicompulsory alcohol intoxication increased the concentration of LPO products in cardiac and cerebral mitochondria by 46 and 45% (diene conjugates), by 97 and 8% (diketones), and by 28 and 81% (malondialdehyde), respectively, reduced activity of antioxidant enzymes in cardiac and cerebral mitochondria by 24 and 45% (glutathione peroxidase) and by 22 and 26% (superoxide dismutase), respectively, and uncoupled the process of respiration and ATP synthesis, which manifested in a decrease in respiratory control (V3/V4 ratio according to Chance). Glutamic acid derivative Neuroglutam (26 mg/kg) and GABA derivative succicard (44 mg/kg) administered intraperitoneally daily for 28 days after termination of alcoholization decreased the levels of primary and secondary LPO products, up-regulated activity of antioxidant enzymes in mitochondria of the heart and brain, and moderated the mitochondrial dysfunction.

[Age-specific changes in the functional indices of rats' cardiac mitochondria in chronic alcohol intoxication.]

The effect of chromic continuous consumption of 5 and 10% ethyl alcohol over 6 months on the respiratory function and oxidant/antioxidant status of rats' cardiac mitochondria of different gender and age has been studied. A decrease in oxygen consumption rate by cardiomyocyte mitochondria in the metabolic conditions V2, V3, V4 according to Chance involving activation of respiratory chain complexes I, I+II and II in elderly (24-month old) animals as compared to young (11-month old) animals. As the rats were ageing, the concentration of lipid peroxidation (LPO) products (malondialdehyde) was increasing, while the activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) was decreasing in cardiomyocyte mitochondria. Chronic alcoholization of 24-month old rats of both genders resulted in a more pronounced decline in the respiratory function activity of cardiac mitochondria, uncoupling of respiration and oxidative phosporylation, reduced activity of antiradical protection enzymes and increased LPO products as compared to younger rats.

[Influence of the dense extract from herb of Primula veris L. On the oxidative stress development and the functional state of the cardiomyocytes mitochondria of rats with experimental chronic heart failure]. / Vliianie gustogo ékstrakta iz travy pervotsveta vesennego na razvitie oksidativnogo stressa i funktsional'noe sostoianie mitokhondrii kardiomiotsitov krys s éksperimental'noi khronicheskoi serdechnoi nedostatochnost'iu.

Experimental chronic heart failure (CHF), caused by administration of L-isoproterenol (2.5 mg/kg twice a day intraperitoneally for 21 days), promotes uncoupling of respiration and oxidative phosphorylation. The rate of mitochondrial oxygen consumption in the metabolic state V3 by Chance in animals with CHF decreased by 53.3% (p<0.05) with malate using (as an oxidation substrate feeding сomplex I of the electron transport chain (ETC)), by 70.6% (p<0.05) with succinate using (сomplex II substrate) and by 63.6% (p<0.05) when malate and succinate were added simultaneously. The respiratory control ratio significantly decreased 2.3 times for сomplex I, 2.5 for сomplex II, and 2.6 times for the simultaneous operation of two respiratory chain complexes in mitochondria of CHF rats compared to intact animals. Mitochondrial dysfunction in experimental CHF is evidently due to the development of oxidative stress. It was revealed that the content of malonic dialdehyde (MDA) in the group of rats with experimental CHF was higher by 54.7% (p<0.05), as compared with intact animals. The activity of superoxide dismutase (SOD) and catalase was lower by 17.5% (p<0.05), and by 18.4%, respectively than in the intact group. The dense extract from herba of Primula veris L. (DEHPV) 30 mg/kg limits the development of mitochondrial dysfunction in rats with experimental CHF, as evidenced by an increase in the role of V3 respiration for the first and second respiratory chain complexes in 1.7 (p<0.05) and 2.0 times (p<0.05), respectively, the ratio of respiratory control (RCR) - 1.7 times (p<0.05) for сomplex I and 2 times (p<0.05) for сomplex II compared with the negative control. The concentration of MDA was by 15.7% (p<0.05), lower and the activity of SOD was by 56.3% (p<0.05) higher.

Effect of Phenibut and Glufimet, a Novel Glutamic Acid Derivative, on Respiration of Heart and Brain Mitochondria from Animals Exposed to Stress against the Background of Inducible NO-Synthase Blockade.

Increased oxygen consumption by heart and brain mitochondria in the absence of ADP and reduced mitochondrial respiration in the presence of ADP were observed in rats exposed to stress simulated by suspension by the dorsal neck skin fold for 24 h, which attests to uncoupling of substrate oxidation and ATP synthesis and can cause electron drain from the respiratory chain, formation of ROS, and oxidative damage to cell structures. Blockade of inducible NO synthase with aminoguanidine (single intraperitoneal dose of 50 mg/kg before stress exposure) increased coupling of respiration and oxidative phosphorylation in heart and brain mitochondria of rats exposed to immobilization-painful stress, which was especially pronounced in cardiomyocytes. The test compounds glufimet (single intraperitoneal dose of 29 mg/kg before stress exposure) and phenibut (single intraperitoneal dose of 50 mg/kg before stress exposure) limited stress-induced mitochondrial damage against the background of inducible NO synthase blockade and without it, which was seen from increased respiratory control ratio in comparison with that in untreated rats exposed to stress (control).

[Protective effects of a new glutamic acid derivative against stress after nNOS blockade]. / Stressprotektornoe deistvie novogo proizvodnogo glutaminovoi kisloty pri blokade neironal'noi NO-sintazy.

We studied the effects of a new glutamic acid derivative, glufimet, on oxidative stress, activity of antioxidant enzymes, mitochondrial respiration, endothelial vasodilation and anti-platelet activity in female rats after exposure to 24-hour immobilization pain stress and 7-nitroindazole, a neuronal nitric oxide synthase (nNOS) inhibitor. A single dose administration of glufimet (29 mg/kg intraperitoneally) 10 minutes before stress exposure caused a decrease of NO metabolites in serum (by 27.2%) and heart homogenate (33.5% (p£0.05), respectively, compared with the control group. Administration of 7-nitroindazole with glufimet also decreased the studied parameters by 14.3% in the heart homogenate and by 30,3% in the brain (p£0.05) compared with stress exposed rats receiving only the nNOS inhibitor. Glufimet decreased the levels of primary and secondary products of lipid peroxidation (LPO), conjugated dienes by 20% (p£0.05) and 17.3% (p£0.05), ketodienes by 16% and 13.7%, malondialdehyde by 15% (p£0.05) and 26.6% (p£0.05) in the heart and brain mitochondria of stress exposed rats, respectively, compared with the control group. Glufimet administration also increased SOD activity (by 14.4% and 13.1%, respectively), catalase (by 19% and 26.8%, respectively) and glutathione peroxidase (GPx) activity (by 45.5% (p£0.05) and 7.3%, respectively). The antioxidant effect of glufimet may be also attributed to increased coupling between the processes of mitochondria respiration and oxidative phosphorylation. This was evidenced by an increase in the respiratory control ratio (RCR) (by 46.0% (p£0.05) for malate/glutamate and by 49,7% (p£0.05) for succinate) in the heart mitochondria. A statistically significant increase in RCR (by 37.3% (p£0.05)) was observed in stress exposed female rat brain mitochondria for succinate. RCRs differed significantly for succinate in the heart and brain of rats receiving glufimet after nNOS blockade. RCR increased by 62.3% (p£0.05) in the heart mitochondria and by 72.2% (p£0.05) in the brain mitochondria compared with the RCRs in stress exposed rats receiving 7-nitroindazole.

[Prоgnosis of motor function recovery in ischemic stroke using diffusion tensor MRI]. / Otsenka prognoza vosstanovleniya dvigatel'noi funktsii u bol'nykh s ishemicheskim insul'tom s pomoshch'yu diffuzionno-tenzornoi magnitno-rezonansnoi tomografii.

AIM: To identify factors of motor recovery in ischemic stroke (IS) using diffusion tensor imaging (DTI). MATERIAL AND METHODS: Forty-seven patients with IS were studied within 1-2, 7-8, 14-15, 20-21 days after stroke. The fractional anisotropy (FA) values of the pyramidal tract were measured in the posterior limb of the internal capsule, cerebral peduncle and pons. Relative values of FA (rFA) ratio (rFA=FA affected side/FA unaffected side) were assessed as well. RESULTS: rFA≤0.7 in the cerebral peduncule and posterior limb of the internal capsule accurately predicted poor motor outcome in ischemic stroke. CONCLUSION: DTI can evaluate the motor deficit quantitatively and may predict the functional prognosis in patients with IS.

[The effect of sulodexide on placental mitochondria function in rats with experimental preeclampsia]. / Vliianie sulodeksida na funktsional'noe sostoianie mitokhondrii platsenty samok krys s éksperimental'noi preéklampsiei.

Substitution of drinking water for 1.8% NaCl in pregnant rats caused a pronounced increase in arterial pressure by 24,3% and urinary protein by 117% to day 21 of pregnancy. State 4 respiration of isolated placental mitochondria in the group of negative control was 3- and 1.5-fold higher with malate/glutamate and succinate as substrates than in placental mitochondria isolated from uncomplicated pregnant animals. This led to a decrease of the respiratory control ratio. These results suggest that development of experimental preeclampsia is accompanied by mitochondrial dysfunction through uncoupling of oxidative phosphorylation. Daily administration of sulodexide to females with experimental preeclampsia (EP) per os at a dose of 30 LE during the whole period of gestation decreased manifestations of the disease as evidenced by a slight increase in blood pressure (by 8,6%) and less pronounces increase in urinary protein (by 58,9%). Sulodexide decreased development of mitochondrial dysfunction in EP rats as shown a decrease of non-stimulated ADP respiration with malate/glutamate and succinate (4.5- and 2.5-fold, respectively) as compared with the negative control group and the corresponding increase in the respiratory control ratio (2.5- and 1.5-fold, respectively). Thus, sulodexide reduces uncoupling of oxidative phosphorylation and enhances the functional activity of mitochondria in EP animals, possibly due to its antioxidant and endotelioprotective effects.

[CHANGES OF THE OXIDATIVE STATUS, MITOCHONDRIAL FUNCTION, BLOOD PRESSURE AND INDICATORS OF HEMOSTASIS IN STRESSED ANIMALS AND IN THE CONDITIONS OF NO-SYNTHASE BLOCKADE].

Changes in the metabolism of female rats hanging by cervical dorsal skin fold within 24 hours were examined. It was found that stress exposure results in an increase of the concentration of the final nitric oxide metabolites in the blood serum and homogenates of the heart and brain of animals, intensification of processes peroxidation lipids and mitochondrial dysfunction in these organs. Thus increase of mean arterial blood pressure by 18.9 % from baseline and violation of platelet and plasma components of hemostasis. Inhibitor of neuronal NO-synthase 7-nitroindazole in the dose of 50 mg/kg aggravates of the studied parameters changes. Administration of an animal selective inhibitor of inducible NOS aminoguanidine (50 mg / kg) contributes to limiting the damaging effects of stress reaction.

[Gravidaprotective action of phenibut in experimental pre-eclampsia].

It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes.

Changes in oxidant and antioxidant status of females with experimental gestosis under the effect of GABA derivatives.

Experimental gestosis, modeled by replacement of drinking water with 1.8% NaCl solution, induced oxidative stress, which was seen from accumulation of MDA (secondary LPO product) and inhibition of SOD and glutathione peroxidase in the brain, liver, and uterus of animals with gestosis. Citrocard and saliphene (GABA derivatives) inhibited LPO (reduced MDA concentrations in the studied organs) and activated antioxidant enzymes in experimental gestosis.

[Effect of GABA derivative--RSMU-151 on the development of oxidative stress in rats with experimental gestosis].

Experimental gestosis induced in rats by drinking 1.8% sodium chloride solution instead of water during the entire period of pregnancy leads to activation of lipid peroxidation (LPO) process, as manifested by increased concentration of diene conjugates and malonic dialdehyde, decreased concentration of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in homogenates of rat brain, liver, uterus, and placenta. The GABA derivatives--RSMU-151 limits the damaging effect of gestosis, which is manifested by a decrease in the concentration of LPO products and by activation of the antioxidant system enzymes in all organs studied.

[The PATRIARCH study: effect of passive training on long term treatment results with myocardial infarction].

In order to study long term results of passive training sessions in myocardial infarction in older patients with the use of electromyostimulation (EMS) of skeletal muscles (the PATRIARCH Study) we examined 94 patients with acute myocardial infarction (IM) older than 60 years. Among patients subjected to EMS training we distinguished groups with age 60-69 years (n=19) and older than 70 years (n=32). Control groups also contained patients aged 60-69 years (n=19), and older than 70 years (n=25). For training we used "Myorhythm-040" apparatus. During 2 hours of a training session we stimulated rectus muscle of abdomen, back extensors, buttocks, quadriceps muscle of thigh, muscles of calf. In hospital course of EMS led to improvement of strength and endurance of skeletal muscles in patients older than 70 years. Strength and endurance of skeletal muscles at discharge from hospital was among factors influencing 5 year survival of patients with MI in older age groups (together with Killip heart failure class and left ventricular ejection fraction). EMS facilitated improvement of results of treatment of patients of main group during 5 years of follow up. Effect on prognosis requires elaboration in studies with greater number of patients.

Effect of Citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication.

Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group.

[Physiological evaluation of work done by female hothouse workers]. / Fiziologicheskaia otsenka truda teplichnits.

The authors studied influence of work conditions and temperature mode on functional state of stove female workers. The results include leading factor of work operations, that determinates work hardiness and jeopardy class for work conditions. Physiologic research demonstrated changes in functional state of some body systems, especially cardiovascular and neuromuscular ones.

[Sensitivity of Escherichia coli O157:H7, a pathogen of hemorrhagic colitis, to antibacterial drugs]. / Chuvstvitel'nost' Escherichia coli O157:H7, vozbuditelia gemorragicheskogo kolita, k antibakterial'noym preparatam.

Antibioticograms of enterohemorrhagic strains of serogroup O157 Escherichia coli isolated in the Russian Federation and Japan were comparatively studied. Strains with multiple drug resistance were detected. The main biochemical characteristics of the isolates were investigated. Significant differences in susceptibility spectra of the isolates and in their fermentative properties were revealed.