[Enhancement of antioxidant status of the elderly patients with ischemic heart disease in response to amino acid composition of MP-33 in combined therapy with trimetazidine]. / Povyshenie antioksidantnogo statusa bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta pri deistvii aminokislotnoi kompozitsii MP-33 v kombinirovannoi terapii s trimetazidinom.

Effects of amino acid composition MP-33 in combination with trimetazidine were studied in metabolic therapy of elderly patients (age 63.3 +/- 1.7 years) with ischemic heart disease (angina pectoris functional class II-III). MP-33 (100 mg 3 times a day subling.), trimetazidine (20 mg 3 times a day per os), trimetazidine + amino acid composition MP-33 in the above doses in addition to basic therapy were given to 30, 15 and 15 patients, respectively. Combined therapy with trimetazidine and MP-33 significantly activated antioxidant enzymes and depressed lipid peroxidation due to GSH-dependent regulation of cellular redox status by MP-33.

Effects of phenobarbital on activity of mitochondrial enzymes in peripheral blood lymphocytes and oxidative phosphorylation in liver mitochondria.

Treatment with phenobarbital (30 mg/kg) for 2 weeks increased succinate dehydrogenase activity in peripheral blood lymphocytes of male rats. In 38% phenobarbital-treated rats succinate-cytochrome c oxidoreductase activity was lower than in the control due to accumulation of cells exhibiting no enzyme activity; in 44% animals this parameter was higher than in the control. The rates of state 3 respiration (oxidation substrate succinate), phosphorylation, and uncoupled respiration in liver mitochondria (oxidation substrate glutamate/malate mixture) increased after 35-day treatment with phenobarbital. The respiratory control and ADP/O ratio for these substrates did not differ from the control.

[Parameters of hemodynamics and red cell redox-status in old patients with ischemic heart disease]. / Sviaz' pokazatelei hemodinamiki i parametrov redoks-statusa éritrotsitov u bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta.

Red cell redox-status and hemodynamic changes were studied in 60 old patients with ischemic heart disease. The treatment consisted of standard therapy (ST), ST + amino acid composition (glutaminic acid, glycine, cysteine) or preductal (15, 30 and 15 patients, respectively). Glutathione levels, activity of glutathione-transferase, reductase, peroxidase, catalase, Cu-, Zn-superoxide dismutase, red cell levels of malonic dialdehyde, hemodynamic parameters according to echo-CG and ECG monitoring were estimated before the treatment and 20 days after it. Endogenic antioxidant defense/hemodynamic parameters correlation coefficients were calculated. Close correlations were not found. However, ST + amino acid composition demonstrated the weakest correlations between the antioxidant defense and hemodynamics, while ST + preductal produced the greatest number of correlations. It is suggested that amino acids promote search for the antioxidant system's optimum while ST + preductal promotes closer correlations between red cell redox status and hemodynamic parameters.

[Effects of metabolic therapy on intracellular level of antioxidant system in elderly patients with ischemic heart disease]. / Effekt metabolicheskoi terapii na vnutrikletochnyi uroven' antioksidantnoi sistemy bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta.

Patients with ischemic heart disease (angina pectoris of functional class II and III) whose mean age was 67.4 +/- 1.67 years were divided into 3 randomized groups. 15 control patients received standard treatment. 30 and 15 patients of group 1 and 2, respectively, received standard treatment plus amino acid composition (100 mg 3 times a day sublingually) or preductal (20 mg 3 times a day)--groups 1 and 2, respectively. The treatment lasted 21 days. Before the treatment and on its day 1, 7 and 21 measurements were made of glutathione level, activity of glutathion-dependent enzymes, catalase, Cu, Zn-superoxide dismutase and malonic dialdehyde in red cells. The amino acid composition was found to raise the level of antioxidant system and suppress lipid peroxidation. Preductal raised the activity of Cu, Zn-superoxide dismutase and had an unbalanced effect on the antioxidant system.

[Increase in radiation resistance of an organism after administration of metabolic drug MR-33]. / Povyshenie radiorezistentnosti organizma pri deistvii metabolitnogo preparata MR-33.

Original MP-33 metabolic drug has inductive action on intracellular levels of glutathione (GSH) and GSH-related enzymes (glutathione peroxidase-GPx, glutathione S-transferase-GST) of animals and human (liver, heart, erythrocytes). Treatment of Wistar male rats with MP-33 per os (6 mg/kg) 30 min before gamma-irradiation with a dose of 7 Gy results in 35% survival and increasing of mean life. In "mother-foetus" system the induction of intracellular level of GSH, GST and GPx by MP-33 leads to enhancement of foetus radioresistance. In contrast to MP-33 us of GSH (6 and 100 mg/kg) is not effective. Perspective of MP-33 us in relation to radioecological crisis is discussed.

[Response to metabolic therapy with amino acid complex in aged patients with ischemic heart disease]. / Otsenka éffektivnosti metabolicheskoi terapii kompleksom aminokislot u bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta.

Aged patients with IHD were randomised into two groups (45 patients each). Mean age of the patients was 65.8 +/- 0.8 years. Control patients received standard treatment, test subjects received the same standard therapy plus metabolic complex of amino acids. The comparison of the groups was made by clinical evidence, data obtained at ECG, echo-CG, Holter ECG monitoring, exercise test. Those patients who had been given adjuvant amino acid composition in a dose 100 mg 3 times a day for 20 days exhibited stronger antianginal, hemodynamic effects, higher exercise tolerance.

[Neuroprotective effects of glycine in the acute period of ischemic stroke]. / Neiroprotektivnoe deistvie glitsina v ostrom periode ishemicheskogo insul'ta.

Both the efficiency of glycine in the acute period of hemispheric ischemic stroke and mechanisms of its action were studied in a double blind placebo-controlled trial including 200 patients. Orgogozo's and Scandinavian scales for objective assessment of the condition severity and of a degree of neurologic deficiency, and Bartel's scale--for evaluation of functional recovery were used and measurements were made of the levels of autoantibodies to the structural component of glutamate NMDA-receptors in blood serum and concentrations of neurotransmitter amino acids and of the products of lipid peroxidation in cerebrospinal fluid. Sublingual glycine application in daily dose of 1-2 g was found effective beginning with the first 6 hours of the stroke development during 5 days. Multicomponent neuroprotective action of glycine was established directed at correction of the unbalance between stimulating and inhibiting aminoacidergic neurotransmitters, as well as at a decrease of excitotoxicity and oxidant stress.

[Comparative efficacy of combined therapy with preductal and amino acid composition in elderly patients with coronary heart disease and class II-III angina]. / Sravnitel'naia éffektivnost' kompeksnoi terapii s vkliucheniem preduktala i kompozitsii aminokislot u bol'nykh ishemicheskoi bolezn'iu serdtsa so stenokardiei II-III funktsional'nykh klassov pozhilogo vozrasta.

AIM: A comparative analysis of effectiveness of combined therapy including trimetazidine (preductal) and composition of amino acids (glutamic acid, glycin and cystein) in elderly patients with coronary heart disease and angina of functional class II-III (FC II-III). MATERIALS AND METHODS: 60 patients (47 females and 13 males, mean age 66.4 +/- 0.5 years) with IHD, angina FC II-III, postinfarction cardiosclerosis and circulatory failure stage I-IIA were randomized into 3 randomized groups. Control patients received conventional antianginal therapy with nitrates, beta-adrenoblockers, calcium antagonists, diuretics, ACI inhibitors, cardiac glycosides and aspirin. Patients of group 1 received conventional treatment + complex of amino acids in dose 100 mg 3 times a day sublingually. Group 2 patients received adjuvant preductal for 20 days in dose 20 mg 3 times a day per os. Assessment was made clinically, with echo-CG data, bimanual isometric loading and Holter 24-h ECG monitoring. RESULTS: All the three methods showed antianginal, hypotensive effects, brought higher tolerance to exercise and improvement of hemodynamics. The basic therapy produced the least effect. CONCLUSION: Metabolic therapy with amino acids and preductal combined with conventional methods brings more pronounced antianginal and hemodynamic effects than combined therapy alone.

The uncoupling effect of some psychotropic drugs on oxidative phosphorylation in rat liver mitochondria.

In the present study an attempt to detect influence of some psychotropic drugs on oxidative phosphorylation has been made. Relanium and melipramine were used in the experiments. They are among tranquilizer and antidepressant drug groups respectively. It was shown that both drugs increased the rate of oxygen consumption and displayed uncoupling properties. Mitochondrial respiration raised up slowly after drug addition in the presence of succinate or beta-oxybutyrate as oxidized substrates. If concentration of relanium and melipramine exceeded 1.2 and 0.8 mM respectively the rate of oxygen consumption began to decrease. There was a small reply on addition of ADP in the presence of drugs. At the same time relanium and melipramine decreased respiration rate if they were added at the state 3. It was shown that the drugs increased conductivity of bimolecular phospholipid membranes.

[New possibilities for metabolic protection from hypoxia in pregnant rats and their progeny]. / Novye vozmozhnosti metabolicheskoi zashchity ot gipoksii beremennykh krys i ikh potomstva.

Individual resistance of pregnant rats and the newborns to acute hypoxic hypoxia was studied. It was found that individual resistance of the organism to hypoxia significantly decreases in the last period of pregnancy. A new drug limontar proved to possess the properties of an active antihypoxia agent. Its administration during the last third of pregnancy stimulated the organism's protective-adaptational reactions, increased the resistance of pregnant, rats and the newborns to hypoxia. Limontar significantly improves the mechanometabolic indices of an isolated perfused heart under hypoxic conditions. Analysis of the obtained data suggests that limontar increases energy formation in the myocardium through activation of a more efficient and energetically beneficial path of succinic acid oxidation.

[The corrective properties of glycine in alcoholic intoxication in the fetal period of pregnancy]. / Korrigiruiushchie svoistva glitsina pri alkogol'noi intoksikatsii v plodnyi period beremennosti.

Natural metabolite glycine administered per os to rats in the fetus period of pregnancy in a dose of 1 mg/kg was found to exert a corrective action with respect to the toxic effect of ethanol in the mother-fetus system. Glycine prevents loss in the body weight, normalizes functional state of the nervous system and metabolic disorders in the maternal organism, improve the redox processes in the lymphocytes changed under alcoholization, and protect the fetus both on the metabolic and microstructural levels.

[The hormonal sensitivity of glomerulonephritis patients]. / Izuchenie gormonochuvstvitel'nosti u bol'nykh glomerulonefritom.

Hormone sensitivity in patients suffering from glomerulonephritis of nephrotic type was assessed cytochemically by corticosteroid action on activity of mitochondrial enzymes (alpha-glycerophosphate dehydrogenase, succinate dehydrogenase) and by sensitivity of peripheral blood mononuclear cells to antiproliferative effect of dexamethasone in vitro. In glucocorticosteroid-sensitive patients the activity of alpha-glycerophosphate dehydrogenase, succinate dehydrogenase rises in interaction with prednisolone in vitro. In the resistant patients enzymatic activity in lymphocytes came down, peripheral blood mononuclear cells before and in the course of treatment retained resistance to glucocorticoids irrespective of the treatment results. Alpha-glycerophosphate dehydrogenase to succinate dehydrogenase index varied from 0 to 0.33 and 0.4 to 5.1 in the resistant and sensitive patients, respectively.

[The protective action of limontar in pregnant animals with acute hypoxic hypoxia]. / Protektornoe deistvie limontara na beremennykh zhivotnykh pri ostroi gipoksicheskoi gipoksii.

A comparative study of individual resistance of rats to acute hypoxic hypoxia was performed. It was shown that individual resistance of the organism to hypoxia significantly decreases in the course of pregnancy. Limontar is shown to be active antihypoxant. Limontar administered during the last third of pregnancy stimulates protective-adaptive reactions in the females, thus increasing their resistance to hypoxia.

[A comprehensive clinico-neurophysiological study of the efficacy of the pharmaceutical preparation glycine in acute ischemic stroke]. / Kompleksnoe kliniko-neirofiziologicheskoe izuchenie éffektivnosti farmatsevticheskogo preparata glitsina v ostrom periode ishemicheskogo insul'ta.

In intensive care unit 226 patients underwent step-by-step clinical and neurophysiological investigation of glycin chemotherapy efficiency in the acute period of ischaemic stroke. Investigation included double-blind placebo controlled method, monitoring (by means of EEG, toposelective mapping of EEG, SSEP, transcutaneous cortical electric stimulation, ENMG) of changes of brain functional state after the first drug dose and course of treatment, analysis of dose-dependent action of the drug, posticchemic follow-up. It was found out, that usage of the drug glycin (daily dose 1-2 grams) in the combined intensive treatment of stroke provided for significant acceleration of regress of disorders of consciousness and other general and focal signs (in comparison with severity-matched control group), and more complete and stable restoration of function to the end of acute period of the disease.

[The molecular-cellular regulation of the mitochondrial respiratory chain]. / Nekotorye aspekty molekuliano-kletochnoi reguliatsii dykhatel'noi tsepi mitokhondrii.

We propose a new concept of molecular-cellular regulation of the mitochondrial respiratory chain. According to this concept, the cell uses acetaldehyde (AcA) as a main regulator of the respiratory chain. AcA expresses its action by changing the structural-functional state of ubiquinone, the key component of the respiratory chain. Studies were made on white random bred rats using the Langendorff's model of isolated perfused heart. We comparatively estimated the mechanometabolic state of myocardium under the conditions of simulated hypoxia of various degree, as well as in the presence of exogenous ethyl alcohol. Both hypoxia and ethyl alcohol induced severe disturbances of energy metabolism in the myocardium, cells at the level of respiratory chain due, apparently, to the increased content of free AcA. Hydroxyquinone and glycine, capable of binding free AcA, were used for pharmacological protection of the cells. Application of these drugs markedly improved the functional-metabolic state of the cell. We propose that AcA exerts both regulatory (in low doses) and inhibitory (in high doses) effect on the respiratory chain. The results obtained allow a novel insight in the processes of alcoholic and hypoxic damage and their pharmacological correction. It is evident that prophylactic and therapeutic measures in case of hypoxia or alcoholic intoxication should be first directed at decreasing the level of free AcA in the cell.