Changes in the Neuronal Population of the Spinal Cord of Mice with Experimental Autoimmune Encephalomyelitis as a Model of Multiple Sclerosis.

We performed a quantitative study of the neuronal population in the spinal cord of mice with acute and chronic model of experimental autoimmune encephalomyelitis. Immunohistological/immunofluorescent analysis with motor neuron marker ChAT revealed a significant decrease in the number of motor neurons in the ventral horns of the lumbar spinal cord in the acute form of autoimmune encephalomyelitis, with the further appearance of large empty (containing no motor neurons) areas in the ventral horns in the chronic form. The development of experimental autoimmune encephalomyelitis is accompanied by degradation and death of neurons, in particular ChAT+ motor neurons.

Methodological Approaches to In Vitro Evaluation of Transcription Activity of Nuclear Factor Kappa B (NF-κB) in Sensory Neurons.

Transcription activity of NF-κB in sensory neurons was analyzed in vitro using classical immunocytochemical methods and transgenic technologies. Activation of NF-κB in NIH3T3 cells and in murine sensory neurons after in vitro stimulation with TNF-α was demonstrated by the immunocytochemical method; however, the expression of the reporter NF-κB/LacZ transgene was detected only after addition of histon deacetylase inhibitor. Hence, formally contradictory conclusions from the results of immunocytochemical analysis and reporter transgene expression were in line with the hypothesis on epigenetic repression of NF-κB activity in sensory neurons mediated by histon deacetylases.

Antiischemic activity of new domestic antioxidant 3-hydroxypyridine etoxidol derivative.

Experiments on rats with myocardium infarction showed that intravenous administration of etoxidol in a dose of 14.2 mg/kg restricted the size of necrosis area and reduced the ratio of necrosis/ischemia zones. The test compound reduced the risk of rhythm and conduction disturbances induced by administration of toxic epinephrine doses to the mice, and increased mouse survival. Etoxidol administered intravenously to cats with acute myocardial ischemia reduced epinephrine concentration and intensity of free radical oxidation in zones of myocardial lesions against the background of the increase in norepinephrine concentration and antioxidant activity in the myocardium. By antiischemic and antioxidant activity, etoxidol was superior to its structural analogue mexidol.

[Hepatoprotective effect of deanol aceglumate on experimental stress-induced gastropathy and diabetes mellitus].

Experiments on mice with streptozotocin-induced diabetes mellitus and stress-induced erosive ulcerous damage of the mucous membrane of stomach showed evidence of the preventive activity of deanol aceglumate in the course of peroral introduction at a dose of 250 mg/kg per 24 h during 4 days. This effect is accompanied by activation of the peristalsis of bowels and by an increase in the blood flow in the wall of stomach.

[Efficiency of etoxidol in treating cardiovascular disorders caused by experimental cerebral ischemia].

A complex pharmacological study of the new cytoprotector drug etoksidol in animals with the disturbances of cerebral blood circulation showed that the intravenous introduction of the drug restores autonomous nomotopic driver of rhythm, conductivity in the atria and atrioventricular connection, and refractoriness of the atrioventricular connection, which were violated a result of sharp cerebral ischemia. The new drug does not suppress the inotropic function of the heart in cats and limits the dimensions of the zone of necrosis in rats with the myocardial infarction on the background of deficiency of the cerebral blood flow.

[Pharmacological properties of phosphorylacetohydrazides in experimental myocardial ischemia].

It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N-acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid reliably reduce ischemia-induced depression of inotropic functions of the left ventricle in cats with experimental myocardial infarction model. The effect of both compounds can be explained by the maintenance of viability of the injured myocardium via a delay of the development of acidosis and the support of oxygen recycling in the ischemized zone. Both compounds show pronounced antiradical properties with a non-standard mechanism of action.

[Cytoprotective properties of 3-oxy-6-methyl-2-ethylpyridine succinate in cell cultures].

Tests on calf coronary vessel cells (CVC) cultures showed that 3-oxi-6-methyl-2-ethylpiridine succinate (OMEPS) in dozes within 5.0-10.0 microg/ml did not decrease proliferation index, monolayer development, and viability factor. OMEPS also did not increase cytotoxicity index and did not change cytomorphological characteristics of the culture. In a concentration of 100 microg/ml, OMEPS exhibited some cytotoxyc properties, but to a lower degree compared to the reference antiarrhythmic drug moricisine (1.0-20.0 microg/ml). However, OMEPS (2.5 microg/ml) reduced the cytotoxicity moricisine introduced into CVC culture in a doze of 1.0 microg/ml.

[The mechanism of antiarrhythmic action of a new ammonium derivative of lidocaine (LKhT-12-02)].

The results of electrophysiological investigation of the effects of LKhT-12-02 (a quaternary ammonium derivative of lidocaine) on the intact cat heart and the isolated ion channels of Lymnaea stagnalis snail showed that this compound belongs to class 1B antiarrhythmic agents (Vaughan - Williams classification). The drug does not suppress the automatic nonmonotonic rhythm driver, does not influence the conductance in ventricles, auricles, and atrioventricular node in the sinus rhythm, and does not elongate the effective refractory period of the auricles and atrioventricular node. LKhT-12-02 decreases the rate of fast depolarization of the action potential, while not reducing its duration. The compound does not influence the conduction of sodium ion channels.

Membrane mechanisms of antiarrhythmic effect of quaternidine.

Complex electrophysiological study of the effects of quaternidine carried out on intact hearts from cats, myocardial fragments from rats, and single ionic channels of large edible snail showed that quaternidine demonstrates properties of class 1B antiarrhythmic drug according to Vaughan-Williams nomenclature. This agent did not suppress nomotopic pacemaker automaticity, did not change conduction in ventricles, atria, and atrioventricular junction in hearts with preserved sinus rhythm, did not prolong refractoriness of the atria and atrioventricular junction, but prolonged efficient refractory period of heart ventricles. Quaternidine decelerated rapid depolarization of the action potential, but had no effect on its duration. It did not affect potassium conductance.

[Anti-arrhythmia activity of derinat in an experiment]. / Protivoaritmicheskaia aktivnost' derinata v éksperimente.

The acute toxicity of the immunostimulant derinat is very low: the LD50 value for intraperitoneal administration exceeds 1000 mg/kg. The drug effectively prevents from acute arrhythmia development upon occlusion in cats and produces antifibrillator effect on a model of reperfusive arrhythmia in a dose of 7.5 mg/kg. Derinat also exhibits the antiarrhythmic activity on the model of adrenalin-induced rhythm violations, but appears ineffective on the calcium chloride model.

A new method for evaluation of safety of antiarrhythmic drugs.

A new method for preclinical evaluation of safety of antiarrhythmic drugs is proposed. During chronic stress, class I antiarrhythmic preparations increased mortality of test animals. By contrast, class II-IV antiarrhythmic agents and antioxidants produced no significant effect on mortality of experimental mice. These data agree with published results of multicenter studies.

[The anti-arrhythmia activity of energy-providing and electron-acceptor compounds]. / Protivoaritmicheskaia aktivnost' nekotorykh énergoobespechivaiushchikh i élektronaktseptornykh soedinenii.

The protective effects of fructose-1, 6-diphosphate, sodium malate and cytochrome C were studied in the experiments on rats with disorders of the cardiac rhythm of various origin. The compounds studied prevent the strophantine and adrenaline-induced cardiac rhythm disturbances, but appeared ineffective on aconitine and calcium chloride models.

[The antiarrhythmic activity of glycolysis and Krebs cycle intermediates in early occlusion and reperfusion arrhythmias in rats]. / Issledovanie protivoaritmicheskoi aktivnosti nekotorykh intermediatov glikoliza i tsikla Krebsa pri rannikh okkliuzionnykh i reperfuzionnykh aritmiiakh u krys.

Acute experiments on unconscious rats have demonstrated that fructose-1,6-diphosphate, phosphoenolpyruvate and malate of sodium produced a marked antiarrhythmic activity in acute occlusive and reperfusion arrhythmias, prevented the development of ventricular fibrillation and tachycardias, considerably reduced the duration of arrhythmia paroxysms, but they were ineffective in ventricular extrasystole.

[The effect of fructose-1,6-diphosphate and phosphoenolpyruvate on the course of early occlusion and reperfusion arrhythmias in rats]. / Vliianie fruktozo-1,6-difosfata i fosfoenolpiruvata na techenie rannikh okkliuzionnykh i reperfuzionnykh aritmii u krys.

Fructose-1,6-diphosphate (150 and 50 mg/kg) and phosphoenolpyruvate (0.5 and 0.1 mg/kg) decreased the development of ventricular tachycardia, ventricular fibrillation and the intensity of ventricular extrasystoles after coronary occlusion in experimental rats. Both compounds were active as anti-fibrillation agents on reperfusion arrhythmias. Fructose-1,6-diphosphate potentiated the effect of lidocaine.

[The effect of a combination of N-propylajmaline bromide and trimecaine on heart arrhythmias of different origins and on the electrophysiological parameters of the myocardium]. / Vliianie kombinatsii N-propilaimalinbromida i trimekaina na aritmii serdtsa raznogo geneza i élektrofiziologicheskie parametry miokarda.

In experiments on dogs and cats with disorders of the atrial and ventricular rhythms of various genesis the combination of N-propylaymalinebromide and trimecaine (the antiarrhythmic drugs of classes IA and IB) was found to potentiate the antiarrhythmic action. This effect was studied in electrophysiological experiments by using the microelectrode technique or on the dog and rat myocardium tissue. The combination of the antiarrhythmic drugs was shown to exert a more significant effect on some electrophysiological parameters determining the arrhythmic readiness of the myocardium.