[MOLECULAR MECHANISMS OF ERK1/2 KINASES REGULATION IN THE GLUTAMATE- AND GABA-ERGIC NEURONS DURING SEIZURE EXPRESSION IN KRUSHINSKY-MOLODKINA RATS].

The aim of the present study was to analyze a role of the ERK1/2 signaling pathway in the regulation of excitation and inhibitory neurons in the hippocampus and the temporal cortex of Krushinsky-Molodkina rats during seizure development finalizing with ataxia. Analysis was done by Western bloting as well as by immunohistochemistry. The results demonstrated significant up-regulation of ERK1/2 activity in the hippocampus in several seconds after sound stimulation. At the same time increased ERK1/2 activity was correlated with enhanced level of SNARE protein SNAP-25 and activation of synapsin I, the proteins which regulate exocytosis machinery. Decreased level of VGLUT2 associated with activation of ERK1/2 and exocytosis proteins supposed activation of glutamate release in the hippocampus, while in the temporal cortex diminished activity of ERK1/2 and synapsin I associated with VGLUT2 up-regulation assumed inhibition of glutamatergic transmission. Our data let us supposed that decreasing of glutamate release in th& temporal cortex could be a trigger for the inhibition of hippocampal glutamatergic system and the beginning of further ataxia stage. Our data demonstrated correlation between expression and activity of exocytosis proteins and ERK1/2 mainly in the glutamategic neurons of the hippocampus and the temporal cortex that let us proposed significant role of ERK1/2 kinases as a positive regulator of glutamate release and as a result initiation of seizure expression.

Role of the ERK signaling pathway in regulating vasopressin secretion in dehydrated rats.

Dehydration activates the vasopressinergic system of the hypothalamus. We analyzed the effects of dehydration induced by water deprivation for 3 days on the activities of ERK1/2 and transcription factors, Elk1 and cAMP response element-binding protein (CREB) in vasopressinergic neurons, as well as the distribution and level of the motor protein, kinesin, in the hypothalamo-neurohypophyseal system. We showed that dehydration resulted in enhanced vasopressin (VP) expression and activation of CREB, and increased the activity of the MEK/ERK/Elk1 pathway in magnocellular neurons of the supraoptic nucleus. The activation of VP secretion was associated also with accumulation of phospho-ERK1/2 in the VP-ergic terminals of the posterior lobe of the pituitary. Analysis of the amount and distribution of kinesin and SNAP25, the proteins associated with transport and secretion, demonstrated that dehydration enhanced kinesin content in the perikarya of magnocellular neurons in the supraoptic nucleus and decreased kinesin and SNAP25 levels in the posterior pituitary. ERK1/2 and ERK1/2-dependent transcription factors, Elk1 and CREB, participate in the regulation of dehydration-evoked VP expression. We propose that ERK1/2 and kinesin participate in regulation of anterograde transport of VP dense core vesicles.

[Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)]. / Effektivnost' razlichnykh doz dopamina pri ostroi ishemii miokarda, oslozhnennoi kardiogennym shokom (éksperimental'noe issledovanie).

The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

[Indications for the use of inosine in myocardial infarct (a clinical and experimental study)]. / O pokazaniiakh k primeneniiu inozina pri infarkte miokarda (kliniko-éksperimental'noe issledovanie).

The effect of the nucleoside Inosie-F (inosin) on the intracardiac hemodynamics and the contraction and relaxation of a diseased myocardium was studied in the clinic and in experiments. An examination was made of 102 patients with macrofocal myocardial infarction (22 received inosin by intravenous drip in a single dose of 200 mg in the acute stage of infarction; 60 patients were given inosin pills in a daily dose of 800 mg in the restoration period for one month, and 20 patients were given placebo). Comparative appraisal of treatment in the period of rehabilitation showed prevailing improvement in the condition of individuals treated with inosin, positive ECG dynamics, increase of cardiac output and decrease of peripheral resistance. In experiments on 28 dogs with a model of acute myocardial ischemia a noticeable improvement in myocardial contraction and relaxation in the absence of negative ECG dynamics was recorded after intravenous infusion of inosin. Inosin achieves maximum effect by 60-90 mins after the beginning of infusion.