Silencing of TERT decreases levels of miR-1, miR-21, miR-29a and miR-208a in cardiomyocytes.

To test the hypothesis that telomerase reverse transcriptase (TERT) as an RNA-dependent RNA polymerase could be involved in the amplification of microRNA (miRNA), we have determined the levels of immature and mature miRNA in cultured neonatal rat cardiomyocytes, during the silencing of TERT by siRNA. The silencing of the TERT gene led to the reduction of both telomerase activity and the TERT mRNA expression when compared with scrambled RNA. TERT gene silencing resulted in the decrement of three studied mature miRNAs levels: miRNA-21, miRNA-29a and miRNA-208a when compared with scrambled RNA; but miRNA-1, it was not changed significantly. At the same time, levels of immature miRNA-1 and miRNA-208a were not changed, although the levels of immature miRNA-29a and pri-miRNA-1 were decreased. The data obtained allow us to permit that TERT is a genome-independent source of mature miRNA, and the changes in telomerase activity can significantly influence the level of miRNA in cardiomyocytes.

[The frequency of polymorphism in promoter gene coding epoxygenase 2J2 in patents with acute coronary syndrome].

G(-50) --> T promoter polymorphism of gene encoding human epoxygenase 2J2 in 107 patients with acute coronary syndrome and in 104 practically healthy people was determined. It was shown that interrelation of genotypes G/G, G/T and T/T was 91%, 9% Ta 0% correspondingly (in control--92%, 7%, 1%; P > 0.05 by chi2-test). The data indicate that epoxygenase 2J2 gene polymorphism is not a risk factor of acute coronary syndrome in Ukrainian population.

ASSOSIATION ANALYSYS OF 11 POLYMORPHISMS OF SNPS WITH ENDOTHELIUM DEPENDENT VASODILATATION IN CHILDREN WITH DIABETES MELLITUS TYPE 1.

We have studied the association with the level of the endothelium dependent vasodilatation (EDVD) among 11 single nucleotide polymorphisms (SNPs) of 10 genes in 45 children suffering from diabetes mellitus type 1. Following polymorphisms have been studied: G894→T of the eNOS exon 7 and Т-786→С of the eNOS promotor, А1266→G of the Eln exon 16, Т-381→C of the NPPB promotor, І\D of the ACE, Arg60→His of the LMP2, Met235→Thr of the AGT, A1166→C of the ATR1, C-1562→T of the MMP9, C-1306→T of the MMP2, and С-8→G of the PSMA6. It was shown that children with genotypes G/T by eNOS (G894→T), G/G by Eln (А1266→G), C/C by NPPB (Т-381→C) and І/D by ACE genes have lower EDVD (Р<0,05) than patients with others allelic variants of these genes, and this does not depend on duration of the disease, level of glicated hemoglobin and initial diameter of a humeral (brachial) artery. The combination of the above-stated genotypes influences most significantly on EDVD decrease (r=0,61; Р<0,01), comparing to each genotype separately.

[Role of nitric oxide in the mechanisms of formation of reflex vasomotor responses].

This review focuses on modem data concerning the role of nitric oxide (NO) in the mechanisms of vasomotor regulation. On the background of the literature data and own experimental results, we have discussed some questions of NO integration into transmission of impulses in central and autonomic nervous system under condition of realization of cardiogenic and sinocarotid pressor and depressor reflexes, reflectory vasomotor responses formation under acute myocardial ischemia. According to literature and own functional and morphological data we suggest species differences in NO participations in mechanisms of reflex self--regulation of circulation.

[The frequency of allelic polymorphism of genes encoding immunoproteasome catalytic subunits in acute coronary syndrome patients].

Large multifunctional protease LMP2 (Arg60-->His) and LMP7 (Lys145-->Gln) gene allelic polymorphism in 200 patients with acute coronary syndrome and in 80 practically healthy people was determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphism is 52, 40.5 and 7.5 % correspondingly (in control group 53.8, 38.7, 7.5 %; P > 0.05 by chi2-test). Analysis of LMP7 gene polymorphism has shown that Lys/Lys - 89.5 %, Lys/Gln - 10.5 %, Gin/Gin - 0 % (in control group 93.8, 6.2, 0 % correspondingly; P > 0.05). The data show that LMP2 and LMP7 gene polymorphism is not a risk factor of acute coronary syndrome in Ukrainian population.

[Frequencies of allelic polymorphism of endothelial NO-synthase gene in patients with acute coronary syndrome in Ukrainian population].

Endothelial NO-synthase (eNOS) gene allelic polymorphism in 221 patients with acute coronary syndrome and in 83 practically healthy people was determined. It was shown that interrelations of normal homozygotes, heterozygotes and pathologic homozygotes in T/C promoter polymorphism analysis accout 48%, 36% and 16% correspondingly (in control--48%, 46%, 6%; P < 0.05 by chi2-test); in G894 --> T polymorphism ofexon 7 analysis--34%, 58%, 8% (in control--29%, 67%, 4%; P > 0.05), and in determination of 4a/4b polymorphism of intron 4--64.5%, 31% and 4.5% (in control--62.5%, 32.5%, 5%; P > 0.05). Obtained data show that eNOS C/C promoter variant is a risk factor of acute coronary syndrome in Ukrainian population.

[Nikolai Nikalaevich Sirotinin and his school]. / Nikolai Nikolaevich Sirotinin i ego shkola.

In a brief review of 50-year scientific activity of professor N. N. Sirotinin and his students the authors emphasize that this broad-minded scientist contributed to development of such disciplines as microbiology, pathophysiology, high-altitude, aerospace medicine. However, his main goal was evolution of reactivity and resistance, approaches to perfection of human health and performance. Much attention was paid to effects of low partial oxygen pressure on human and animal body, to hypoxic states of different origin. Methods of hypoxytherapy and hypoxic training are widely used in Russia and abroad. The contribution of academician N. N. Sirotinin to modern pathophysiology, high-altitude and aerospace physiology, internal and sport medicine is highly appreciated in Russia.

[Study of the relation between cardiac function and the tonus of resistant vessels in experimental disorder of coronary circulation]. / Issledovanie vzaimootnoshenii mezhdu funktsiei serdtsa i tonusom rezistivnykh sosudov pri eksperimental'nom narushenii koronarnogo krovoobrashcheniia

In tests set up on dogs under morphine-chloralose anesthesia features specific for upset cardio- and hemodynamics following a primary and repeated (against the background of a preliminarily provoked myocardial infarction) acute disruption of the coronary circulation were investigated. The development of an acute ischemia of the myocardium in animals with preliminarily induced chronic disruption of the coronary circulation was shown to be attended by more intensive than in healthy dogs hemodynamic shifts and functional disorders of the heart, whereas the reflex component of the reaction, the vasodilating reactions of the peripheral vessels, in particular, proved much less marked. Possible mechanisms accounting for differences in the derangement of the cardio- and hemodynamics in primary and repeated ischemia of the myocardium are discussed.

[The effect of the 5-lipoxygenase inhibitor quercetin on the functional and morphologic manifestations of myocardial lesions in ischemia and reperfusion of the heart]. / Vliianie blokatora 5-lipoksigenazy kvertsetina na funktsional'nye i morfologicheskie proiavleniia porazheniia miokarda pri ishemii i reperfuzii serdtsa.

In experimental canine myocardial infarction induced by an hour coronary artery occlusion, followed by 5-hour reperfusion, quercetin solution, 10 mg/kg, was demonstrated to improve left ventricular myocardial contractility, to reduce the incidence of rhythm and conduction disturbances, to promote the limitation of an ischemic lesion area, to produce a protective effect on the ultrastructure of coronary artery, contributing to the maintenance of vessel integrity, improvement of coronary blood flow, and prevention of intravascular thrombus formation.

[Cardiogenic influences on the blood circulation]. / Kardiogennye vliianiia na krovoobrashchenie.

The nature of cardiogenic influences on the circulation and the sensitivity of cardiac receptors to several substances after local immune damage of the heart, were studied: 30 min. after immune damage of the heart the depressor reflexes from the heart disappeared, and afferent impulse vagal activity was decreased. After immune damage of the heart, cardiac sympathetic afferent fibres are more sensitive to endogenous biologically active substances that vagal ones. The sympathetic cardiac afferent system seems to be more sensitive to chemical agent, being a decisive factor in the form of cardiogenic influences on the circulation during pathological processes in the heart.

[Disordered ion-transport processes in the cardiomyocyte membranes in the immune action on the heart]. / Narushenie ion-transportnykh protsessov v membranakh kardiomiotsitov pri immunnom vozdeistvii na serdtse.

Intracoronary administration of anticardiac cytotoxic serum increased the sarcolemma passive permeability for Ca2+ ions and reduced the activity of Na+-Ca2+ and Na+,K+-ATPase exchange in dogs. Electronic microscopy revealed thinning of glycocalix, destabilizing of the sarcolemma phospholipid bilayer, and development of intracellular oedema. Disturbances of the sarcolemma structure and function seem to be able to cause the development of cardiac insufficiency of immune origin.

[Blood oxygenation in the lungs and characteristics of the development of a hypoxic state during hyperthermia]. / Oksigenatsiia krovi v legkikh i osobennosti razvitiia gipoksicheskogo sostoianiia pri gipertermii.

The effect of 3-hr hyperthermia on the oxygen body regimen parameters and lung blood oxygenation was studied in dogs. A hypoxic state was shown to develop specific by arterial and venous hypoxemia, an imbalance between arterial oxygen transport and oxygen consumption, as well as hypocapnia and acid-base disturbances.

[Comparative characterization of the lipoprotein spectrum and status of free radical processes in the blood of rabbits exposed to external gamma-irradiation and cholesterol administration]. / Sravnitel'naia kharakteristika lipoproteinovogo spektra i sostoianiia svobodnoradikal'nykh protsessov v krovi u krolikov pri vneshnem gamma-obluchenii i vvedenii kholesterina.

Characteristic of lipoprotein spectrum and state of free-radical processes in the animals under action of ionizing radiation and cholesterin diet are comparatively studied. The content of lipids in the blood serum increases on the 5th day after irradiation and then decreases on the 15th and 30th days. Cholesterin diet increases the content of cholesterin under practically unchanged content of triglycerides in the blood serum in all the terms of investigations. Total decrease of the intensity of induced chemiluminescence of the blood serum and erythrocytes after irradiation is shown. Peroral introduction of cholesterin evokes differently directed changes in the light sum of chemiluminescence--a decrease in erythrocytes and increase in the blood serum.

[The correlations between changes in coronary vascular tonus and eicosanoid formation during an immune action on the heart]. / Sootnosheniia mezhdu izmeneniiami tonusa koronarnykh sosudov i obrazovaniem éikozanoidov pri immunnom vozdeistvii na serdtse.

Activation of the lipoxygenase way of the arachidone acid metabolism was shown to play a major role in development of pathological processes in the heart. The data on interrelationship between the formation of eucosanoids and the character of the heart immune response to inhibition of lipoxygenase, were obtained. A correlation was found between the increase in the LTS4 in the blood and the development of prolonged constrictor responses of the coronary vessels.

[Effect of lipoxygenase derivatives of linoleic acid on functional activity of neutrophils]. / Vliianie lipoksigenaznykh proizvodnykh linolievoi kisloty na funktsional'nuiu aktivnost' neitrofilov.

The effect of lipoxygenase derivatives of 13-hydroperoxylinoleic acid (13-HPODE) and 13-hydroxylinoleic acid (13-HODE) on zymosan-induced chemiluminescence of rat neutrophils in vitro was evaluated. It was found that both derivatives inhibit functional activity of neutrophils. The extent of inhibition was changed by preincubation of neutrophils with arachidonic or linoleic acid. On the other hand, in experiments with dogs it was shown that the extent of such inhibition considerably increases after ischemia and reperfusion of myocardium. Thus we assume that the ratio of lipoxygenase derivatives of arachidonic and linoleic acid play the regulative role in functional activity of neutrophils. It was concluded, that lipoxygenase derivatives of linoleic acid inhibited the neutrophils functional activity.

[Mechanisms of the development of cardiogenic vagosympathetic reflexes]. / O mekhanizmakh razvitiia kardiogennykh vagosimpaticheskikh refleksov.

Mechanisms of development of cardiogenic vagosympathetic depressor reflexes during adrenergic heart stimulation and local immune and ischemic damages of the left ventricle were studied in anesthetized dogs and cats by recording afferent and efferent impulsation from cardiac nerves as well as cardiodynamic indices. Impulse activity in cardiac nerves showed reciprocal changes: an increase in frequency of afferent impulsation in vagal nerves and inhibition of efferent impulsation in sympathetic nerves. The data obtained suggest that stimulation of heart mechanoreceptors due to the increase of myocardial contractility and asynergy of the left ventricle, is a triggering mechanism for reflex inhibition of sympathetic impulsation and depressor reflex.

[The heart as an endocrine organ]. / Serdtse kak éndokrinnyi organ.

Modern data on atrial natriuretic factor (ANF) are presented. Synthesis of this factor, its storage and release from cardiac atria are described. The role of ANF in the body fluid volume regulation and blood pressure homeostasis is discussed. ANF is regarded as a circulating hormone.

[Correction of the level of peptide leukotrienes as mediators of ischemia and shock]. / Korrektsiia urovnia peptidoleikotrienov--mediatorov ishemii i shoka.

The review generalizes certain data on application of inhibitors and antagonists of biochemical ways for arachidonic acid conversion.

[Interaction of inotropic effects on acetylcholine, adrenaline and increase of atrium stimulation frequency in rats adapted and non-adapted to physical exercise]. / Vzaimodeistvie inotropnykh vliianii atsetilkholina, adrenalina i uvelicheniia chastoty stimuliatsii predserdii u adaptirovannykh i neadaptirovannykh k fizicheskoi nagruzke krys.

It is shown in experiments carried out on the isolated strips of the left and right atria of the rat that adrenaline decreases the inotropic effect of acetylcholine while interatrial differences of chrono-inotropy are elevated by acetylcholine and adrenaline. Training of animals changes interaction of regulatory effects in such a way that an increase of the negative chrono-inotropy is compensated and efficiency of the cardiac muscle regulation grows.

[Disorders of cardio- and hemodynamics in endotoxic shock]. / Narusheniia kardio- i gemodinamiki pri éndotoksicheskom shoke.

Relative significance of cardiac and vessel components as well as the role of arachidonic acid metabolites in the development of endotoxic shock have been investigated in two series of experiments on the mongrel dogs. It is determined that endotoxin exerts no direct negative inotropic influence on the myocardium: blood pool in peripheral capacitance vessels plays a main role in the development of the first phase of the endotoxic shock (the first 30 min), that is a result of prostacyclin influence on these vessels, while in the subsequent phase it is a result of the bloodflow disturbance in the myocardium or arachidonic acid metabolites influence on the myocardium. Administration of endotoxin to the bloodflow significantly increased concentration of prostanoids; thromboxane A2 and prostacyclin in it. Indomethacin, inhibitor of prostaglandin synthesis, prevents development of the endotoxic shock.