Endogenous Sensitizer of Beta-Adrenergic Receptors (ESBAR) as a Component of Humoral Links Element of Autonomic Nervous System and Its Analogs (Review).

Kirov State Medical Academy, Kirov The results of the 20-years studies of the presence in blood serum and other body fluids of endogenous modulators of adrenergic and M-cholinergic impact a A COMPONENT of humoral element of autonomic nervous system. The article is devoted to the endogenous sensitizer of beta-adrenergic receptor (ESBAR) - water-soluble low molecular weight substances, analogues of which are histidine, tryptophan, tyrosine, mildronat and preduktal. It is shown, that separate dilutions of human serum and animal (as a source of ESBAR) and ESBAR - analogues ways to enhance the effectiveness of activation of beta-adrenoceptors (AR) of smooth muscle (uterus, coronary and renal arteries, trachea, stomach), myocardium and erythrocytes and platelets (respectively influenced of histidine and tryptophan). It is reported? that content of ESBAR in human serum (according to the titers of its dilution) depends on the sex and the presence of somatic diseases, and at women are also on the stage of reproduction and obstetric complications It is discussed hossible mechanisms of ESBAR action, its physiological role, including as a component of beta-adrenoreceptor myometrium inhibitory mechanism, as well as the prospect of the use of analogues ESBAR, including for the prevention of preterm labor, and for the treatment of bronchial asthma, coronary heart disease, hypertension and heart failure.

[Influence of high altitude on the functional status and morbidity of teenagers].

With the aim to determine the influence of the high latitudes on the main indices of the blood and morbidity, physical development of adolescents of 14 years old residing in Kirov (n = 139) and Ukhta (n = 253), the evaluation of basic parameters of their blood, physical development and morbidity has been performed accordingly to standards methods. The inhabitancy of adolescents in high latitudes (Ukhta) in comparison with their peers from temperate latitudes (Kirov) leads to body weight gain of 4.7 kg in girls and 5.8 kg in boys, gives rise to the increase in gender diferences in hemoglobin concentrations and ESR and boosts overall morbidity.

[Comparison of the physical development of 17-18-years old girls in 1996 and 2007].

The screening studies conducted in 2007 indicated that there was a reduction in the physical development of 17-18-year-old girls (n = 530) in the Kirov Region in the past decade (1996-2007). With their higher height, the 2007 girls showed decreases in body weight, chest circumference, vital capacity, diastolic blood pressure, but higher heart rate, as compared with the 1996 population. There were also reductions in weight-to-height ratio, Quetelet index, Rohrer index, and vital index and increases in the Pignet index, effective circulation index, and Quass endurance factor. The use of centile tables showed that 30 and 11% in the 2007 population had disharmonious and very disharmonious development, respectively; and microsomatic body build was seen in 81%. Therefore, the asthenization or deceleration of physical development in 17-18-year-old girls, which was ascertained in the late 20th century, also continues in the early 21st century.

[Influence of amino acids alimentary on contracts ability in 13-adreno- and M-cholinoreactivity of smooth muscles].

It was studied the influence of 20 amino acids on beta-adreno- and M-cholinoreactivity of longitudinal strips (n = 268) of rat uterus horn (n = 46) with the help of adrenaline (10(-8) g/ml) and acetilcholine (10(-6) g/Ml) accordingly. It is shown, that 3 amino acids from 20, including L-histidine (3 x 10(-8) - 3 x 10(-5) g/ml), L-triptophan (10(-8) - 10(-5)) and D-, L-tyrosine (2 x 10(-8) - 2 x 10(-5)), not changing M-cholinoreactivity of uterus smooth muscles, everyone or complexly essentially raised their beta-adrenoreactivity, i.e. expressed their beta-adrenosensibilisatory activity. It allows to consider that this amino acids are possible components of endogenic sensibilisator of beta-adrenocepters. It is discussed the question about using this amino acids in a dietary meal and complex therapy at insufficiency of beta-adrenergic influences on visceral organs.

Bone marrow stem cells repopulate thyroid in X-ray regeneration in mice.

The aim of this study was to clarify the regeneration mechanisms of thyroid in post-irradiated C57Bl/6 mice chimeric with transgenic green fluorescent protein (GFP) positive C57Bl/6 mice after 5 and 7.5Gy X-ray exposures with the aid of morphological and immunocytochemical research of GFP-positive cell distribution. Cryostat slides of larynxes with thyroid glands were fixed by mixture of cold methanol and ethanol, cell nuclei were stained with propidium iodide. After immunocytochemical staining the slides of larynx with thyroid gland were investigated by means of confocal LSM 5 PASCAL microscope. True GFP nature of green signals in tissue slides was confirmed via additional treatment by anti-GFP antibody and Texas Red labeled second antibody. Separate GFP-positive cells were observed in the walls of follicles and between follicles of chimeric mice 9-10 months after X-ray exposure. GFP signal was viewed as cytoplasmic droplets and within the colloid of follicles. The share of GFP-positive follicles reached 6.1±1.8%. There was also co-localization of GFP signals and positive staining for thyroglobulin by monoclonal antibody. As many as 20.8±1.8% among all propidium iodide positive blood cells and 52.3±8.3% among propidium iodide positive bone marrow cells were at the same time GFP-positive. In conclusion, the results show that the bone marrow stem cells participate in the thyroid gland regeneration after 5Gy X-ray exposure.

Histidine increases beta-adrenoreactivity of myocardium in frogs.

Histidine (3x10(-5) g/ml) had no effect on contractility and chronoinotropic relationships in frog myocardium, but rapidly and reversibly increased myocardial beta-adrenoreactivity (increased myocardial response to 7x10(-8), 3x10(-7), and 4x10(-6) g/ml epinephrine) and potentiated the positive effect of epinephrine (7x10(-8), 3x10(-7) g/ml) on chronoinotropic relationships in the myocardium. Histidine is considered to be a component of endogenous sensitizer of beta-adrenoceptors in human blood modulating the function of cardiomyocytes.

Ability of L-histidine to decrease desensitization of the myometrium to epinephrine.

Experiments were performed with 62 longitudinal strips of the uterine horns from 10 nonpregnant rats. The ability of continuously infused epinephrine in high concentration (10(-6) g/ml, 30 min) to suppress spontaneous contractions due to activation of beta-adrenoceptors progressively decreased, which was associated with receptor desensitization. Histidine in a concentration of 3 x 10(-11) g/ml had no effect, while in concentrations of 3 x 10(-8), 3 x 10(-7), and 3 x 10(-6) g/ml decreased the degree of desensitization. Our results indicate that histidine not only potentiates beta-adrenoceptor activation, but also prevents the development of desensitization. These data should be taken into account during therapy with beta-adrenoceptor agonists.

[Effect of ozone exposure on contractile activity and chemoreactivity of uterus horns longitudinal muscles of nonpregnant rats]. / Vliianie ozona na sokratitel'nuiu aktivnost' i khemoreaktivnost' prodol'noi muskulatury roga matki neberemennykh krys.

With the purpose of studying the mechanism of ozone action on uterus smooth muscles it was investigated the influence of ozone-content (approximately 0.50 mkg/ml) Krebs' solution or its 10- and 100-fold dissolution on contractile activity and beta-adrenoreactivity of 56 longitudinal strips of uterus horns of 17 nonpregnant rats. Ozone at concentration approximately 0.50 mkg/ml (but not in concentration of approximately 0.05 and approximately 0.005 mkg/ml) reversibly raised frequency, amplitude and total contractile activity of intact myometrium strips, and also fast and reversibly reducel its beta-adrenoreactivity, i.e. decreased of inhibitory action of adrenaline (10(-8), 10(-7), 10(-6) g/ml), but did not change uterostimulatory effect of acetylcholine (10(-6) g/ml) and oxiyocin (5 x 10(-4) ME/ml), what evident about specificity of ozone beta-adrenoblokate effect. Ozone (approximately 0.50 and 0.05 mkg/ml) did not change ov value of potassium contracture of myometrium strips which was depolarized by hyperpotassium (60 mM KCL) Krebs' solution, but reduced inhibitory action of adrenaline (10(-8) g/ml). The question is being discussed about mechanisms of ozone beta-adrenoblocade actions, about clinical role of this phenomenon, and the possibility of using beta-adrenoreceptor sensibilizators direct action (histidine, tryptophan, tyrosine, trimetazidin and mildronat) at ozonotherapy with the purpose reduction of its negative effects.

[The role of endogenous modulators of chemoreactivity in the regulation of coronary blood flow]. / Izuchenie roli éndogennykh moduliatorov khemoreactivnosti v reguliatsii koronarnogo krovotoka.

32 circulatory bands of coronary arteries of 5 pigs were studied. It has been revealed that the bands develop long-term tonic contraction activity in Krebs's solution (30 mM of KCl). In this case adrenalin in concentration of 10(-7) g/ml causes mild relaxation. In concentration of 10(-6) g/ml, it causes obvious relaxation. Trimetazidin and mildronat do not affect tonic contraction of the bands. They can quickly and reversibly increase relaxation effects of adrenaline. The preparations can increase ten-fold beta-adrenoreactivity of smooth muscles. This shows an important role of endogenic sensibilizers of beta-adrenoreceptors in regulation of coronary blood flow in humans.

[Effect of physical training on M-cholinergic-blocking activity of blood serum in acute coronary disease]. / M-kholinoblokiruiushchaia aktivnost' syvorotki krovi pri ostrom koronarnom intsidente i vliianie na nee fizicheskikh trenirovok.

On 93 longitudinal strips of 31 rats' uterus horns, M-cholinoblocking agent activity in 50-, 100-, 500-, 1000- and 10,000-fold dilution of the blood serum taken from 10 healthy older subjects and 40 patients after an acute coronary incident, was studied, 10 patients being engaged in physical training. Findings suggest presence of an endogenous M-cholinoreceptor blocking agent in the blood with lisophosphatidylcholin as the basic component. An acute coronary incident seems to reduce the efficiency of the M-cholinergic effect on the heart and vessels.

Effect of physical training on blood level of endogenous modulators of beta-adreno- and m-cholinoreactivity in patients with a history of myocardial infarction.

The relative content of myocyte-active factors and endogenous muscarinic receptor blocker in the blood increased, while the concentration of endogenous beta-adrenoceptor sensitizer decreased in coronary patients with a history of acute myocardial infarction. Physical training produced a therapeutic effect, normalized the content of these factors and, probably, improved beta-adrenergic and muscarinic cholinergic regulation of the heart and vessels.