Vol 13, No 3 (2015)

Articles
Medical clinical perspectives of the hypoxia adaptation factor inhibitors
Novikov V.E., Pozhilova E.V., Levchenkova O.S.
Abstract
The protein regulatory factor HIF-1α (hypoxia-inducible factor-1alfa) plays a leading role in mechanisms of adaptation of the organism tissue to hypoxia, including tumor hypoxia. HIF-1α is a potent inducer of angiogenesis in the field of tumor growth. The importance of HIF-1α in development of tumors and possibility of target pharmacological action on HIF-1α and the related growth factors with help of their inhibitors is discussed in the article. Such approach is represented to have the perspectives in pharmacotherapy of oncological, rheumatic and other diseases in pathogenesis of which hypoxia and ischemia takes the inducing role.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):9-17
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Antihypoxic effects of new metal-complex copper-containing substances
Sosin D.V., Shalayeva O.E., Evseev A.V.
Abstract
In experiments on mice in 3 different models of acute exogenous hypoxia, 12 new substances concerning to a group of copper-containing physiologically compatible antioxidants were investigated. It was discovered that substances πQ262, πQ1077 А and πQ1079 А significantly increase lifetime of mice during development of all used variants of hypoxias. On the example of the most active agents in the studied group (πQ262, πQ1077 A, πQ1079 A) shows that their anti-hypoxic effect on the development of acute exogenous hypoxia is accompanied by a marked decrease in the standard of energy metabolism, as well as a significant inhibitory effect on the state of the cardio-respiratory system of experimental animals. The obtained results allow attributing such substances as πQ262, πQ1077 А and πQ1079 А to the antihypoxant group of metabolic action.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):18-23
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Assessment of efficacy in treatment of inflammatory and degenerative damages of the parodont smooth tissue with tooth pastes according to oxidative status indexes in rats
Mokrenko E.V., Shabanov P.D.
Abstract
A rat model of inflammatory and degenerative damages of the smooth parodont tissue by means of administration of 2 % formaldehyde water solution into the smooth parodont tissues was described. The oxidative status of rats including lipid peroxidation and antioxidant defense system indexes was assessed because of their high sensitivity to inflammation process. The lipid peroxidation indexes (malonic dialdehyde and dienic conjugates level) were 2-3-fold higher in the blood serum and parodont tissue in 7 days after inflammation beginning. The system of antioxidant defense (recovered glutatione level and activity of superoxide dismutase) was more sensitive in comparison with lipid peroxidation. The recovered glutation content in the blood serum was decreased from 2.02 ± 0.09 till 0.88 ± 0.21 µM/ml, and superoxide dismutase activity was reduced from 0.78 ± 0.10 till 0.28 ± 0.04 А/mg protein, that was these indexes were decreased in 2.5-3 times. The same regularity was observed in the smooth tissues of the parodont. The recovered glutation level was decreased in 2.1 times and superoxide dismutase activity was reduced in 7 times. Therefore, the curative and prevention action of tooth pastes and stomatologic drugs could be assessed with this model of inflammation. In particular, the tooth pastes lesmin-dent > clamin-dent > zhemchug (in order of descending activity) attenuate or abolish signs of inflammatory and degenerative damages of the smooth parodont tissue in rats assessed on lipid peroxidation and antioxidant defense system indexes.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):24-28
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Experimental assessment of the KK1 peptide effectiveness for prevention of the CNS delayed impairments after acute intoxication with carbon monoxide
Tolkach P.G., Basharin V.A., Grebenyuk A.N., Kolobov A.A.
Abstract
Intoxication with the carbon monoxide leads to the development the early and delayed neuropsychological impairments. Oxygen therapy is used usually as an antidote for the treatment of acute carbon monoxide poisoning. The synthetic analogues of endogenous peptides were shown to prevent the neuropsychological impairments. One of them is KK1, a tetrapeptide acetyl-(D-Lys)-Lys-Arg-Arg-amide, assessed as a structural analogue of corticotropine. The efficiency of the synthetic tetrapeptide KK1 for the prevention of the CNS delayed impairments after acute carbon monoxide poisoning has been evaluated in this study.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):29-34
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Experimental assessment of inflammatory effect of hypoxen
Khnychenko L.K., Okunevich I.V.
Abstract
The experimental model of acute carrageenan-induced inflammation and chronic model of the “cotton wool`s granuloma” in mice and rats were used in the experinent. The changes in the volume of damaged limb with oedema and granuloma mass in groups of animals were registered. The effect of hypoxen (polydihydroxyphenylenthiosulfonate sodium) and comparative drugs simvastatin and ibuprophen on the inflammatory reaction was studied. Ibuprophen and simvastatin were shown to reduce the development of inflammatory reaction. The administration of hypoxen in dose of 50 mg/kg has got the significant efficiency in lowering of oedema degree and significant decreasing of inflammatory tissue assessed by granuloma mass.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):35-38
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Changes in intracellular potentials and ionic currents of the mollusk and activity of Cl--channels under exposure to some inhibitory amino acids and new litium-containing compounds of them
Shabanov P.D., Vislobokov A.I., Shilov G.N., Bulay P.M., Lugovskii A.P.
Abstract
The Changes of membrane rest potential (RP), action potential (AP), impulse activity (IA) as well as sodium, calcium and potassium ionic currents in neurons of isolated central nervous system of the Planorbarius corneus mollusk (pedal ganglia) under the extracellular action of inhibitory amino acids GABA, glycine and β-alanine and their litium-containing derivatives (LCD) in 0.1, 1 and 5 mM concentrations have been studied using a microelectrode technique. They induced the same dose-dependent and irreversible depolarization of neurons on 2-10 mV accompanied by increase of AP frequency, prolongation of their duration and decrease of summmerized ionic currents (dV/dt). According to degree of depolarization, the drugs were placed in the following range in decreasing activity: compound 3 > compound 2 > compound 1. In identified pedal ganglion neurons (PPed1), compound 3 in contrast to other compounds induced hyperpolarization by 2-10 mV and blocked impulse activity. The amplitude of sodium and calcium channels was decreased by 7-15 %, in the same degree after application of all compounds exposed in concentration of 5 mM. Efflux potassium ionic currents were increased in dose-dependent manner and irreversibly about by 3-7 % assessed on amplitude indexes without changes in kinetic parameters after application of LCD. Therefore, the decrease of ionic current amplitudes was due to both depolarization of neurons and direct action of LCD on ionic channels. Thus, LCD possess membranotropic activity and can modulate functional state of neurons. In the study of chloride channels in cells culture of rat glioma C6 in vitro by patch-clamp method, GABA, glycine, β-alanine and their LCD 10 µM/l activated chloride channels, shifting equiliblium membrane potential of glioma cells from -90… -70 mV to -55... -60 mV. All compounds (transmitters and LCD) were placed in the following range: glycine > GABA > β-alanine and compound 1 > compound 3 > compound 2 according to descending activity. Therefore, the most active compounds activating Cl--channels were glycine and compound 1 (LCD). Glycine was shown to be coagonist GABA receptors and its litium salt possessed significant membranotropic activity.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):39-47
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Statokinetic stability improvement in healthy volunteers by pharmacological drugs (pilot study)
Buinov L.G., Sorokina L.A., Buznik G.V., Shabanov P.D.
Abstract
In 26 healthy volunteers of 18-20 years old, the statokinetic stability before and after 10-days course of the complex of pharmacological drugs MAOP (metaprot 0.25 g, aerovit 1 tab., potassium orotate 0.5 g twice a day) was studied. The statokinetic stability was determined by time of maximal endurability of unbroken cumulation of Kariolis’ accelerations (UCKA) with registration of severity of sensory, vegetative and somatic reactions of volunteers. Prescription of MAOP complex improved endurability of UCKA. Time of maximal endurability of UCKA was increased by 91.2 %, sense of heat was reduced by 50 %, headache and painful sense in the head - by 60 %, sickness - by 62.5%, hyperhidrosis - by 53.8%. Improvement of statokinetic endurability in volunteers was supported by the complex computer stabilography data. It is suggested that statokinetic stability can be improved by means of preventive course of pharmacological complex of MAOP.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):48-52
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Probable molecular genetic predictors for development of the locomotor system pathology in the extreme physical exertion
Kozlova A.S., Pyatibrat A.O., Buznik G.V., Melnov S.B., Shabanov P.D.
Abstract
The article presents the basic results of the theoretical analysis of currently available data on modern and future using of molecular genetic markers to determine predisposition to musculoskeletal system diseases in athletes and subsequent regenerative capacity of the organism. The basic genetic markers associated with athletes resistance to injuries are described. It has been shown that one of the most important factors is genetic predisposition to osteoporosis.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):53-62
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Tactics of diabetes treatment according to the principle “opposite with opposite” in the Avicenna’s “Canon of Medicine“ and its relevance to modern medicine
Sharofova M., Nuraliev Y.N., Sagdieva S.S.
Abstract
In the article, at the junction of Avicenna's medical system and the achievements of modern medical sciences, used as evidence, the nature, indications for use of the tactics of therapy, “the opposite with opposite” and its significance for modern medicine as pathogenetic therapy of diseases pathogenesis of which is associated with the development of metabolic syndrome is analyzed.
Reviews on Clinical Pharmacology and Drug Therapy. 2015;13(3):63-68
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