Vol 16, No 2 (2018)

Articles
Metformin and vildagliptin combination: A new approach of endothelial nitric oxide synthase activity regulation and metabolism in diabetes mellitus type 2
Urakov A.L., Gurevich K.G., Sorokina I.A., Lovtsova L.V., Zanozina O.V., Monakhov A.A.

Abstract

This review analyzes the research results of additional effects and mechanisms of action of sugar-reducing drugs. Hence it has been suggested that asymmetric dimethylarginine may be a target molecule for metformin, vildagliptin, and combinations thereof.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):5-12
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Cardioprotection of Ischemic Myocardium
Bulion V.V., Krylova I.B., Selina E.N.

Abstract

Aim. Cardioprotective effect of precursors in the synthesis of the uridine-5ʼ-diphosphate (UDP) – the mitochondrial ATP-dependent potassium channels (mitoKATP channels) endogenous activator – uridine and uridine-5ʼ-monophosphate (UMP) and the relation between there mechanism of action and activity of mitoKATP channels were studied.

Methods. The experiments were performed on the male Wistar rats weighing 300-350 g. Acute myocardial ische mia (MI) lasting 60 min was produced by occlusion of the descending branch of the left coronary artery (LCA) under artificial pulmonary ventilation. Animals were anesthetized with sodium ethaminal (50 mg/kg). Uridine or UMP in the dose of 30 mg/kg was injected intravenously 5 min prior to LCA occlusion. A selective blocker of these channels 5-hydroxydecanoate (5-HD, 5 mg/kg intravenously 5 min prior to injection of uridine or UMP) was used to detect the involvement of mitoKATP channels in the effects of drugs. ATP and creatine phosphate (CP) was determined in the heart homogenates. The intensity of lipid peroxidation (LPO) was estimated by the content of lipid hydroperoxides (LHP) and the state of the antioxidant system (AOS) by superoxidedismutase (SOD) activity and the reduced glutathione (GH) content.

Results. Occlusion of the LCA during 60 min led to the decrease of ATP and CP content in the myocardium by 35% and 59% respectively. At the same time changes in LPO and AOS were observed. The amount of LHP increased by 97%, the activity of SOD was reduced by 28% and the content of GH decreased by 30%. Uridine and UMP given 5 minutes prior to LCA occlusion prevented the development of these metabolic disorders in the ischemic myocardium. Selective blocker of mitoKATP channels 5-HD eliminated the protective effect of both drugs.

Conclusion. Uridin and UMP have the evident cardioprotective effect in the acute MI, stabili zing the miocardium energy metabolism, preventing the AOS function depression and excessive activation of LPO. The mechanism of protective action of the drugs is associated with the activation of mitoKATP channels.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):13-17
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Comparative analysis of metal-complex and aminothiol antihypoxants efficiencies in the experiment
Evseev A.V., Surmenev D.V., Evseeva M.A., Sosin D.V., Tishkova Y.V.

Abstract

Aim. Comparative analysis of the efficiency of metal-complex (πQ1983, πQ2721) and aminothiol (Amtizole, Sunazole) antihypoxants in experiments on rats exposed to acute hypoxia with hypercapnia.

Methods. Experiments performed on 182 male rats of Wistar line weighing 150-170 g. The study of antihypoxic activity of substances was carried out on the model the AH+Hc. The condition of acute hypoxia in rats was formed by placing them in glass airtight containers with a free volume of 1.0 L. Antihypoxic effect was evaluated by the life expectancy of animals in the described conditions. Substances πQ2721, πQ1983, Amtizole and Sunazole was administered once intraperitoneally at doses of 25, 50 and 100 mg/kg. Previously each substance was dissolved in 0.9% NaCl (1.0 ml). Testing the effectiveness of the substances on AH+Hc model was carried out after 1 h after administration of the substances and after 24 h. Animals of control groups were injected with 1.0 ml of 0.9% NaCl. In animals exposed to test AH+Hc in 1 h after administration were performed measurements of the rectal temperature before the experiment and through 1 h after administration, i.e. before AH+Hc. In animals selected for 24-hour observation, rectal temperature was measured before the experiment, and then after 1, 3, 6, 12, 18 and 24 h of observation, after which they were exposed to AH+Hc.

Results. The antihypoxic effect of a selenium-containing substance πQ2721 based on Zn2+ was confirmed in experiments on rats. In a number of substances for comparison the πQ2721 proved himself not only as equally effective. It is found that after 1 h after administration at a dose of 50 mg/kg πQ2721 superior to all studied compounds, including antihypoxant with succinate Sunazole. An important advantage of the new promising antihypoxic agent was the preservation of its action for 24 hours after injection.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):18-24
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Antisurdant properties of the structural analogue of taurin
Khnychenko L.K., Petrova N.N., Il'inskaya E.V., Tanchuk A.E.

Abstract

The article presents the results of the study of the otoprotective effect of the structural analog of taurine in the case of sensorineural hearing loss. The work was performed on guinea pigs using electrophysiological and cytochemical methods. It is proved that the structural analogue of taurine has an antisurdantant (otoprotective) property, which manifests itself in restoring the amplitude-time characteristics of the potential of the auditory nerve action and the microphone potential of the cochlea.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):25-32
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Blockade of orexin receptors in the bed nucleus of stria terminalis increases serotonin level only in the left hypothalamus
Karpova I.V., Bychkov E.R., Lebedev A.A., Shabanov P.D.

Abstract

The aim of investigation was to study the role of the hypothalamic serotoninergic system in mechanisms of blocking action of the orexin receptor antagonist on amphetamine-induced self-stimulation in rats.

Methods. 27 male Wistar rats weighing 250-300 g were the object of the investigation. One week before the experiment, the microelectrodes were implanted into the lateral hypothalamus for self-stimulation and microcannulas into the bad nucleus of stria terminalis (BNST) for microinjections. The electrodes were implanted bilaterally and cannulas unilaterally (right or left). Intact rats and rats treated with amphetamine were controls. On the day of the experiment, amphetamine 1 mg/kg i.p. was injected, and then SB-408124 1 µg in 1 µl was administered into the BNST in 10 min. The rats were decapitated in 15 min after microinjection of SB-408124. The level of serotonin (Ser) and its metabolite 5-HIAA was determined in the right and the left hypothalamus by HPLC with electrochemical detection.

Results. In intact rats, the 5-HIAA level in the left hypothalamus was higher than in the right one (p < 0.05). After systemic administration of amphetamine the ratio of 5-HIAA/Ser was significantly decreased both in the left (p < 0.05) and the right (p < 0.05) hypothalamus. The levels of Ser and 5-HIAA stated symmetrical. It is important that effects of orexin antagonist after amphetamine administration appeared only on the side contralateral to microinjection being significantly only in the left hypothalamus. After administration of orexin antagonist into the right BNST, the level of Ser in the left hypothalamus increased compared both to intact rats (p < 0.05) and rats treated with amphetamine (p < 0.05).

Conclusion. The results suggest that the left hypothalamus plays a leading role in developing of self-stimulation reaction and support the hypothesis that the serotoninergic system is involved in mechanism of blocking action of orexin receptors antagonist on self-stimulation activated with amphetamine.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):33-36
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Asymmetry of reinforcing properties of the lateral hypothalamus in the self-stimulation test
Efimov N.S., Bessolova Y.N., Karpova I.V., Lebedev A.A., Shabanov P.D.

Abstract

In the protocols of modern pharmacological studies of a self-stimulation reaction in rodents, stimulating electrodes are implanted as a rule unilaterally. The reinforcing properties of the left and right hypothalamus were suggested to be identical.

The aim of the study was to clear up if the possibilities of the left and right hypothalamus to produce self-stimulation are similar or not.

Methods. The study was carried out on adult male Wistar rats. The electrodes were implanted into the lateral hypothalamus bilaterally. The rats, in which an approach reaction was observed, learned self-stimulation in the Skinner box with stimulation of the left or right hypothalamus as a reinforcing agent descending thresholds of stimulation up to minimal one.

Results. Self-stimulation of the left hypothalamus gave an approach reaction in the majority of rats (81.8%), self-stimulation reaction was developed in 72.7% of rats. Only 46.2% rats reacted on stimulation of the right hypothalamus, self-stimulation reaction was developed in 30.8% of rats. The thresholds of positive and negative reactions registered after electrical stimulation of both sides of hypothalamus were significantly differed (H(3, N = 31) = 14,92; p = 0,002). And these changes were not connected with lateralization but with sign of reaction: in general the thresholds of approach reaction were higher than thresholds of avoidance.

Conclusion. In the paper, the fact of different possibility of approach reaction and self-stimulation development as a result of electrical stimulation of the left and right hypothalamus in rats has been described. After stimulation of the left hypothalamus, a possibility to receive positive reaction and to form self-stimulation on its basis is higher than after stimulation of the right hypothalamus.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):37-41
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The administration of acetazolamidum for the symptom prophylaxis of an acute mountain sickness when short-term dislocation from middle mountains to highlands takes place
Vetryakov O.V., Bykov V.N., Fateev I.V., Khalimov Y.S.

Abstract

The development of mountain sickness symptoms is one of the limiting factors of successful physical performance in middle mountains and highlands. Among drugs with established effectiveness for the prophylaxis of an acute mountain sickness carbonic anhydrase inhibitor acetazolamidum is also viewed, but at presence there is no universal approach to this issue and drug dosage regimen for its administration have not been elaborated.

Aim. А comprehensive analysis of acetazolamidum being administered in the range of effective doses has been carried out.

Methods. During the experiment the effect of acetazolamidum on physical performance and resistance of rats to an acute hypobaric hypoxia when administered in the range of effective doses (20, 40 and 80 mg/kg) was studied. During full-scale approbation the effect of acetazolamidum in various dosages on adaptation processes in the course of a rapid dislocation from middle mountains to highlands (glade Azau-the Elbrus mountain) was assessed.

Results. The undertaken study showed that the administration of acetazolamidum to rats beginning from a daily do sage 20 mg/kg, that corresponds to human intake of 250 mg of the drug, promotes significant increase of survival time of rats following acute hypoxic exposure as well as growth of an animal performance ability factor under hypoxia.

Conclusion. In the course of full-scale approbation it was established that prophylactic intake of acetazolamidum in examined doses prevents the development of symptoms of an acute mountain sickness when rapid dislocation from middle mountains (2300 m) to highlands (5000 m) takes place in the background of physical activity according to the results of sportsmen’s performance of Lake Louise test.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):42-48
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Antibacterial therapy in the treatment of ascites peritonitis in liver cirrhosis
Ivanusa S.Y., Onnitsev I.E., Khokhlov A.V., Zubarev P.N., Yankovsky A.V., Bugaev S.A.

Abstract

Ascites-peritonitis is a severe complication in patients with decompensated cirrhosis. The effectiveness of treatment of ascites of peritonitis depends largely on its early diagnosis. The main component of the treatment of ascites-peritonitis – a complex and targeted antibiotic therapy. Third-generation cephalosporins are recommended as empirical antibiotic therapy. The article presents the results of treatment of ascites peritonitis depending on the method of administration of antibacterial drug – cefbactam. The drug was administered in three ways: intravenous, endolymphatic and combined. The results of pharmacokinetics of the drug depending on the method of administration, as well as the results of the effectiveness of the antibacterial effect in the compared groups of patients.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):49-56
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Problems of rational medicines use: the situation in Kyrgyzstan
Zurdinova A.A.

Abstract

The article discusses the problems of irrational medicines use at the hospital level of the health care system from the perspective of evidence-based medicine and assessment of the adherence of doctors to follow the recommendations from the developed clinical guidelines and protocols of the Kyrgyz Republic.

The study purpose was to analyze the use of medicines and assess the problems of irrational use in hospital-based health facilities in the Kyrgyz Republic.

The material of the study was the sheets of prescriptions from the case histories and the questionnaire on the study of the determinants for using and prescription of medicines by methods of excavation, questionnaires and the analysis of the prescriptions to clinical guidelines and protocols.

The results of our study showed that doctors admit inefficient use of medicines – polypharmacy, prescription of drugs with unproven efficacy and safety, do not follow recommendations from clinical guidelines and protocols under different pretexts. Data from the questionnaires of doctors revealed an inverse correlation between the prescriptions of medicines in accordance with approved national clinical guidelines and protocols and work experience, i.e. the longer the work of the doctor, the less they are guided by the clinical guidelines and protocols (p < 0.05). The results indicate a low level of adherence of doctors to the use of clinical guidelines and protocols, gaps in the awareness of the population on the use of drugs, the lack of a single information system in the sphere of drug circulation.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):57-61
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To the mechanisms of the protective effects of regional anesthesia in relation to the development of postoperative cognitive dysfunction
Strashnov V.I., Zabrodin O.N.

Abstract

The review of data on epidemiology, etiology and pathogenesis, methods of prevention and treatment of postoperative cognitive dysfunction (POCD) is presented. A comparative analysis of the influence on the development of POCD of general anesthesia (OA) and regional anesthesia (RA) was carried out. The substantiation of advantages of RA and its combination with components of OA against OA is given.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):62-68
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Antistress and antidepressant activity of a plant drug in a mild chronic stress model
Muruev B.A., Gulyaev S.M., Shantanova L.N., Mondodoev A.G.

Abstract

The effect of a complex herbal remedy on the function of the central nervous system in rats on a model of chronic unpredictable mild stress was studied in the present work. The level of stress disorders was determined by the behavioral responses in rats using the methods of “open field”, “elevated plus maze”, “forced swimming test” and “tail suspension model”, weights of target organs. It is established that the complex herbal remedy has adaptogenic, anti-stress and antidepressant effects.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):69-73
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Mechanism of diabetogenesis by Avicenna and diabetogenic risk factors
Sharofova M.U., Nuraliev Y.N., Sagdieva S.S., Sukhrobov P.S.

Abstract

In the article the views of Avicenna on the development of diabetes, based on the theory of mizadzh and the impact of certain foods on the pH level of body fluid are presented. The results of experimental studies confirming the occurrence of pH shift toward acidosis after 2-week using of 6 types acidic products defined as the diabetogenic risk factors are shown.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):74-79
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