Vol 16, No 3 (2018)

Articles
Vasopressin in mechanisms of stress reactions and modulation of emotion
Belokoskova S.G., Tsikunov S.G.
Abstract

The review presents modern conceptions about the role of the vasopressinergic system in regulating reactions to stress and modulation of emotions in animals and humans. The contribution of vasopressin to activation of the hypothalamic-pituitary-adrenal system in conditions of acute and chronic stress is reflected in the work. It is noted that the activation of vasopressin receptors of type 1 enhances the response to stress, which contributes to the development of psychopathology. It is emphasized that the role of vasopressin receptors of type 2 in the regulation of emotions has been studied little. At the same time, there is evidence that the activation of vasopressin receptors of type 2 in patients with depressive disorders after a stroke is accompanied by effects that are opposite in direction to the effects of activation of vasopressin receptors of type 1. The review examines promising areas of further studies of the involvement of vasopressin receptors of type 2 in modulating stress reactions and emotions. The use of receptor antagonist’s vasopressin of type 1 and receptor agonists of type 2 in the treatment of depressive and anxiety disorders are discussed.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):5-12
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Tablet as a pharmaceutical form of medicinal products intended for administration inside: advantages and disadvantages
Urakov A.L.
Abstract

The review of the literature shows that modern tablets turn drugs into artificial stones with excessively high physical-chemical activity, which can cause caries, stomatitis, gastritis and stomach ulcers. The ways to increase the safety of tablets and their intake is indicated.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):13-18
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The influence of cholinergic drugs on EEG of the brain of the castrated rabbit males
Kuznetsova N.N., Losev N.A.
Abstract

Aim. We investigated the influence of various cholinoceptive drugs on spontaneous activity of a brain at the intact rabbit and in the conditions of deficit of gonadal hormones, and also studied of reciprocal influence of cholinergic drugs on changes of character of a range of EEG at the intact and castrated rabbits.

Methods. Our researches were carried out on 32 rabbit males of breed the Chinchilla. Bipolar nichrome electrodes implanted to rabbits by stereotactic operaition into a caudate nucleus, a hippocampus and a reticular formation of a mesencephalon and also cortical monopolar chlorsilver electrodes with a diameter of 1 mm - to the optic and frontal area of cortex. Registration of EEG carried out in a shielded chamber with use of the electroencephalograph-analyzer EEGA-21/26 “Encephalan-131-03”. The averaged EEG range power was analyzed with a 60 s recording epoch. In 3 weeks after implantation of electrodes we studied the influence a number of cholinergic drugs on spontaneous EEG: M-cholinolytic metamizyl (1 mg/kg i.p.), N-cholinolytic gangleronum (5 mg/kg i.p.), inhibitor of acetylcholinesterase (AChE) galantamine (0.5 mg/kg i.p.). Registration was carried out in 1, 2 and 3 hours after an injection. Under the combined investigation of preparation galantamine was entered in 20 minutes after an injection of cholinolytics. Then, we carried out removal of a testis at rabbits — males under etherization. The spontaneous electric activity of a brain of that rabbits and influence of cholinergic drugs was registered in 30 days after operation of bilateral gonadectomy.

Result. The gonadectomy of Chinchilla rabbits causes the deceleration of EEG range power twice in comparison with intact animals in a chronic experiment. The analysis of influence of cholinoceptive substances on EEG showed that the most sensitive to the change of balance between M- and N-cholinoreceptors are cerebral cortex and caudate nucleus. The intensity of the activating effect accompanying blockade of M-cholinoreceptors is higher in cortical structures, than in subcortical nuclei in all animals. The reaction of caudate nucleus to the blockade of M-cholinoreceptors is the most sensitive among subcortical nuclei. It “answers” with increase in EEG range power. The blockade of N-cholinoreceptors in this structure after insignificant potentiating is followed by decrease of EEG range power. The activity of hippocampus is least dependent on the level of androgens in organism.

Conclusions. The analysis of influence of cholinoceptive substances on spontaneous activity of a brain showed that the most sensitive to change of balance between M-cholinoreceptors and H-cholinoreceptors were a cerebral cortex and a caudate nucleus. As at the intact as the castrated animals the expressiveness of the activating effect accompanying blockade of M-cholinoreceptors is higher in cortical structures than in subcortical nuclei.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):19-24
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Correction of hypoxic state by metabolic precursors of endogenous activator of mitochondrial ATP-dependent K+channels
Krylova I.B., Safonova A.F., Evdokimova N.R.
Abstract

Aim. The antihypoxic properties of uridine and uridine-5'-monophosphate (UMP), which are the metabolic precursors of the natural activator of mitochondrial ATP-dependent K+ channels (mitoKATP channels) uridine diphosphat were investigated on the models of hypoxic hypoxia with hypercapnia (HHH), hemic hypoxia and local circulatory hypoxia.

Methods. HHH was created in males and females white mice weighing 28-30 g. The animals were placed one by one in hermetically closed container and the duration of their life was determined. The antihypoxic activity of the substances was compared with the reference anthypoxant amtizole (50 mg/kg). Hemic hypoxia was caused in Wistar rats weighing 350-370 g by the injection of sodium nitrite (intramuscularly, 100 mg/kg). Uridine or UMP 30 mg/kg was injected intraperitoneally 30 minutes before the onset of HHH and hemic hypoxia. Local circulatory hypoxia was modeled in male Wistar rats weighing 250-300 g. Acute coronary occlusion lasting 60 min was reproduced by legation of descending branch of the left coronary artery (LCA). Uridine or UMP (30 mg/kg) was administered intravenously 5 minutes prior to LCA occlusion. Selective blocker of mitoKATP channels 5-hydroxydecanoate (5 mg/kg, intravenously, 5 minutes prior uridine or UMP) was used to determine the role of these channels in the mechanism of antihypoxic action of the studied drugs. The volume of the damaged myocardium was used as the marker of antihypoxic activity of uridine and UMP.

Results. Different resistance to hypoxia in female and male mice was observed in HHH. The female mice were more resistant, their life duration was 43% more than the males. Uridine and UMP displayed antihypoxic activity only in male mice, increasing their life duration by 25% and 20% respectively. This effect was 2 times less than that of amtisol. In similar conditions in females mice the preparations did not show a protective effect. In hemic hypoxia the life duration of rats treated with uridine and UMP did not differ from the control values. Circulatory hypoxia, caused by occlusion of the LCA, led to the formation of a local zone of myocardial damage. Uridine or UMP decreased the damage zone in 2 and 3,5 times respectively. The inhibitor of mitoKATP channels blocked the protective effect of these compounds.

Conclusion. Uridine and UMP have a distinct antihypoxic effect in HHH and a marked protective effect in local circulatory hypoxia. The antihypoxic activity of druges in HHH is manifested differently in female and male mice. It may be due to sexual differences in the resistance to hypoxia. The maximum effect is observed in male who have initially low resistance to oxygen deficiency. The mechanism of the protective action of uridine and UMP in the circulatory hypoxia is associated with the activation of mitoKATP channels.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):25-31
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Effect of the anticancer drug methotrexate on the ascites form of a teratocarcinoma and survival of mice
Dyban P.A.
Abstract

The dose-dependent effect of a methotrexate is established as on an ascite form of a teratocarcinoma CBA9H6, and mice-recipients, however various doses of the entered methotrexate (6; 4 and 2 mkg/g body weights of an animal), at repeated introduction at an interval of 48 and 24 hours, don't destroy all population of embrioid bodies. So, at 3-fold and even 10-fold daily injections in a dose of 2 mkg/g of body weight in an abdominal cavity of mice 1,6 ± 0,2% and 0,038 ± 0,01% embrioid bodies (ascite form of a teratocarcinoma ) remain, respectively, at survival of mice 93,0 ± 8,5% and 14,0 ± 3,0%. The morphological analysis of a mode of a differentiation of embrioid bodies retransplantated from experimental animals to intact has shown earlier that the methotrexate hasn't had effect on histoblastic potentialities of stem cells of a teratocarcinoma CBA9H6.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):32-35
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Linezolid in treatment of multidrug-resistant forms of tuberculosis
Shabanov P.D.
Abstract

The Federal clinical recommendations on treatment of pulmonary tuberculosis with multidrug-resistanсe to micobacteruim tuberculosis contain of algorhythm of actions to correct negative side effects appearing in the process of chemotherapy after linezolid prescription. According to this algorhythm, if the negative side effects in form of myelosuppression (inhibition of blood development) or neuropathies are developing, administration of linezolid can be abolished, and the drug prescription can be recovered beginning the dose of 300 mg per day after normalization of blood analysis, under blood analysis control, and then with 2-fold increase of oral dose (300 mg twice a day) to prevent repetitive development of negative side effect. In this case, dispensary prescription of linezolid 300 mg is permitted for tuberculosis treatment. In the paper, a comparative analysis of usage of different doses of linezolid for tuberculosis treatment with argumentation to use median (300 mg) doses of linezolid has been done.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):36-46
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Assessment of the effect of long-term continuous stay in the artificial hypoxic gas-air environment at normal atmospheric pressure on the functional state of the cardiovascular system
Lyubimov A.V., Ivanov A.O., Bezkishkii E.N., Shakhnovich P.G., Cherkashin D.V.
Abstract

In the vast majority of clinical cases, hypoxia and hypoxia are considered as negative pathological processes that require urgent correction with subsequent pharmacological support for the restoration of functioning, and in some cases, the structure of the involved organ and system. The loss of full functionality as a result of local or general exposure to the hypoxia is confirmed by numerous studies. However, there are research data showing that subliminal exposure to hypoxia can be used as a positive adaptation factor, which increases the overall health of the body, stamina, and tolerance to physical load. This mechanism is actively used in training athletes of different levels of functional fitness, sports and ages. There is a question of balance of adaptive and damaging properties of hypoxia. Threshold values at which the hypoxic state will have positive adaptive or negative — damaging properties are not clearly defined at the moment. The key criterion for a hypoxic environment is the concentration of oxygen in the inhaled air. At the same time, physiological or pathophysiological response to changes in concentration is purely individual and primarily depends on the parameters of homeostasis. This issue is relevant because clinical manifestations characteristic of the hypoxic state develop in patients with different forms of coronary heart disease. The purpose of our study was an attempt to document the functional changes from the cardiovascular system of healthy individuals with prolonged continuous exposure to artificial hypoxic conditions while maintaining normal atmospheric pressure using standard diagnostic methods that are generally available.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):47-53
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Problems of promoting drugs in the Kyrgyz Republic
Zurdinova A.A.
Abstract

The article describes the results of the assessment methods of medicines promotion in health care organizations The purpose of our study was to study the factors affecting the prescribing, consumption and dispensing of medicines to develop measures to contain unethical drug marketing. For study this issue was used the method of interviewing and questioning of doctors, pharmacists and patients. Our results have shown that there are numerous factors in the health system, which contribute to a violation of the practice for rational prescribing and dispensing of medicines, as well as the absence of regulatory mechanisms in the medicines promotion on the market in the Kyrgyz Republic. The results of the study among this category of respondents confirm the limited access of doctors and pharmacists to quality sources of medicines information, which explains the shortcomings in informing patients on their part, which also serves unethical drug marketing. A direct correlation was established between information sources of about medicines and work experience, i.e. than more work experience, the more information is used from medical representatives and activities conducted by pharmaceutical companies (p < 0.05). The identified factors are associated with unethical medicines promotion, inadequate implementation of the generic strategy, non-prescription dispensing of all medicines, inadequate provision of quality reliable information, low awareness, lack of skills in critical assessment of the information provided. In connection with this, there is a high sensitivity of specialists to various incentives from pharmaceutical companies. All of the above in aggregate contribute to the irrational use of medicines, with all the ensuing consequences.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):54-59
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Comparative estimation vassseland hepatoprotective properties galenic plant drugs of 16 Caragana Lam. species
Barnaulov O.D., Belodubrovskaya G.A.
Abstract

According to reductions traditional Chinese and Tibetian medicines Caragana Lam. species are using for treating patients with a lot of diseases including vascular and hepatobiliary pathology. Substantiation such using are confirmed experimentaly. Decoctions overground parts 13 from investigated 16 Caragana species demonstrated hepatoprotective properties keeping detoxycal liver function of mice after injection CCL4 and 8 of them prevented the losing glycogen concentration in liver. Vessel protective properties were demonstrated by 12 decoctions and 15 etanol tincturеs caragana species.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):60-67
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Hyperoxia and hypoxia influence to adaptive processes at muscular work
Radchenko A.S., Shabanov P.D.
Abstract

In this brief review we will state the use of hyperoxia (HO) in sports training. HO training has been recommended by some authors for athletes to increase their performance. Herewith, there is no reliable knowledge about physiology mechanisms that provides the athlete level of growth during long-term training under HO conditions. Concurrently in the last half century, the athletes’ performance in endurance sports has grown remarkably due to natural and artificial hypoxia application in training process of many kinds of sports. Long-term adaptation mechanisms to muscular work under hypoxia conditions are shortly summarized for comparison with HO effects and we emphasized that the prospectivity of searching the ways for regular usage HO to increase athletic performance is too questionable.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):68-77
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