Vol 16, No 1 (2018)

Biological activity of fullerenes - reality and prospects
Dumpis M.A., Nikolayev D.N., Litasova E.V., Iljin V.V., Brusina M.A., Piotrovsky L.B.

Abstract. The review deals with the properties of fullerenes and their derivatives and the possibility of their use in biology and medicine. Fullerenes can exert an antioxidant effect in biological systems, catching active forms of oxygen, and oxidative, giving the fullerene photosensitizing properties. The lipophilic fullerene molecules possessing membrane — tropic action interact with various biological structures and can change the functions of these structures, increasing the lipophilicity of the active molecule (amino acids, nucleic acids, proteins, etc.). Data on the biological effect of fullerenes in in vitro and in vivo experiments are given. Examples of targeted delivery of known therapeutic agents.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):4-20
Autism spectrum disorders: etiology, treatment. models and experimental studies
Lavrov N.V., Shabanov P.D.

Abstract. The study of disorders of brain activity related to the violation of socialization is the current scientific problem. The article presents a review of the literature regarding the epidemiology, etiology and treatment of autism spectrum disorders. Special attention is paid to experimental models of autism, since simulation allows to test hypotheses about the nature of the disease and to carry out testing of new treatment methods.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):21-27
The study of the effects of dipeptide mimetic of a brain derived neurotrophic factor with antidepressant activity during prolonged use and after withdrawal
Garibova T.L., Krayneva V.A., Valdman E.A., Gudasheva T.A., Kotelnikova S.O., Seredenin S.B.

Abstract. The antidepressant activity of the GSB-106, dipeptide mimetic of the 4th loop of BDNF, during long-term use was studied in doses of 1.0 mg/kg and 5 mg/kg for. When comparing antidepressant activity in the “forced swimming Porsolt test” on the 14th and 28th day of administration, it was established that the antidepressant effect did not change. It was shown that a withdrawal of prolonged administration for 28 days did not lead to an increase in anxiety in the “elevated plus-maze test” and to the development of disturbances in the exploratory behavior of animals and motor activity in the “open field” test. It was concluded that during long-term administration of GSB-106 the tolerance for the main antidepressant effect did not developed, and cessation of long-term administration of GSB-106 did not lead to the development of withdrawal syndrome.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):28-33
Effect of SB-408124, an orexin A OX1R receptor antagonist, on the compulsive behavior and the level of anxiety after the vital stress in rats
Tissen I.Y., Yakushina N.D., Lebedev A.A., Pshenichnaya A.G., Bychkov E.R., Tsykunov S.G., Shabanov P.D.

Abstract. The effect of the orexin A OX1R receptor antagonist SB-408124 of on the compulsive behavior and the anxiety in rats after the presentation of vital stress in a number of behavioral tests: marble test, elevated plus maze, in the open field and in the test “resident intruder”. In the buring marble test, the behavioral components of the obsession  (obsessive  and obtrusive thoughts) and compulsions (obtrusive behavior), aimed to reduce anxiety, were modeled. Mental trauma was caused by a stressful effect, the essence of which was the experience of the animals of the circumstances of the death of a partner from the actions of a predator. A group of rats were placed once in the terrarium to a tiger python. After the action of vital mental stress in rats, two connected behavioral phenomena were observed: a high level of anxiety and an increase in the number of buried balls. This was accompanied by a decrease in communicability. Intranasal administration (for 7 days) of orexin A antagonist OX1R receptor SB-408124 after presentation of the vital stress reduced the level of anxiety, and also normalized the communicative activity of animals and the number of buried balls, i.e. compulsive behavior. Thus, the orexin system of the brain is an important component of psychotraumatic mechanism. OX1R antagonists of orexin A receptors can potentially be considered as correctors of obsessive-compulsive disorders on the background of posttraumatic stress disorder (PTSD). Use of intranasal administration of OX1R antagonists of orexin A receptors in the clinic will allow the use of small doses of substances and thereby reduce their possible toxic effects.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):34-42
Behavioral, biochemical and morphological characteristics of experimentally changed thyroid status of female mice C3H-A
Kozyrko E.V., Glushakov R.I., Shabanov P.D.

Abstract. The purpose of the paper was to study changes in neurogenesis and functional state of the central nervous system in female mice С3Н-А predisposed to hormone-dependent tumors in experimental hypo- and hyperthyroidism.

Methods. Experimental hyperthyroidism was modeled by intraperitoneal administration of L-thyroxine 50 ug/day and hypothyroidism by oral administration of propylthiouracil 0.4 mg/day for 40 weeks to female mice С3Н-А.

Results. Chronic hypo- and hyperthyroidism was characterized by motor (motility) and emotional disorders in mice beginning with 18 day of the experiment, with preferable increase of quantitative indexes of all component of explorative activity and grooming in hyperthyroid mice and disturbance of explorative activity (decrease of hole reflex) in hypothyroid animals. Behavioral disorders was increasing progressively within the experiment (till 40 weeks). In hyperthyroid mice, the dopamine level in the cortex and hippocampus was elevated and in hypothyroid animals, the level and turnover of serotonin was reduced in the same structures of the brain. The changes in thyroid status of С3Н-А mice (hypo- and hyperthyroidism) effected on expression of neurogenesis and angiogenesis factors contradirectory. In hypothyroidism, the expression of GFAP and VEGF was reduced preferably with elevation of expression of PDGFR-α in the neocortex and hippocampus, and in hyperthyroidism, on the contrary, the expression of GFAP and VEGF was increased with decrease of PDGFR-α expression  in the same structures of the brain. In the cortex of С3Н-А mice with hyperthyroidism, the stable structural signs of strengthening the protein synthesized activity in the cytoplasm was observed, that was appeared with reduction of heterochromatin density in the nucleus, increase of polysomes number and hypertrophy of Golgi complex. At the same time, there were mediate signs of destruction of myelin fibers and disturbances in axon-spine synapses, capillarostasis and signs of dystrophic changes of endotheliocytes and perivascular space. In hypothyroidism, disorders involved myelin fibers preferably, spine apparatus and only slight changes of presynaptic terminals.

Conclusion. Therefore, it is concluded on the base of behavioral, biochemical and morphological characteristics that hypothyroidism can provoke depressive state development.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):43-53
The heterogeneity of drug response as the basis of identification of essential tremor subtypes
Muruzheva Z.M., Karpenko M.N., Klimenko V.M.

Abstract. Introduction. Essential tremor (ET) is one of the most common movement disorders. It is mainly characterized by postural and kinetic tremor, affecting arms and other body parts. Progression of ET violates social activity, lowers self-esteem, and occasionally leads to the patient’s disability. Selection of an effective drug therapy for ET is mostly carried out empirically and takes long time, which causes additional negative psycho-emotional effects, distrust of the doctor and abandonment of the treatment. Present study is aimed at the implementing a novel approach to the segregation of ET subtypes based on the heterogeneity of the pharmacological response.

Results. Neuroanatomical, electrophysiological and biochemical data published to date are outlined in the current paper, to designate parameters for identification of ET subtypes with deterministic pharmacological response. Before prescribing pharmacotherapy for patients with ET, it is necessary to perform asurface electromyography to identify the patterntype of antagonist muscles contractions. In addition, the concentration of glutamate and gamma-aminobutyric acid in peripheral blood should be determined.

Conclusion. The heterogeneity of pharmacological response among patients with ET necessitates a more subtle classification within the syndrome by neuroanatomical, electrophysiological and biochemical indicators. The approach proposed in the review will increase the effectiveness of therapy and improve the lifequality of patients  with ET.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):54-59
Maintenance pharmacotherapy of atopic dermatitis
Petrova I.V., Omarov N.N., Sargsyan M.S., Khamroeva S.A., Osmanova Z.S., Proshin S.N.

Abstract. Atopic dermatitis (AD) — multifactorial inflammatory disease of skin characterized by pruritus, chronic recurrent process and age-related features of localization and morphology of lesions. This is one of most spread disease of skin up to 40%, meeting in all countries, in both sexes, in different age groups.

The aim. Prevention of severe forms of AD and complications.

Methods. To estimate the degree of atopic dermatitis was used international scale SCORAD (Scoring of Atopic Dermatitis). Results and discussion. At present time the pathogenesis of atopic dermatitis is discussed in terms of heredity resulting in disturbance of skin barrier, deficiency of immune system. The later means the stimulation of Th2-cells resulting in hyperproduction of IgE, hypersensitivity to allergens and nonspecific stimulants, colonization by pathogenic microorganism such as Staphylococcus aureus, Malassezia furfur and so on. The imbalance of autonomous nerve system with increased production of inflammatory mediators is strongly considered in the pathogenesis of atopic dermatitis too.

Conclusion. Considering the multifactoriality of atopic dermatitis the maintenance pharmacotherapy is of particular importance.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):60-63
Experience of determination of antitumor drugs concentrations as a method of providing the safety of pharmacotherapy
Rodionov G.G., Shantyr’ I.I., Ushal I.E., Kolobova E.A., Svetkina E.V., Oseshnyuk R.A., Shabanov P.D.

Abstract. Background. The undesirable side effects in the process of pharmacotherapy are forced to look for ways to prevent them. The most effective means for this is to carry out individual therapeutic drug monitoring. This is especially true for patients who undergo chemotherapy. A narrow therapeutic range of antineoplastic agent concentrations requires an individual approach to the management of each patient.

The purpose of this study is to justify the need for therapeutic drug monitoring to provide the safety of antitumor drugs.

Methods. Methods for the quantitative determination of the active metabolite of fludarabine, imatinib and gefitinib in human blood plasma have been developed and validated. A study of pharmacokinetics of antitumor drugs: fludarabine — 36 patients, gefitinib — 24 healthy volunteers, imatinib — 24 healthy volunteers.

Results and Discussion. The work shows the magnitude of interindividual differences of the pharmacokinetics of various antitumor drugs. High interindividual variability of pharmacokinetic parameters was revealed both in patients and in healthy volunteers.

Conclusion. Experience of the Research Laboratory of Toxicology and Drug Monitoring, The Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia on the application of therapeutic drug monitoring showed its relevance and effectiveness for patients undergoing chemotherapy.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):64-70
“Сhinese date” - elite plant drug of the ancient Asiatic traditional medicines
Barnaulov O.D.

Abstract. The assimilation of traditional medicines experience is declared by World Health Organization as a priority direction of medicine development in XXI century. A lot of experimental and clinical results demonstrated the highest effectiveness of Zizyphus jujubа eatable fruits and leaves (tea substitute) in treating the patients with hypertension and its complications. Water infusions and decoctions of this thing posess antihypertensive, antineurotic, diuretic, antiatherogenic and some other actions. Author’s own clinical experience including usage of Zizyphus jujubа fruits and leaves in polycomponent plants species permits to register truth lowering of high blood pressure, vessel catastrophes: strokes, infarctions, transit ischemic attacks. Hypertonic disease and its complications is “the killer number one”, so expressing introduction this elite plant drug of traditional medicines is very actual task.

Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):71-78

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