Vol 16, No 4 (2018)

P-glycoprotein (Pgp, ABCB1-protein) is a membrane efflux protein transporter located in hepatocytes, enterocytes, epithelial cells of the proximal renal tubules, histogematic barriers, and also in tumor cells, which releases the substrates from cells and plays an important role in pharmacokinetics of drugs. Inhibition of Pgp functional activity is promising for increasing the effectiveness of drug treatment of oncological diseases and pharmacoresistant epilepsy, but today no synthetic inhibitor of the transporter can be used in clinical practice because of side effects development. The aim of this review is to prove the relevance to use polysaccharides of plant origin, their derivatives and chemical modifications as effective, safe and cost-effective inhibitors of the transporter protein. The article describes the chemical structure of Pgp substrates and inhibitors, the ability to predict the drugs belonging to the transporter protein substrates or inhibitors. Some results of investigations of the belonging of oligo- and polysaccharides to Pgp substrates and inhibitors are presented. They are premises for carrying out appropriate experiments for polysaccharides of plant origin both in vitro and in vivo.

Background. Partial agonists of α4b2 nicotinic acetylcholine receptors are the most effective treatment strategy for tobacco smoking cessation. They are able to alleviate withdrawal symptoms and to reduce smoking satisfaction.

The aim of this study was to review the efficacy and safety of nicotinic receptor partial agonists varenicline and cytisine, for smoking cessation.

Methods. A search for randomized controlled trials was done using the terms (“cytisine”, “tabex”, “varenicline” or 'partial agonists of nicotinic receptors’) in MEDLINE, EMBASE, eLibrary in May 2018. Types of participants, the doses and duration of the treatments, efficacy and safety parameters, quality of randomization and blinding procedures were evaluated. Bayesian network meta-analysis was performed.

Results. Cytisine overcame placebo in the 12, 24 and 52 weeks of therapy with the following odds ratios (ORs) for abstinence: 3.3 (95% CrI 1.8–5.8), 3.9 (2.4–6.7), 3.8 (CrI 1.3–11,9) accordingly. Varenicline in 2 mg/day dose overcame placebo in the 12, 24 and 52 weeks of therapy with the ORs: 4.0 (3.3–4.7), 3.1 (2.5–3.7), 2.9 (2.2–4.1) accor dingly. Varenicline in 1 mg/day dose overcame placebo in 12 and 52 weeks of therapy, the ORs were 3.0 (2.0–4.7) and 2.3 (1.3–4.4) accordingly. Varenicline in 0.5 mg/day dose overcame placebo in 12 weeks of therapy only with the OR 2.4 (1.3–4.4). Cytisine and varenicline 2 mg/day were associated with more gastrointestinal disturbances than placebo with the ORs 6.2 (2.1–22.8) and 2.4 (2.0–2.8) accordingly. Cytisine and varenicline 2 mg/day were associated with more psychiatric problems than placebo with ORs 5.2 (1.9–15.1) and 1.6 (1.3–1.9) accordingly. There was no difference in serious adverse events between the investigated drugs and placebo: OR for cytisine was 2.4 (0.8–6.8), varenicline 0.5 mg/day – 2.0 (0.5–6.6), varenicline 1.0 mg/day – 1.0 (0.3–2.7), varenicline 2 mg/day – 1.0 (0.7–1.4).

Conclusion. Cytisine was proved to be as effective and safe aid for smoking cessation as varenicline.

In the experiments on an reproducible adequate model of multiple sclerosis – experimental autoimmune encephalomyelitis as a result of the creation of pathological condition by immunization of guinea pigs with an encephalitogenic mixture in the complete Freund’s adjuvant, a pronounced inhibitory effect of the Ttriafen preparation was shown. The synthesized preparation of Ttriafen with antihypoxic and antioxidant properties on the experimental autoimmune encephalomyelitis model was used for chronic administration for 35 days, orally at a dose of 50 mg/kg. This drug is known to be free radical scavenger. A number of immunological indices and the clinical picture of neurological complications and the severity of central nervous system damage in experimental guinea pigs were studied. The circulating antibody production was estimated using the complement fixation test. In the peripheral blood, the content of lipid peroxidation products and antioxidant defense enzymes was evaluated. In another series of experiments, the lethality of animals after inoculation of the encephalitogenic mixture in Freund’s complete adjuvant and the protective effect of Triafen’s preparation were reproduced. In the present study, it has been established that the synthetic preparation of the aminothiol Triafen series on the experimental model of multiple sclerosis shows a neuroprotective and immunomodulating property, and increases the resistance to the intensification of LPO processes.

Psoriasis is one of the most common skin diseases and occurs in 1-2% of the population of developed countries. The problem of pathogenetic treatment of psoriasis remains relevant despite the annual appearance of new drugs. The anti-keratinizing effect is particularly important in the treatment of psoriasis. The effect is based on suppression of the proliferation of epidermal keratinocytes, normalization of the differentiation of the nonkeratinizing epithelium and the decrease in the adhesion of horny cells. The last decade is characterized by a deepening of ideas about the biological properties and mechanism of action of vitamin D₃. However the vitamin D₃ does itself not have therapeutic activity. In this connection the use of synthetic analogues of vitamin D₃ which have therapeutic activity is particular of importance.

The aim. To evaluate the effectiveness of vitamin D₃synthetic analogs for the treatment of psoriasis.

Methods. It was retrospective analysis of multicentric studies by a double-blind, randomized method of the effectiveness of vitamin D₃ analogs for the treatment of psoriasis in Russia and foreign clinics. The PASI index in assessing the clinical manifestations of psoriasis.

Rеsults and discussion. The study of the clinical efficacy of oral forms of the vitamin indicates a positive therapeutic effect in 70-90% of patients but this requires an average of 2.8 months. Therefore for the treatment of psoriasis more widely used synthetic analogue of vitamin D₃ – calcipotriol (MS-903), developed exclusively for topical application. Calcipotriol gives minimal side effects and has an intense antipsoriatic effect. The mechanism of action of calcipotriol is based on interaction with specific receptors on keratinocytes which causes inhibition of proliferation, accelerates the morphological differentiation of psoriatic cells, inhibits the activity of interleukin-1 and reduces interleukin-2 production, i.e. has an effect on the pathogenetic mechanisms of psoriasis.

Conclusion. Vitamin D₃ analogues are effective antipsoriatic drugs that can be used both as monotherapy and in the complex treatment of patients with severe psoriasis.

The data on the etiology and pathogenesis of acute postoperative pancreatitis (APP) are analyzed. It is noted that in its pathogenesis, currently, the main attention is paid to the factors of aggression in the pancreas: the activation of proteolytic enzymes and autocatalytic reactions leading to damage of the acinous cells, microcirculation disturbance, and enhancement of free radical oxidation. This determines the prevention and treatment of acute postoperative pancreatitis with the use the inhibition of protease and exocrine secretion of pancreas, antioxidants and cytostatics. Biochemical mechanisms of resistance of the pancreas tissue to damage are given much less attention. The authors substantiate the proposition that organ tissue resistance, besides adequate microcirculation and oxygenation, is determined by the mechanisms of nerve tropism mediated through the sympathetic nervous system. Experimental and clinical data are presented that irritation of the reflexogenic pyloroduodenal zone, in particular during operations in conditions of inadequate anesthesia, leads to hyper activation of the sympathetic nervous system, increased release of the noradrenaline, subsequent depletion of its content in the pancreas tissues. Therefore adrenergic support of trophic (energy and plastic processes) in the pancreas is disrupted, contributing to the development of postoperative complications, including acute postoperative pancreatitis. Taking into account that epidural anesthesia performs afferent and efferent, including sympathetic, blockades; the substantiations are given for use epidural anesthesia for acute postoperative pancreatitis prevention in abdominal operations in combination with the components of general anesthesia.

Relevance. In recent years, the popularity of phytotherapy, despite the great success in the development of chemical medicines, is increasing. Interest in natural healing substances and preparations created on their basis is increased due to both the unique properties of phytopreparations and rapidly developing research technologies in biology, medicine and the production of medicines.

Methodology. The analysis of the publications studying medicinal plant preparations in the VINITI databases, in the electronic resource of the Russian National Library, search engines Yandex, Google, Cyberleninka and Scholar Google for 2000-2014 was carried out.

Results. Studies conducted with human participation are few and account for 15% for drugs with names and 25% for drugs presented as original studies without a name from the total number of complex drugs studied. The spectrum of the revealed pharmacological effects was extremely wide, and the revealed effects, as a rule, were multicomponent. The greatest number of publications is devoted to the results of the study of Noofit. The drug was studied primarily in experimental studies.