Репозиторий Университета

© 2018 The Author(s). Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov University (Russia, Moscow), digital System for drug prescription management is being developed. Artificial intelligence methods to the control of drug therapy will greatly enhance the ability of the automated control System to identify potential problems in drug therapy and provide recommendations for their elimination. Introduction of this System into commercial operation will make it possible to translate the civil circulation of medicines into a single information space and increase the effectiveness of the ongoing pharmacotherapy.

© 2018 Irina Nikolaevna Dominova, Vitaly Anvarovich Kasymov, Ekaterina Vladimirovna Silina, Victor Aleksandrovich Stupin, Natalia Nikolaevna Shusharina and Maksim Vladimirovich Patrushev. A fragment of the research project devoted to the development of genetic control of exocytosis is presented in the work, which can further ensure the success of targeted therapy of various diseases, including neurodegenerative ones. For the purpose of specific transfection of intracellular cascades in astrocytes in vivo, we have developed an experimental sample of the reagent kit. The latter represents lentiviral genetic construction LVV-GFAP-Case12. The results of testing of experimental samples of the reagent kit for specific transfection of astroglial cells are presented with the purpose of targeted control of intracellular cascades in vivo on acute slices of different parts of the brain in adult Wistar rats. We selected regions of interest with cells expressing calcium indicator Case12 and responsible for ATP application by >2-fold amplification of fluorescence. We have developed instructions for using the reagent kit for specific transfection of astroglial cells with the purpose of targeted control of intracellular cascades.

© 2018, SPb RAACI. The theory of polyetiological tumorigenesis is one of the most important theories of carcinogenesis. A great place in this theory is given to the role of inflammatory component, which is implemented via the factors of innate immunity. I.e., toll-like receptors (TLRs), chemokines and their receptors are related to innate immunity. Activation of TLRs may lead to regress or progression of cancer process. It is known that TLR3, TLR5, TLR7, TLR9 have the greatest anti-Tumor effect due to the dendritic cells (DCs)-mediated activation of type I T helpers, activation of M1-Type macrophages and Treg inhibition. Stimulation of TLR2 and TLR4 exerts an activating effect upon the tumor, by the MyD88 hyperactivation and secretion of IL-6 and TNFα, but exact mechanisms are not fully understood. In addition to TLRs, chemokines and their receptors have a great influence on the cancer development. It is shown that CCL2, CCL4, CCL17, CCL22 and CXCL12, which are secreted by cancer microenviroment, activate chemotaxis of tumor cells. It is also known that the chemokines activate CXCR4 and CCR7 (expressed by tumor cells) thus leading to metastasis. It is shown that there is an association between some gene polymorphisms of TLRs', chemokines and their receptors, and development of cancer. Thus, we may conclude that the role of TLRs and chemokines is important in oncogenesis. Further study of innate immunity factors influencing tumorigenesis are important for finding new approaches to cancer therapy and new potential vaccines against cancer.

© 2018 Sychev et al. Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.

© 2018 Bentham Science Publishers. Atherothrombosis-related diseases are one of the world’s leading causes of mortality, and thus the search for new therapeutic approaches in this area remains a very urgent task. Modern pharmacogenomic technologies make it possible to obtain valuable data on disease pathogenesis and optimal therapeutic approaches. One promising research direction is the study of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis. This review summarizes the recent evidence and suggests that systematic works in this area are creating new and promising opportunities in the treatment of patients with cardiovascular diseases.

© 2018 Izdatel'stvo Meditsina. All rights reserved. BACKGROUND: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder (DD), which worsens adversely affects the prognosis of the course of both diseases and their outcomes. For the treatment of DD, drugs from the group of selective serotonin reuptake inhibitors, whose representative is fluvoxamine, are used. Fluvoxamine therapy is often associated with a risk of development is shown to be ineffective, and a part of patients develop dose-dependent adverse drug reactions (ADR) and pharmacoresistance. OBJECTIVE: To study the effects of CYPD6 isoenzyme activity on the efficacy and safety of fluvoxamine therapy in patients with depressive disorders, comorbid with alcoholism. METHODS: The study was conducted on 117 Russian patients with DD, alcohol-dependent comorbid. For the purpose of correction of depressive disorders within the framework of cyclothymia, fluvoxamine (Fevarin) was administered to patients at a dosage of 50−150 mg/day. Genotyping was carried out by the method of polymerase chain reaction in Real-time mode with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of ADR. To evaluate the activity of CYP2D6, the method of high performance liquid chromatography with mass spectrometry was used to measure the urinary content of the endogenous substrate of this isoenzyme and its metabolite, the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline. RESULTS: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was statistically significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.0; 5.0] (p<0.001); safety indicator, estimated on a UKU scale: 3.0 [2.0; 4.0], (GA) 4.0 [4.0; 4.2] (p<0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.0] (p<0.001); safety indicator, estimated on a UKU scale: (GG) 9.0 [9.0; 10.0], (GA) 6.0 [6.0; 7.0] (p<0.001). The calculation of the correlation coefficients between the difference in the number of scores on psychometric scales and the metabolic ratio showed a statistically significant inverse correlation of the average power degree between the efficiency index estimated by the HAMD scale (r=-0.467, p<0.05). There was no connection with the difference on the UKU scale (r=0.173, p>0.05). CONCLUSION: In a study of a group of 117 patients with DD, comorbid with alcohol dependence, the effect of CYP2D6 activity, estimated by the ratio of the endogenous substrate concentrations of pinolin and its metabolite 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, on the efficacy of fluvoxamine therapy. This effect was also shown using the results of genotyping. The results of genotyping also showed the existence of a difference in the safety index in patients with different genotypes from the polymorphic marker CYP2D6 1846G>A.

© 2018 Kryukov et al. Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at —70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.

© 2018 Saint Petersburg Pasteur Institute.All Rights Reserved. Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.

© 2018 Czech Academy of Sciences. The population structures of different species of Calliphoridae flies are highly diverse at different locations. We investigated populations of the Eastern European L. sericata using chaetotaxy and eight microsatellite loci. Our results strongly indicate that a panmictic population of L. sericata exists in the area studied, possibly with a high rate of intra-population gene flow. Analysis of chaetotaxy also supports the panmictic population hypothesis.