Клинико-фармакологические технологии персонализации фармакотерапии сердечно-сосудистых заболеваний: фокус на прямые оральные антикоагулянты

One of the main causes for adverse reactions development is not taking into account the pharmacokinetics of drugs and the dose. Pharmacokinetics of drugs is mostly defined by the cytochrome P-450 isoenzymes activity, carboxylesterases and many other isoenzymes of drug metabolism, as well as ADME transporters (P-gp etc.) which take part in the process of drug metabolism. The activity of these isoenzymes is defined by the genetic aspects of patients and non-genetic aspects such as comorbidity and drug-drug interactions. The development of complex algorithms for personalization of therapy based on the results of pharmacogenetic studies and in the form of a decision support system will play an important role in reduction of adverse drug reactions. A lot can be achieved for personalization of Direct Oral Anticoagulants for treatment of cardiovascular diseases. New approaches are being developed based on the results of pharmacogenetic and pharmacokinetic testing that will help diminish adverse effects of drugs.Одной из важных причин развития ятрогенных лекарственных поражений внутренних органов является недоучет врачами при выборе лекарственных средств (ЛС) и их режимов дозирования индивидуальных особенностей фармакокинетики препаратов в организме пациента, которая во многом определяется активностью ферментативных систем биотрансформации ЛС (ферменты I фазы ― изоферменты цитохрома Р-450, карбоксиэстеразы и др., ферменты II фазы ― N-ацетилтрансфераза и др.) и активностью транспортеров, участвующих в процессах всасывания, распределения и выведения ЛС (Р-гликопротеин, транспортеры органических анионов и катионов). При этом активность этих систем зависит от генетических особенностей пациентов (полиморфизмы соответствующих генов ― предмет изучения фармакогенетики) и негенетических факторов, таких как сопутствующие заболевания и состояния, а также межлекарственных взаимодействий. С этих позиций разработка комплексных подходов к прогнозированию и профилактике развития ятрогенных лекарственных поражений внутренних органов с использованием как фармакогенетических (уже активно проводятся), так и фармакокинетических (мониторинг равновесных концентраций лекарств в биологических жидкостях, малоинвазивная оценка активности ферментативных систем, и прежде всего изоферментов цитохрома Р-450) исследований, которые будут доступны врачам (в т.ч. с помощью информационных технологий ― за счет разработки компьютеризированной системы поддержки принятия клинических решений), позволит им персонализировать применение лекарств, сводя к минимуму нежелательные лекарственные реакции и снижая тем самым инвалидизацию и смертность от них. Таким образом, актуальными представляются комплексные (фармакогенетические и фармакокинетические) подходы к прогнозированию и профилактике (на основе создания алгоритмов выбора ЛС и их режимов дозирования) ятрогенных лекарственных поражений внутренних органов у пациентов с социально значимыми заболеваниями

Problems of developing the multi agent systems in the tasks of management technological processes and productions.

In this paper several issues related to the development of industrial multi-agent systems within scope of managing complex technological processes and production with taking into account: the variety of solution methods; the availability of variety of information subject to incomplete and dispersed nature of technological processes, uncertainty in models and wide range of time frames for various system tasks and production situations are considered. To show that or the full disclosure of the potential of multi-agent systems reconfigurable production systems with performance adaptation are in demand. The tasks of developing an agent architecture, its functional organization and creating an agent community in distributed computing environments are considered, when the effective organization of interacting entities leads to problem solutions of cooperation, coordination and self-organization, and due actions of agents stimulate the execution of necessary processes

The Observation of the Martensite-Like Shear Diffusionless α→γ Transformation in Carbon Steels with Pearlitic Structure

The structure of eutectoid carbon steel with the initially pearlitic structure was studied by transmission electron microscopy and electron diffraction after laser heating. It is shown that, under ultrarapid laser heating, the α-γ phase transformation can proceed by a shear-type diffusionless mechanism that results in the deformation of cementite platelets. The crystallographic characteristics of shear planes involved in the α-γ transformation are determined. Austenite formation was found to occur through the diffusionless shear mechanism, with orientation relationships close to those of Kurdjumov-Sachs

The CES1 Gene rs2244613 minor allele impact on the safety profile of dabigatran etexilate: Meta-analysis [Влияние носительства минорной аллели rs2244613 гена CES1 на профиль безопасности дабигатрана этексилата: мета-анализ]

Aim. A meta-analysis of studies on the CES1 gene c.1168-33A>C polymorphism (rs2244613) carriage influence on the equilibrium concentration and the risk of bleeding during dabigatran taking. Material and methods. The search was carried out in the Russian Science Citation Index, Google Academy, Medline PubMed, Embase databases. The meta-analysis included patients who according to the indications (atrial fibrillation, stroke, joint orthopedic surgery) were prescribed dabigatran in various doses. The association was identified in rs2244613 allele C carriers (genotypes AC and CC) and non-carriers (genotype AA). Quantitative synthesis was performed using OpenMetaAnalyst software. In statistical analysis the fixed effects model was used to estimate the influence of the allele C carriage on the any bleeding frequency and the random effects model was used to estimate the influence on the equilibrium plasma concentration level of dabigatran. The homogeneity of the analyzed studies was verified by Cochrane Q-test. Results. The analysis resulted in selection of 5 works matching all meta-analysis inclusion/exclusion criteria. All selected works included 2030 patients in total. The carriage of the rs2246613 allele C was associated with reduction of risk of any bleeding during dabigatran taking (risk ratio [RR] 0.732, 95% confidence interval [CI] 0.629-0.851; p<0.001). The heterogeneity test did not reveal any reliable differences between the study results (Q=2.183; p=0.535). The level of equilibrium residual concentration of dabigatran was not statistically significant lower for the carriers of C allele of the rs2244613 (mean difference -69.324, 95%CI -236.687-98.039; p=0.417). This might be related to the small sample size and the number of studies included in the meta-analysis. The heterogeneity test did not reveal statistically significant differences between studies (Q=0.388; I2=0%, p=0.534). Conclusion. The carriage of minor C allelic variant of rs2244613 reduces the risk of any bleeding during dabigatran taking, however, no significant association with decrease in dabigatran concentration was found. © 2020 Stolichnaya Izdatelskaya Kompaniya. All rights reserved