Significance of L-carnitine in internal medicine.

The review presents the results of a number of experimental and clinical studies proving the prospects of using L-carnitine in the clinic of internal diseases. Due to the antioxidant and antihypoxant properties, the additional use of L-carnitine in addition to the main etiopathogenetic therapy is prescribed by cardiologists, nephrologists, neurologists, gerontologists. Experimental studies we conducted earlier showed no effect of L-carnitine on the activity of the P450 CYP 3A4 system, which reduces the likelihood of drug-drug interaction at the level of metabolism of drugs metabolized by P450 3A4. When using L-carnitine as part of complex pharmacotherapy, the drug has an increased safety profile in comorbid patients taking L-carnitine. Keywords: L-carnitine, P450 CYP 3А4, chronic heart failure, myocardial infarction, chronic renal failure, inter-drug interaction, antioxidant, antihypoxant.

[Essential questions of training of dentists for accreditation]. / Aktual'nye voprosy podgotovki vrachei-stomatologov k akkreditatsii spetsialistov.

The paper presents sociological study aimed to analyze the conditions and methodological rationale for the basic directions of optimization of accreditation procedure for dentists. The study included 129 graduates of dental faculties of educational institutions of Sechenov First Moscow State Medical University. The material was collected by questionnaire survey and interviewing. The obtained results show that the introduced system of professionals' accreditation is an innovative educational technology allowing objectively assess the level of theoretical and practical training of dentists. Much of its effectiveness depends on the quality of produced and updated on a timely basis uniform base of assessment tools, the selection of the most prepared members for the accreditation commissions and creation of adequate conditions for its implementation in educational and scientific organizations.

[Pathogenesis of myocarditis in patients with bronchial asthma and pecilomycosis].

We studied the influence of activation ofpecilomycotic infection in blood on the morphofunctional state of myocardium based on the clinical and pathomorphological data. The study included 23 patients with bronchial asthma (BA) concomitant with pecilomycosis after acute viral respiratory infection; protocols of autopsies and pathological sections of the heart muscle of the patients who died from asphixy and acute cardiac insufficiency were analyzed. Histological sections showed up vascular dystonia of the microcirculation bed, arteriole spasms, wall destruction in small and medium-size vessels and the adjacent muscular tissue, stromal oedema, valvular swelling, andperiwall endocarditis. Cardiac cavities and coronary vessels contained erythrocyte-rich thrombi with ferulas of Paecilomyces at different stages of development. Clinical manifestations of destructive changes in the heart muscle developing under effect of Paecilomyces infection had the form of rhythm and conductivity disorders. The local protective inflammatory reaction of productive type had the form of intermediate and vascular-type myocarditis passing to postmyocarditic cardiosclerosis. Periodic bursts of activation ofpecilomycotic infection in blood with the accumulation of fungal phospholipase A2 and lipid metabolites produced membranotoxic effect and can play the key role in the development of atherosclerosis and hypertensive disease in patients with BA and pecilomycosis.

[The clinical immunologic characteristic and laboratory diagnostic of bronchial asthma under pecilomycosis.]

The actuality of the problem is is conditioned by detection of infection of patients' blood with fungi genus paecilomyces in the form of carriage or activation of pecilomycosis infection with clinical manifestation of allergic diseases and bronchial asthma. The purpose of study is to analyze clinical and immunologic characteristics of bronchial asthma under pecilomycosis and to develop new approaches to its laboratory diagnostic in conditions of the primary health care unit. The complex examination of patients that included collection of allergy anamnesis, physical examination, application of laboratory, cytology, immunology and microbiology analysis was carried out. The diagnosis of pecilomycosis was established at the basis of express-diagnostic using direct count of mature spherules and yeast-like cells of fungi genus Paecilomyces in blood sample, detection of specific IgE- and IgG antibodies to allergen of fungus Paecilomyces spp. in blood of patients and cultural analysis. The clinical immunological characteristics of atopic and endogenous (non-atopic) forms of bronchial asthma in 143 patients were examined. The activation of pecilomycosis was established in 120 (83.9%) patients: the content of mature spherules of fungus genus Paecilomyces in blood varied from 8 000 to 55 000 (in average 17 500±755) in 1 mkl at the standard 1000-6000 (in average 3417±433) in 1 mkl. The specific IgE- and IgG antibodies to allergen of fungus Paecilomyces spр. were detected (57% and 81% correspondingly). The development of bronchial asthma is induced by activation of pecilomycosis in blood: it occurred against the background of acute respiratory viral infection in 74 patients (62%), seasonal and age fluctuations of immune status in 34 patients (28%), under stress impact in 12 patients (10%). The immune response to infection with fungus genus Paecilomyces is conditioned by mechanisms of non-specific resistance and specific immunity. The eosinophils and natural killers are involved into sanation of blood from fungal cells of non-phagocyting sizes using antibodies-mediators of specific IgE and IgG antibodies to allergen of fungus Paecilomyces as effector cells in reaction of antibody-dpendent and cell mediated cytotoxicity. The phagocytosis of small fungal forms was detected: endospores by monocytes, neutrophils, eosinophils and cytolysis of fungal cells by erythrocytes. The obtained data permits to differentiate carriage or activation of pecilomycosis in blood of patients with bronchial asthma, to mark out individuals with atopic or non-atopic profile of immune reaction determining specificity of their immune defense from agent of fungal infection and clinical picture of disease. The algorithm is proposed concerning diagnostic of bronchial asthma of pecilomycosis etiology in conditions of primary health care unit.

[Influence of the Potassium Channels Activator Nicorandil to the Quality of Life in Patients With Ishemic Heart Disease and Stable Angina Pectoris].

The aim of the study to assess the influence of medicamentous therapy to the quality of life of ischemic heart disease patients with stable angina pectoris by activator potassium channels nicorandil in comparison with traditional therapy by isosorbide dinitrate. The study included 84 ischemic heart disease patients. Authors consider quality of life as an estimated category of state of the subject in an illness situation. The dynamic of physical and psychological components of quality of life are compared in ischemic heart disease patients under the treatment by nicorandil and isosorbide dinitrate. Indicators of quality of life, defined on the basis of a questionnaires of SAQ and GHQ supplementing an illness picture, are an multiple-factor criterion of an assessment of a condition of this category of patients. The benefits of nicorandil in influence on quality of life indicators were revealed in the study.

[ACCREDITATION OF THE HEALTH PROFESSIONAL AS A LAUNCH PAD FOR CONTINUING MEDICAL EDUCATION.]

The rapid development of medical science and health care practice, the need to improve the quality of health care, the ongoing modernization of education was the basis for scientfic rationale and implementation of the system of continuous medical education, which will be gradually expanded to cover individuals who have undergone 2016 accredited specialist.

[ACTUAL QUESTIONS OF TEACHING PALLIATIVE CARE IN A SYSTEM OF FURTHER PROFESSIONAL EDUCATION.]

In response to the introduction ofpalliative care as a new kind of medical care in Russian Federation (Federal law No.323 from 21.11.2011), Russian Federation Health Ministry has taskedfurther educational institutions with teaching doctors about this new kind of care. I.M Sechenov First Moscow State Medical University has answered this plea in 2015 by introducing a new course focused on palliative care. The program of education was prepared in accordance with rec- ommendations of World Health Organization (WHO) and European Association for Palliative Care (EAPC). A special attention was paid to the pain relief communication skills and organization ofpalliative care for adults in ambulatory and stationary treatment. The program integrates different teaching methods including eLearning, trainings on pain relief and practical trainings on communication skills for interaction with palliative patients and their relatives using the technology of <>.

EFFECT OF CYP2C19 GENETIC POLYMORPHISMS ON THE EFFICACY OF PROTON PUMP INHIBITOR-BASED TRIPLE ERADICATION THERAPY IN SLAVIC PATIENTS WITH PEPTIC ULCERS: A META-ANALYSIS.

INTRODUCTION: Several meta-analyzes reported the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. Most of the studies which were included in these meta-analyzes were held on Asian population. Thus, there is lack of information about the effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients with peptic ulcers. The aim of the study - to determine whether CYP2C19 affect the efficacy of proton pump inhibitor-based triple eradica- tion therapy in Slavic patients with peptic ulcers. METHODS: Data search was performed using Russian index of scientific citation database, Google Scholar and MEDLINE PubMed. Statistics was held in Review Manager v 5.3. The odds ratio (OR) and 95% confidence interval (95% Cl) for eradication of H.pylori was estimated in a fixed-effect model when no heterogeneity across the studies was indicated. RESULTS: Four articles published between 2008 and 2015 were included in meta-analysis (three Russian studies, one Polish study). Eradication rates were significantly lower in CYP2C19 extensive metabolizers of proton pump inhibitors than in a combined group of intermediate and poor metabolizers (OR = 1,90, CI-95% 1,08-3,34, p = 0,03; heterogeneity: 12= 0%, p = 0,74). We also found that proton pump inhibitor-based triple eradication therapy achieved higher rates in poor metabolizers than in a combined group of intermediate and extensive metabolizers of CYP2C19 (OR= 5,48 CI-95% 1,51-19,93, p = 0,01; heterogeneity: F= 0%, p = 0,66). CONCLUSION: The impact of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple eradication therapy in Slavic patients appears significant.

[HIGH FREQUENCY OF CYP2C19 ULTRARAPID METABOLIZERS IN RUSSIAN PATIENTS WITH PEPTIC ULCER].

INTRODUCTION: The main enzyme responsible for metabolism of proton pump inhibitors (PPI) is cytochrome P-4502C19 (CYP2C19). Among all CYP2C19 polymorphisms ulrarapid CYP2C19*17 allele plays an important role in clinical practice as in CYP2C19*17 allele carriers acid suppression achieved with PPI including eradication regimens may be insufficient. THE AIM OF THE STUDY: To find the frequency of CYP2C19 ultrarapid metabolizers in Russian patients with peptic ulcer METHODS: We retrospectively reviewed the results of pharmacogenetic tests of 971 Russian patients with endoscopically and histologically proven ulcers, 428 male (44%) and 543 female (56%). The mean age was 44.6 ± 11.9 years (range 15-88 years). DNA was extracted from EDTA whole blood samples (10 mL). The polymorphisms CYP2C19 *2, *3 *17 were evaluated using real-time polymerase chain reaction (RT-PCR). RESULTS: We found that among 971 peptic ulcer patients ultrarapid metabolizers (CYP2C19*1/*17, CYP2C19*17/*17) were the most frequent genotype--39.75%. Extensive metabolizers with CYP2C19*1/*1 genotype were less frequent--32.65%. Frequency of poor and intermediate metabolizers was found to be 1.5% and 25.85% respectively. We were the first to investigate CYP2C19*17 allele frequency in Russian patients with peptic ulcer which was found to be 27.4%. CONCLUSION: High frequency of CYP2C19 ultrarapid metabolizers in Russian patients with peptic ulcer may be associated with insufficient response to proton pump inhibitors.

[Preclinical investigation of pharmaceuticals impact against cytochrome P450 activity and prognosis of substrate affinity as means for providing substrate therapy safety].

Tricyclic antidepressants, not influencing the P450 3A4 activity, are safe in combination with drugs of other groups used in the treatment of comorbid patients. Azaphen is is one of the agents most widely used in the clinical practice. The in vitro electrochemical analysis showed that pipofezin (azaphen) was not a substrate, inductor, and/or inhibitor of cytochrome P450 CYP3A4 isoenzymes. The Guzar programme computer modelling and the literature data demonstrated the substrate affinity of pipifezin to CYP1A2.

[Role of an educational-and-methodological complex in the optimization of teaching at the stage of additional professional education of physicians in the specialty "anesthesiology and reanimatology"].

An educational-and-methodological complex (EMC) in the specialty 'Anesthesiology and Reanimatology", which promotes manageability, flexibility, and dynamism of an educational process, is of great importance in solving the problem in the systematization of knowledge and its best learning by physicians at a stage of additional professional education (APE). EMC is a set of educational-and-methodological materials required to organize and hold an educational process for the advanced training of anesthesiologists and resuscitation specialists at the stage of APE. EMC includes a syllabus for training in the area "Anesthesiology and Reanimatology" by the appropriate training pattern (certification cycles, topical advanced training cycles); a work program for training in the specialty "Anesthesiology and Reanimatology"; a work curriculums for training in allied specialties (surgery, traumatology and orthopedics, obstetrics and gynecology, and pediatrics); work programs on basic disciplines (pharmacology, normal and pathological physiology, normal anatomy, chemistry and biology); working programs on the area "Public health care and health care service", guidelines for the teacher; educational-and-methodological materials for the student; and quiz programs. The main point of EMC in the specialty "Anesthesiology and Reanimatology" is a work program. Thus, educational-and-methodological and teaching materials included into the EMC in the specialty 'Anesthesiology and Reanimatology" should envisage the logically successive exposition of a teaching material, the use of currently available methods and educational facilities, which facilitates the optimization of training of anesthesiologists and resuscitation specialists at the stage of APE.

[Innovation structure of postgraduate medical education in the specialty of anesthesiology as a constituent of the continuing professional development concept in the light of the Bologna Declaration provisions].

To implement the basic provisions of the Bologna Declaration for postgraduate professional education of anesthesiologists-resuscitators, to upgrade the quality of training specialists, it is important that, by preserving the existing forms of an educational process, to introduce into continuing professional development the following innovation educational technologies, by taking into account the existing forms and technologies of the Russian higher medical school: to realize the continuing professional development (CPD) concept; a credit accumulation system as a generalizing function during CPD; distance and multimedia learning; and a modular organization of a learning and educational process.

[Conceptual and methodological rationales for the use of innovational and traditional educational technologies for the postgraduate training of physicians in the area of anesthesiology and reanimatology].

BACKGROUND: Implementation of an innovational educational space program by the I. M. Sechenov Moscow Medical Academy envisages for the specialty "Anesthesiology and Reanimatology "first of all the development of a new-generation state educational standard, that considers the underlying principles of the Bologna Declaration, its introduction into educational process practice, and the maintenance of the high competence of a physician throughout his/her professional activity. The subject of the study was a system for controlling the educational process of continuous postgraduate training of anesthetists-resuscitation experts, by developing a model of the state educational standard taking into account the European educational traditions that adequately unified in form and content and the specific features of the Russian national school of higher medical postgraduate education. The object of the study was to modernize approaches to transforming the continuous postgraduate educational system for physicians in the area of anesthesiology and reanimatology, which had been laid down and vested in the new-generation state educational standard taking into account the new forms and technologies of an educational process in accordance with the principles of the European educational system. The aim of the study was to provide conceptual and methodological rationales for the use of innovational and traditional educational technologies for the postgraduate training of physicians in the area of anesthesiology and reanimatology according to the measure schedule within the general plan "Development of draft new state standards projects, including the state certification in the specialties "Internal Medicine", "Pharmacy", "Nursing", "Medical and Preventive Science", "Dentistry", "Pedagogics", etc., to elaborate plans of training and subjects, a range of specialties, as well as qualification characteristics in a specialty, etc." within the innovational educational space program by the I. M. Sechenov Moscow Medical Academy. The tasks of the study: 1) to provide conceptual and methodological rationales for the incorporation of innovational educational technologies into the Russian national system for the postgraduate medical training in the area of anesthesiology and reanimatology; 2) to adapt the European educational traditions to the Russian national normative base of the postgraduate medical education in the specialty "Anesthesiology and Reanimatology"; 3) to develop ways of mating the methods for estimation of professional competence within the continuous professional improvement system for the specialty "Anesthesiology and Reanimatology", which are accepted in the countries of the European Union and which are customary for the Russian Federation. METHODS: a conceptual and methodological analysis and adaptation of the European experience of postgraduate education of anesthetists and resuscitation experts to the Russian educational system, by working out a new-generation state educational standard that provides for the use of innovational educational technologies. NOVELTY: The authors first present the conceptual and methodological rationales for the use of innovational educational technologies to develop a new-generation state educational standard in the specialty "Anesthesiology and reanimatology", which is based on the incorporation of the European educational traditions and innovational educational technologies into the Russian postgraduate medical training system. They first propose the model for reforming the structure of postgraduate education of anesthetists and resuscitation experts, which has been adapted to the World Medical Education Federation requirements stated in the Bologna Declaration. CONTENTS OF THE STUDY: The concept and methodology of development of the form- and contents-uniformed state educational standard of postgraduate training in specialty 14.00.37 "Anesthesiology-Reanimatology" for the postgraduate training of medical specialists in Russia in accordance with the principles of the Bologna declaration.

[Main points of a modular approach to developing educational programs for the postgraduate training of physicians in the area of anesthesiology and reanimatology].

The uniquely shaped and contained structure of a modular approach to organizing an academic process, which comprises a conceptual rationale for the conversion of an educational process in accordance with a modular design, is detailed in the paper. All learning modules have the similar structure consisting of the following sections: background, general and specific objectives, contents, methods of teaching and assessment, the place and conditions of training. The authors provide evidence for the use of a module as a form of organization of individual educational programs, curricula, and academic plans of subject-matter during postgraduate training of physicians. Module education is shown to get over the fragmentariness of an academic process, by working out a comprehensive educational program and making a problem presentation of the contents in the module. The development of educational modules is to eliminate parallelism, temporary and logic gaps between various topics, to upgrade the quality of education, and to enhance the efficiency of a medical specialist's self-work. The authors analyze in detail the advantages of the module approach in improving an academic process during postgraduate training of physicians. They also present guidelines for the introduction of module technology in accordance with the principles of the European educational system.

[Potentialitis of phosphodiesterase inhibitors in management of patients with chronic heart failure complicating cardiac ischemia].

In spite of the advances in understanding the pathogenesis and approaches to the treatment of chronic heart failure, it remains one of the main causes of the patients invalidism and death, that makes the cardiologists all over the world develop new drugs for the treatment of the disease. The aim of the study was to show possible long-term use of enoximone, a new agent from the group of phosphodiesterase inhibitors, in doses of 75-150 mg a day in traditional combined pharmacotherapy of the patients with chronic heart failure. Thirty eight patients with chronic heart failure III-IV FC (NYHA) and 30% left ventrical efflux function were observed. The dynamics of the disease clinical signs, the heart hemodynamic and morphofunctional parameters, the heart bioelectric activity and the hospitalization frequency were investigated to estimate the therapy efficacy and safety. The use of enoximone in the traditional combined pharmacotherapy, including inhibitors of angiotensin-transforming enzymes, diuretics, beta-adrenoblockers and aldosterone antagonists, resulted in a reliable improvement as for the disease clinical signs, 17.8% increase of the left ventrical efflux function vs. the initial indices, less frequent hospitalization. The enoximone tolerability was good, no side effects requiring discontinuation of the drug use were recorded.

[On the use of statins in patients with chronic cardiac insufficiency].

Today, the necessity to use hypolipidemic agents belonging to the group of statins as means of primary and secondary prevention of coronary artery disease (CAD) and its complications is not doubted. The results of numerous large studies conducted in many different countries during the last 10 to 15 years confirm this statement. The appropriateness of statin application to patients with chronic cardiac insufficiency (CCI) is still under discussion, because there are no sufficient data on whether hypolipidemic therapy is able to improve the prognosis in this category of patients. The authors conducted a long-term research into the use of statins in combination with basic combined therapy in patients with CCI complicating the course of CAD. A reverse correlation between the levels of total cholesterol, low-density protein cholesterol, and the degree of CCI severity was demonstrated. Long-term continuous therapy of CCI patients with a combination of medications including statins did not worsen the clinical symptoms. However, hypolipidemic therapy should be administered to CCI patients on a differentiated basis, taking into account the initial state of lipid profile and the severity of the underlying disease.

[Role of a credit system in the development of continuous postgraduate training of physicians within the framework of the innovation educational space formation program of the I. M. Sechenov Moscow Medical Academy].

Russia 's joining the European higher educational space and an increase in the international competitive capacity of the European higher educational system envisage first of all that the European credit test system (ECTS) should be accepted and introduced into all national higher educational schools, which ensures both credit test and cumulative functions and guarantees the academic recognition of the education abroad. The issues of modernization of approaches to reforming the continuous postgraduate training of physicians, by using the credit test system, as well as new forms and technologies for an educational process in accordance with the European educational system principles are under discussion. The novelty of the proposed development is that the credit test system is first applied to the continuous postgraduate training of physicians within the framework of the Russian higher medical educational system. The Russian continuous postgraduate medical training pattern that is common in form and content is proposed in accordance with the Bologna declaration principles; approaches have been developed to incorporating the European educational traditions into the Russian national continuous postgraduate medical training system, by employing the credit test system; criteria have been elaborated for adapting the European credit test system at all stages of reformation of the Russian educational system; guidelines have been worked out for the conversion of academic load of various forms of the continuous postgraduate training of physicians to the credit test system; ways of introducing the new forms and technologies into an educational process have been proposed in accordance with the European education system principles, by taking into account the credit test system. The introduction of new technologies of an educational process, by using the credit test system will contribute to personality formation in a physician who has a high competence, a capacity for valuable independent work in health cared facilities and further postgraduate training during his/her professional activities, which is required to provide a high-skill aid to patients in compliance with his/ her work status and employment place.