Репозиторий Университета

Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.

© 2018 Institute of Europe Russian Academy of Sciences. All Rights Reserved. Introduction. In the modern world, volunteering is one of the most effective ways for successful social development and improvement of the quality of human life. By the Decree of the President of Russia Vladimir Putin, the year of 2018 has been declared the Year of Volunteer in the Russian Federation. Voluntary activity has a positive impact not only on people who are provided with help but also on volunteers. Volunteering is beneficial for the formation and strengthening of moral position and citizenship, development of philanthropy, responsiveness, sense of justice, leadership skills. Besides, youth volunteering abroad has long been used as an important element of preparation to perform professional duties. Participating in the professionally focused volunteering, the student has an opportunity to gain professional experience, to check the correctness of own professional self-determination and career aptitude. Similar volunteer service is especially relevant for representatives of the “caring” professions - teachers, social workers, psychologists and doctors, i.e. people who have to be a priori ready for pro-social activity and have such qualities as goodwill, communicability and conscientiousness. The aim of the paper is to study the dynamics of the psychological characteristics of future health-care professionals regularly participating in professionally-oriented volunteer activities. Methodology and research methods. The research is based on competency-based and activity approaches to education. Also, research methodology involves the key provisions of the concept of a humanization of the pedagogical process of the higher education institution, and the basic principles of volunteers' activity declared in documents of the “United Nations Volunteers” (UNV) programme. The survey among students was the main method of information collection. Psycho-diagnostic tools involved: the assessment technique for communicative and organizing tendencies of an individual (V. V. Sinyavsky, V. A. Fedoroshin); the questionnaire for assessing the development level of empathic tendencies (A. Megrabyan, N. Epstein); the methodology for studying of valuable orientations of the individual (M. Rokich); the questionnaire “Motivation of Assistance” (S. K. Nartov-Bochaver). To objectify the data obtained, the Mann-Whitney U Test statistical technique was applied to reveal a difference in values of the parameter between small selections. Results and scientific novelty. The volunteer team was organized at the Department of Psychology of Health and Correctional Psychology of the Kursk State Medical University. This team is engaged in volunteering at the boarding school for children with disabilities. The authors came to the conclusion that the real directions of quasi-professional voluntary student unionism substantially correspond to the abilities and skills required of future health professionals. The authors analyzed the two-year dynamics of changes in students' psychological characteristics and professional competencies under the influence of their constant involvement in the volunteer movement. The key personality traits of an experienced student volunteer were designated: orientation towards humanistic values; motivation and readiness of providing assistance to needy people; well-developed communicative abilities and empathy. It has been established empirically that the level of development of these professionally important qualities among the student volunteers is initially above, compared with fellow students who were not involved in volunteering. Also, the level mentioned above continues to evolve actively due to the performance of the professionally focused and socially important volunteer mission. Practical significance. Results of the undertaken research prove convincingly that inclusion in the pedagogical process of higher education institution of professional volunteering as one of the priority activities contributes to the spiritual-moral education of students, the formation of professional and general humanistic outlook. In addition, student volunteering allows future graduates to find the necessary experience in the chosen field of employment.

© 2018, Dynasty Publishing House. All rights reserved.  Objective: to evaluate the possibility of creating a human model of acute Helicobacter pylori infection in healthy volunteers after infecting them with a mutant rifampicin-resistant strain of H. pylori KM-11 (Rif R ), to obtain evidence of H. pylori survival and invasion into the gastric mucosa, describe the symptoms, and assess the efficacy of H. pylori eradication therapy with Stimbifid plus. Materials and methods. In our experiments, we used conventional white mice of both genders weighing 18–20 g. The concentration of bifidobacteria, lactobacilli, and Escherichia (CFU) in animal faeces was determined by inoculating tenfold dilutions of biomaterial onto solid media and further counting of bacterial colonies grown after the incubation period. Microorganisms were cultivated in an anaerobic incubator and then identified by morphological evaluation and using biochemical identification kits. We created a murine model of H. pylori infection by oral administration of H. pylori KM-11 (Rif R ) suspensions to immunocompromised mice that had earlier undergone intramuscular administration of dexamethasone. For a human model of H. pylori infection, we selected healthy male volunteers. They took suspensions of H. pylori KM-11 (Rif R ) isolates in isotonic sodium chloride solution. Fecal specimens were collected from volunteers on daily basis during the entire follow-up period and then 2 weeks and 1 month after treatment completion. Fecal suspensions in isotonic sodium chloride solution were inoculated onto the selective hemin-containing solid media with rifampicin at a concentration of 160 µg·mL –1 . The results of this experiment (H. pylori colony count) were used to evaluate the efficacy of H. pylori eradication therapy with Stimbifid plus. Results. Both in vitro experiments and murine models demonstrated high anti-H. pylori activity of Stimbifid plus and its ingredients, restoration of the gastric microbiota, restoration of gastric colonization resistance, and eradication of H. pylori KM-11 (Rif R ). Self-infection with H. pylori KM-11 (RifR) caused acute infection in volunteers. The disease manifested with mild ailment, epigastric discomfort, belching, increased stool frequency, and changes in the color of stool. The detection of H. pylori KM-11 (Rif R ) in the faeces of volunteers and isolation of pure cultures prior to treatment initiation indicated bacterial adhesion to gastric mucosa and survival of microorganisms. Treatment with Stimbifid plus caused gradual decrease in the number of bacteria isolated from feces and their complete elimination by day 11 of therapy. All fecal specimens collected 2 weeks and 1 month after therapy completion from volunteers were negative for H. pylori KM-11 (Rif R ). None of the study participants required in-patient treatment. Conclusion. The results of our experiments obtained in both murine and human models of H. pylori infection will be used for more detailed assessment of this pathological process, clinical manifestations, impact of H. pylori virulence factors on the host, choosing new methods for the prevention and treatment of chronic gastritis caused by H. pylori, and monitoring the efficacy of eradication therapy.