Aim: demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Materials and methods. To monitor the basic effects of FMT, we performed targeted DNA sequencing of 16S rRNA gene (V3–V4) using MiSeq platform as well as multiplex real-time PCR, MS/gas chromatography technique, immunophenotyping of blood lymphocytes, histological and immunohistochemical techniques.Clinical case. A 40-year-old female patient diagnosed with myelodysplastic syndrome, with a history of two unsuccessful allo-HSCTs due to graft failure, underwent the third haploidentical HSCT (haplo-HSCT) from her father as ‘salvage’ therapy. Due to early viral/bacterial colitis post-transplant associated with a multidrug-resistant strain of K. pneumoniae and herpes virus type 6, FMT was performed on days 46 and 47 after allo-HSCT. Complete resolution of the enteropathy symptoms was noted following FMT. However, immunosuppressive therapy was canceled on D+106 after haplo-HSCT due to the detection of minimal residual disease causing development of the ‘overlap’-type GVHD with damage skin lesions grade 4, and intestinal mucous membranes grade 3. This complication required resumption and subsequent intensification of immunosuppressive therapy with complete resolution of GVHD symptoms. Following FMT treatment, the patient showed complete resolution of clinical colitis symptoms. According to results of 16S rRNA sequencing, the species-specific diversity of fecal microbiota increased significantly, along with decreased relative contents of opportunistic bacteria (Klebsiella, Enterococcus, Streptococcus genera). A significant growth was revealed for commensal Bacteroidota, and re-emergence of Faecalibacterium, Blautia, Roseburia. Acute gastrointestinal GVHD promoted by tacrolimus withdrawal was associated with repeated depletion of intestinal microbiota. Upon resolution of GVHD and resumed immunosuppression, increased microbiota diversity (Shannon index) was again recorded, and the parameters of patient’s fecal microbiota reached the donor values. The microbiota shifts at all clinical stages (before and after FMT, at the peak of acute intestinal GVHD and intensive immunosuppressive therapy) showed some relations with metabolism of bile and fatty acids in blood plasma and immune parameters.Conclusions. FMT may be a component of complex therapy aimed at early reconstitution of immune system and organic acid metabolism in patients after allo-HSCT. The composition of fecal microbiota, metabolic profile and spectrum of lymphocyte subpopulations may be markers for monitoring complex rehabilitation after allo-HSCT.

Введение. Распространенность желчнокаменной болезни (ЖКБ) демонстрирует постоянный рост и достигает в развитых странах 15%. Основным способом ее лечения остается холецистэктомия, которая, по данным исследователей, ассоциирована с неблагоприятными метаболическими последствиями. Цель работы: изучение влияния холецистэктомии на метаболизм липидов и желчных кислот в плазме крови пациентов с ЖКБ. Материалы и методы. 96 пациентов в возрасте 22–45 лет с ЖКБ (камни в желчном пузыре), которым выполнялась плановая лапароскопическая холецистэктомия, распределены по липидному профилю плазмы крови на 2 группы. Использованы клинические данные, анкетирование, липидограмма, хромато-масс-спектрометрия желчных кислот плазмы крови и желчи. После оперативного лечения половина пациентов с изменениями липидного спектра 3 месяца получала препараты урсодезоксихолевой кислоты. Повторное обследование через 3 месяца и через 1 год после холецистэктомии. Результаты. Показатели липидограммы в группах различались статистически значимо. Уровни желчных кислот плазмы крови значимо различались для холевой и урсодезоксихолевой кислот (УДХК). В группе «Нормальный липидный спектр» через 3 месяца наблюдалось улучшение, а через год — значимое ухудшение показателей липидограммы. В группе «Изменения липидного спектра» через 3 месяца улучшение показателей липидограммы отмечалось только у пациентов, принимавших урсодезоксихолевую кислоту. Через год статистически значимых изменений не выявлено. Выводы. У пациентов с ЖКБ имеет место дисбаланс ЖК: повышение уровней холевой, дезоксихолевой, гликохолевой, таурохолевой кислот и снижение уровня хенодезоксихолевой кислоты. Уровни УДХК в плазме крови и в желчи имеют прямую корреляционную связь. После холецистэктомии в плазме крови снижаются концентрации повышенных кислот, а также исходно сниженной хенодезоксихолевой. У пациентов с нормальным липидным спектром крови холецистэктомия негативно влияет на показатели липидограммы. Холецистэктомия повышает риск ухудшения показателей липидного спектра в 1,6 раза. Прием препаратов УДХК улучшает показатели липидного спектра крови. Introduction. The prevalence of cholelithiasis shows a constant increase and reaches 15% in developed countries. The main method of its treatment remains cholecystectomy, which, according to researchers, is associated with adverse metabolic consequences Aim: to study the effect of cholecystectomy on the metabolism of lipids and bile acids in the blood plasma of patients with cholelithiasis. Materials and methods: 96 patients aged 22–45 years with cholelithiasis (gall bladder stones) who underwent elective laparoscopic cholecystectomy were divided into 2 groups according to the lipid profile of the blood plasma. Clinical data, questioning, lipidogram, chromato-mass spectrometry of bile acids in blood plasma and bile were used. After surgical treatment, half of the patients with changes in the lipid spectrum received ursodeoxycholic acid preparations for 3 months. Re-examination after 3 months and 1 year after cholecystectomy. Results. Lipidogram parameters in the groups differed statistically significantly. Plasma bile acid levels differed significantly for cholic and ursodeoxycholic acids. In the “Normal lipid spectrum” group, after 3 months, an improvement was observed, and after a year, a significant deterioration in lipidogram parameters. In the “Changes in the lipid spectrum” group, after 3 months, an improvement in lipidogram parameters was noted only in patients taking ursodeoxycholic acid. A year later, no statistically significant changes were found. Conclusions. In patients with cholelithiasis, there is an imbalance of fatty acids: an increase in the levels of cholic, deoxycholic, glycocholic, taurocholic acids, and a decrease in the level of chenodesoxycholic. UDCA levels in blood plasma and bile are directly correlated. After cholecystectomy in the blood plasma, the concentrations of elevated acids, as well as the initially reduced chenodesocholic acid, decrease. In patients with a normal blood lipid spectrum, cholecystectomy negatively affects the lipid profile. Cholecystectomy increases the risk of lipid spectrum deterioration by 1.6 times. Taking UDCA preparations improves the parameters of the blood lipid spectrum.

Введение. Распространенность желчнокаменной болезни (ЖКБ) демонстрирует постоянный рост и достигает в развитых странах 15%. Основным способом ее лечения остается холецистэктомия, которая, по данным исследователей, ассоциирована с неблагоприятными метаболическими последствиями. Цель работы: изучение влияния холецистэктомии на метаболизм липидов и желчных кислот в плазме крови пациентов с ЖКБ. Материалы и методы. 96 пациентов в возрасте 22–45 лет с ЖКБ (камни в желчном пузыре), которым выполнялась плановая лапароскопическая холецистэктомия, распределены по липидному профилю плазмы крови на 2 группы. Использованы клинические данные, анкетирование, липидограмма, хромато-масс-спектрометрия желчных кислот плазмы крови и желчи. После оперативного лечения половина пациентов с изменениями липидного спектра 3 месяца получала препараты урсодезоксихолевой кислоты. Повторное обследование через 3 месяца и через 1 год после холецистэктомии. Результаты. Показатели липидограммы в группах различались статистически значимо. Уровни желчных кислот плазмы крови значимо различались для холевой и урсодезоксихолевой кислот (УДХК). В группе «Нормальный липидный спектр» через 3 месяца наблюдалось улучшение, а через год — значимое ухудшение показателей липидограммы. В группе «Изменения липидного спектра» через 3 месяца улучшение показателей липидограммы отмечалось только у пациентов, принимавших урсодезоксихолевую кислоту. Через год статистически значимых изменений не выявлено. Выводы. У пациентов с ЖКБ имеет место дисбаланс ЖК: повышение уровней холевой, дезоксихолевой, гликохолевой, таурохолевой кислот и снижение уровня хенодезоксихолевой кислоты. Уровни УДХК в плазме крови и в желчи имеют прямую корреляционную связь. После холецистэктомии в плазме крови снижаются концентрации повышенных кислот, а также исходно сниженной хенодезоксихолевой. У пациентов с нормальным липидным спектром крови холецистэктомия негативно влияет на показатели липидограммы. Холецистэктомия повышает риск ухудшения показателей липидного спектра в 1,6 раза. Прием препаратов УДХК улучшает показатели липидного спектра крови.

Relevance . Individuals of stressful professions, including the emergency response officers (firefighters and rescuers) of the Ministry of Emergency Situations of Russia, are prone to the early onset of circulatory system diseases (CSD). At in-depth examinations the CSD detection rate in EMERCOM response officers is above 10%. Earlier studies report that CSD risk factors are widespread among EMERCOM of Russia response officers. Therefore, it is relevant to identify the predisposition to CSD as soon as possible in order to maintain good health and longevity among highly qualified professionals of the Ministry of Emergency Situations of Russia. The pathophysiological mechanism underlying progression of atherosclerosis affects complicated interactions between vasculature, immune system and lipid metabolism. Evidence shows that intestinal microbiome exacerbates all compound risk factors for atherosclerosis, both directly and indirectly, thus playing an important role in CSD development. Numerous studies revealed that elevated levels of plasma homocysteine and other aminothiols strongly correlate with manifestations of vascular dysfunction in atherosclerosis, coronary heart disease, myocardial infarction, stroke, and thrombosis, which makes it possible to isolate homocysteine as an independent risk factor for CSD progression. Our objective is to evaluate intestinal microbiome metabolism indicators and plasma aminothiols as early CVD risk markers in emergency response officers of the Ministry of Emergency Situations of Russia. Methodology . A comprehensive clinical and laboratory examination was performed in 96 emergency response male officers of the Russian Ministry of Emergency Situations at a regular medical check-up in the outpatient center of the Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia, St. Petersburg. The average age of response officers was (35.9 ± 0.8) years, with average work experience in the EMERCOM of Russia of (8.8 ± 0.5) years. All emergency response officers were split in 3 groups: group 1 included 56 practically healthy males, group 2 - 20 males with risk of CVD development, group 3 - 20 males with established CVD diagnosis. Chromatography with mass-spectrometric determination of short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and aminothiols was performed in plasma samples from all examined patients. Results and analysis . TMAO level was elevated by 30 % in group 3 compared to group 1. Acetic acid level decrease by 32 % was found in group 2 and by 45 % in group 3 compared to group 1. Plasma valeric and butyric acids were decreased by 1.9 and 2.5 times respectively in group 3 compared to group 1, as well as by 2 times in group 3 compared to group 2. It was found that in group 3 cystine concentration was decreased by 30 % compared to group 1 and reduced glutathione was elevated by 2 times compared to group 2. Conclusion . The revealed changes in the level of SCFA, aminothiols and TMAO in emergency response officers of the Ministry of Emergency Situations of Russia indicate a metabolic imbalance, which expands our understanding of the interactions between the intestinal microbiome and human body. This is fundamentally important for CSD early diagnosis, prevention and correction in emergency response officers of the Russian Ministry of Emergency Situations.

Relevance. Professional activity of operational staff of the Russian EMERCOM in the Arctic zone is associated with adaptive changes in the body resulting in changes in all types of metabolism, appearance of functional abnormalities and, without proper correction, development of various diseases. The complex system of metabolic interaction between humans and the microbiota is well described by the “microbiota-gut-brain” axis, which includes endocrine, immune, and neurohumoral pathways. Dysfunction of this axis in humans may be involved in pathogenesis of various diseases and somatic psychoneurological disorders.Intention is to study features of the intestinal microbiota in operational staff of the Russian EMERCOM working in the adverse conditions of the Arctic zone.Methodology. A study group included 94 firefighters and rescuers of the Russian EMERCOM working in the Arctic zone of Russia and was divided into subgroups depending on relevant work experience (0–5 years, 6–10 years, 11 years and more), as well as on age (22–35 years and 36–56 years). A control group included 98 rescue workers from the North-West regional search and rescue team and employees of the territorial fire departments of St. Petersburg (males aged 32.1 ± 0.5 years). Quantity and composition of the parietal intestinal microbiota were assessed based on microbial markers in the blood plasma using gas chromatography-mass spectrometry.Results and Discussion. Negative changes in the quantity and structure of the parietal intestinal microbiota were revealed in operational staff of the Russian EMERCOM working in the Arctic zone of Russia as compared with the control group: the total number of microbial markers was reduced by 34 %, beneficial flora – by 44 %, opportunistic flora – by 10 %, aerobes – by 25 %, anaerobes – by 32 %. In the structure of beneficial microflora, the proportion of Lactobacillus was 1.5 times greater and the proportion of Bifidobacterium was 3 times fewer. The most pronounced changes in the intestinal microbiota with increase of work experience were found in rescuer workers (a decrease in opportunistic flora and aerobes, an increase in the ratio of anaerobic to aerobic flora). According to the Kruskal–Wallace test, the amount of microbial markers of Bifidobacterium, Propionibacterium/Cl. Subterminale, aerobes, endotoxin, as well as the ratio of anaerobic to aerobic flora depends on the work experience of operational staff of the Russian EMERCOM working in the Arctic zone of Russia.Conclusion. Ecological and professional stress in operational staff of the Russian EMERCOM working in the Arctic zone disturbs trophism of various types of endogenous microflora and its regulatory relationships with the human body and, hence, results in quantitative and qualitative changes in the composition of the microflora.

Based on a long-term dynamic study of the state of health of liquidators of the consequences of the Chernobyl accident, it was found that 75 % of patients have a metabolic syndrome, burdened with concomitant somatic pathology. The article presents literature data on the key role of adipokine levels in the development of the metabolic syndrome of adipose tissue, hormonal indicators, vitamins and other nutrients, which require modern methods of laboratory diagnostics to determine.The aim. To develop a clinical and laboratory algorithm for diagnosing metabolic syndrome in liquidators of the consequences of the Chernobyl accident using new medical technologies.Methods. 122 liquidators of the consequences of the Chernobyl accident with cerebrovascular diseases, diseases of the digestive system and endocrine system pathology were examined. Based on the International recommendations of 2009, two groups were formed: those with the absence (n = 32) and the presence (n = 90) of metabolic syndrome (MS). The control group consisted of 30 people with MS who were examined and treated at the clinic, but did not have contact with radiation. All patients were male, with an average age of 64–66 years. The main biochemical parameters in blood serum were determined. Immunochemiluminescent method was used to determine hormonal parameters. Mass spectrometry was used to determine the indicators of oxidative stress (MDA, fat-soluble vitamins A, E, D, polyunsaturated fatty acids), and trace elements.Results and analysis. A characteristic feature of MS in LPA is a signifcantly (p < 0.05) low level of total testosterone in the blood serum and the calculated ratio of testosterone/estradiol. With increasing number of MS components signifcantly (p < 0.05) increases in serum level of basal insulin and HOMA IR, leptin levels, decreases the concentration of adiponectin. The analysis of the obtained results did not reveal signifcant differences in the content of the main markers of MS in LP and patients of the control group with MS. In 25% of LPA with MS, adiponectin values are determined below the lower limit of the reference range (less than 5.6 μg/ml), and the leptin content is higher than 21.0 ng/ml at the upper limit of the reference range of 5.6 ng/ml. there Is a stable tendency to reduce HDL cholesterol. When comparing the studied indicators for MS in patients with MS at the Chernobyl NPP and the control group, a statistically signifcant increase in the concentration of vitamin E (9.7 [6.8–12.7] and 6.3 [5.3–7.7]; p = 0.001) was found by 54 % and a decrease in the level of linoleic acid (230.9 [184.6–293.0] and 262.3 [214.1–426.3]; p = 0.014) by 12 %. A decrease in selenium, zinc, copper and iodine was detected.Conclusion. The results of the study demonstrated that liquidators of the consequences of the Chernobyl accident with metabolic syndrome may develop various pathogenetic variants of MS, which can be clarifed by the proposed additional criteria of the diagnostic algorithm. Identifying the pathogenetic variant of MS opens up the possibility of a personalized approach to MS therapy and prevention of the development of circulatory diseases and diabetes.

Fludarabine is a purine antimetabolite with a pronounced immunosuppressive effect. The inhibitory effect of fludarabine depends on its concentration in blood plasma. In addition, the phenotypic characteristics of patients affect the pharmacokinetic and pharmacodynamic profile of the drug, which necessitates a personalized approach to the dosage regimen. The chromatography-mass spectrometric method for the quantitative determination of 2-fluorine in blood plasma was developed for studying the individual parameters of pharmacokinetics of the international non-proprietary name (INN) fludarabine in patients with B-cell chronic lymphocytic leukemia during the standard course. Such method for the quantitative determination of 2-fluorine in blood plasma was developed and validated in accordance with international requirements. Significant individual variability of the main pharmacokinetic parameters in patients with B-cell chronic lymphocytic leukemia with a single oral administration of the drug with INN fludarabine at a dose of 40 mg/m2 was established, so the coefficient of variability Cmax was 42 %, Tmax — 92 %, AUC0-t — 45 %, Kel — 23 %, T1/2 — 26 %. It should be noted that there is a high interindividual variability of fludarabine, for example, 24 hours after taking the study drug, the maximum and minimum plasma concentrations of the fludarabine metabolite 2-fluoro-ara-A in different in patients with B-cell chronic lymphocytic leukemia differed 9 times. Individual variability of pharmacokinetic parameters characterizing absorption (Cmax/AUC0-t) and total clearance of the active metabolite of fludarabine is statistically significantly associated with a combination of gender and anthropometric factors.

A high demand for sildenafil-based drugs puts a premium on the development of methods for quantitation of sildenafil in bio-substrates to facilitate pharmacokinetic analysis in bioequivalence studies. High performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was proposed for the method development due to its high sensitivity, selectivity, reproducibility, and performance. The aim of the study was to develop and validate an HPLC-MS/MS method for quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. Approbation of the developed technique in the study of the pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil in healthy volunteers in the study of the bioequivalence of the drug sildenafil in the form of a spray. Materials and methods: the method was implemented using the Agilent 1200 high-performance liquid chromatography system with the Agilent 6440 triple quadrupole system, and Poroshell 120 EC-C18 chromatographic column, 4.6 m × 150 mm × 2.7 μm. Calibration samples were prepared using sildenafil citrate and N-desmethyl sildenafil reference standards with 99.5 and 98.5% purity, respectively. Vardenafil was used as an internal standard. Pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil were studied in 44 healthy male volunteers as part of a bioequivalence study approved by the Ministry of Health of the Russian Federation. The primary data processing was performed using Mass Hunter software version B 06.00, and statistical processing was performed using Microsoft Office Excel 2010 and Statistica 6.1. Results: the authors developed and validated a method for quantitation of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. The developed method was used successfully to study pharmacokinetic profiles of the discussed compounds in healthy volunteers. Conclusions: the developed method of quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma is simple, reproducible, fast, and robust. The results of the pharmacokinetic studies using the developed method demonstrated bioequivalence of the test product and the reference product.

A high demand for sildenafil-based drugs puts a premium on the development of methods for quantitation of sildenafil in bio-substrates to facilitate pharmacokinetic analysis in bioequivalence studies. High performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was proposed for the method development due to its high sensitivity, selectivity, reproducibility, and performance. The aim of the study was to develop and validate an HPLC-MS/MS method for quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. Approbation of the developed technique in the study of the pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil in healthy volunteers in the study of the bioequivalence of the drug sildenafil in the form of a spray. Materials and methods : the method was implemented using the Agilent 1200 high-performance liquid chromatography system with the Agilent 6440 triple quadrupole system, and Poroshell 120 EC-C18 chromatographic column, 4.6 m × 150 mm × 2.7 μm. Calibration samples were prepared using sildenafil citrate and N-desmethyl sildenafil reference standards with 99.5 and 98.5% purity, respectively. Vardenafil was used as an internal standard. Pharmacokinetic profiles of sildenafil and N-desmethyl sildenafil were studied in 44 healthy male volunteers as part of a bioequivalence study approved by the Ministry of Health of the Russian Federation. The primary data processing was performed using Mass Hunter software version B 06.00, and statistical processing was performed using Microsoft Office Excel 2010 and Statistica 6.1. Results : the authors developed and validated a method for quantitation of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma. The developed method was used successfully to study pharmacokinetic profiles of the discussed compounds in healthy volunteers. Conclusions : the developed method of quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil in human plasma is simple, reproducible, fast, and robust. The results of the pharmacokinetic studies using the developed method demonstrated bioequivalence of the test product and the reference product.

Relevance. Increasing prevalence of concomitant pathology among the Chernobyl accident recovery workers is associated with long-term adverse health effects. Due to a significant role of dyslipidemia, microbiological disorders of the gastrointestinal tract should be assessed along with individual indicators of cholesterol metabolism. Intention. To study the features of the gut microbiome composition in the Chernobyl accident recovery workers. Methods. Lipid metabolism was assessed based on the total cholesterol in the blood serum. Parietal intestinal microbiota was studied via gas chromatography-mass spectrometry of microbial markers. The study group consisted of 94 Chernobyl accident recovery (1986-1990) workers aged 53-80 years with various somatic pathology. Results and discussions . It was found that patients with elevated serum cholesterol had numerous microbial markers of Lactobacillus and Rhodococcus in the mucosal layer of the intestine, as well as aerobic bacteria which are the sign of dysbiosis. The most pronounced differences in the structure of the interrelations of “useful” and other intestinal microorganisms are associated with Lactobacillus. Representatives of “useful” gut microbiome, in addition to Lactobacillus, obviously correlate with each other. Conclusion. According to the study results, there is a relationship between gut microbiome composition and lipid metabolism. Lipid metabolism disorders are associated with qualitative and quantitative changes in the composition of gut microbiome in Chernobyl recovery workers. No statistically significant correlations were observed between parameters under study and radiation exposure or the year of participation in recovery work.

Relevance. Today gastric cancer is still one of the oncologic diseases most often leading to death. H. pylori eradication reduces risk of gastric cancer, but its efficacy depends on gastric mucosa state. Atrophy of gastric mucosa is more common in Chernobyl nuclear power plant (CNPP) accident recovery workers than in patients who have not been involved in CNPP accident recovery works. It seems especially important to investigate the features of antibiotics transport to H. pylori colonization area in this contingent.Intention – to determine the features of amoxicillin secretion by gastric mucosa in CNPP accident recovery workers with atrophic and nonatrophic gastritis undergoing H. pylori eradication.Methodology. 65 CNPP accident recovery workers were divided into groups depending on state of gastric mucosa according to endoscopic and histological examination, immunosorbent assay of pepsinogens I and II and gastrin-17 basal serum levels. On the first day of eradication therapy, gastric secretion samples were obtained via nasogastric probe 30, 60, 120, 180 and 240 minutes after oral amoxicillin administration. Drug concentrations in gastric secretion were assessed via liquid chromatography-mass spectrometry.Results and discussion. Amoxicillin concentrations in gastric secretion samples were lower (р < 0.01) in patients with atrophic antral gastritis than in patients with normal gastric mucosa and atrophic fundal gastritis. Patients with fundal atrophy were characterized by lower amoxicillin concentrations 30 and 60 (p = 0.02) minutes after drug intake than in patients with normal gastric mucosa, and higher concentration in the 120th (p < 0.01) and 180th (p = 0.02) minute than in patients with antral atrophy. Amoxicillin concentrations in patients with antral atrophy were lower (p < 0.01) than in non-atrophy group in the 30th, 60th and 120th minute. In the 240th minute, amoxicillin concentrations in patients with fundal atrophy exceeded concentrations in both other groups (p < 0.01). Amoxicillin concentration peak was registered in patients with fundal and antral atrophy in the 180th minute, in patients without atrophy – from the 30th to 120th minute.Conclusion. Atrophy of gastric mucosa is characterized by decreased transport of orally administered amoxicillin from bloodstream to gastric lumen. Depending on gastric mucosa state, amoxicillin concentrations in gastric secretion should be evaluated at different time points after drug administration: in patients with atrophic gastritis – in the 180th minute, in patients without atrophy – in the 120th minute. While predicting the efficacy and choosing H. pylori eradication regimen, morphological and functional state of gastric mucosa should be taken into account.

Our objective was to develop a model of systemic inflammatory response syndrome (SIRS) by chemical induction of colon injury and antibiotic-associated intestinal dysbiosis in rats with primary visceral obesity (PVO) for studies of myocardial resistance to ischemia-reperfusion injury. The experiments were performed with adult Wistar male rats with PVO under improved conditions of a conventional animal clinic. The chemically induced inflammatory colon disease (CIICD) was accomplished by intragastric administration of a mixture of broad-spectrum antimicrobial agents (AMA) for 3 days. Five days later, immunological and biochemical studies were carried out, as follows: composition of the intestinal microbiota in feces and shortchain fatty acids in blood, morphological changes in the structure of the colon, hemodynamic parameters and myocardial stability with modified Langendorff system. In PVO rats, the mass of visceral fat deposits and the content of lipopolysaccharides (LPS) in the blood were significantly increased when giving them fatcarbohydrate diet (FCD). In animals with CIICD, in addition to LPS, there was a significant increase in proinflammatory cytokine concentration (TNF, IL-8, MCP-1), and after oral administration of the AMA mixture, pronounced disturbances of food behavior and evacuatory function of gastrointestinal tract, deep destructive changes in colon, as well as qualitative and quantitative composition of intestinal microbiota with characteristics typical to the first-grade dysbiosis. High levels were shown for IL-8 cytokine only. An increase in acetic and propionic acid concentrations were shown in blood in animals with CIICD, and, to a greater extent, in rats with antibiotic-induced dysbiosis (AID). FCD was followed by significantly reduced levels of lactobacilli and bifidobacteria in colonic contents. CIICD leads to detection of Escherichia coli, and intestinal dysbiosis leads to the manifestation of Proteus. A comorbid combination of pathological changes in the immune and digestive systems caused a significant increase in the area of myocardial necrosis (by 35 percent) in isolated heart by, thus presuming decreased myocardial resistance to ischemia-reperfusion injury (IRI). The SIRS model induced by chemical trauma to large intestine is aggravated by the introduction of AMAs mixture, and it is characterized by a controlled change in inflammatory markers. Deterioration of morphofunctional characteristics in isolated heart included decrease in resistance to IRI seems to correspond to acute inflammatory bowel disease with induced intestinal dysbiosis. This model can be used in experimental medicine in the field of cardiology, endomicroecology, gastroenterology, and immunology.

Relevance. Professional activities of firefighters and rescuers are usually associated with aggressive chemical exposure with increased physical exertion and psychological stress. Therefore, for professional selection and monitoring the health status of firefighters and rescuers of EMERCOM of Russia it is necessary to evaluate the activity of cytochrome P450 isoenzymes that are directly involved in detoxification pathways in the liver.Intention. To evaluate the activity of the CYP3A4 enzyme by phenotyping methods and to establish the frequency of allelic variants of the gene of this enzyme (rs2740574 and rs4987161 polymorphisms) in firefighters and rescuers of EMERCOM of Russia for targeted treatment, rehabilitation and prevention.Methodology. Polymorphisms (rs2740574 and rs4987161) of the CYP3A4 gene and also CYP3A4 activity by the ratio of 6-β-hydroxycortisol / cortisol in the urine were determined during routine periodical medical examination of 64 rescuers and firefighters of rescue units of EMERCOM of Russia. The average age of examined persons was (29.8 ± 5.5) years; 30 of them are rescuers of the North-West Regional Search and Rescue Squad and 34 are firefighters of the territorial fire departments of St. Petersburg.Results and Discussion. According to the results of genotyping of rs2740574 polymorphism of the CYP3A4 gene, EMERCOM employees were divided into 2 groups depending on the presence or absence of a minor allele: “poor” and “rapid” metabolizers (9.4% and 80.6%, respectively). According to the results of genotyping of the rs4987161 polymorphism of the CYP3A4 gene, the examined were classified as “rapid” metabolizers, because patients with a minor allele were not identified. Depending on the ratio of 6-β-hydroxycortisol / cortisol in the urine, the activity level of CYP3A4 was “normal” in 67 %, “poor” in 13 % and “rapid” in 20 % of cases. The ratio of 6-β-hydroxycortisol / cortisol in the urine tended to increase with an increase in work experience and age. No relationship between the studied polymorphic variants of the CYP3A4 gene and the established enzyme activity was observed.Conclusion. Genotyping methods made it possible to identify allelic variants of the CYP3A4 gene that could affect the functionality of the enzyme; however, no association of the studied polymorphisms with enzyme activity was found. In such cases, in the absence of informative genetic markers, it is recommended to evaluate the enzyme activity by phenotyping methods.

Aim: To study intestinal microbiota and the parameters of oxidative stress in patients with metabolic syndrome (MS). Methods: The sample consisted of 50 patients with MS aged 55-65 years and residing in Saint Petersburg. The reference group consisted of 129 individuals of similar age without MS. The quantitative and qualitative composition of parietal intestinal microbiota was studied by gas chromatography with mass spectrometry using microbial markers in plasma. Oxidative stress the final oxidation products of protein molecules and lipids including 8-hydroxy-2-deoxyguanosine and malonic aldehyde were estimated. Nutritional antioxidants including vitamin E, unsaturated fatty acids etc. were assessed by chromatography mass spectrometry and mass spectrometry. Results: In the parietal layer of the intestine in individuals with MS, the total number of microbial markers is positively associated with the markers of the opportunistic microflora and lower levels of normal microflora. In MS patients, the ratio of normal microflora to conditionally pathogenic microflora is twice as low as in the reference group. Level of malonic dialdehyde and 8-hydroxy-2-deoxyguanosin were 48 % and 39 % higher in the MS group. Moreover, plasma concentrations of vitamin E and zinc were lower by 42 % and 80 % in patients with MS compared to the reference group. Сonclusions: The observed differences in the quantitative and qualitative composition of the parietal microbiota of the intestine in individuals with MS compared to the reference group suggest development of intestinal dysbiosis in MS patients. The intestinal dysbiosis is accompanied by oxidative stress manifested by an increase in the level of malonic dialdehyde in the blood plasma and 8-hydroxy-2-deoxyguanosine in the urine, as well as a decrease in the level of vitamin E and zinc in the blood plasma.

The presented study is devoted to one of the urgent problems of the conservative treatment of chronic pancreatitis — relief of painful abdominal and dyspeptic syndromes. Polymorphism of the etiopathogenetic variants of the formation of pancreatic diseases naturally justifies the need for complex therapy, including secretolytics, antispasmodics medications and polyenzyme drugs. The use of Meteospasmyl in complex therapy effectively relieves abdominal pain and dyspepsia, modifies the composition of the intestinal microbiota and improves the quality of life in patients with chronic pancreatitis.

Relevance. Due to their carcinogenic, oxidative and toxic potential, chemical compounds from burning products are especially dangerous for rescuers and firefighters and result in the oxidative stress as a precursor of many diseases. Therefore, it is necessary to diagnose the oxidative stress before its serious effects.Intention. To assess oxidative stress markers in plasma of rescuers and firefighters of EMERCOM of Russia via modern methods for targeted treatment and preventive actions.Methodology. Malonic dialdehyde, fat-soluble vitamins (A and E), polyunsaturated omega-3 and omega-6 fatty acids in plasma were determined by gas and liquid chromatography during routine periodical medical examination of 98 rescuers and firefighters of rescue units of EMERCOM of Russia. The average age of the examined persons was (32.1 ± 0.5) years; of them, 21 were rescuers from the North-West Regional Search and Rescue Squad and 77 were firefighters from the territorial fire departments of St. Petersburg.Results and Discussion. Malonic dialdehyde plasma concentrations in rescuers and firefighters were 1.5-1.7-fold higher than reference values. Docosahexaenoic and arachidonic acids were increased in all examined groups. In firefighters with work experience of > 10 years, plasma concentrations of eicosapentaenoic and docosahexaenoic acids were increased. Their antioxidative potential is decreased.Conclusion. According to the obtained results, rescuers and firefighters can be assigned to a high-risk group in terms of health deterioretion, especially those with work experience for more than 5 years. Periodic correction of the observed changes is recommended.

Mitochondrial respiratory chain enzyme activities were determined by spectrophotometric enzyme assay in lymphocytes of 100 patients with acute myocardial infarction. A significant decrease in the activity of complexes II–III and IV and an increase in the activity of complex I of the respiratory chain were found. According to the correlation analysis, the feedback of troponin T and I concentrations in the serum and the activity of complex IV of the respiratory chain was detected. A decrease in the activity of the IV complex of the mitochondrial lymphocyte respiratory chain below 2.87 IU/g of protein indicates an increased level of clinical risk in patients with acute myocardial infarction.