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Acotiamide is a prokinetic with a novel mechanism of action - an antagonist of muscarinic M 1 and M 2 receptors and an acetylcholinesterase inhibitor. Acetylcholine is the central mediator of the tone of the muscular components of the gastrointestinal tract, increasing its motor activity. Blockade of presynaptic M 1 and M 2 receptors neutralizes the inhibitory effect of the feedback mechanism on the acetylcholine synthesis, while inhibition of acetylcholinesterase in the synaptic cleft reduces the acetylcholine degradation. Currently, the clinical efficacy of acotiamide in the population of patients with functional dyspepsia is demonstrated in more than 10 clinical studies in different regions of the world, demonstrating a reduction of the symptoms of the disease during treatment with this agent and an improvement in the quality of life of patients. In addition, the combination of acotiamide with proton pump inhibitors optimizes the management of patients with gastroesophageal reflux disease.

Aim: Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation., Materials and Methods: As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin)., Results: According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%)., Conclusion: Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.

Background: To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis., Methods: Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1 β , IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis ' parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman-Keuls parametric criterion was used for intergroup comparison. LD 50 indexes were calculated by probit analysis., Results: LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1 β level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10 -6 to 10 -3  M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na + channels of isolated neurons in a dose-dependent manner., Conclusions: The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Ekaterina V. Blinova et al.)

Aim: The goal is to evaluate the effectiveness of pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin preparations for the correction of nutritional status in patients with chronic pancreatitis (CP) and associated exocrine pancreatic insufficiency (EPI)., Materials and Methods: The study included 58 patients with CP who were divided into two groups depending on the results of a laboratory assessment of indicators of nutritional status: group I (n=30) consisted of patients with CP and signs of EPI (according to low elastase test values) without deviations in nutritional status; Group II (n=28) consisted of patients with CP with a EPI and an abnormal nutritional status. In both groups, patients during the entire observation period (8-12 months) received PERT using microencapsulated pancreatin preparations at a dose adjusted for the severity of permanent residence permit. Before and after the PERT course, the dynamics of anthropometric [body weight, body mass index (BMI)] and laboratory indicators of nutritional status (total protein, albumin, vitamins D and B12, transferrin, iron and magnesium) were evaluated., Results: After the completion of PERT, a significant tendency towards an increase in BMI in patients was noted in both groups. In group I, this indicator increased from 21.45 [95% confidence interval (CI) 19.80-23.92] kg/m2 to 22.15 (95% CI 20.31-23.86) kg/m2, and in II group - from 19.22 (95% CI 18.33-21.99) kg/m2 to 22.0 (95% CI 19.97-24.08) kg/m2. At the same time, the duration of PERT (months) significantly correlated with the dynamics of the patient's body weight (r=0.4679; 95% CI 0.2384-0.6479, p=0.0002). When assessing laboratory markers of nutritional status after PERT, a general tendency was found to increase the levels of total protein, albumin, vitamin D, magnesium, transferrin, and iron in both groups, however, statistically significant differences in the dynamics were observed mainly in group II patients. So, the level of total protein in group II increased from 69.05 (95% CI 65.6717-70.9000) g/l to 72.8 (95% CI 71.1358-74.9000) g/l, vitamin D - from 10.6 (95% CI 32.8397-38.9603) ng/ml to 17.1 (95% CI 12.0166-23.6232) ng/ml, magnesium - from 0.72 ( 95% CI 0.6892-0.7825) mmol/L to 0.795 (95% CI 0.7692-0.8800) mmol/L, and transferrin from 2.91 (95% CI 2.1800-3.3656 ) g/l to 2.92 (95% CI 2.4000-3.5200) g/l., Conclusion: A prospective observational study demonstrated the effectiveness of PERT using microencapsulated pancreatin preparations in the correction of nutritional status in patients with CP.

Aim: Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia., Materials and Methods: A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire., Results and Discussion: The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58)., Conclusion: This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.

Vibrational micro-spectroscopy is a powerful optical tool, providing a non-invasive label-free chemically specific imaging for many chemical and biomedical applications. However, hyperspectral image produced by Raman micro-spectroscopy typically consists of thousands discrete pixel points, each having individual Raman spectrum at thousand wavenumbers, and therefore requires appropriate image unmixing computational methods to retrieve non-negative spatial concentration and corresponding non-negative spectra of the image biochemical constituents. Here, we present a new efficient Quantitative Hyperspectral Image Unmixing (Q-HIU) method for large-scale Raman micro-spectroscopy data analysis. This method enables to simultaneously analyse multi-set Raman hyperspectral images in three steps: (i) Singular Value Decomposition with innovative Automatic Divisive Correlation which autonomously filters spatially and spectrally uncorrelated noise from data; (ii) a robust subtraction of fluorescent background from the data using a newly developed algorithm called Bottom Gaussian Fitting; (iii) an efficient Quantitative Unsupervised/Partially Supervised Non-negative Matrix Factorization method, which rigorously retrieves non-negative spatial concentration maps and spectral profiles of the samples' biochemical constituents with no a priori information or when one or several samples' constituents are known. As compared with state-of-the-art methods, our approach allows to achieve significantly more accurate results and efficient quantification with several orders of magnitude shorter computational time as verified on both artificial and real experimental data. We apply Q-HIU to the analysis of large-scale Raman hyperspectral images of human atherosclerotic aortic tissues and our results show a proof-of-principle for the proposed method to retrieve and quantify the biochemical composition of the tissues, consisting of both high and low concentrated compounds. Along with the established hallmarks of atherosclerosis including cholesterol/cholesterol ester, triglyceride and calcium hydroxyapatite crystals, our Q-HIU allowed to identify the significant accumulations of oxidatively modified lipids co-localizing with the atherosclerotic plaque lesions in the aortic tissues, possibly reflecting the persistent presence of inflammation and oxidative damage in these regions, which are in turn able to promote the disease pathology. For minor chemical components in the diseased tissues, our Q-HIU was able to detect the signatures of calcium hydroxyapatite and β-carotene with relative mean Raman concentrations as low as 0.09% and 0.04% from the original Raman intensity matrix with noise and fluorescent background contributions of 3% and 94%, respectively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission.

Aim: to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA)., Subjects and Methods: Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA., Results: Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells., Conclusion: The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

Background . Comorbidity of chronic obstructive pulmonary disease (COPD) and asthma (asthma COPD overlap syndrome, ACOS) is a significant problem in pulmonary practice, whose pathogenetic issues are not clarified yet. Objective . To study the features of the regulation of immune response in patients with comorbid COPD and asthma. Methods . We assessed the levels of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + , CD19 + , CD25 + , HLA-DR, total IgE, TNF- α , IL-4, IFN- γ , TXB 2 , and LTB 4 in patients with comorbid COPD and asthma. Results . The study involved 44 people with COPD, 39 people with asthma, and 12 people with comorbid COPD and asthma. The specific features in comorbid COPD and asthma were lymphocytosis, increased absolute count of T-helper cells, increased cytotoxic T-lymphocytes in relative and absolute count, increased relative and absolute numbers of B-lymphocytes, and high levels of total IgE. The elevated levels of TNF- α and IL-4 and inhibition of IFN- γ production were detected. The content of LTB 4 was maximal; TXB 2 levels were higher than in control group but lower than in COPD and asthma. Conclusion . In comorbid COPD and asthma inflammation increased even during stable period. High levels of eicosanoids, low production of Th1-type cytokines, and active synthesis of opposition IL-4, along with increased IgE, indicate the activation of Th2-type immune response.

The article presents results of study of membrane potential of mitochondria of thrombocytes in patients with chronic obstructive disease of lungs. The index of membrane potential of mitochondria reflects both disorders of oxygen consumption by blood cells and development of hypoxia. At the same time, index denotes formation and progression of bronchopulmonary pathology. The direct relationship is established between the degree of bronchial patency and condition of mitochondrial apparatus of cell. The lower bronchial patency is the lesser index of membrane potential of mitochondria is. This dependence testifies lesion of mitochondrion and development of mitochondrial dysfunction. Therefore, the established pattern can be taken into account in the process of development of medical technologies of prognostic of disorders of bronchial patency under diseases of respiratory organs.

A method for evaluating mitochondrial membrane potential in isolated leukocyte suspension with the use of sensitive fl uorescent cation-active dye 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine (JC-1) and spectrophotometry is described. JC-1 monomer rapidly penetrates through mitochondrial membrane of living cell and form aggregations characterized by red fl uorescence (λ = 585 nm). In case of mitochondrial membrane depolarization (early sign of apoptosis), JC-1 is not accumulated in the mitochondria and is present in the cytoplasm as a monomer characterized by green spectral fl uorescence (λ = 510 nm). The method can be used for evaluation of the function of living cells and mechanisms regulating energy metabolism by evaluating the mitochondrial membrane potential.

Background: Disturbances of the fatty acids composition in plasma and red blood cells and eicosanoid synthesis play an important role in the metabolic syndrome (MS) formation., Methods: The observation group included 61 people with metabolic syndrome (30 patients with MS and normal levels of insulin, 31 people with MS and insulin resistance--IR). The parameters of carbohydrate and lipid metabolism in blood serum were examined. The composition of nonesterified fatty acids (NEFA), fatty acid (FA) of red blood cells lipids was analyzed by gas-liquid chromatography. Eicosanoids level in MS patients blood serum was studied by enzyme immunoassay., Results: In MS patients in the absence of glucose-insulin homeostasis disturbances and in patients with IR the accumulation of polyunsaturated fatty acids (18:2 n6, 18:3 n3, 22:4 n6) and lower pool of saturated FA (12:0, 14:0, 16: 0, 17:0) in plasma were discovered. A deficit of polyunsaturated FA (18:3 n3, 20:4 n6) with a predominance of on-saturated FA (14:0, 18:0) in erythrocyte membranes was revealed. In MS patients regardless of the carbohydrate metabolism status high levels of leukotriene B4 and 6-keto-prostaglandin-F1α in serum were found. The development of IR in MS patients leads to increased synthesis of thromboxane A2., Conclusion: The results revealed a disturbance in nonesterified fatty acids of plasma lipids and red blood cells, eicosanoid synthesis in MS patients. The breach of the plasma and cell membranes fatty acids compositions, synthesis of vasoactive and proinflammatory eicosanoids is an important pathogenetic part of the MS development.

It is investigated conditions of system "lipid peroksidation - antioxidant protection" at rats of the line Wistar at prolonged formation alimentary dyslipidemia (DLP). It is established, that at formation DLP during 46 days in cells there was no increase in resistance and capacity of processes antioxidant protection. In prolonged DLP (90 days) was characterized by occurrence of the compensation-adaptive answer in the system "lipid peroksidation - antioxidant protection".

Gas liquid chromatography was used to analyze the composition of plasma free fatty acids (FA) and erythrocyte lipid FAs in patients with metabolic syndrome (MS) in various glucose-insulin homeostasis. The serum lipids of oxylipins were studied in patients with MS, by applying enzyme immunoassay. The patients with MS in the absence of glucose-insulin homeostatic disorders and those with significant insulin resistance (IR) were found to have accumulation of polyenic FA (18:2 omega6), 18:p omega3, 22:4 omega6) and a decreased pool of saturated FA (12:0, 14:0, 16:0, 17:0) in the plasma with simultaneous polyunsaturated FA (18:3 omega3, 20:4 omega6) with a preponderance of fatty FA (14:0, 18:0) in the red blood cells. The high serum concentrations of leukotriene B, and 6-keto-prostaglandine-F1a, were detectable in the examinees with MS. Increased thromboxane A2 synthesis was observed when the patients with MS developed IR. The findings suggest that there are impairments in the composition of plasma free FA and erythrocyte lipid FA and in the synthesis of oxylipins in patients with MS.

The condition of the system "prooxidants-antioxidants" in dynamic model alimentary dyslipidemia in Vistar rats of the lines were studied. General antioxidant activities, activities of antioxidant enzymes (katalase, glutathione reductase, glutathione peroxidase), levels of glutathione, products of lipoperoxides in blood and liver, intensive forming of the oxide nitrogen and monoxide carbon were investigated. The role of the signal molecules (oxide nitrogen and monoxide carbon) in regulation oxidative stress was discussed. It is shown that breach of the dynamic balance between synthesis of oxide nitrogen and monoxide carbon displaces the compensation response in the "prooxidants-antioxidants" system. The reinforcement formation of monoxide carbon decreases synthesis of oxide nitrogen by cells, activation of the lipoperoxidation processes, progressive oxidative stress, apoptosis induction signal.

The work was designed to study levels of serum prostaglandin F1a (6-keto-PGF1a), thromboxane B2, and leukotriene B4 (LTB4)--stable products of cyclooxygenase and lipogenase-catalyzed reactions of arachidonic acid, in patients with metabolic syndrome (MS) differing in glucose homeostasis. It was shown that MS is associated with excess production of anti-inflammatory oxilipines (LTB4) regardless of the presence or absence of insulin resistance. LTB4 are known to influence inflammatory processes due to compensatory synthesis of vasodilating eicosanoids (6-keto-PGF1a) that antagonize vasoconctriction and inflammation. Combination of MS with insulin resistance in patients with elevated LTB4 and 6-keto-PGF1a levels is associated with enhanced synthesis of thromboxane A2 responsible for vasoconstriction, platelet formation, and development of endothelial dysfunction. The study suggests disturbed synthesis of eicosanoids in patients with MS and their important role in pathogenesis of this condition.

Clinical and pharmacological characteristics of phenotropil were given. Its efficiency in premedication of patients with different individually typological features during out-patient treatment was shown. Also its neurotropic effect and influence on some psychophysiological and hemodinamical indices were studied.

We have analyzed factors causing stress during out-patient dental treatment. The psychological characteristic of people with prevalence of sthenical and asthenical features were given and dependence of the effect of the medicine on individual features was shown.

The development of new drug formulations of pancreatine based on the principle of microdosage with a pH-sensitive coating produced the most demonstrative clinical result--a considerable increase in duration and quality of life of patients with chronic pancreatitis and cystofibrosis, most of which are children. Clinical studies confirmed high efficiency and safety of Panzytrat in open and double blind comparative clinical studies with the participation of 4,557 patients with chronic pancreatitis, mucoviscidosis, and pancreathogenous digestion disorders. In addition to the above-mentioned symptoms, indications for application of Panzytrat also include any clinical symptoms of the pancreas relative excretory insufficiency, in particular, states after oncological diseases and surgical operations (obstruction of ducts, resection, cholecystectomy, etc.) up to a failure to adhere to a diet and overeating.

The main factor determining the size of sanitary losses (SL) and the share of injuries with different degree of severity is intensity of earthquake. At the same time dependence of SL structure on the types of populated area (including the peculiarities of their building) and the character of population allocation at the moment of earthquake is rather small. It allows to substantiate the common medical-and-evacuation indices of the casualties for the given intensity of earthquake. The normative indices given in the article are of reference significance and depending on concrete situation require closer definition.

It was shown in experiments on rabbits that dimethoxyphosphates of rare-earth elements injected intravenously displayed a marked anticoagulant activity. The highest effect was produced by compounds of neodymium, holmium, terbium, europium, thulium, dysprosium, and erbium.