Репозиторий Университета

© 2018, The Author(s). Introduction: Heart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina. Methods: This multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio. Results: At the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001). Conclusion: In patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration. Trial Registration: ISRCTN30654443. Funding: Servier.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Echocardiographic parameters were assessed in patients with non-ST segment elevation acute coronary syndrome, who underwent emergency percutaneous coronary intervention followed by various outpatient physical cardiac rehabilitation programs. The patients underwent physical rehabilitation for 3 months under conditions of diagnostic centre in the rehabilitation unit according to the standard program including in treadmill or bicycle exercise in the exercise therapy room or with Nordic walking in the main training block. After rehabilitation course, the left ventricular mass index significantly decreased and systolic volume and left ventricular ejection fraction significantly increased in both groups. Nordic walking training for 3 months non-ST segment elevation acute coronary syndrome induced similar positive shifts in the parameters of intracardiac hemodynamics, as standard treadmill or bicycle training program, which allows considering it as an alternative cardiac rehabilitation method.

© 2017 Elsevier GmbH The modification hot curing poly(methyl methacrylate) (PMMA) denture base “Villacryl H Plus” in RF-discharge plasma is described The plasma chemical modification of PMMA plates in the oxygen RF-discharge (13.56 MHz) decreased the water contact angles by 1.5–2.5 times with respect to unmodified samples while their surface free energy increased up to 1.5 times due to the formation of additional oxygen containing polar chemical groups at the plasma-modified PMMA surfaces. Although the ageing effect of modified PMMA was observed, its wettability was still higher than that of the original PMMA at least after 7-day storage. The technique has been successfully applied for the modification of removable PMMA denture, which was used in clinical practice for oral orthopedic rehabilitation of a patient after the treatment of buccal mucosa cancer. When using the non-modified denture the patient complained of discomfort and food chewing problems and the hypertrophic red flat oral lichen formed at the patient's cheek. The full regression of lichen nodules and associated inflammation was observed after the usage of the plasma modified denture for one week. Within six-month ware of the plasma modified denture no pathological elements or neoplasms were found on the patients’ oral mucosa.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. An HPLC-MS/MS method for determining dabigatran in human blood serum was developed. Samples were prepared by precipitation of proteins using MeOH followed by centrifugation and dilution with deionized H2O. The developed method had a simple sample-preparation procedure, short analysis time, and wide analytical range (from 1 to 1,000 ng/mL). This method was suitable for routine bioanalytical studies, in particular, therapeutic drug monitoring.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A method for simultaneous determination of metoprolol and bisoprolol in human blood serum by HPLC-MS/MS was developed and validated. The analytical ranges of the method were 5 – 250 ng/mL and 1 – 250 ng/mL for metoprolol and bisoprolol, respectively. The suitability of the developed for therapeutic drug monitoring during treatment for arterial hypertension and other cardiovascular diseases was demonstrated. In particular, the proposed method could identify patients at high risk for developing adverse effects and help to monitor a switch between metoprolol and bisoprolol while changing the pharmacotherapy regime.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We developed an optimal protocol for preparing and culturing of olfactory ensheathing cells from human olfactory mucosa. Using this protocol, we obtained a culture enriched with human olfactory ensheathing cells. Immunofluorescence analysis by simultaneous expression of GFAP and p75NTR markers showed that the content of ensheathing cells was maximum in passage 3 and 4 cultures (94 and 89.5%, respectively). The developed protocol can be recommended for obtaining autologous preparations of human ensheathing cells for cell therapy of spinal cord injuries.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We analyzed cultures of 5 independent myoblast lines from human skeletal muscles. It was shown that the content of desmin-positive cells in cultures at early passages exceeds 90%. Typical morphofunctional signs of myogenic differentiation disturbances were identified and their dynamics was studied. Signs of alternative adipogenic and chondrogenic differentiation of cells were revealed. Based on these data, limitations for the use of myoblast cultures of certain passages for biomedical research and cell therapy were evaluated.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Tetra(aryl)tetracyanoporphyrazines are the promising group of dyes for photodynamic therapy of tumors with unique combination of photosensitizer properties and sensitivity of fluorescence parameters to the environment viscosity. However, in vivo application of such hydrophobic photosensitizers requires using of drug carriers ensuring efficient delivery to the tumor site. The present study is focused on obtaining liposomes loaded with tetrakis(4-benzyloxyphenyl)tetracyanoporphyrazine and examining their properties depending on lipid composition. An efficient loading of the dye and a high long-term stability were proved for the liposomes composed of phosphatidylcholine with cholesterol and phosphatidylglycerol. This can be explained by the presence of negatively charged lipids in the bilayer and, as a consequence, a high value of the surface potential. A high rate of cellular uptake and a strong photoinduced toxicity give the prerequisites for the further use of the liposomal form of the photosensitizer for photodynamic therapy of tumors.

© 2018  The antioxidant activity of Ge-132 (2-carboxyethylgermanium sesquioxide, [(O 0.5 ) 3 GeCH 2 CH 2 COOH] n ), a widely used organic germanium dietary supplement, was assessed by cyclic voltammetry and through its interaction with a stable radical 2,2,-diphenyl-1-picrylhydrazyl (DPPH) monitored by UV-Vis and EPR spectroscopy in water, CH 3 CN, DMF, MeOH, and their mixtures with water. The results obtained by these methods are coherent in that Ge-132 can manifest its antioxidant activity only in the absence of water because the latter hydrolyses its Ge-O-Ge fragment responsible for quenching free radicals. Thus, contrary to a common use of Ge-132 as a water-soluble agent, it can act as an antioxidant solely in a lipid environment, which is important for understanding the mechanism of its biological activity.

© Springer Science+Business Media, LLC 2017.  Sandwich enzyme-linked immunosorbent assay (ELISA) of sulfonamides based on double-competitive interaction between haptenized protein as a captured antigen and analyte for binding to immobilized and enzyme-labeled antibodies was developed. This experimental assay format was examined in analytical properties and matrix effect resistance in comparison with usual ones: indirect, direct antigen-coated and antibody-coated ELISAs. All four assay formats were designed on the basis of interactions between the previously prepared monoclonal antibody and immunizing hapten, 4-(4-(4-aminophenylsulfonamido) phenyl)butanoic acid, providing the uniform output optical signal for correct comparison of each assay characteristic. The sensitivity (IC 50 ) of the developed competitive sandwich assay was rather below 100 ng/ml for 11 sulfonamides which was suitable for their determination in milk, muscles and animal sera at established maximum residue limit concentration. Comparative examination did not reveal changes in assay specificity, and advantages in sensitivity, matrix effect resistance, and procedure duration before commonly used assay formats. Moreover, new design of assay was shown to be three-fold more consumable in antibody reagents in comparison with direct assay formats.

© 2018, Pediatria Ltd.. All rights reserved. In 2011, a cohort for prospective follow-up was chose from the general population of newborns in Moscow. In 3 years of life, information on atopic dermatitis (AtD) symptoms was collected. Skin tests with allergens were performed in mothers and in children aged 1 year. Objective of the research – to correlate the sensitization of a child at the age of 1 year and sensitization of his mother with subsequent possible development of AtD in his early childhood. Study materials and methods: mother's sensitization and sensitization of a child at 1 year of age were examined separately for the possible appearance of AtD diagnostic signs at the age of 1, 2, 3 years of a child and in general in early childhood. The results of each study are presented by several methods of statistical processing: 1) analysis of conjugation tables, incl. hierarchical log-linear; 2) logistic regression models in which: a) the sensitization degree was considered, b) the sensitization was analyzed as a qualitative sign, in the presence of a papule. Results and discussion: рrospective monitoring of the cohort shows the dynamics of AtD frequency in early childhood, the number of sensitized mothers and their children. Mother's sensitization was not significant for AtD signs appearance in a child in early childhood. The sensitization of a child at the age of 1 year showed the importance of chicken egg allergen in relation to AtD signs appearance in early childhood. Study result: conclusions about the possible relationship of sensitization with AtD development in a child in early childhood.

© 2018, Pediatria Ltd. All rights reserved. The article presents results of conjugated pneumococcal vaccine use in combination with basic therapy in 64 children with chronic compensated tonsillitis. The study showed that vaccination assists activation of T-lymphocytes subpopulation, increases sensitization to bacterial antigens, normalization of proinflammatory cytokines content, which is clinically manifested in a significant decrease in acute respiratory infections incidences and antibacterial therapy courses for 2 years after vaccination compared to patients receiving a traditional therapy course.

© 2018, Pediatria Ltd. All rights reserved. Materials and methods: the study assessed safety and clinical efficacy of combined use of vaccine preparations against S. pneumoniae and H. influenzae type b, leading pathogens in bronchopulmonary diseases exacerbations development, in previously unvaccinated 38 children aged 2–17 years with chronic bronchopulmonary diseases: 19 with malformations of the bronchi and lungs (MBL); 10 with malformations of bronchi and lungs in combination with bronchial asthma (MBL+BA); 9 with bronchial asthma (BA). The control group consisted of 19 unvaccinated children of the same age with a similar pathology. Combined vaccination against these infections, as well as their separate administration, did not cause adverse effects. Results: a year after the introduction of Pneumo-23 vaccine, the incidence of acute respiratory infections (ARI) and exacerbations of the main disease decreased by 2,3 times; Act-HIB by 2,3 and 2,1 times respectively; by 1,7 and 1,5 times respectively with simultaneous administration of these preparations. In children with BA the duration of one exacerbation decreased by 3,4 times, the average duration of temperature reaction by 1,9 times and the systemic antibiotic therapy of one exacerbation episode by 2,4 times. In the group of children with MBL+BA these indicators decreased by 2,1, 1,8 and 1,6 times, respectively, and in patients with MBL by 1,6, 1,5 and 1,4 times, respectively. Conclusion: vaccination against pneumococcal and hemophilic type b infections using one or both vaccines in patients with MBL and with MBL+BA is safe and positively affects the clinical course of the main disease.

© 2018 Meditsina Publishers. All rights reserved. Results of the medico-sociological research directed to studying of the ideas of the HIV-infected widespread in modern Russian society are presented in article. The obtained data have allowed to design a modern social portrait of the HIV-infected Russian. Now in representations of Russians the typical HIV-infected - the young childless and single man regardless of sexual orientation who is living in the large city, having an average special educations or being in process of that receiving which level of income we will compare with a living wage. The HIV-infected has been infected as a result of a youth error (the unprotected sexual contact or the intravenous use of drugs) and lives with this diagnosis several years, leads a risk-free life more often, at the same time usually hides the diagnosis and separates from social communications.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The one-pot process of anodic transformation of N-alkyl-3-aminopyrazoles into azopyrazoles under conditions of membraneless electrolysis in an aqueous solution of NaBr was studied for the first time. It was found that under these conditions the aminopyrazoles, which do not have a substituent at position 4, transform into the corresponding 4,4´-dibromoazopyrazoles. The corresponding yield was in the interval of 28—80%, depending on the structure of the products. The transformation of 4-substituted aminopyrazoles resulted in the formation of azopyrazoles in the yields lying within 62—86% when this process was implemented under conditions with the anodically generated Br2 acting as a mediator. A convenient method of anodic synthesis of azopyrazoles in an aqueous medium without the use of additives of chemical oxidants was proposed. The process is environmentally sound and is characterized by a high atom efficiency (>85%).

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The review summarizes information on cyclopropane as an independent pharmacophore group and as a fragment for modification of pharmacological activity level of medicines used in practice. The advantages of a cyclopropane fragment over its bioisosteres are that, on the one hand, this fragment imposes conformational rigidity on the molecules of physiologically active compounds and, on the other hand, the replacement of acyclic terminal and “linker” groups with a cyclopropane fragment increases the metabolic stability of the target structures and extends the scope of their therapeutic action.

© 2018, Pleiades Publishing, Inc. The article presents empirical data on the possible use of transcranial Doppler sonography as a method for the identification of functional specialization of hemispheres. We investigated intrahemispheric differences in the increase in blood flow velocity indicators during the performance of cognitive tasks with verbal and nonverbal stimuli in 20 healthy right-handed participants and 20 right-handed patients with local unilateral vascular brain lesions. We observed interhemispheric and intrahemispheric differences in blood flow velocity indicators between arteries during the performance of cognitive tasks with different variants of verbal stimuli in all participants. It has been found that one of the hemispheres plays a dominant role in verbal and nonverbal stimulus processing.

© 2017 Elsevier Inc. A wide range of methods are known to increase the prokaryotic intracellular recombinant proteins solubility, for instance, growth at low temperature, supplementation of culture media with “chemical chaperones” (proline, glycine-betaine, and trehalose), co-expression with chaperones or highly soluble fusion partners. As an alternative, we have introduced the polyglutamate tag, which, as it has been shown, increased the protein solubility and facilitated folding. In this study we evaluated the minimal quantity of high density negatively charged EEEEVE amino acid repeats (pGlu) necessary to switch the recombinant receptor-binding domain of human alpha-fetoprotein (rbdAFP) expression almost entirely from the inclusion bodies to the soluble cytoplasmic fraction in E. coli. For this purpose, genetic constructs based on pET vectors coding rbdAFP and containing from 1 to 4 additional EEEEVE repeats at the C-terminus have been prepared. It was found that 3 pGlu repeats is the minimal number, that leads to a complete shift of the expression to the soluble cytoplasmic fraction in E. coli SHuffle Express T7 while 4 repeats were required for that in E. coli BL21(DE3). The rbdAFP contained 4 pGlu repeats was purified making use of ion-exchange chromatography and characterized by circular dichroism and ability to bind and accumulate in AFP receptor positive cancer cells in order to check for the structural and specific activity alterations related to the additional polyanionic sequence introduction.

© 2018, Pleiades Publishing, Ltd. X-ray diffraction is used to determine the structure of a new 3-(benzo[d]oxazole-2-yl)-1-(2-(1,3,3- trimethylindoline-2-ylidene)ethylidene)naphthalene-2(1H)-one zinc chloride complex 1. It is demonstrated that the ligand molecule in complex 1 has a trans–trans–cis conformation in which the indoline nitrogen atom is oriented in the same direction as the chelate ring, which could promote an additional coordination with the complexing atom.

© 2018, Pleiades Publishing, Ltd. The identification of factors that determine the structure and rate of mortality is a topical complex task requiring unification of efforts of medical science and social disciplines. The authors contribute to its solution through a comparative study of mortality indicators in two Russian megalopolises—Moscow and St. Petersburg. Analyzing statistical data, they form several hypotheses that help explain the significant differences in the mortality rates of the two cities. The focus is not only on the socioeconomic and climatic features of Moscow and St. Petersburg but also on the state of the financial and resource support of the health care systems of these cities. The results obtained are only the first step, but a necessary one, toward an adequate system of measures to decrease mortality, implying subsequent studies on the significance of each of the factors considered.