Репозиторий Университета

© The Author 2018. SLURP-1 is a member of three-finger toxin-like proteins. Their characteristic feature is a set of three beta strands extruding from hydrophobic core stabilized by disulfide bonds. Each betastrand carries a flexible loop, which is responsible for recognition. SLURP-1 was recently shown to act as an endogenous growth regulator of keratinocytes and tumor suppressor by reducing cell migration and invasion by antagonizing the pro-malignant effects of nicotine. This effect is achieved through allosteric interaction with α7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in an antagonist-like manner. Moreover, this interaction is unaffected by several well-known agents specifically alpha-bungarotoxin. In this work, we carry out the conformational analysis of the SLURP-1 by a microsecond-long full-atom explicit solvent molecular dynamics simulations followed by clustering, to identify representative states. To achieve this timescale we employed a GPU-accelerated version of GROMACS modeling package. To avoid human bias in clustering we used a non-parametric clustering algorithm Affinity Propagation adapted for biomolecules and HPC environments. Then, we applied protein-protein molecular docking of the ten most massive clusters to α7-nAChRs in order to test if structural variability can affect binding. Docking simulations revealed the unusual binding mode of one of the minor SLURP-1 conformations.

© 2018 Ruslania. All rights reserved. Liver cirrhosis and hepatocellular carcinoma are the most common outcomes of chronic hepatitis B. Hepatitis B virus (HBV) induces transformation and cell death in chronic hepatitis B (CHB). DNA double strand breaks (DSBs) represent the most dangerous type of genome damage. It was shown previously that generation of phosphorylated histone H2AX foci is a reliable marker of DSBs. The aim of this study was to analyse generation of yH2AX foci in HBV and hepatitis D virus (HDV) infection in vitro and in liver biopsies of patients with CHB and CHB with delta-agent (CHD). Human hepatoma cell line HepG2-1.1merHBV with activated HBV life cycle was used to perform real-time PCR for analysis of pregenomic RNA, HBV DNA, HBV cccDNA and for immunocytochemical analysis of yH2AX. Liver biopsies from CHB and CHD patients were analyzed to confirm the results. HBV induces multiple discrete yH2AX foci in HepG2-1.1merHBV cells in vitro and in biopsies of CHB and CHB+D patients. The ratio of hepatocytes w/o yH2AX foci is significantly lower (49,9+7-12,3% vs. 85,5+/-0,9%, p<0,05), while the proportion of cells with 1-10 yH2AX foci is higher (49,3+7-12,6% vs. 14,5+/-0,9%, p<0,05) compared to healthy control. There is a significant increase In the mean number of yH2AX foci in biopsies from CHB+D patients (3,5+7-1,1 and 5,5+/-1,5 vs. 0,5+/-0,16 in control hepatocytes, p<0.05). The ratio of hepatocytes w/o yH2AX foci is significantly lower in CHB and CHB+D patients, while percentage of cells with 1-10 yH2AX foci is higher. Rare hepatocytes with multiple (11-30 yH2AX foci per cell) foci appear in CHB and CHB+D patients. In conclusion, yH2AX foci are generated in hepatocytes of CHB and CHB+D patients and can be utilized to assess genome damage, associated with HBV and HDV viral infection.

© 2018 by the authors. The article contains the results of an empirical study on self-perception and cognitive style of students. The issue of what psychological variables accompany the process of interpersonal interaction in small groups is considered from a viewpoint of cognitive structures of individual members that comprise such groups. The article also presents a theoretical and methodological analysis of personal and cognitive features of students with different sociometric status. The novelty of this work consists in studying self-perception of group members with different sociometric status, and personal and cognitive characteristics and features given to group members through a system of their opinions about each other. It was concluded from the results of the study that the subjects with different sociometric status are perceived differently by the group: leaders appear to be more aggressive and authoritarian than outsiders. The subjects-leaders when coming across the circumstances that subjectively experienced as unpleasant ones, are able to minimize negative experience and find positive moments in such situations. The outsiders are unable to see the positive aspects of situations they subjectively experience as unpleasant. The cognitive space of the subjects-leaders includes the binary opposition construct “optimistic – pessimistic” what can be determined as cognitive complexity. While the subjects-outsiders perceive the cognitive field of the construct as a one-sided structure, and in unpleasant situations they see the surrounding reality not from the positive side, but only from the negative one. The results presented in this article can be useful to optimize interpersonal relations in student groups, as well as to be a source of additional information to develop measures of a psychological impact.

© Pushkareva M.V., Shevyreva M.P., Goncharuk N.N., May I.V., Andrishunas A.M., 2018. The article contains information on hazardous chemical wastes, reasons that cause their occurrence and accumulation in the environment as well as issues related to accumulation of persistent organic pollutants (POPs) in the environmental objects. The authors outline specific features of POPs and their possible influence on the environment and a human body; they also dwell on priority activities accomplished in the RF in relation to POPs after Stockholm Convention on Persistent Organic Pollution was ratified. Provisions of international law in the sphere of providing chemical safety are being consolidated now and operating bodies of Basel, Rotterdam, and Stockholm Conventions interact with each other in order to fix concentrations for chemicals which are persistent organic pollutants and to determine their low contents in wastes. The European Union countries and Canada have submitted their proposals on concentrations of 21 various chemicals in wastes for consideration by all the concerned parties. Scientific validity of the proposed concentrations has been analyzed; the analysis results are given in the article. Given the hazards caused by chemicals wastes that contain POPs for people and the environment, the authors suppose that additional research should be performed on substantiation of POPs safe concentrations in wastes. Taking into account national security and common provisions of international laws related to solving global, national, and regional tasks, the authors note that it is necessary to update legislation on state regulation in the sphere of providing chemical safety; they also give grounds and outline conceptual approaches to creation of the Federal Law "On chemical safety". The article gives a basic idea of this law; its purpose; an object of its regulation; people or economic entities whose activities are subject to its force; a place this law, when passed, is going to have in the RF federal legislation and a system of international agreements that are ratified by the RF. It should be noted that when the Federal Law "On chemical safety" is adopted, it will allow to reduce negative effects produced by hazardous chemical wastes on population and the environment and will have both medical and social-economic outcomes.

© 2018 Stavropol State Medical University. All Rights Reserved. Type I Diabetes mellitus (DM), or insulin-dependent diabetes, is the most common endocrine pathology among children and teenagers. The purpose of this study is to research the content of 1A melatonin receptor and antibodies to it in blood serum of children and teenagers. We examined 71 children and teenagers aged 1.9 to 17 years. We measured the content of 1A melatonin receptor and antibodies to it in hemolymph using an immunofluorescence assay test system (IFA). We found that the lowest levels of the 1A melatonin receptor were prevailing in children with a serious condition at the DM decompensation stage, median values were diagnosed in children in a state of moderate severity, and the maximum quantities are fixed in children against the background of the compensation of DM. The obtained data confirm the hypothesis about the possible involvement of the corpus pineale (epiphysis) in the pathogenesis of Type I Diabetes mellitus.

This paper presents a literature review considering the role and mechanism of apoptosis in the pathogenesis of ischemic stroke (IS). The authors introduce a new concept: the functional request of the patient as a set of external (the nature and intensity of rehabilitation measures, characteristics of everyday life, diet, etc.) and internal (genetic factors, internal picture of the disease, availability of rental and other psychological facilities and etc.) attributes. This concept allows a new angle in understanding the pathogenesis of IS and creates fundamental and clinical potential for more successful approaches to therapy and rehabilitation after IS.

© 2018 Ima-Press Publishing House. All Rights Reserved. Objective: to develop a Russian version of the modified Rankin Scale (mRS) and to assess its psychometric properties. Patients and methods: The investigation involved 50 patients (25 women, 25 men) over 18 years of age (mean age, 56 years) with an acute cerebrovascular accident diagnosis. During the validation procedure, the authors carried out the linguocultural ratification of mRS, prepared its Russian-language version, and then assessed its psychometric properties (reliability, sensitivity, validity). Results and discussion: Translation and linguistic adaptation of mRS was successfully completed. The results obtained in assessing the psychometric properties of the developed Russian version of the scale reflect its high reliability and the valid and reliable indicators of its sensitivity. A statistical study of constructive and content validity also determined the high significance of differences. Conclusion: The investigation has resulted in the official Russian version of mRS, which is recommended for use by neurologists and rehabilitation specialists in both daily clinical practice and in clinical trials.

© 2018, SPb RAACI.  Modern studies have shown a high plasticity and phenotypic diversity of neutrophilic granulocytes (NG) provided by different receptors, which are diagnostic markers for the functional capacity of the cell in the course of their activities. We investigated NG from peripheral blood, obtained from healthy people of both sexes aged from 26 to 66 years. Evaluation of the neutrophil membrane receptor expression was carried out by flow cytometry. The relative amount of neutrophilic granulocytes expressing membrane CD62L, CD63, CD66d receptors and the intensity of their expression were determined according to their fluorescence intensities. The surface NG membrane receptors, i.e., CD62L, CD63, CD66d were studied upon the in vitro experimental influence of the following bacterial peptides: N-formyl-methionyl-leucyl-phenylalanine (FMLP, model 1); glucosaminylmuramyldipeptide (GMDP, model 2), and simultaneous incubation of NG blood with fMLP and GMDP (model 3). The in vitro treatment with fMLP in the in vitro model was used to transform the NG phenotype of conventionally healthy subjects, expressing CD62, CD63, CD66d molecules. The treatment caused a significantly decrease in both CD62L and the CD62L expression in relative amounts of neutrophilic granulocytes with a parallel increase of CD63 expression density. The effect of GMDP on the NG phenotype of conditionally healthy subjects did not change the amount of CD62L + NG and CD63 + NG, and did not affect CD62L and CD63 expression density on the surface of NG. However, the amount of CD66d + NG was significantly increased with the unchanged expression of CD66d molecules. GMDP introduced together with the bacterial fMLP peptide was shown to neutralize some features of the NG phenotype transformation caused by fMLP, i.e., the amount of CD62L + NG was restored by 22 % and the CD62L expression density increased significantly. At the same time, GMDP did not correct the negative effect of fMLP upon the number of CD63 + NG and CD66d + NG, and on the CD63 and CD66d expression. Simultaneous addition of fMLP and GMDP did significantly increase the amount of CD66d + NG and expression density of CD63 molecules on the CD63 + NG membrane as compared to intact NG of conditionally healthy subjects. The obtained data are important in order to justify some new immunotherapeutic strategies aimed at correction of the negatively transformed NG phenotype, which accompanies some infectious and inflammatory diseases of bacterial etiology with atypical clinical course.

© Bionika Media Ltd. The paper analyzes the data available in the modern scientific literature on the possibility of human umbilical cord tissue cryopreservation and its further clinical application. It describes protocols to obtain various biomedical products (vascular matrix, Wharton jelly-based grafts, and multipotent stromal cells) from the frozen umbilical cord, as well as prospects of their clinical use. The analysis of the literature data may be indicative of the active development of a promising cell biotechnology area, such as human umbilical cord cryopreservation.

Copyright © 2018 Loppini, Gizzi, Ruiz-Baier, Cherubini, Fenton and Filippi. We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The article contains the results of studying homeostasis of the cardiovascular system by the method of cardiointervalography in students with limited abilities of various programs of study at university. A psychological assessment of the attitude of students with limited abilities to their health was made. The problem of the components of the personal-adaptive potential has been studied. A study of the level of human potential of students on a separate component of “health” and in the aggregate has been conducted, as well as conclusions based on this research work have been drawn. Method: To solve the objectives set in the study, the following methods were used: the review of scientific and methodological literature, instrumental and calculated physiological research methods: variational pulsometry; mathematical analysis of the heart rate variability; calculation method for assessing adaptive capacity-adaptive capacity offered by Bayevsky; the questionnaire “Psychological features of a person’s attitude to his health”, in the framework of a study of the human potential index (health component), a questionnaire was developed based on a questionnaire for assessing the quality of life, developed at the Institute of Stress Medicine (USA) in 1993, methods-descriptive mathematical statistics and testing the hypothesis by Student’s t-test. Results: The analysis of the activity index of the sympathic regulation link-mode amplitude (AMo%) according to the standards of homeostasis, in view of variation pulsograms, is characterized in the studied groups, as moderate sympathicotonia. The AMo index in the groups is not statistically different, reflects the stabilizing effect of centralization of the heart rate control, and indicates the activation of the sympathic division of the autonomic nervous system (ANS). AMo 1 year = 40.8 ± 8.1%; AMo 2 year = 44.9 ± 4.8%; AMo 3 year = 43.9 ± 8.8% the index is in the upper limits of the norm, the index is normal only in the group of first year students. It can be stated that the body of students with limited abilities reacts with a nonspecific adaptive response to the study load, and this depends on the specifics of the diseases and functional reserves that are low in this category of students. The indicator of urgent adaptation-vagosympathetic balance (LF / HF) shows the greatest stress in the group of first-year students. The index is statistically reliably different from the LF / HF1 year = 2.074 ± 0.39 * (according to the paired Student’s t-criterion of dependent indices p ≤ 0.5) from that of students in the second LF / HF2 year = 1.174 ± 0.25 and the third LF / HF3 year = 1.308 ± 0.26 years of study, indicating an increase in sympathic influences. A decrease in the ratio of the LF / HF index in the groups of second and third year students can be interpreted as a positive effect. There was general adaptation to the educational process at the university, and the correct construction of training and health-related workloads, in accordance with the medical diagnosis, led to a balanced regulation of the sympathic and parasympathic nervous system. Conclusion: The stress level of regulatory systems is assessed by the value of the adaptation potential. The higher is the adaptive capacity of the circulatory system, the lower the values of the adaptive potential. The adaptive potential is an indicator that determines the interrelation of two opposite concepts: “health” and “disease”, morpho-functional changes. In case of illness, a shift towards disadaptation takes place.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The relationship of situational (reactive) and personal anxiety in the sample of respondents with post-trauma stress disorder (PTSD) has been considered in the article. The study found that a significant level of situational anxiety and an average level of personal anxiety is observed in respondents with post-trauma stress disorder. Method: The survey and testing of respondents was conducted on the basis of their voluntary and anonymous participation among the staff of public authorities and law enforcement bodies. Clinical, psychopathological and statistical research methods were used in this work. While conducting a psychopathological survey, the Mississippi scale (MS), military and civilian variants, the severity questionnaire for psychopathological symptoms (AFPS), and the scale for assessing the level of reactive and personal anxiety (Charles D. Spilberger, Yu. L. Khanin) were used to determine the qualitative and quantitative parameters. The levels of reactive and personal anxiety were determined on a scale: up to 30 points-low anxiety; from 31 to 45 points-moderate anxiety; 46 points or more-high anxiety. The statistical processing of research results included the calculation of the arithmetic mean value for the quantitative (M) and qualitative (P) indices and their errors (m and p). When comparing the data obtained in groups and subgroups, the Student’s t-test was used, while the correlation analysis of interrelationships-the Spearman correlation coefficient was used. The sample comprised respondents with signs that meet the diagnostic criteria for PTSD (ICD-10 \ DSM-R). Results: The manifestation of the influence of the experienced psychological trauma on the level of anxiety is: an increased heart rate; Blanchet syndrome; a nervous condition; tension of all groups of muscles; feeling a sense of guilt; a feeling of fever followed by shivers; long confusion; insomnia; migraine; uncontrollable anger. The symptoms of anxiety persist and accumulate, at the time of a stressful situation, and after its resolution, contributing to a decrease in performance, fatigue and exhaustion. In addition, the results of the study indicate that anxiety and its level plays an important role, both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. For both male and female subjects, high indices of personal anxiety are more significant than situational in the development of PTSD of different severity levels. Conclusion: Anxiety and its level, plays an important role both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. High indices of personal anxiety are more significant for both male and female subjects than situational one in the development of PTSD of different severity levels. The level of personal anxiety in men increased as the severity of PTSD increased. In women, the high level of anxiety increased with increasing severity of the disorder and stabilized with severe PTSD. Most women and men with PTSD are characterized by a high level of personal anxiety. Moreover, the prevalence of women with a high level of personal anxiety in comparison with men is essential with a mild severity of the disorder. With a moderate degree of the disorder, the differences in the proportion of men and women with a high level of personal anxiety are practically insignificant, and in case of a severe degree of the disorder, their proportion levels off, reaching 100%, both among men and women.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. Introduction: Prenatal atrioventricular septal defect (AVSD) on frequent occasions coexists with other cardiac or extracardiac abnormalities or malformation which may change the prognosis and the management with the fetus and the newborn. The aim of the research was to assess the prognosis and the outcome of prenatally diagnosed AVSD based on the classification which also includes coexisting extracardiac abnormalities and malformations as well as its influence on the prenatal consultation. Methods: It was a retrospective analysis of 113 patients with prenatally diagnosed AVSD. The group was selected out of 871 patients with CHD. Out of 113 fetuses with AVSD we exclude those in whom AVSD was coexistent with other cardiac malformations (n = 41). Extracardiac abnormalities [ECA] were defined as problems which do not require surgical intervention after delivery, they were usually markers of a genetic syndrome. Extracardiac malformations [ECM] were defined as problems requiring surgical interventions after delivery or lethal malformations. All 72 fetuses with an isolated AVSD were classified to one of the three groups: (1) Simple AVSD–(sAVSD)–a fetus with isolated AVSD without coexisting ECA and ECM (n = 6), (2) sAVSD + ECA–a fetus with isolated AVSD, with coexisting ECA (n = 28), (3) sAVSD + ECM–a fetus with isolated AVSD, with coexisting ECM (n = 38). Results: The pregnancy from the groups sAVSD + ECM were, in fact, more often referred to the prenatal cardiology centers on account of the existing ECM (p=.03). There were no differences between the two subgroups in regard to: the mean age of the pregnancy, the mean age of the fetus at the time of diagnosis and during diagnostic testing at the referral center, the gender of the fetus. An increased nuchal translucency (NT) was most often found in fetuses from the group AVSD + ECA (n = 13/23), which was connected with more frequent occurrence of abnormal karyotype (p=.048). The trisomy 21 more frequently referred to pregnancy with sAVSD + ECA than those with sAVSD + ECM (p=.0006). In the group sAVSD + ECM there was the highest number of fetuses small for the gestational age detected −48.65% (p=.01). Most often premature deliveries were found in the group sAVSD + ECM (72.73%). The duration of gestation in the group sAVSD + ECM turned out to be much shorter than that in the group with the isolated sAVSD (p=.01) and sAVSD + ECA (p=.03). The lowest Apgar score was in the newborns from the group sAVSD + ECM (p=.002). Longer period of gestation was connected with the higher score on Apgar scale (R = 0.541; p=.001). The average delivery weight of the newborns was the lowest in the group sAVSD + ECM (p=.04). sAVSD + ECM was connected with the significantly higher death rate than the isolated sAVSD (p=.0047) or sAVSD + ECA (p<.00001). The fatality rate of the newborns/ fetuses from the pregnancies lasting less than 37 weeks turned out to be much higher than in the case of the remaining pregnancies (sAVSD p=.002). Conclusions: (1) The majority of fetuses with AVSD remained the patients of just obstetricians and prenatal cardiologists because of highly heterogeneous of the coexisting malformations and abnormalities and since they perish in the period of fetal or neonatal life usually they are not seen by the pediatricians or cardiac surgeons. (2) The classification of the AVSD in fetus to a particular group of the prognostic classification of the fetal heart defects helps to plan perinatal management and supplies information regarding the prognosis. (3) The highest mortality rate was in a group of AVSD + ECM, probably due to shorter time of pregnancy duration, fetuses grow restriction and low Apgar score in 1 minute of life.

© ISUCT Publishing. Macrolide antibiotics represent a valuable class of broad-spectrum, high active natural compounds with polyketide structure. A well-known FOF1 ATP-synthase inhibitor,[1] namely oligomycin A (1), is a 26-membered α,β-unsaturatedpolyketide lactone with conjugated diene, fused to spiroketal moiety. Oligomycin A possesses strong antifungal, antiactinomycotic and cytotoxic activity, but lacks antibacterial activity. According to recent investigations, the development of anti-cancer drugs based on oligomycin A is quite perspective due to its high cytotoxic activity toward tumor cells, ability to inhibit a multidrug resistance protein p-gp and to prevent an activation of oncogenic K-Ras by inhibition of its localization at the plasma membrane.[2-4] However, high toxicity for mammalian cells and low water solubility are significant limitations of oligomycin A, making it unacceptable for clinical application. Chemical modification is a promising way to improve pharmacological properties of natural compounds. Recently we have found that site-selective modifications of oligomycin A afforded semi-synthetic derivatives with high antiproliferative activity against tumor cell lines[5-7] or selective antifungal activity against Candida spp.[8] and, at the same time, with lower toxicity toward mammalian cells. Also, semi-synthetic oligomycin A derivatives are useful tools for molecular genetic studies of additional targets for this family of antibiotics.[9,10] Previously Ramirez F. et al. have described the reaction of oligomycins with sodium borohydride resulting in mixture of diastereomeric 7-dihydro-and 7,11-tetrahydro derivatives without further separation and characterization of individual products.[11] Also, there is no data on biological activity of these reduced oligomycins against fungal/actinomycetes strains and tumor cell lines in article mentioned above. Thus, in this paper we report regio-and stereoselective methods for borohydride reduction of oligomycin A, structure determination of obtained derivatives and investigation of theirs antiproliferative, antifungal and antiactinomycotic properties. The feasibility of regio-and stereoselective reduction of C7-carbonyl group in a core structure of oligomycin A was proposed due to the presence of haptophilic hydroxyl groups[12] at C5 and C9 positions and sterical hindrance of C-11 carbonyl group. Actually, treatment of oligomycin A with bulky sodium triacetoxyborohydride in acetic acid according to the method[13] led to (7S)-dihydrooligomycin A (2) in a good yield. The second carbonyl group (C-11) reduced in more harsh conditions: only the extended treatment of (7S)-dihydrooligomycin A with sodium borohydride in ethanol give (7S,11R)-7,11-tetrahydrooligomycin A (3) as major product. Reaction proceeds with acceptable stere-oselectivity and gives tetrahydro derivative 3, but in low yield (35 %), which associated with low stability of oligomycins in basic conditions.[14] Structure of compounds 2 and 3 was confirmed by high resolution mass spectrometry (HRMS ESI) and NMR spectroscopy. Absolute configurations at C7 and C11 positions of obtained derivatives were unambiguously confirmed by observed interactions between neighboring protons in corresponding1H-1H ROESY spectra. Testing of antimicrobial properties of oligomycins 2 and 3 against Candida spp., filamentous fungi and S. fradiae (strain, extremely sensitive to oligomycins) that of the parent antibiotic in comparison with starting oligomycin A revealed that reduction of carbonyl groups led to decreasing of activity (except strain M. canis). Also, reduced derivatives 2, 3 were less potent against human colon carcinoma cell line HCT116 and its doxorubicin-resistant subline HCT116(-/-), while activity against leukemia cell line K562 and doxorubicin-resistant subline K562/4 retained at the same level as for 1. It might be pointed that biological properties of (7S)-dihydrooligomycin A and (7S,11R)-7,11-tetrahydrooligomycin A are quite similar, consequently C7-carbonyl group has a greater influence on biological activity of oligomycin A than C-11 carbonyl group.

© 2018, Media Sphera Publishing Group. All rights reserved. The current national immunization calendar is intended for the pediatric population; the general concept of adult immunization is absent, which does not protect target groups under the conditions of the changing epidemic situation and the state of population immunity. Objective - to substantiate and design a national vaccine schedule for adults. Material and methods. The investigation was conducted using the data available in the Russian and foreign literature, the assessments of the epidemic situation among the adult population in the Russian Federation, and the authors’ own studies. Results. The draft national adult immunization calendar consisting of two sections was designed and substantiated. The first section includes information on immunization of different age groups; the second contains that on immunization of groups at epidemiological and social risks. Conclusions. The introduction of the national adult immunization calendar and improvements in the institutional framework of vaccination will achieve further reductions in morbidity and mortality rates in the country.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To analyze the association between the polymorphic markers in CTLA4, TNF, IL10 and IL16 genes and the risk of manifestation of endocrine ophthalmopathy (EO) in patients with Graves' disease (GD). Materials and methods. Case-control study included 248 patients with GD. Using polymerase chain reaction we studied the distribution of alleles and genotypes of polymorphic markers such as A60G (rs3087243) in CTLA4 gene, G(-308)A (rs1800629) in TNF gene, G(-1082)A (rs1800896) in IL10 gene, T3249C (rs4778641) in IL16 gene among 141 patients with Graves' disease and EO and 107 patients with GD without EO. Results and discussion. The frequencies of A alleles and the AA genotypes were significantly increased and the frequencies of G alleles and the GG genotype polymorphic markers rs3087243 of CTLA4 gene and rs1800896 of IL10 gene, as well as the GG genotype polymorphic marker rs1800629 of TNF gene were reduced in patients with GD and EO. The polymorphism in CTLA4 gene was also associated with the activity and the severity of EO. The comparative analysis of the allele and genotype frequency distribution of polymorphic markers of IL16 gene did not show the significant difference. Conclusion. The risk of manifestation and the development of EO in patients with Graves' disease can be caused by not only environmental, but also genetic risk factors.

AIM: To study the state of cerebral hemodynamics and platelet hemostasis in patients with carotid stenosis (CS). MATERIAL AND METHODS: The prospective study included 123 patients with atherosclerotic CS. The 1st group included 53 patients (mean age 52±12.5 yrs) who underwent carotid endarterectomy (CEA); the 2nd group - 70 patients who were treated conservatively (mean age 58.5±15.9 yrs). The state of blood flow through the main arteries of the head (Doppler flowmetry), platelet aggregation induced by adrenaline, the frequency of acute cardiovascular events that occurred during 12 months were evaluated. RESULTS AND CONCLUSION: The severity of neurological deficits and cognitive impairment increased with increasing of the degree of CS. CEA leads to an improvement of cerebral hemodynamics and stabilization of cognitive functions. The adverse course of the disease occurred in 23.6% of patients (stroke/heart attack during the year in 5.7%, progression of cerebral ischemia in 20%, restenosis within 5 years after CEA in 15%). Hyperaggregation of platelets induced by ADP and epinephrine and decreased aggregation of platelets induced by collagen in patients receiving ASA were identified in 53% of the operated and in 60% of non-operated patients. The use of combined antiplatelet therapy normalize the platelet hemostasis and reduce the frequency of acute cardiovascular events.

© 2018 Bentham Science Publishers. Ischemic Heart Disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect and manipulating their car-diomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June 2018.

© 2018 Giuseppina Nocca et al. A reverse phase high performance liquid chromatographic (RP-HPLC) method was developed for identification and estimation of 18-β-glycyrrhetinic acid (GA) in HepG2 cell line. The analysis was carried out using a JASCO HPLC system with a C-18 (3 μm) Supelco reversed phase column (150 x 4.7 mm) using a mobile phase of 80% CH3OH and 20% of CH3CN: tetrahydrofuran: water (10:80:10, v/v/v). The method was linear in the concentration range of 1.5-120 μg /mL (n = 5). The LOD and LOQ were determined based on standard deviation of the y-intercept and the slope of the calibration curve. The LOD and LOQ values were found to be 11.46 μg/mL and 34.72 μg/mL, respectively. The mean percentage recovery by standard addition experiments of GA is 92.4 % ± 5.2%. The intracellular GA concentration value, obtained as mean of five different determinations, was 45.8 ± 7.45 μg/mL. We have developed a HPLC-UV method for quantitative determination of GA inside cells, with advantages in the cost reduction and economy of the analytical process.

© Bionika Media Ltd. The article highlights the clinical and pathogenetic relationships between endometriosis/adenomyosis and chronic endometritis (CE) within reproductive failures. It describes a cause-and-effect relationship between endometriosis/ adenomyosis and CE by the example of its clinical symptomatology and the pathogenic mechanisms involving an autoimmune process, aseptic inflammation, and altered endometrial receptivity. Endometriosis/adenomyosis and CE have a number of common pathogenetic mechanisms of development and clinical manifestations (infertility, miscarriages, and assisted reproductive program failures). This implies the necessity to qualitatively assess the endometrium in women with endometriosis and adenomyosis during pregravid preparation, as well as the search for new therapeutic ways to correct autoimmune disorders. The use of sodium desoxyribonucleate (derinat) showing the pharmacological properties of an activator of the cellular and humoral immune system and a stimulator of reparative and regenerative processes is a promising approach to drug therapy.