Репозиторий Университета

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose of the study. To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. Materials and methods. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m- 38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. Results. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the extraocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), increased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in patients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Conclusion. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

© 2018 Medical Education. All rights reserved. The aim of this study was pharmacoeconomic evaluation of treatment with reslizumab compared to omalizumab in severe eosinophilic asthma. Methods. The study was based on indirect comparison between omalizumab and reslizumab in patients with severe asthma using published data. Costs of treatment with omalizumab, reslizumab, combinations of inhaled corticosteroids and long-acting beta-agonists (ICS/LABA), outpatient treatment, treatment of exacerbations and adverse events were also compared. Сost-effectiveness analysis and budget impact analysis were used. Results. According to results of cost-effectiveness analysis, therapy with reslizumab dominated over therapy with omalizumab in patients with severe asthma in term of exacerbation rate requiring treatment with systemic steroids. According to results of budget impact analysis, switching of 100 patients from omalizumab to reslizumab could save RUB 51.99 million per year that corresponds to 36.6% reduction in general direct costs for treatment of severe asthma. Conclusion. The results of this study demonstrated economic advantage of reslizumab over omalizumab in patients with severe eosinophilic asthma.

© ISUCT Publishing. The macrolide antibiotic oligomycin A (1), produced by actinomycetes Streptomyces,[1] is a well-known inhibitor of FO F1 ATP-synthase, which is regarded as a molecular target for new drugs in the treatment of tumors and infections. Oligomycin A (1) exhibits antifungal and cytotoxic activities, but Gram-negative and Gram-positive bacteria are resistant to 1 except actinobacteria.[2] In micromolar concentrations, oligomycin binds to FO c-subunit, blocks proton translocation and disrupts bioenergetic metabolism.[3] However, a clinical application of oligomycin A is limited by high cytotoxicity for mammalian cells. The searches of new derivatives of oligomycin A with more selective pharmacological activity and low toxicity for normal cells are of great interest. New semi-synthetic oligomycins also would be valuable for SAR studies and depicting the mechanism of FO F1 ATP-synthase inhibition. The complicity of oligomycin structure and its lability in basic conditions[4] significantly impede modifications and an applicability of this antibiotic. However, previously we have managed this challenge and developed some modifications of the side chain and chemical transformations of the lactone moiety of 1.[4-9] In this paper, throughout our research we describe synthesis and biological investigation of novel oligomycin A derivatives, namely 16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3) and 33-O-formyloligomycin A (4). First, we have studied Prilezhaev epoxidation of double bonds in core structure of oligomycin A. It was found that treatment 1 with m-CPBA at -17oC in dichloromethane led to 16,17-epoxyoligomycin (2). Unfortunately, all attempts for isolation of product 2 were failed due to its instability on silica gel, and, consequently, we were unable to determine the structure of 2 by direct physicochemical and spectral methods. The presence of epoxide at C16-C19 positions was confirmed by tandem mass spectrometry, but its exact localization was still elusive. We assumed that it might be at C16-C17 positions, because C18-C19 double bond is hindered by ethyl side chain at C20. In order to obtain a stable oligomycin A derivative we performed an epoxide ring-opening reaction by the treatment of the crude epoxyoligomycin 2 with formic acid. This acid-catalyzed opening of the epoxide accompanied with acylation of 33-OH group and led to16,33-O,O-diformyl-16,17-dihydro-16(S),17(R)-dihydroxyoligomycin A (3). The structure of 3 was confirmed by NMR spectroscopy and high resolution mass spectrometry. Configurations at C16 and C17 positions were determined by detecting correlations in1H-1H ROESY spectrum. Obtained results allowed to confirm an assumption about localization of the epoxide ring and establish the structure of 2 as (R,R)-16,17-epoxyoligomycin A, since inversion of configuration has taken place at the attacked carbon atom.[23] It is known that O-acyl derivatives of pharmacologically active agents are widely used as prodrugs.[24] Acylation of 2-hydroxypropyl side chain in 2 prompts us to examine the reaction of oligomycin A (1) with formic acid. Thus, stirring the solution of 1 in HCOOH (98 %) for 2 h at room temperature afforded 33-O-formyloligomycin A (4) in a good yield. The structure of 4 was confirmed by NMR-spectroscopy and high resolution mass spectrometry. Also, biological data of new derivatives were evaluated. The modification of C16-C17 positions of the macrocycle as well as acylation of C33 hydroxyl group led to the decreasing of activity against S. fradiae, Candida spp. and filamentous fungi. Obtained results were in agreement with docking studies. A simulation of an interaction of 1, 3 and 4 with the FO subunit of the ATP-synthase (PDB: 4f4s) revealed that these modifications led to a significant change in the solvation energy and an increase in the conformational capacity of the ligands during the binding with the target. This resulted in decrease of the binding affinity for derivatives 2, 3. However, 33-O-formyloligomycin A (4) showed similar antiproliferative activity against tumor cell lines (HCT-116 colon carcinoma, К562 myeloid leukemia cell lines and MDR K562/4 subline) as for 1, but less cytotoxic for non-malignant human cells.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to investigate the morphological and metabolic features of primary hippocampal cultures formation on hydrogel films and scaffolds based on hyaluronic acid glycidyl methacrylate. Materials and Methods. Hydrogel films and scaffolds with certain architectonics were developed by micromolding technique on the basis of hyaluronic acid glycidyl methacrylate. Primary hippocampal cells obtained from C57BL/6 mouse embryos (E18) were cultured on the created constructs more than 14 days. Testing cell viability, morphometric assessment, and analysis of spontaneous calcium activity of primary hippocampal cultures were performed on day 14 of cultures development in vitro. Results. This study revealed that the material for the development of scaffolds with given architectonics is non-toxic for the nervous system cells. Dissociated hippocampal cells were actively attached to the scaffold surface and were assembled into cell conglomerates, which exhibited spontaneous calcium activity. Conclusion. Scaffolds designed on the basis of hyaluronic acid glycidyl methacrylate have a high biocompatibility with the nervous system cells. Architectonics and adhesive properties of scaffold contribute to the formation of functionally active cell conglomerates.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to demonstrate a good diagnostic potential of atomic force microscopy (AFM) in tracking morphological changes in the extracellular matrix (ECM) of connective tissue due to pathological processes. Here we summarize our experience in AFM application in a number of biomedical studies on the connective tissue disease, both for the research and clinical purposes. Materials and Methods. Depending on the project application (experimental or clinical), the tissue specimens were harvested either from animals, or from patients in the course of their surgical treatment, or post mortem. AFM images of fixed tissue slices on glass slides were acquired with a Solver P47 AFM instrument (NT-MDT, Russia), in the semi-contact mode. For mechanical properties mapping, the images were acquired on air in the PeakForce Quantitative Nanomechanical Mapping mode (PeakForce QNM®), using a MultiMode 8 atomic force microscope (Bruker, USA). The regions of interest for scanning were selected in accordance with the histological assignments for the same sample, based on the view of a sample in the built-in optical microscope of the AFM instrument setup. To quantify the changes in the ECM morphology visualized by AFM imaging, we applied flicker-noise spectroscopy parameterization. Results. AFM has been shown to reveal visible deviations from the normal morphology of the ECM in diseased tissues. We found that AFM and related techniques are capable of tracking disease-related changes at different levels of collagen organization in the ECM. At the microscale, AFM may detect loosening and disorganization of collagen fibers (e.g., in a dysplastic process), or the opposite process of their packing into tight parallel bundles in a fibrotic process. AFM may also monitor the ratio between collagen and non-fibrous material of the ECM, for example, in inflammatory and neoplastic processes. At the level of collagen fibrils, AFM may reveal early signs of the matrix destruction and remodeling not visible at the microscopic level. The flicker-noise spectroscopy parameters provide quantification of the morphological changes visualized by AFM. The PeakForce QNM® and nanoindentation studies give a further insight into the state of ECM via tracking changes in the local mechanical and adhesive properties. All our AFM studies appeared in a good agreement with the histological findings and generally had a superior sensitivity to pathology-related ECM rearrangements. Conclusion. AFM may serve as a valuable complementary diagnostic tool for tracking pathological changes in the connective tissue.

© 2017 Elsevier Inc. A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-D-Arg-Phe-Gly-NH2 was modified with the inclusion of a (D-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (D-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32–1 mg/kg) and TDP (0.32–1.8 mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10 mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7 days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.

© Springer Science+Business Media New York 2016. A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

© 2018 Ima-Press Publishing House. All Rights Reserved. The paper presents the proceedings of the Round Table with the participation of leading neurologists, which is devoted to chronic cerebrovascular diseases. It is noted that chronic cerebral ischemia (CCI), or dyscirculatory encephalopathy (DEP), is one of the most common neurological diagnoses in our country. The pathogenesis, clinical presentations, diagnosis and treatment of CCI (DEP) and its matching with vascular cognitive impairment (CI), which is regarded in foreign literature as the main manifestation of chronic cerebrovascular disease (CVD) were considered. The authors analyze clinical trials evaluating the efficacy of vinpocetine (Cavinton) in chronic CVD, dizziness, Cl, as well as the use of new vinpocetine formulations, such as Cavinton Comforte, in various neurological diseases, dysphagia in particular, in poststroke patients.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. agnetic iron oxide nanoparticles (MNP) show great potential as the contrast agent for magnetic resonance imaging (MRI). Purpose. To evaluate the efficiency and safety of the contrast agent based on HSA-coated MNP on the model of the C6 glioma. Materials and methods. Extensive preclinical research of specific activity has been performed. Studies were conducted on the model of the orthotopic C6 glioma. Results. In the preclinical studies, it was demonstrated that HSA-coated magnetic iron oxide nanoparticles (MNP-HSA) accumulate in the tumor and its large vessels. Conclusion. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.

© 2018 Bentham Science Publishers. Introduction: One promising target for novel psychotropic drugs is the 5-HT6 receptor, G-Protein-Coupled Receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked procognitive effects. Methods: An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models. The present study is devoted to a detailed QSAR analysis of 61 drugs (26 agonists and 35 antagonists) acting on the 5-HT6 receptor (rattus norvegicus and homo sapiens). Five classification methods were used: k-Nearest Neighbors (k-NN), Logistic Regression (LG), Linear Discriminant Analysis (LDA), Random Forest (RF), and Support Vector Machine (SVM). Multiple Regression Analysis (MRA) was involved also for regression analysis. Spectra of Inter Atomic Interactions (SIAI) were applied in the search for ligand centres interacting with the 5-HT6 receptor. Results & Conclusion: SAR and QSAR models based on the use of HYBOT, MOLTRA, VolSurf+, and SYBYL programs, and having cross-validated coefficients of determination of at least 0.80, show a predominant influence of H-bond acceptor ability and hydrophobicity on the type of ligand activity and degree of inhibition.

© 2018 Elsevier Inc. Immunoglobulin E (IgE)-associated allergy is the most common immune disorder. More than 30% of the population suffer from symptoms of allergy which are often severe, disabling, and life threatening such as asthma and anaphylaxis. Population-based birth cohort studies show that up to 60% of the world population exhibit IgE sensitization to allergens, of which most are protein antigens. Thirty years ago the first allergen-encoding cDNAs have been isolated. In the meantime, the structures of most of the allergens relevant for disease in humans have been solved. Here we provide an update regarding what has been learned through the use of defined allergen molecules (i.e., molecular allergology) and about mechanisms of allergic disease in humans. We focus on new insights gained regarding the process of sensitization to allergens, allergen-specific secondary immune responses, and mechanisms underlying allergic inflammation and discuss open questions. We then show how molecular forms of diagnosis and specific immunotherapy are currently revolutionizing diagnosis and treatment of allergic patients and how allergen-specific approaches may be used for the preventive eradication of allergy.

© 2018 by the MediaSphere. The materials of the National Consensus reflect the modern domestic and international experience on this issue. Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation. A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child's height is < –2.0 SDS, if the difference between the child's height SDS and child's midparental height SDS exceeds 1.5 SDS and/or a low growth velocity. The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation. The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day. With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum. GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphy-seal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient's desire and his parents / legal representatives satisfied with the achieved result of the final height. Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation. If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

© 2018 Park-media, Ltd.  Common marmosets are small New World primates that have been increasingly used in biomedical research. This report presents efficient protocols for assessment of the parameters of adaptive cell-mediated immunity in common marmosets, including the major subpopulations of lymphocytes and main markers of T- and B-cell maturation and activation using flow cytometry with a multicolor panel of fluorescently labelled antibodies. Blood samples from eight common marmosets were stained with fluorescently labeled monoclonal antibodies against their population markers (CD45, CD3, CD20, CD4, CD8) and lymphocyte maturation and activation markers (CD69, CD62L, CD45RO, CD107a and CD27) and analyzed by flow cytometry. Within the CD45 + population, 22.7±5.5% cells were CD3 - CD20 + and 67.6±6.3% were CD3 + CD20 - . The CD3 + subpopulation included 55.7±5.5% CD3 + CD4 + CD8 - and 34.3±3.7% CD3 + CD4 - CD8 + cells. Activation and maturation markers were expressed in the following lymphocyte proportions: CD62L on 54.0±10.7% of CD3 + CD4 + cells and 74.4±12.1% of CD3 + CD8 + cells; CD69 on 2.7±1.2% of CD3 + CD4 + cells and 1.2±0.5% of CD3 + CD8 + cells; CD45RO on 1.6±0.6% of CD3 + CD4 + cells and 1.8±0.7% of CD3 + CD8 + cells; CD107a on 0.7±0.5% of CD3 + CD4 + cells and 0.5±0.3% of CD3 + CD8 + cells; CD27 on 94.6±2.1% of CD3 + cells and 8.9±3.9% CD20 + cells. Female and male subjects differed in the percentage of CD3 + CD4 + CD45RO + cells (1.9±0.5 in females vs 1.1±0.2 in males; p < 0.05). The percentage of CD20 + CD27 + cells was found to highly correlate with animals' age (r = 0.923, p < 0.005). The basal parameters of adaptive cell-mediated immunity in naïve healthy marmosets without markers of systemic immune activation were obtained. These parameters and the described procedures are crucial in documenting the changes induced in common marmosets by prophylactic and therapeutic immune interventions.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). Materials and methods: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym-oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. Results. Mean duration of follow-up was 64414.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 38956.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2-VASc, and ORACLE scores, respectively.

© 2018 SPIE. Application of terahertz (THz) spectroscopy for biological tissues is strongly limited by the extremely low penetration depth due to THz absorption by tissue water. One of the possible solution of such problem is the usage of THz wave penetration-enhancing agents (PEA) for optical clearing of tissues. In the present paper, the transmission-mode THz spectroscopy of a set of PEAs (polyethylene glycol with different molecular weight, propylene glycol, ethylene glycol, and dimethyl sulfoxide) was performed in order to reconstruct their dielectric properties and compare them with that of water. The obtained results emphasize the feasibility of using PEG to enhance the depth of THz wave penetration into tissues.

© 2018 Ima-Press Publishing House. All Rights Reserved. In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". These guidelines were drawn up to improve the use of NSAIDs, our country's most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE. Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world's leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice. The guidelines are intended for physicians of all specialties.

© 2018 Altai State University. All rights reserved. The critical revision of Trollius L. (Ranunculaceae) in the Far East of Russia was made, in which nine species were recognized. The identifcation key and taxonomical synopsis of the genus have been provided. Synonymy, geographical distribution and coeno-ecological peculiarities of each species of these nine species are presented. For the frst time Trollius japonicus Miq. was found in the territory of Russia (the Kurile Islands: Iturup, Kunashir). Furthermore, we found that the information on the distribution of this species on Sakhalin Island is wrong owing to the incorrect identifcation. The information about the medical use of each of nine Trollius species is also provided.

© 2018 Russian Association of Endocrinologists. All rights reserved. The presented paper is a third revision of the clinical recommendations for the treatment of morbid obesity in adults. Morbid obesity is a condition with body mass index (BMI) ≥40 kg / m2 or a BMI ≥35 kg / m2 in the presence of serious complications associated with obesity. The recommendations provide data on the prevalence of obesity, its etiology and pathogenesis, as well as on associated complications. The necessary methods for laboratory and instrumental diagnosis of obesity are described in detail. In this revision of the recommendations, the staging of prescribing conservative and surgical methods for the treatment of obesity are determined. For the first time, a group of patients with obesity and type 2 diabetes mellitus is selected, in whom metabolic surgery allows a long-term improvement in the control of glycemia or remission of diabetes mellitus.

© 2018 Bentham Science Publishers. Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders. In this concern, the involvement of UT II in the pathophysiology of many processes determines the perspectives for the development of blockers of urotensin receptors for the treatment of the aforementioned diseases. It is important that even today this kind of perspective is feasible due to the synthesis of a series of GPR14 blockers. The objective of this review is to discuss current molecular mechanisms of biological activity, regulatory functions of UT II, its role in the pathogenesis of different nosologies, as well as analysis of the possible routes of exposure to GPR14 as potential therapeutic targets.

Autophagy is an evolutionary conserved intracellular catabolic process of vital importance to cell and tissue homeostasis. Autophagy is implicated in the pathogenesis of atherosclerosis but participating cells, molecular mechanisms and functional outcomes have not been fully elucidated. T-cadherin, an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules, is upregulated on smooth muscle cells (SMCs)¹ in atherosclerotic lesions. Here, using rat and murine aortic SMCs as experimental models, we surveyed the ability of T-cadherin to regulate autophagy in SMCs during serum-starvation stress. Ectopic upregulation of T-cadherin in SMCs resulted in augmented autophagy characterized by increased autophagic flux, LC3-II abundance and autophagosome formation. Analysis of signal transduction pathway effectors and use of specific pharmacological inhibitors demonstrated that T-cadherin-associated enhancement of the autophagic response to serum-deprivation was dependent on MEK1/2/Erk1/2 activation and independent of PI3K/Akt/mTORC1, reactive oxygen species or endoplasmic reticulum stress. T-cadherin upregulation on SMCs conferred a survival advantage during prolonged serum-starvation which was sensitive to inhibition of MEK1/2/Erk1/2 by PD98059 or UO126 and to blockade of autophagy by chloroquine. Loss of T-cadherin expression in SMCs diminished autophagy responsiveness and compromised survival under conditions of serum-starvation. Overall our findings have identified T-cadherin as a novel positive regulator of autophagy and survival in SMCs.