Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature.  We studied the influence of magnetite nanoparticles (FeO•Fe 2 O 3 ) and quantum dots (CdSe/ZnS coated with mercaptopropionic acid) on the expression of 5 common reference genes (BA, B2M, PPIA, UBC, and YWHAZ) in peripheral blood cells from 20 volunteers by reverse transcription PCR method. The stability of the expression of reference genes varied depending of the cells type and chemical structure of nanoparticles. The level of YWHAZ mRNA after exposure by nanoparticles demonstrated highest stability in lymphocytes, neutrophils, and monocytes. Stability of YWHAZ expression was confirmed by Western blotting. Our findings suggest that YWHAZ is the most suitable as the reference gene.

© 2018 The Author(s). Blockchain as technology described to be used in closed Systems to conduct registers of official data in public healthcare. Also this technology had found its use in different other ways, for example it is education of medical staff, control of the contracts for healthcare ServiceS. And the role of Blockchain in CALS / PLM-technologies suggested.

© 2018 The Author(s). Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov University (Russia, Moscow), digital System for drug prescription management is being developed. Artificial intelligence methods to the control of drug therapy will greatly enhance the ability of the automated control System to identify potential problems in drug therapy and provide recommendations for their elimination. Introduction of this System into commercial operation will make it possible to translate the civil circulation of medicines into a single information space and increase the effectiveness of the ongoing pharmacotherapy.

© Ima-Press Publishing House. All rights reserved. Peripheral nervous system involvement may be a main manifestation of systemic amyloidosis or occur in the later stages of the disease in the presence of multiple organ pathology. Focal, multiple mononeuropathy, radiculopathy, polyneuropathy, autonomic nervous system dysfunction, and myopathy develop depending on the localization of amyloid deposits in the peripheral nervous system. The most characteristic symptom in systemic amyloidosis is sensorimotor polyneuropathy accompanied in most cases by the involvement of autonomic nerve fibers in the pathological process. In cases of systemic amyloidosis, peripheral nervous system involvement is progressive, leading to disability, which makes the early diagnosis of the disease and its neurological manifestations and subsequent pathogenetic therapy relevant.

© ABC-press Publishing House. All rights reserved. Today it is noted that the most cases of the hypospadias, cryptorchidism, testicular microlithiasis, as well as problems of semen quality and testicular germ cell tumours can be a clinical manifestation of testicular dysgenesis syndrome caused by abnormal development of reproductive organs. In the last decade, technological progress in the molecular genetics has made possible to carry out a directed search for genetic factors associated with reproductive disorders in men. In the review we attempted to analyze available literature data on the testicular dysgenesis syndrome and its constituent condition and also to consider the risk factors associated with its development. We give particular attention to the consideration of genetic factors that determine the manifestation of testicular microlithiasis, cryptorchidism and testicular germ cell tumors, both individual clinical conditions and in the syndrome of testicular dysgenesis. Knowledge of the genetic aspects of reproductive damage will allow us to characterize the complex interconnection of the human genome with the clinical phenotype, clarify the role of unfavorable factors of the environment and the lifestyle of the individual, and suggest new approaches to treatment.

© Bionika Media Ltd. Aim. To estimate the effectiveness of the thrombin generation assay (TGA) in identifying high thrombogenic risk in pregnant women. Material and methods. The study comprised 30 healthy non-pregnant women (control group) and 32 women in the third trimester of pregnancy. Of the latter group, 22 women with complicated pregnancy comprised the study group while the remaining ten women made up the comparison group. After delivery, the patients in the study group were divided into subgroups with a favorable (n = 15) and adverse (n = 7) pregnancy outcomes. The state of the hemostatic system was examined using standard coagulation tests and TGA. Results. Thrombin generation assessed as endogenous thrombin potential (ETP), was statistically significantly higher in pregnant than in non-pregnant women (2300 ± 400 vs. 1700 ± 400, respectively, p <0.005). The patients with adverse pregnancy outcomes had statistically significantly higher ETP compared with women with favorable outcomes (2700 ± 600 vs. 2300 ± 300, respectively, p <0.005). Conclusion. TGA can be used to predict adverse pregnancy outcomes. Elevated ETP is associated with adverse pregnancy outcomes.

© 2018, Dynasty Publishing House. All rights reserved. Chronic pancreatitis, being a complex multifactor clinico-genetic phenomenon, is a significant medical, social and economic problem. Study of pancreatitis remains a topical theme also for the paediatric cohort, especially taking into account practically similar morbidity rates in adults and children. The review presents information and analyzes main genetic risk factors of the development of pancreatitis. Mutations and polymorphisms of the CFTR, CTRC, SPINK1, CPA1, PRSS1, PRSS2 genes that are significant for functioning of the pancreas are discussed in detail. Examples of genetic variants associated with increased or decreased risks of developing disease are given. Special attention is paid to difficulties of interpreting the results of molecular-genetic testing associated with certain gene homology, presence of pseudogenes and disease cases conditioned by spontaneous mutation. Detection of genetic risk factors of chronic pancreatitis allows to early prevent the development of disease in the proband’s relatives, and also to take a more personalized approach to the patient’s treatment.

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. The development of express method for assessing the state of skin graft by the spectroscopic properties of tissue components involved in the healing of the affected skin or healing of skin grafts was carried out in present work. The proposed method for assessing the state of the skin by the spectroscopic properties of tissue components (using photosensitizers, fluorescent dyes (methylene blue and IcG) and nanophotosensitizers aluminum phthalocyanine nanoparticles (NP-AlPc) applied locally) will evaluate the physiological condition of the skin and assess the degree and rate of engraftment or rejection while also controlling several biochemical and physiological parameters in the entire graft, or the whole area of the skin lesions. Such parameters include the oxygenation of hemoglobin in the tissue microvasculature; the blood supply level; blood flow and lymph flow; assessment of intracellular metabolism; assessment of the cellular respiration type (aerobic/anaerobic).To assess the extent of inflammation the spectrally sensitive to biological environment nanoparticles of aluminum phthalocyanine (NP-AlPc) were also used.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. To assign genetically engineered biologic drugs, we need data on the predictors for response to therapy. Prognostic factors for the response to tocilizumab in patients with juvenile idiopathic arthritis (JIA) without systemic symptoms are poorly studied. Objective. Our aim was to reveal early predictors for the response to tocilizumab therapy in patients with JIA without systemic symptoms. Methods. A retrospective cohort study enrolled patients with JIA without systemic symptoms who received tocilizumab therapy between July 2009 and August 2017. We assessed the association between the initial demographic, clinical, and laboratory parameters in patients and the best response (according to the ACR90 criteria) to treatment after a year. Results. The study included 95 (girls 85%) patients; the mean age was 10.3 (6.0; 13.6). During the first year of therapy, 71 (75%), 55 (58%), 38 (40%), and 22 (23%) patients achieved the improvement according to ACR30/50/70/90 criteria, respectively; 22 (23%) patients reached disease inactive stage according to the Wallace criteria. When performing multivariate analysis, the following improvement predictors were revealed based on the ACR90 criteria after a year of treatment: decrease in serum C-reactive protein level during the first month of therapy [odds ratio (OR) 1.024; 95% confidence interval (CI) 1.007-1.051], decrease in disease activity score on the visual analogue scale according to the parent/patient assessment (OR 1.048; 95% CI 1.005-1.105), early onset of the disease (OR 0.38; 95% CI 0.16-0.72), persistent oligoarthritis according to the ILAR (OR 9.9; 95% CI 1.5-109.3). During the first year of tocilizumab administration, neutropenia was registered in one patient, leukopenia - in three cases, and urticaria - in one case. Conclusion. The variant of JIA, the age at the disease onset, and the disease course pattern in the first month of tocilizumab therapy are the predictors of treatment efficacy throughout the year.

© Team of authors, 2018. Objective. To investigate the expression of transporters of different neurotransmitters (glutamate, aspartate, lactate, choline) in the culture of astrocytes isolated from different regions of the brain (cortex, hippocampus and brainstem) in 3- and 11-day rats. Material and methods. An experimental study was performed on 24 3-(n=12) and 11-days (n=12) old rats (Rattus norvegicus). The results of high-performance sequencing were analyzed. Results. The expression of glutamate and aspartate transporters in the brainstem of 3-day rats was higher than in other regions, however, an opposite effect was observed in 11-day rats. The expression of lactate transporters with age became identical to those of the cortex. Conclusion. The data demonstrate the particular qualities of neuro-astrocytic connections and the important role of astrocytes in signal transmission. Results of the study performed by using genetic methods developed by the authors for the study of neurotransmitter transporters make it possible to recommend these methods to control the neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The healing process in the adult rabbit conjunctiva and sclera tissues after translimbal microdrainage with the use of either biodegradable antiglaucomatous drainage (BDAD) or iGen was studied. Wound areas showed similar acute inflammatory response to the implantation of both matrixes on the 7th day. Complete lysis degradation of iGen and BDAD was observed on 30th day and 60th day, respectively. Within 60 - 90 days after BDAD implantation, the wound areas of conjunctiva and sclera showed intensive angiogenesis and poor extracellular matrix scarring. In contrast, on the 90th day after iGen implantation, a decrease in angiogenesis and intensive extracellular matrix scar formation were observed. As a result of scarring the thin-walled vessels were compressed, which led to the reduction of aqueous humor outflow.

© 2018 Media Sphera Publishing Group. All rights reserved. The review considers modern ideas about the clinic and pathogenesis of minimal hepatic encephalopathy (MHE). It is discussed the present of cognitive impairment in this category of patients. The data of functional MRI are analyzed, and these results allow taking a fresh look at the origin of clinical disorders in this condition. The importance of cerebral connections disruption is emphasized. It is focused on the fact that in the functioning of the central nervous system the spontaneous activity of the brain has a significant importance. Separately is analyzed "the resting state". It is concluded that MHE, despite its minimal manifestations, is a clinically significant condition requiring attention of a specialists. With that, it is often not diagnosed on time in clinical practice, which could lead to more severe damage of the cerebral functions. As evidenced by the data obtained at the present time, quite extensive changes in the neuronal activity are underlid of the cognitive deficit.

© 2018 Human Stem Cell Institute. All rights reserved. Cell therapy is one of the most promising directions in the treatment of critical limb ischemia (CLI). In spite of certain advances achieved in this field in the last decades, which are related to application of bone marrow stem cells (BMSC), a large number of problems still remain unsolved. In this review, we discuss the BMSC biology, mechanisms of their therapeutic effect in the CLI treatment and results of the most notable BMSC-based clinical studies in detail.

© 2018 Dynasty Publishing House. All rights reserved. The systematic review provides a justification for the value of innate immunity as an initial, necessary and determinant stage in the development of adaptive immunity. The participation of TLRs as a leading component of PRRs-system in maintaining natural congenital anti-infection resistance and homeostasis of the organism, in launching and dynamics of development of adaptive immunity to pathogens of infectious and non-infectious genesis was studied in detail. The importance of the influence of these pathogens on the homeostasis of the organism, on the formation of disturbances in anti-infective resistance at the organism and local levels, revealing new pathophysiological and immunological pathogenetic mechanisms of the development of these pathological processes is established. The colossal gap between fundamental studies of the biology and morphology of microorganisms and clinical studies of the diseases they cause is shortening. In an accessible form, explanations are provided for the absence of symptoms, the possibility of atypical manifestations, and the asymptomatic course of infection. There are new wide opportunities to improve and enhance the information content and personalization methods of diagnosis, treatment and prevention, as well as the creation of pharmaceuticals that act detrimental to all forms of cycle of development of pathogens, and new immunomodulatory drugs for the most effective treatment and prevention of diseases.

© 2018 Irina Nikolaevna Dominova, Vitaly Anvarovich Kasymov, Ekaterina Vladimirovna Silina, Victor Aleksandrovich Stupin, Natalia Nikolaevna Shusharina and Maksim Vladimirovich Patrushev. A fragment of the research project devoted to the development of genetic control of exocytosis is presented in the work, which can further ensure the success of targeted therapy of various diseases, including neurodegenerative ones. For the purpose of specific transfection of intracellular cascades in astrocytes in vivo, we have developed an experimental sample of the reagent kit. The latter represents lentiviral genetic construction LVV-GFAP-Case12. The results of testing of experimental samples of the reagent kit for specific transfection of astroglial cells are presented with the purpose of targeted control of intracellular cascades in vivo on acute slices of different parts of the brain in adult Wistar rats. We selected regions of interest with cells expressing calcium indicator Case12 and responsible for ATP application by >2-fold amplification of fluorescence. We have developed instructions for using the reagent kit for specific transfection of astroglial cells with the purpose of targeted control of intracellular cascades.

© 2018 Ima-Press Publishing House. All rights reserved. Cognitive impairment (CI) is a basis for the clinical presentation of chronic cerebral ischemia (CCI). However, the role of the mechanisms of inflammation and angiogenesis in the origin of CI is unclear, as is its relationship to the number and localization of foci during a neuroimaging examination. Objective: to investigate the relationship between the presence of CI, focal brain tissue changes, and the plasma and serum levels of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) in patients with CCI. Patients and methods. Examinations were made in 59 patients with CCI and in 20 apparently healthy individuals. The investigators evaluated the cognitive status using the Mini-Mental State Examination (MMSE) and the clock drawing test), performed brain magnetic resonance imaging (MRI), duplex scanning of cerebral vessels, and determined laboratory indicators: the serum levels of MCP-1 and C-reactive protein, and the serum and plasma concentrations of VEGF. Results. The patients with CI were found to have higher values of inflammatory markers, lower serum and plasma concentrations of angiogenic factors, and a greater number of focal changes on MRI than those without CI (5.06±0.23 and 2.36±0.3 scores, respectively; p(0.05). Imbalance of angiogenic and antiangiogenic factors can cause disease progression and moderate vascular CI in patients with CCI.

© 2018, SPb RAACI. The theory of polyetiological tumorigenesis is one of the most important theories of carcinogenesis. A great place in this theory is given to the role of inflammatory component, which is implemented via the factors of innate immunity. I.e., toll-like receptors (TLRs), chemokines and their receptors are related to innate immunity. Activation of TLRs may lead to regress or progression of cancer process. It is known that TLR3, TLR5, TLR7, TLR9 have the greatest anti-Tumor effect due to the dendritic cells (DCs)-mediated activation of type I T helpers, activation of M1-Type macrophages and Treg inhibition. Stimulation of TLR2 and TLR4 exerts an activating effect upon the tumor, by the MyD88 hyperactivation and secretion of IL-6 and TNFα, but exact mechanisms are not fully understood. In addition to TLRs, chemokines and their receptors have a great influence on the cancer development. It is shown that CCL2, CCL4, CCL17, CCL22 and CXCL12, which are secreted by cancer microenviroment, activate chemotaxis of tumor cells. It is also known that the chemokines activate CXCR4 and CCR7 (expressed by tumor cells) thus leading to metastasis. It is shown that there is an association between some gene polymorphisms of TLRs', chemokines and their receptors, and development of cancer. Thus, we may conclude that the role of TLRs and chemokines is important in oncogenesis. Further study of innate immunity factors influencing tumorigenesis are important for finding new approaches to cancer therapy and new potential vaccines against cancer.

© 2018 ABV-Press Publishing House. All rights reserved. Early childhood autism, or autism spectrum disorders, is an extremely heterogeneous group of conditions that share similar symptoms of dysontogenesis. Epilepsy is the most significant comorbidity in autism. The present article covers various aspects of comorbidity between epilepsy and autism, described in the literature over the last 50 years. This review aims to analyze the development of epilepsy and autism during ontogenesis and to identify causal relationships between these diseases, considering the information on the two age peaks for epilepsy onset in patients with autism.

© 2018 ABC-press Publishing House. All rights reserved. Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.

© 2018 Sychev et al. Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.