Репозиторий Университета

© 2018, Dynasty Publishing House. All rights reserved. The objective is to study the results of treatment of female patients with endometrial hyperplasia considering the 2014 WHO Classification and to make adjustments in tactics of conducting it, based on the individual approach. Patients and methods. Eighty-two (82) female patients at the age from 19 to 47 years (37.5 ± 2.6 years) were examined. Most of them (54/65,8%) were in the reproductive period. Methods of diagnosis: a) 2D and 3D transvaginal ultrasound scan with the use of color Doppler; b) video histeroscopia; C) histologic study of endometrial scratching or macropreparations, removed during the surgery. Results. It has been found in the analysis of the 2014 WHO Classification and Protocol RCOG & BSGE that when EH diagnosed for the first time in women of reproductive age after 3 months of taking NET, it is advisable to use estrogen-progestin products (COCP) for another 3 months with prolongation if necessary for further protection from unwanted pregnancy. The morphological picture of AEH should be carefully estimated, taking into account that in its simplest form total ablation of the endometrium is valid. Conclusion. No algorithm is able to cover all possible clinical situations and to adhere to individual approach in the choice of patient treatment tactics with endometrial hyperplasia.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This article provides a short history of the creation of hypnotics, examines their mechanisms of action, and conducts a comparative analysis of the main groups of hypnotics such as barbiturates, benzodiazepines, "nonbenzodiazepine" benzodiazepine receptor agonists, melatonin receptor agonists, orexin receptor antagonists, histamine H1-receptor antagonists.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Introduction of amendments to the registration dossier is the responsibility of the marketing application holder (MAH). Increased knowledge on pharmaceuticals, its manufacturing and control processes can reduce the number of documents submitted to the regulatory authorities. The existing requirements establishing the procedure for the introduction of amendments differ in terms of change classification, period of notification of regulatory authorities, ways of conformity validation of pharmaceutical properties, etc. ICH proposed draft guideline Q12 «Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management» which covers the problem of harmonization of regulatory approaches to the changes provided in the «Quality» section of CTD during the commercial phase of drug life cycle. The new guideline can be considered as the continuation and elaboration of previous ICH documents. The article provides explanations on the main provisions and regulatory mechanisms introduced by the draft guideline ICH Q12: categorization of post-approval changes, established conditions, post-approval change management protocol, and drug product lifecycle management.

© 2018 Media Sphera Publishing Group. All rights reserved. The exact cause of the development of anxiety disorders (AD) in present time has not been fully established and is a subject of debate in many countries. Interest in studying the mechanisms of action of proteins of S100 group, in particular, neurospecific protein S100b, is caused by its participation in processes of integrative activity of brain/neuron and development of diseases of nervous system. The functions of S100 proteins determine their influence on synaptic plasticity and participation in the regulation of stress-realizing and stress-limiting systems, the imbalance of which (primarily, the insufficiency of the GABA-ergic system) is the neurobiological basis of the majority of anxiety-depressive pathologies. Preparations regulating the activity of S100 protein have a distinct clinical anti-anxiety effect and additionally contribute to the restoration of neuronal plasticity processes.

© 2018 Russian Association of Endocrinologists. All rights reserved. The development of effective methods of obesity treatment with the goal of preventing many associated diseases is among the priorities of modern biomedical research. In 2016 glucagon-like peptide-1 analog (GLP-1) liraglutide 3 mg (Saxenda®) was approved in the Russian Federation for the treatment of obesity. This review presents literature data on the effects of GLP-1 and liraglutide on appetite and body weight as well as an analysis of the effectiveness and safety of drug Saxenda based on the results of major clinical trials.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II - 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7-10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II - 5.5±0.06 years and 2.4±0.07 years, respectively (p<0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p<0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p<0.001). Immunohistochemical analysis of the endometrium on the 18th-24th day of the cycle established high expression of CD16, CD20, CD56, and HLADRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p<0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p<0, 05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16, CD20, CD56 and HLA-DRII .

© 2018, Media Sphera Publishing Group. All rights reserved. Inflammasomes are macromolecular complexes that contain many copies of receptors recognizing molecular patterns of pathogenic agents (PAMP) and damage-associated structures (DAMP), and also include molecules of adapter protein ASC and procaspase- 1. Activation of inflammasomes leads to the formation of active caspase-1 that, in turn, provides the maturation of pro-IL-1β and pro-IL-18 to IL-1β and IL-18. The latter cytokines play an important role in control of neuroinlfammation in the central nervous system contributing to the pathogenesis of a series of neurological, neurodegenerative and mental disorders. The review discusses the involvement of NLRP3 inflammasome and other their types in the development of the traumatic brain injury, ischemic and hemorrhagic stroke, brain tumors, CNS infections, Alzheimer’s and Parkinson’s diseases, epilepsy, amyotrophic lateral sclerosis, depressiver, and consequences of alcohol abuse. The elucidation of molecular mechanisms and signaling pathways controlled by inflammasomes will allow the development of new therapeutic measures for diseases, in which neuroinflammation plays a leading pathogenetic role.

© 2018 Media Sphera Publishing Group. All rights reserved. Àim. To compare the efficacy of prophylactic administration of mineral-vitamin complexes "Feroglobin-B12" and "Complivit iron" with different degrees of Fe valence. Materials and methods. 120 female subjects were examined. To determine the quality of life, the SF-36 questionnaire was used. The presence of anxiety was determined on the Spielberger-Khanin Alarm Scale. 30 women with a deficit of Fe were divided into 2 groups of 15 people each. The first group received "Ferroglobin-B12", the second – "Complivit iron" for a month. Results. In a month after the initiation of preventive therapy in women of the 1 group the content of Fe serum was normalized. In the second group, its concentration approached the control values. The difference in Fe content in the 1 and 2 groups was of a reliable nature. Conclusion. The intake of "Ferroglobin-B12" was not accompanied by side effects, and performance indicators, social activity and mental health reached control values, unlike the group of patients taking Complivit iron.

© 2018 Maik Nauka-Interperiodica Publishing. All rights reserved. Changes in the power and coherence of the EEG theta-1 (4-6 Hz) and theta-2 (6-8 Hz) activity were studied in subjects (31 males, 18-21 years old) with different performance levels in logical tasks. EEG was recorded to the International 10-20 System from the occipital (O2, O1), parietal (PA, P3), central (C4, C3), frontal (FA, F3), and temporal (T4, 73) leads. The achievement of better performance during the tests based on logical reasoning positively correlated with higher spectral power of theta-1 band potentials in the left cortical areas. The theta-1 band potential power increased during testing and compared to the previous period in the left occipital, parietal, central and temporal cortical areas. The simultaneous increasing in intrahemispheric coherence of theta-1 band potentials was observed in the left frontal and central areas, as well as in the left frontal and parietal cortical areas. The spectral power of theta-2 band potentials decreased during testing and compared to the previous period in the right central frontal and temporal cortical areas. The inter- and intrahemispheric coherence of the EEG theta-2 band potentials decreased during testing in the system of relationships with the focus in the left and right occipital and right parietal cortical areas. The desynchronization in the EEG theta 2 band in all cortical areas was observed at transition from a state of quiet wakefulness with eyes closed to a state with eyes open. The conclusion is made about the different functional significance of the electrical activity of the low and high frequency theta EEG bands under cognitive activity.

© 2018 The Author(s). Background: Cornea protects the eye against natural and anthropogenic ultraviolet (UV) damage and mechanical injury. Corneal incisions produced by UV lasers in ophthalmic surgeries are often complicated by oxidative stress and inflammation, which delay wound healing and result in vision deterioration. This study trialed a novel approach to prevention and treatment of iatrogenic corneal injuries using SkQ1, a mitochondria-targeted antioxidant approved for therapy of polyethiological dry eye disease. Methods: Rabbit models of UV-induced and mechanical corneal damage were employed. The animals were premedicated or treated with conjunctival instillations of 7.5 μ M SkQ1. Corneal damage was assessed by fluorescein staining and histological analysis. Oxidative stress in cornea was monitored by measuring malondialdehyde (MDA) using thiobarbituric acid assay. Total antioxidant activity (AOA) was determined using hemoglobin/H2O2/luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays. Results: In both models corneas exhibited fluorescein-stained lesions, histologically manifesting as basal membrane denudation, apoptosis of keratocytes, and stromal edema, which were accompanied by oxidative stress as indicated by increase in lipid peroxidation and decline in AOA. The UV-induced lesions were more severe and long healing as corneal endothelium was involved and GPx and SOD were downregulated. The treatment inhibited loss of keratocytes and other cells, facilitated re-epithelialization and stromal remodeling, and reduced inflammatory infiltrations and edema thereby accelerating corneal healing approximately 2-fold. Meanwhile the premedication almost completely prevented development of UV-induced lesions. Both therapies reduced oxidative stress, but only premedication inhibited downregulation of the innate antioxidant activity of the cornea. Conclusions: SkQ1 efficiently prevents UV-induced corneal damage and enhances corneal wound healing after UV and mechanical impacts common to ocular surgery. Its therapeutic action can be attributed to suppression of mitochondrial oxidative stress, which in the first case embraces all corneal cells including epitheliocytes, while in the second case affects residual endothelial cells and stromal keratocytes actively working in wound healing. We suggest SkQ1 premedication to be used in ocular surgery for preventing iatrogenic complications in the cornea.

Literature data devoted to transplantation of Langerhans cells have been analyzed. The main stages, indications, dissection of islets, immunosuppressive therapy, complications and data of the latest clinical trials were discussed.

© 2018 Russian Electronic Journal of Radiology.All right reserved. This article presents the clinical case of an extragastric large gastrointestinal stromal tumor combined with osteomyelofibrosis. It made great differential diagnostic difficulties with regard to the tumor location. Modern radiology methods are described, which allow to reveal and establish the organogenesis of the tumor as well as its histological characteristics.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Infections are the main cause of death for patients with autoimmune rheumatic diseases. In adult patients with rheumatoid arthritis (RA), mortality caused by respiratory infections is 2-5 times higher than in the population. One of the frequent infectious complications in the course of treatment with tocilizumab, the first-choice drug for treating systemic juvenile idiopathic arthritis (sJIA), is pneumonia characterized by a poor clinical picture, normal values of laboratory indices of the disease activity (ESR, C-reactive protein) with pronounced changes in the lungs revealed by computed tomography. In case of acute respiratory infection in children with systemic JIA, immunosuppressants and genetically engineered biological preparations (GEBP) are discontinued. This often leads to an exacerbation of the underlying disease and the progression of a pathological process. At present, vaccination against pneumococcal infection in Russia is not included in the standard for managing patients with rheumatic diseases. Studies of the safety and efficacy of vaccination with 13-valent pneumococcal conjugate vaccine (PCV) in patients with sJIA receiving genetically engineered biological preparations were not conducted. Clinical Case Description. The article shares the experience of vaccination of a girl aged 9 years with a 13-valent PCV that was conducted in the course of a scientific investigation, which studied the efficacy and safety of vaccination of children with systemic JIA prior to prescription of GEBP tocilizumab. Vaccination did not cause a deterioration in the course of the main disease (1 month), led to a reduction in the incidence of acute respiratory infections (from 4 to 1 time within 6 months before and after vaccination), and discontinuation of antibacterial drugs within 6 months after vaccination. Conclusion. The safety of a 13-valent PCV in a child with sJIA and a decrease of the incidence of respiratory diseases after vaccination, their complications, and the use of antibacterial drugs have been shown.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferon-based schemes found to be non-effective or contraindicated. 3D therapy was the only available etiotropic option for them. New safety data published after the start of our study significantly limited usage of this regimen among patients with non-compensated cirrhosis. The aim of this study was to evaluate efficacy and safety of the 3D interferon-free regimen among HCV Gt1b patients with non-compensated cirrhosis. Method: 66 patients (26 males and 40 females) with HCV Gt1b and non-compensated cirrhosis were enrolled. All of them were treated with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks. Ribavirin was discontinued after 4 weeks of therapy due to onset of new data on the efficacy of 3D regimen without ribavirin in Turquoise III study published in September 2015 before the change of package insert. Child-Pugh score was assessed before the start of antiviral therapy as follows: 21 patients (31,8%) – 9 points, 11 patients (16,7%) – 8 points, 34 patients (51,5%) – 7 points. The key method used to evaluate study results was modified intent-to-treat (mITT) analysis because number of analyzed patients within treatment period changed after withdrawal caused by safety reasons but followed by assessment of efficacy among patients who discontinued treatment. Per protocol (PP) method was also used in addition to mITT. Results: Aviremia after 14 days of treatment was reached among 35 out of 65 patients (53,8%), rapid virologic response – among 79,7% patients (51/64). Each patient who received full 12-week course of treatment (n=60) including those who discontinued due to safety reasons (n=3) between 14th and 30th days of therapy reached SVR12 and SVR24. Assessment of Child-Pugh score in 6 months after EOT demonstrated decrease by 3-4 points among 21 patients (33,9%) and by 1-2 points among 35 patients. 66,1% patients reached clinical improvement in MELD score. Treatment discontinuation was caused by progression of hepatic encephalopathy and/or jaundice (4 cases). Those adverse events regressed among majority of patients after discontinuation of therapy. 3 deaths were reported (bacterial endocarditis, progression of hepatic encephalopathy and bleeding from gastric ulcers) during treatment period and 1 death in follow-up period due to progression of hepatocellular carcinoma. Conclusion: 3D therapy was effective in 100% patients (mITT) with HCV GT1b and non-compensated cirrhosis both among those who completed full therapy course and those who discontinued the therapy due to safety reasons. Safety analysis demonstrated that the rate of severe adverse events was comparable with natural course of HCV-infection in patients on non-compensated cirrhotic stage without antiviral treatment.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Vitamin D deficiency is widespread worldwide and present in about 30-50% of population. In most cases, this problem is associated with musculoskeletal system pathology: Rickets in children, and osteomalacia or osteoporosis in adults. However, in recent years, convincing data was obtained on the links between Vitamin D deficiency and cardiovascular pathology. Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe cardiovascular diseases, including strokes and infarctions. It has been demonstrated that Vitamin D has a strong vasoptotective effect via endothelial dysfunction improvement, prevents blood vessels and myocardium remodeling, improves blood pressure parameters, reduces the risk of development of left ventricular hypertrophy, slows down fibrosis, reduces the risk of atherosclerosis, reduces insulin resistance, and also affects inflammation and immunity. This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic heart failure.

© 2018 Ima-Press Publishing House. All rights reservbed. The socially significant problems in patients with prior stroke include post-stroke cognitive impairment (PCI), the prevalence of which is high (from 24 to 70%). The causes of disability in these patients are that the role of cognitive impairment is often underestimated and attention is paid only to motor defects. The pathogenesis of PCI may include not only vascular, but also neurodegenerative (due to Alzheimer's disease) mechanisms of brain damage. The diagnosis of early PCI is of great practical importance, as it is most effective to treat mild PCI. The paper considers current approaches to preventing and treating PCI. The authors give their own experience in treating a patient with moderate PCI.

© 2018 Media Sphera Publishing Group. All rights reserved. According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CÀNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative antiinflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

© 2018 Media Sphera Publishing Group. All rights reserved. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

© 2018 Nutritec. All rights reserved. The results of assessing the sufficiency offolic acid of the residents of the Moscow region have been presented depending on rs1801133 MTHFRgene polymorphism and rs9939609 FTO gene polymorphism. A total of 326 people were examined, including 74 men and 252 women aged 20 to 65 years. The results of determining the level of folic acid in blood serum showed insufficiency of this vitamin among the population of the Moscow region of the Russian Federation. The expressed vitamin deficit (level <3,0 ng/ml) was detected in 24.2% of the surveyed residents, in 22.8% folic acid level was at the lower bound of the norm (3.0-4.5 ng/ml). The results of genotyping showed a statistically significant association of low folic acid level with rs1801133 MTHFR gene polymorphism in carriers of A allele of rs9939609 FTO gene polymorphism both in the homozygous state (genotype AA) and in the heterozygous (genotype AT) state, OR=4.26; CI (1.40-12.9), p=0.008, as well as with rs9939609 FTO gene polymorphism in carriers of the T allele of rs1801133 MTHFR gene polymorphism both in the homozygous (genotype TT) and heterozygous (CTgenotype) state, OR-3.29; CI (1.07-10.1), p=0.03. In carriers of 3 alleles of risk offolic acid deficiency [rs9939609 FTO gene polymorphism and rs1801133 MTHFR gene polymorphism (genotypes CT/AA and TT/AT)] blood serum level of folic acid was below the norm, that indicated folate deficiency in this category of persons.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Organic nitrates are widely used in clinical treatment of cardiovascular diseases, but the problem of developing tolerance during long-term therapy remains urgent. The analysis of published works shows that the nitrate tolerance development is caused by various mechanisms, including disturbances in neurohormonal regulation of vessel tonus and biochemical pathways of realization of the nitrate effect. This review summarizes the current notions of the mechanisms of nitrate tolerance development and vascular changes during nitrate drug application and analyzes potential efficiency of using coenzyme Q10 for preventing the development of nitrate tolerance and nitrate-induced endothelial dysfunction.