Репозиторий Университета

© Russian Association of Endocrinologists, 2018. BACKGROUND. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. AIMS. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemic-hypoglycaemic clamp. MATERIALS AND METHODS. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 ± 5.6 years, A1C 9.7 ± 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. RESULTS. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin-23.9%, ADP-30.6%, arachidonic acid-30.9%, collagen-69.4% and ristocetin-70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. CONCLUSIONS. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemic-hypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Indomethacin, a non-steroid anti-inflammatory drug (NSAID), has been used in different spheres of medicine since the 1960s. It is successfully administered as an anti-inflammatory and pain-relieving medication in rheumatoid and other diseases. According to recent research, indomethacin may become a promising drug enhancing endogenous remyelination in patients with multiple sclerosis. Also, indomethacin affects cell proliferation and invasion, thus it is used to manage pancreatic cancer in patients with hyperglycemia. In addition, indomethacin can inhibit protein synthesis in colorectal carcinoma and other types of cancer cells. The article reviews modern indomethacin medications and the different dosage forms on the Russian pharmaceutical market. Indomethacin poor water solubility is one of the reasons for decreasing its biopharmaceutical characteristics. According to the conducted research, a prospective way to improve indomethacin solubility and bioavailability is the Solid Dispersion (SD) method. SDs are bi- or multicomponent systems consisting of the drug and the carrier. They are a highly dispersed solid phase of the drug or molecular-dispersed solid solutions with a partial formation of a variable composition complex and a carrier. The article provides a brief overview on different aspects of obtaining, investigating, and applying indomethacin SDs with various polymers.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The problem of childbearing in patients with myasthenia gravis (MG) is extremely important, since the disease most often affects women in the reproductive period. Has not yet been determined neither the prognostic criteria for myasthenia exacerbation during pregnancy, nor the predictors for the development of the transient neonatal myasthenia gravis (TNM). The article analyzes the literature data from the first descriptions of pregnancy in patients with myasthenia and TNM until the present days. The evolution of the concept of the role of a high titer of antibodies to acetylcholine receptors (anti-AChR Ab) in the development of exacerbations of MG in the mother and TNM in her newborn is shown. The role of Ab against γ-subunits of AChR in the development of arthrogryposis and THM is discussed. The importance of planning the pregnancy in myasthenic mothers is emphasized. These observations show that the same woman has either a favorable course of MG with the birth of a healthy child, or has a severe exacerbation until the postpartum myasthenic crisis with the birth of baby with TNM depending on quality of remission before pregnancy. Based on the literature data and own experience, the indisputable role of thymectomy in the prevention of exacerbations of MG and TNM is shown. Own observation of cases of TNM demonstrates the crucial role of neostigmine test in the recognizing of «floppy baby» syndrome. For the first time in Russia, a study of anti-fetal/anti-adult AChR Ab ratio in the umbilical cord blood was conducted. For the first time in the world, a unique case of the birth of a healthy child in a couple of patients with juvenile MG is presented. The husband suffering of the severe refractory MG with elevated titre of anti-AChR Ab up to 20.8 nmol/l and a lot of congenital stigmas of dysembryogenesis. The wife had a mild course of MG. She was carefully prepared for pregnancy by thymectomy and glucocorticoid-therapy and had a stable condition for more than 10 years at the time of pregnancy. The titer of anti-AChR Ab was relatively low (9.0 nmol/L), however, the pool of anti-AChR Ab in the umbilical cord blood mainly contained anti-fetal AChR AB (92%). This example shows that it is the quality of remission of the mother's MG at the time of pregnancy determines the course of the disease during pregnancy and the risks of TNM. This case allows us to consider genetic factors as secondary and once again emphasizes the autoimmune nature of myasthenia gravis.

© 2018 Ima-Press Publishing House. All rights reserved. Chronic cerebral ischemia (CCI) is one of the most common diagnoses in middle-aged and elderly patients in the practice of an outpatient neurologist. Unfortunately, the diagnosis of CCI in these patients is often established only on the basis of complaints of headache, dizziness, instability during walking, and lower mood. At the same time, other diseases that cause these symptoms are not diagnosed, patients do not receive treatment, which considerably worsens quality of life and leads to anxiety and depression. A variety of diseases, such as headache, peripheral vestibular vertigo, depression, Alzheimer's disease, and Parkinson's syndrome, are frequently hidden under the diagnosis of CCI. The leading neurological syndrome in CCI is cognitive impairment that can be both moderate and reach the level of dementia. Approximately 40% of patients with chronic cerebrovascular disease complain of headache that is usually caused by mixed primary headache. The management tactics for a CCI patient suffering from headache is aimed at treating primary headache, modifying vascular risk factors, and managing cognitive impairment. The paper discusses the use of choline alphoscerate in patients diagnosed with CCI.

© 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, Bionika Media Ltd. All rights reserved. Background. Hatching from the zona pellucida is one of the most important stages of human preimplantation embryo development and spontaneous hatching inability is one of the causes of implantation failure in assisted reproductive technology (ART) cycles. The use of mechanical integrity disorders or complete destruction of the zona pellucida (assisted hatching) can be an effective way to enhance the effectiveness of infertility treatment programs using ART techniques. Objective. To assess the results of ART programs depending on the performance and type of assisted hatching. Material and methods. The prospective cohort investigation enrolled 309 patients treated for infertility with in vitro fertilization (IVF). According to the type and performance of assisted blastocyst hatching, the patients were divided into 3 groups: 1) 106 patients undergoing laser hatching with partial removal of the zona pellucida; 2) 103 patients having pronase hatching with complete removal of the zona pellucida; 3) 100 patients with no assisted blastocyst hatching. The degree of maturity and the quality of oocytes and embryos were assessed; hatching was monitored using light microscopy. Results. The pregnancy rates were noted to be statistically higher in Group 1 than in Groups 2 and 3; the multiple pregnancy rates were significantly lower in Group 1. Conclusion. Complete zona pellucida removal is a new approach to assisted hatching, in which, firstly, there is no mechanical separation of the cells forming the embryo, and, secondly, there is a rapid contact with endometrial cells during implantation. This contributes to the reduction of the risk of monozygotic pregnancies during the transfer of one morphologically normal blastocyst, by enhancing the effectiveness of ART programs.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to determine the minimal and maximum volume of blood droplets freely falling from various droplet-forming surfaces and to characterize the specific morphological features of the resulting stains. The experiments were designed so that the blood droplets were allowed to fall down from the height of 10 cm to 1.5 m. The drop volume varied from 5 mcl to 134 mcl depending on the shape of the objects and the area of the droplet-forming surfaces. The size of the blood stains ranged from 0.4 to 2.4 cm. The stains of a smaller size were regarded as splashes while a stain resulting from the fall of a droplet having a volume greater than 200 mcl was considered to be a result of merging of several droplets and was termed «blood volume». The morphological features of the blood stains of different volume are described.

© Bionika Media Ltd. Objective. To evaluate the efficiency of methodological approaches to optimizing the care of pregnant women with gestational diabetes mellitus (GDM) under the present-day conditions of a progressive increase in the incidence of this disease in case of a specialized obstetric hospital. Materials and methods. The statistical data on the 2015–2016 activities of the Outpatient Department and the Maternity Department, Moscow City Clinical Hospital Twenty-Nine, were retrospectively analyzed. Results. GDM was diagnosed in two thirds of the pregnant women at more than 30 weeks’ gestation in primary outpatient care services. In the management of pregnant women with untimely detected GDM, the sensitivity of ultrasound fetometry using the specific markers of diabetic fetopathy (DF) was 65.5%. Programmed labor (PL) was one of the leading methods during childbirth. Conclusion. Ultrasound fetometry using specific markers for DF and the strict continuity of outpatient and inpatient care permitted the frequency of DF to be reduced about 1.5-fold. The use of PL methods in GDM contributed to a two-fold decrease in the cesarean delivery rate without deteriorating the perinatal outcomes of labor.

© 2018 by the authors. Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. There are limited data on the efficacy of long-term enzyme replacement therapy (ERT) in children with mucopolysaccharidosis (MPS). Objective. Our aim was to study the efficacy and safety of long-term ERT in children with MPS type I, II and VI. Methods. We analyzed the results of ERT with laronidase, idursulfase and galsulfase in children with MPS type I, II and VI admitted to the federal research center from January 2007 to November 2016. The response rate was assessed by the level of normalized urinary excretion of glycosaminoglycans (GAGs) (the ratio of GAGs concentration to urine creatinine) recalculated in percent (%) exceedance of the upper limit of normal for the corresponding age. Data on the administered therapy and its results, including adverse events, is extracted from the medical records of in-patients. Results. The results of treatment (intravenous infusions, intervals between administrations from 4 to 10 days) were studied in 33 children (5 of them were girls) with MPS type I (n =4; laronidase at a dose of 0.58 mg/kg), II (n =26; idursulfase at a dose of 0.5 mg/kg), and VI (n =3; galsulfase at a dose of 1 mg/kg). A decrease in the normalized urinary excretion of GAGs from 376% (172; 791) to 54% (0; 146) exceedance of the upper limit of normal for the age (p <0.001) was noted in the course of ERT lasting (median) 27 (14; 41) months. A decrease in the normalized GAGs excretion below the upper limit of normal for the age was established in 12/33 (36%) patients. ERT-associated adverse events were identified in 12 patients; one case required a two-fold therapy interruption. The development of nephrotic syndrome in the course of ERT in patients with severe MPS II was first described. Conclusion. Long-term ERT in children with MPS type I, II and VI is characterized by acceptable efficacy and safety.

© 2018, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.  Modifiers of membranes cause local defects on the cell surface. Measurement of the rigidity at the sites of local defects can provide further information about the structure of defects and mechanical properties of altered membranes. The purpose of the study: a step-by-step study of the process of a nonlinear deformation of red blood cells membranes under the effect of modifiers of different physico-chemical nature. Materials and methods. The membrane deformation of a viscoelastic composite erythrocyte construction inside a cell was studied by the atomic force spectroscopy. Nonlinear deformations formed under the effect of hemin, Zn 2+ ions, and verapamil were studied. Results. The process of elastic deformation of the membrane with the indentation of a probe at the sites of local defects caused by modifiers was demonstrated. The probe was inserted during the same step of the piezo scanner Δz displacement; the probe indentation occured at the different discrete values of Δh, which are the functions of the membrane structure. At the sites of domains, under the effect of the hemin, tension areas and plasticity areas appeared. A mathematical model of probe indentation at the site of membrane defects is presented. Conclusion. The molecular mechanisms of various types of nonlinear deformations occurring under the effect of toxins are discussed. The results of the study may be of interest both for fundamental researchers of the blood cell properties and for practical reanimatology and rehabilitology.

© 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 Media Sphera Publishing Group. All Rights Reserved. The characteristics of mortality in the Russian Federation are that the greatest years of potential life lost are due to deaths among 50-60-year-old men. Objective - to investigate the characteristics of nutrition patterns in a sample of 41-44-year-old Moscow residents with overweight and obesity, by taking into account the role and significance of overweight in the development of cardiovascular diseases and events. Material and methods. Actual nutrition was evaluated according to the special computer program 1C. Value of Nutrition through a 24-hour dietary recall, by applying a special food atlas. A constructed mathematical model and tables of the chemical composition of nutrients were used to obtain information about the energy value of a diet and the pattern of nutrition. Results. A total of 301 men aged 41-44 years were examined. 38.3% of them were overweight. 29% of the men were found to be obese; 83 (28.6%) men had abdominal overweight. Comparative analysis showed that overweight and obese persons consumed statistically significantly more protein and total fat than normal weight ones and people with abdominal obesity ate more saturated fats and cholesterol. There was a paradoxical decrease in the intake of simple and complex carbohydrates with increases in both weight and waist circumference. Conclusion. The findings can be used to improve methods for nutrition assessment and differentiated technology for overweight correction in primary health care facilities.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. The article is focused on the issues of clinical efficacy of telmisartan - angiotensin II type 1 receptor blocker from the perspective of its influence on cardiovascular risk in systemic hypertension patients. The results presented, of a variety of studies, witnessing potent antihypertensive and protective properties of telmisartan. The opportunities described, for usage of the drug in high risk patients, its efficacy in cardio- and nephroprotection. Special attention is paid for an exclusive property of telmisartan to be an agonist of PPAR γ-receptors, hence to correct glucose and lipid metabolism in patients with metabolic syndrome and diabetes.

© 2018 Media Sfera. All Rights Reserved. Purpose: to assess the neurophysiological effect and clinical effectiveness of transcranial direct current stimulation in combination with drug therapy in amblyopic children. Material and methods. The study involved 32 healthy children in the age of 5-12 years and 97 patients of the same age with refractive strabismic amblyopia. All study subjects underwent standard examination including ophthalmological (visometry, refractometry in normal conditions and in cycloplegia, biomicroscopy, ophthalmoscopy, type of vision), neurophysiological methods (determination of retinal electric sensitivity threshold, electric lability of optic nerve, amplitude and latency period of visual evoked potentials, electroencephalogram wave amplitudes, localization of peak electrical activity area of the cerebral cortex), assessment of neuropsychic development and estimation of mental development coefficient with age tests. Results. Dynamics of neurophysiological parameters shows that healthy children develop fully functional retina, visual cortex and cortical-subcortical connections by 12 years. Children with refractive strabismic amblyopia in all age groups show statistically significant (p<0.05) deterioration of neurophysiological parameters of the visual analyzer, retardation of corticalsubcortical connections formation and lower electrical activity of the cerebral cortex. Amblyopic children show lower coefficients of mental development accompanied by intellectual deficiency and deterioration of learning ability. Proposed treatment method improved neurophysiological parameters of the visual analyzer in 83.5% of cases and increased visual acuity in 81.4% of cases. Improvement of psychological development resulted in better logical thinking, memory reinforcement and better adaptation to school educational environment in 86.6% of children.

The paper deals with the mechanisms of a T-cell immune response, which depends on the balance between costimula-tory and coinhibitory signals that have been called as immune checkpoints (ICP). The imbalance of T-cell activation within ICTs (CTLA4/CD28 and PD1/PD1L) is considered to be a fundamental mechanism not only of autoimmune disease, but also impaired antitumor immunity underlying the development of malignant tumors. The use of monoclonal antibodies against negative regulatory ICTs (CTLA4, PD1, and PD1L) is a major achievement in the treatment of malignant neoplasms in the early 21st century. However, since CTLA4 and PD1 control the activation of auto-reactive T cells, the inhibition of these ICTs is associated with the development of autoimmune disease that is defined as immune-mediated adverse even. The paper considers the clinical manifestations of IMAR, primarily rheumatic ones and discusses the prospects of pharmacotherapy from the standpoint of achievements of modern rheumatology.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to determine the biological age of the unrecognized individuals based on the analysis of CT-scanograms of the skull and the craniovertebral region in the sagittal projection. We investigated the structure of the spongy substance of the clinoid plate of the sella turcica and the clivus of the cranium, involution of the vertebrae configuration in the medial atlantoaxial articulation, frontal and sphenoidal sinuses. A total of 80 skulls of Caucasoid individuals at the age ranging from 4 to 84 years belonging to an Eastern Slavonic population (free from the pathological lesions in the above cranial structures) were available for the examination. The results of the multifactorial analysis gave evidence of the possibility to estimate the age of individual subjects based on the comprehensive aggregate qualitative and quantitative characteristic in the framework of the linear regression model by making use of the age-related changes in the frontal and sphenoidal sinuses, the sella turcica and the clivus of the cranium, the first and the second cervical vertebrae with an accuracy to within 6 years. It is concluded that the application of the systems for the automated statistical analysis of the images for the purposes of forensic medical expertise would allow to obtain the results of great practical and scientific value.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to elucidate the characteristic features of the injuries inflicted to the victims of a road traffic accident inside the passenger compartment of a moving car equipped with the modern personal safety systems. The materials available for the present work included the lesions documented in 210 drivers and 150 occupants of the car passenger compartments. Both comparative, morphometric and statistical methods were used to analyze the data obtained. The morphometric analysis included identification of the form of the injury, such as extravasation, wounds, fractures, and lesions of the internal organs (e.g. hemorrhages, ruptures, etc.), their number and localization. Special attention was given to the specific features of the injuries to the occupants of the cars equipped with the modern personal safety systems. The study has demonstrated that the form, frequency, and localization of the injuries inflicted to the victims of a road traffic accident inside the passenger car compartment (including the drivers and other occupants) can be used for determining the positions of the victims at the moment of the accident.

© 2018 Media Sphera Publishing Group. All rights reserved. The detection of grade II-III central obesity on a corpse in conjunction with the identification of two additional criteria (such as arterial hypertension and impaired glucose tolerance) provides, if combined with the autopsy data (including the visual reduction of muscular mass, the increased total amount of the adipose tissue, gynecomastia in men together with hypertrophied abdominal adipose tissue accumulation, decreased face and body pilosis), a basis for diagnostics of metabolic syndrome (MS). The objective parameters for this purpose are waist circumference measurements, corpse weight and height, the degree of visceral obesity, narrowing of the renal arteries as a result of their compression by the surrounding adipose tissue, and accumulation of epicardial fat confirmed by the results of the biochemical analysis. The signs of plasmorrhagia combined with fibrinoid degeneration of the vascular walls in the microcirculatory bed make it possible to suspect, with a high degree of probability, the development of hypertensive crisis that may result in a sudden death of the patients presenting with metabolic syndrome.

© 2018 Media Sphera Publishing Group. All rights reserved. This article presents an overview of the literature publications concerning pathological changes in the cerebral blood vessels and the factors underlying the development of hemorrhagic complications leading to sudden death of young people. The special emphasis is placed on the most important causes behind the changes in the vascular wall (including the congenital ones) responsible for the high risk of rupture of the intracerebral vessels associated with the development of hemorrhagic complications.