Репозиторий Университета

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review article considers the modern notions about glucocorticoid hormones. Particular attention is paid to their molecular mechanisms of action, with emphasis on the importance of studying new compounds of the group of selective modulators of glucocorticoid receptors.

© Bionika Media Ltd. Objective. To carry out a systems analysis of the data available in the current literature on the pathogenesis, therapy, and prevention of vaginal infections caused by the pathogens of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The paper highlights the main pathways of pathogenesis and the causes of recurrent vaginal coinfection. It describes methods for the treatment of women with BV and VVC and presents the optimal therapy and prevention schemes for recurrent vaginal infectious diseases, which have evidence-based effectiveness. Conclusion. The features of a microbial portrait and immune status predispose to recurrent BV and VVC, the presence of which results in coinfection. The cause of the latter is also repeated therapy for recurrent monoinfection. First-line therapy for BV is recognized to include metronidazole and clindamycin; the advantages of the latter are a wider spectrum of activity against the microorganisms that are difficult to identify. To treat coinfection and to prevent VVC in patients with BV, it is advisable to use fluconazole that also remains a first-line treatment option for vaginal infection caused by Candida albicans.

© 2018 Ima-Press Publishing House. All rights reservbed. Objective: to study of the individual aspects of the relationship and interaction of menstrual and generative function and depressive disorders in women. Patients and methods. 120 women aged 18-65 years with recurrent depressive disorder (RDD) who had experienced at least two depressive episodes (a study group) and 120 mentally healthy women of the same age (a control group) were clinically examined using a specially designed map with subsequent statistical processing of the findings. Results and discussion. In 71.7% of women, depression manifests itself during hormonal rearrangement periods (puberty, postpartum, and menopause). 65.0% of women with RDD have premenstrual syndrome (PMS), the pattern of which shows depressive symptoms. Depression affects menstrual function: the later onset and irregularity of menstruation, the earlier restoration of menstrual function after childbirth, and the earlier onset of premenopause, which has an adverse impact on generative function (a reduction in the number of pregnancies, births, and babies). Depression, the onset of which is observed during puberty, exerts the most malignant effect on menstrual and generative function. Overall, depressive patients are less socially and family-friendly than healthy women. Menstrual and generative function and adaptation minimally suffer in women with postmenopausal depression. Conclusion. The onset of depressive disorders is associated with the hormonal rearrangement periods. The presence of depressive symptoms in the pattern of PMS is a prognostic sign of future depression or indicates partial remission. At the same time, menstrual function is impaired in women suffering from RDD, which along with psychic manifestations of depression (a decrease in sexual drive and contacts, as well as anesthesia of feelings, etc.) leads to infertility.

© 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 Meditsina Publishers. All rights reserved. The spread of a latent tuberculosis infection - 2.3 billion people - is of emergency importance for the global task of mankind - to eliminate tuberculosis as a common disease by 2035. For children, due to the limited use of the radiological diagnosis methods, the main methods today are the immunological tests for the detection of tuberculous infection. The most common used method is the tuberculin skin test (Mantoux test) due to its lack of specificity has significant drawbacks, especially in countries using mass BCG vaccination. Relatively new methods using specific recombinant MTB proteins, both in vitro tests and in new skin tests, allow to determine tuberculosis infection in latent or active form much more specifically, however, they are somewhat less sensitive, in comparison with the Mantoux test, which requires development of these methods with the introduction of new additional specific antigens. It is obvious that crucial task is the development of new methods for distinguishing active and latent tuberculosis infection or being able to predict progression from latent to active TB diseases both in children and in adult population. The article shows new diagnostic techniques of blood cells and plasma samples based on the use of flow cytometry with the detection of antigen-specific T-cells producing interferongamma and tumor necrosis factor alpha, T-cells specific markers, as well as using combinations of the identification of various protein factors that have the prospect to determining active tuberculosis infection signs. However, these methods are still time-consuming and expensive. Currently, some new promising approaches based on the using of new genetically engineered products are being developed to determine specific antibodies in the blood serum. With the development of accelerated methods for the analysis of the expression of specific genes in blood cells, this direction also has the prospect of introducing into healthcare practice.

© 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 Dynasty Publishing House. All rights reserved. A systematic review substantiates the significance of mutual influence and interaction between infection pathogens, humoral and cell-mediated innate immunity that condition triggering or termination of infectious process, its prodromal period, severity of clinical manifestations and outcomes of urogenital infections in pregnant women. The determining factor is the result of TLRs response to microbial patterns taking into account the preparedness and state of innate immune receptors. The latter might ensure a higher anti-infection resistance to the pathogen up to termination of disease, or to promote the development of infectious process with marked inflammatory reaction, or to make the infectious process chronic up to damaging the tissue cells of the macroorganism. The understanding of the mechanisms of natural anti-infectious resistance and enhanced sensitivity and susceptibility to infectious agents has been objectified. TLRs act as molecular genetic markers of anti-infection resistance of the body and its state of health.

© 2018 Media Sfera. All rights reserved. The article reviews development mechanisms of different refractive errors accompanied by marked defocus of light rays reaching the retina. Terminology used for such ametropias includes terms extreme, ultra-high and complicated. Justification of their usage for primary ametropias, whose symptom complex is based on changes in axial eye length, is an ongoing discussion. To comply with thesaurus definitions of «diagnosis» and «pathogenesis», to characterize refractive and anatomical-functional disorders in patients with primary ametropias it is proposed to use the terms «hyperaxial and hypoaxial syndromes» with elaboration of specific symptoms instead of such expressions as extreme (ultra-high) myopia and hypermetropia.

© 2018 Media Sfera. All rights reserved. Bioinorganic chemical composition of the lens of human and experimental animals (cows, dogs, rats, rabbits) have been analyzed in various studies. In most cases, the studies employed different methods to determine the gross (total) composition of chemical elements and their concentrations in the examined samples. Less frequently, they included an assessment of the distribution of chemical elements in the lens and correlation of their concentration with its morphological changes. Chemical elements from all groups (series) of the periodic classification system were discovered in the lens substance. Despite similar investigation methods, different authors obtained contradicting results on the chemical composition of the lens. This article presents data suggesting possible correlation between inorganic chemical elements in the lens substance with the development and formation of lenticular opacities. All currently employed methods are known to only analyze limited number of select chemical elements in the tissues and do not consider the whole range of elements that can be analyzed with existing technology; furthermore, the majority of studies are conducted on the animal model lens. Therefore, it is feasible to continue the development of the chemical microanalysis method by increasing the sensitivity of Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS) with the purpose of assessing the gross chemical composition and distribution of the elements in the lens substance, as well as revealing possible correlation between element concentration and morphological changes in the lens.

© 2018 Ima-Press Publishing House. All rights reserved. Cranial dystonia is a common disease of the extrapyramidal nervous system. The clinical manifestations of dystonia are extremely variable; many of its forms are often undiagnosed. Dystonia is a sensorimotor disorder of the nervous system. Damage affects not only one structure, but also a network of the nodes interacting with each other in the somatosensory cortex and associative sensory and motor fields, which play a role in the integration of various sensory modalities coming from both outside the body and from the receptors within it. Botulinum toxin preparations show the highest efficacy in treating cranial dystonia. If their administration cannot achieve a positive result, oral drugs and surgical treatments should be used.

© Bionika Media Ltd. Objective. To carry out a systematic analysis of the data available in the current literature on the modern view on Trousseau’s syndrome Material and methods. The review included the data of foreign and Russian articles published in the past 10 years and found in e-Library and PubMed on this topic. Results. This paper provides a pathogenetic explanation for the increased thrombotic potential in cancer patients, which underlies tumor growth and metastasis. In addition to direct thrombotic events, the paper also describes hemorrhagic complications resulting from systemic coagulopathy, including disseminated intravascular coagulation, hemolytic thrombotic microangiopathy, and excessive fibrinolysis. Conclusion. At present, any manifestation of thrombohemorrhagic complications in patients with malignant tumors can be classified as a paraneoplastic syndrome (Trousseau’s syndrome). In addition to Virchow’s classic triad, hyperproduction of tissue factor (TF), the main initiator of the extrinsic coagulation pathway, underlies the pathophysiology of Trousseau’s syndrome. At the same time, the substantial release of microparticles from TF-bearing tumor cells is critical not only for clot formation, but also for the progression of tumor growth.

© 2018 Vitebsk State Medical University. All rights reserved. This clinical case demonstrates the development of severe streptococcal (Streptococcus pyogenes) necrotizing soft tissue infection as a result of perforation of the sigmoid neoplasm. The rapidly progressive necrotic process in the soft tissues of the lumbar and gluteal region as well as necrotic process in the left thigh (with the predominant lesion of the superficial fascia, subcutaneous fat and skin) led to the formation of an extensive postnecrectomic wound defect with an area of more than 1000 square centimeters. In addition to the severity of illness, the patient's belated treatment and the underestimation of the clinical situation by surgeons who provided emergency care contributed to such an extensive spread of the pathological process. The development of sepsis was accompanied by severe multiple organ failure. Because of the severity of the patient's condition, the surgical removal of the sigmoid neoplasm extended in the abdomen wall became possible only after its stabilization as a result of surgical focal sanation and complex intensive therapy in the conditions of the ICU. The most important point of the stage-by-stage surgical treatment was the choice of methods for the plastic closure of an extensive postnecrectomic wound that involved the entire left gluteal region, part of the lumbar and antero-inner surface of the left thigh. Taking into account the size and localization of the defect, the plastic reserves of the surrounding skin, the wound was closed in three stages with the help of combined plastic surgery techniques: with local tissues by the method of tissue expansion and a split-thickness skin graft.

© Rational Pharmacotherapy in Cardiology 2018. Background. Carriership of CYP4F2*3 (rs2108622, Val433Met) allelic variant can affect antiplatelet effect of clopidogrel, thus changing efficacy and safety of its standard dose. Aim. To study the impact of carriership of at least one CYP4F2*3 allele on the risk of resistance to clopidogrel in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Material and methods. The study enrolled 81 patients with ACS and PCI: 64 males and 17 females, mean age 63.9±10.9 years. CYP4F2 allelic variants were detected by the method of real-time polymerase chain reaction. Platelet functional activity was evaluated by a portative aggregometer - the VerifyNow P2Y12 assay. Results. Pharmacogenetic testing showed that 40 (49.4%) of ACS patients had normal genotype (CC), 38 (46.9%) patients were carriers of one associated with reduced drug metabolism allele (CT genotype), and 3 (3.7%) patients were homozygotes for T (TT genotype). Genotype and allele distribution was in the Hardy-Weinberg equilibrium (χ2=2.79; p=0.095). There were no statistically significant differences in CYP4F2*3 allele frequency between patients that are resistant to clopidogrel (PRU > 208) and in patients with a normal response to clopidogrel (PRU < 208): 36.8% vs 54.8% (p=0.17). Average platelet reactivity units (PRU) and average platelet inhibition (%) in patients with and without T allelic variant of CYP4F2 also were not significantly different: 165.34±51.03 PRU vs 174.8±51.06 PRU (p=0.407), respectively, and 29.51±21.59% vs 27.72±18.35%, respectively (p=0.69). Conclusion. Carriership of CYP4F2*3 allelic variant does not affect antiplatelet effect of clopidogrel in ACS patients. Further research on larger samples is needed to determine the role of CYP4F2 polymorphisms in personalization of clopidogrel antiplatelet therapy.

© Copyright 2018, Mary Ann Liebert, Inc. 2018. Background: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters. Methods: The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months. During the study period, Doppler ultrasound was performed weekly to assess the clot dynamics and recanalization time. Results: We found a direct statistically reliable correlation between CYP3A4 activity and both peak and trough rivaroxaban levels. A correlation was also found between the initial clot length and the time to full recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found between either the glomerular filtration rate and peak rivaroxaban concentrations or between CYP3A4 activity and the treatment effectiveness parameters. No connection between renal function and rivaroxaban concentration was established in our study, which agrees with the clinical trials data that allow unlimited rivaroxaban use in patients with glomerular filtration rate >30 mL/min. Conclusions: The direct link between the initial clot length and time to full recanalization that has been found means that patients with more advanced stages of thrombosis need more time to reach recanalization than their counterparts with a less severe condition.

Previously, atherosclerosis was considered a disease accompanied exclusively by lipids accumulation. At present time success of fundamental and experimental science confirmed that atherosclerotic process is also associated with neovascularization and prolonged inflammatory response at all stages of atherogenesis from initial manifestations to thrombotic complications. The cause of atherosclerotic plaque instability is neovascularization, which is accompanied by intra-plaque hemorrhage and damage. Complications of carotid arteries atherosclerosis are strokes and transient ischemic attacks. The use of a wide range of diagnostic and pathohistological techniques is required for assessing this pathology. The most promising diagnostic technique is Contrast Enhanced Ultrasonography (CEUS) which allows to assess neovascularization degree in atherosclerotic plaque through the injection of a contrast agents.

© 2018 S. Karger AG.All right reserved. Atypical hemolytic-uremic syndrome is a rare life-threatening disease from the group of thrombotic microangiopathies, caused by the hyperactivation of the complement system. In the most cases it is associated with genetic disorders in the cluster of complement genes. Currently, a large number of different variants of the complement system genes associated with the development of aHUS are described in different countries. In our country, data on the genetic features of pediatric aHUS patients and obstetric aHUS have been published. Genetic changes in the complement system in adult aHUS patients in Russia were not so far presented. Aim: studying the genetic profile of the complement system in adult patients with aHUS. Materials and methods. The study included 20 patients with aHUS: 9 men (45%) and 11 women (55%). All patients underwent molecular-genetic analysis (search for mutations in the clinically significant part of the human genome − exome) by sequencing (Genotek laboratory). Genes CFH, CFHR1-5, CFB, CFI, DGKE, THBD, MCP, C3, С5, ADAMTS13 were analyzed. Results. Genetic variants (mutations) of the complement system associated with aHUS development were detected in 5 patients (25%). Two patients had one mutation, 2 patients − 2 and one patient - 3 mutations. In 3 patients, different genetic variants of the C3 gene were found. Two patients showed the same changes in the CFHR5 gene. In 3 patients, rare changes in the ADAMTS-13 gene, clinically associated with the development of thrombotic thrombocytopenic purpura were found. In all 20 patients, genetic variants of the complement genes with unknown clinical significance were identified, including rare variants of the C3 gene in 9 patients (45%).

© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.  Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens ® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f 2 . Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f 2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f 2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f 2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

© 2018 American Leather Chemists Association. All rights reserved. The regenerative potential of biodegradable collagen matrix (hemostatic sponge) for healing full-thickness rabbit conjunctival injury was studied. Results of histological investigation and scanning electron microscopy showed evidence of the progressive degradation of collagen matrix followed by granulation tissue formation from periphery to the center of the conjunctival wound. The ungrafted conjunctival defect was substituted with granulation tissue from the intact edges of wound to the center. Both matrix-grafted and ungrafted full-thickness conjunctival defects were covered completely with loose stroma and stratified squamous epithelium within 30 days. Thus, high regenerative potential of biodegradable collagen matrix (hemostatic sponge) implanted into the zone of injury for healing full-thickness defect of rabbit conjunctiva was established.

© 2018, Media Sphera Publishing Group. All rights reserved. Objective. To compare release parameters of various betahistine drugs in vitro using a comparative dissolution kinetics test. Material and methods. Objects of research are solid dosage forms (tablets) containing betahistine in a dose of 24 mg permitted for medical use in the Russian Federation. A method of comparative dissolution kinetics test was carried out as follows. The study was performed on a paddle stirrer at a speed of 50 rpm in three different pH dissolution media (pH 1.2, 4.5, 6.8), simulating the main sections of the digestive tract in which the active ingredient was decomposed, released and absorbed. This was performed in a quality controlled environment using a citrate buffer solution with pH 6.8. The time points for sampling the medium were 10 min, 15 min, 20 min and 30 min. Results. The results of betahistine release were significant (RSD<10%) for all time points, except the first time point (RSD<20%). Regardless of pH, there was a complete release (≥85% over 15 minutes, <10%) of betahistine from betaserc, 24 mg, tablets (manufactured by Mylan Laboratories SAS). The dissolution profiles of betahistine in other investigational drugs did not show complete drug release (parameter <85% in 15 minutes, <10%) in different pH media. Therefore, dissolution profiles of the studied drugs were not comparable to the reference profile. Conclusion. Starting from 10 minutes, the reference drug of betahistine (be taserc, 24 mg) has a consistently higher release at different pH levels (representing the various stages of gastric digestion), vs. other studied generic analogues showing significantly lower levels of betahistine release. None of the studied drugs were found to be equivalent in vitro.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Tumour necrosis factor alpha inhibitors are widely used in the treatment of juvenile idiopathic arthritis (JIA). To achieve maximum efficiency of genetically engineered biologic drugs, it is necessary to study predictors of the response to therapy. Objective. Our aim was to identify early predictors of the response to adalimumab therapy in patients with JIA without systemic manifestations. Methods. A prospective cohort study analysed treatment results of patients with JIA without systemic manifestations, who were prescribed adalimumab for the period from August 2008 to August 2014. We studied the relationship between baseline demographic indicators as well as baseline and registered after one month of treatment clinical and laboratory parameters and the best (remission according to the Wallace criteria) response to therapy after one year. Results. In the first year of therapy, 94 (43.9%) of 214 patients achieved remission according to the Wallace criteria. In a multivariate analysis, predictors of achieving remission after one year of adalimumab therapy were the improvement according to the ACR70 criterion after one month of therapy [odds ratio (OR) 3.3; 95% confidence interval (CI) 1.7-6.7], a history of uveitis (OR 1.86; 95% CI 1.03-3.33), a decrease in the number of joints with active arthritis after one month of therapy (OR 1.09; 95% CI 1.02-1.16). During therapy, injection reactions in the form of pain were observed in 36 (16.8%) of 214 patients, infectious diseases of ENT organs - in 85 (39.7%), of the respiratory tract - in 17 (7.9%), and tubinfection - in 13 (6.1%) children. Conclusion. The presence of uveitis, rapid reduction in the number of joints with active arthritis and a high level of response to treatment after one month of adalimumab therapy are predictors for achieving remission during the first year of treatment.