Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A validated method for quantitative determination of flupirtine in human blood plasma using liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) was proposed. Biological samples were prepared by precipitating proteins using MeOH. The chromatographic separation used a Zorbax Eclipse Plus C18 column with gradient elution. A Shimadzu 8040 triple quadrupole mass spectrometer in multiple-reaction-monitoring mode (+MRM) with chemical ionization at atmospheric pressure (APCI) was used to determine the molecular ion of flupirtine with m/z 305.2. Acalibration curve for flupirtine was linear (R = 0.994) in the concentration range 25 – 2,500 ng/mL with a lower detection limit of 25 ng/mL. Validation of the method indicated that it was highly sensitive, specific, accurate, and precise and that the analyte was stable. The method was successfully applied to comparative pharmacokinetic studies of drugs containing flupirtine.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Experimental validation of the method for regulation of stem cell proliferation and differentiation is carried out. The method consists in exposure to ultrahigh frequency electromagnetic radiation, modulated by infralow frequencies with variable parameters. A specially designed programmer, setting up the parameters of exposure, is connected to the source of radiation. The zones of anatomical location of the red bone marrow of rats were exposed for 15 min to the amplitude-modulated electromagnetic radiation of ultrahigh frequency range. The parameters of exposure were determined in previous studies. The red bone marrow was collected from the sternum and head of the femur. The cellular composition of the red bone marrow was evaluated 1, 2, 3, and 6 days after the exposure. The optimal therapeutic mode of irradiation was then chosen, leading to stem cell activation with subsequent proliferation and differentiation into mature red bone marrow cells.

© Springer Science+Business Media, LLC 2017.  Sandwich enzyme-linked immunosorbent assay (ELISA) of sulfonamides based on double-competitive interaction between haptenized protein as a captured antigen and analyte for binding to immobilized and enzyme-labeled antibodies was developed. This experimental assay format was examined in analytical properties and matrix effect resistance in comparison with usual ones: indirect, direct antigen-coated and antibody-coated ELISAs. All four assay formats were designed on the basis of interactions between the previously prepared monoclonal antibody and immunizing hapten, 4-(4-(4-aminophenylsulfonamido) phenyl)butanoic acid, providing the uniform output optical signal for correct comparison of each assay characteristic. The sensitivity (IC 50 ) of the developed competitive sandwich assay was rather below 100 ng/ml for 11 sulfonamides which was suitable for their determination in milk, muscles and animal sera at established maximum residue limit concentration. Comparative examination did not reveal changes in assay specificity, and advantages in sensitivity, matrix effect resistance, and procedure duration before commonly used assay formats. Moreover, new design of assay was shown to be three-fold more consumable in antibody reagents in comparison with direct assay formats.

© 2017, Springer Science+Business Media New York. Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay. Our results indicated that hMSCA-CM improved cell viability, reduced nuclear fragmentation, attenuated the production of reactive oxygen species, and preserved mitochondrial membrane potential and ultrastructural parameters. In addition, hMSCA-CM upregulated neuroglobin in T98G cells and the genetic silencing of this protein prevented the protective action of hMSCA-CM on damaged cells, suggesting that neuroglobin is mediating, at least in part, the protective effect of hMSCA-CM. Overall, this evidence suggests that the use of hMSCA-CM is a promising therapeutic strategy for the protection of astrocytic cells in central nervous system (CNS) pathologies.

© 2017 Elsevier B.V. A novel ternary intermetallic germanide CeIrGe2 has been studied by means of x-ray diffraction, magnetization, specific heat and electrical resistivity measurements, performed in wide ranges of temperature and external magnetic fields. The compound crystallizes in an orthorhombic structure of the CeNiSi2-type (space group Cmcm). It exhibits a Kondo lattice behavior and orders antiferromagnetically at 4 K.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The pharmacokinetics, bioequivalence, and safety of Femorix®(Valenta Pharm Co., Russia) and Aubagio®(SanofiWinthrop Industrie, France) film-coated tablets (14 mg) were compared in a double-blind randomized investigation in parallel groups of healthy volunteers. The bioavailabilities of Femorix®film-coated tablets (14 mg, Valenta Pharm Co., Russia) were 96.18% [87.92 – 105.22%] for ln(Cmax) and 96.24% [88.67 – 104.44%] for ln(AUC0–72) of those for Aubagio®film-coated tablets (14 mg, Sanofi Winthrop Industrie, France), which fell in the commonly accepted range (80 – 125%) for proving the bioequivalence of the tested products.

© 2017 Elsevier Ltd The novel cerium germanide Ce2IrGe3 was studied by means of x-ray diffraction, magnetic, electrical transport and heat capacity measurements. The compound was found to crystallize with slightly disordered hexagonal structure of Ce2CoSi3-type. The experimental results revealed that Ce2IrGe3 is a ferromagnetic-like Kondo lattice that orders at TC=4K.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley  &  Sons Ltd. Aims: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence-based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade. Materials and Methods: Systematic searches for articles published from January 1, 2004 to August 1, 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form. Results: The final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low- to middle-income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta-analysis. Conclusions: Therapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low- and middle-income countries, in view of their high prevalence of type 2 diabetes.

© 2017 Informa UK Limited, trading as Taylor  &  Francis Group. Background: Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria. Methods: We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety. Results: We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG. Conclusion: The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments’ future recommendation in selected patients.

© 2018 Paediatrician Publishers, LLC. All Rights Reserved. The article provides the characteristic of a tumor from cells of cartilaginous tissue - chondroblastoma. Current data on etiology, key links of pathogenesis, types of tumor, General clinical manifestations, approaches to diagnosis and treatment in children are analyzed.

Under the modern market conditions, the process of development of the methods for the combined rehabilitation of the patients is becoming increasingly more complicated. For the reduction of potential risks and leveling the factors responsible for the uncertain market situation influencing the creation of new methods, it is necessary to carry out the full-scale pilot studies with the use of the marketing analysis methods. The objective of the present work was to create and elaborate the rationale for the graphological structure (the scheme) of the process of exploratory research with a view to the development of the combined rehabilitation methods as exemplified by phyto- and physiotherapeutic modalities. The work is based on the application of the existing approaches to the structural, comparative, systemic, and situational analyses. The proposed graphological structure (scheme) of the exploratory research process consists of 6 stages. Its distinctive features are as follows: a fractional stage by stage evaluation of a variety of issues including the study of physical factors, characteristic of the means of herbal medicine with special reference to the mechanisms of their production and application under the current market conditions, monitoring the marketing environment with the constant focus on the trends and behavior of the target market, the parallel pursuing of serial studies with the application of the iterative procedures; the use of the previously created data bank to expand medical services at the stages of development and maturation of the life cycle, the evaluation of the possibility of establishment of the industry of parapharmaceutical products.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To determine vitamin D status in children with rheumatic disease who live on the territory of Russia. Patients and methods. A pilot study was conducted that included 52 children (35 girls and 17 boys) aged 5 to 17 years (11.88 ± 0.48 years), among them 29 children with systemic connective tissue disorders (SCTD) and 23 children with juvenile idiopathic arthritis (JIA). All patients underwent complex clinical-laboratory and instrumental examination in order to confirm the diagnosis and assess the patients’ health. Vitamin D status was assessed by 25(ОН)D serum levels using the method of chemiluminescence immunoassay. Results. Sufficient levels of 25(ОН)D (>30 ng/l) were found only in 5 (9.5%) children, vitamin D insufficiency (25(ОН)D 21–30 ng/l) was observed in 6 (11.5%) children, deficiency (25(ОН) <20 ng/l) in 41 (79.0%) children, among them in 7 (13.4%) it was severe (25(OH)D <10 ng/l), in spite of a long-term intake of low-doses of cholecalciferol (100–400 U/day) by 40 (76.9%) patients. Average levels of 25(ОН)D in patients with SCTD were significantly higher than in patients with JIA (20.86 ± 2.15 ng/l vs. 14.98 ± 0.91 ng/l, p = 0.0151), deficiency was more rarely found in these patients (69.0% vs. 91.3%), which was to a certain degree conditioned by more intensive vitamin D therapy. Conclusion. Insufficiency/deficiency of vitamin D is noted in an overwhelming majority of children with RD. Standard therapy with low doses of cholecalciferon offered to patients with RD is not sufficient for obtaining optimal 25(ОН)D levels and needs correction.

© 2018, Dynasty Publishing House. All rights reserved. At present the incidence rates of urogenital chlamydiosis maintain the leading positions among sexually transmitted infections. Special attention to this infection is conditioned by a high risk for development of complications on the part of the reproductive system in both women and men. The ability of Chlamydia to affect various tissues accounts for a broad spectrum of clinical manifestations of urogenital pathologies: urethritis, vulvovaginitis, cervicitis, endometritis, salpingitis, epididymitis, prostatitis, proctitis, and also extragenital forms of disease. Taking into account a possibility of transition of Chlamydia infection into a latent stage with subsequent development of a chronic persisting course, early and adequate management of infection is of considerable importance. Etiotropic therapy of Chlamydia infection employs antibacterial drugs capable of penetrating into cells. Tetracycline antibiotics are the most effective drugs of choice administered as part of complex therapy. Minolexin is a tetracycline antibiotic that demonstrates the best effectiveness in the fight against infectious agents affecting the urogenital tract. The article presents the author’s clinical experience of using minolexin for management of urogenital chlamydiosis in 60 patients.

© 2018 Cardiovascular Therapy and Prevention. Modern appropriate treatment of hypertension involves the use of combination antihypertensive therapy. According to updated version of European Society of Cardiology 2018 guidelines, renin-angiotensinaldosterone system blockers must be used as first-line drugs, including in combination with hydrochlorothiazide. This article presents the algorithms for the management of patients with uncomplicated and asymptomatic (with target lesions) arterial hypertension. It also described the management of patients with concomitant cardiovascular, cerebrovascular, renal pathology and diabetes mellitus, and use of fixed combination of candesartan and hydrochlorothiazide. The article presents research data that confirmed not only the high antihypertensive efficacy of this combination, but also demonstrated its neutral metabolic profile, organ-protective effects, the ability to use in patients with chronic kidney disease, chronic heart failure, prior stroke, as well as high tolerability and treatment adherence.

© 2018 Media Sphera Publishing Group. All rights reserved. Aim. To perform a comparative analysis of anemia of chronic disease (ACD) and iron-deficiency anemia (IDA) in late middle-aged and elderly patients with chronic heart failure (CHF) by ferrokinetic parameters, inflammation indexes, and their associations. Materials and methods. 65 patients with ischemic heart disease were evaluated, including 35 patients with CHF and ACD, 10 patients with CHF and IDA, and 20 patients without CHF, ACD, and IDA (control group, CG). Results. Patients with CHF and IDA had true iron deficiency whereas 54% of patients with CHF and ACD had functional iron deficiency, and 46% of patients had no iron deficiency. Levels of acute phase proteins, ferritin and hepcidin, C-reactive protein (CRP), and interIeukin-6 (IL-6) were highly sig-nificantly different in patients with CHF and ACD and patients with CHF and IDA; positive and significant correlations were found for levels of IL-6 and ferritin, IL-6 and CRP, and CRP and hepcidin. In patients with CHF and IDA, levels of acute phase proteins, ferritin and hepcidin, CRP, and IL-6 were low and correlations of IL-6 with ferritin, IL-6 with CRP, and CRP with hepcidin were non-significant. Concentrations of erythropoietin were significantly higher in patients with CHF and ACD and patients with CHF and IDA compared to the control group; however, significant differences between them were absent.

© 2018 Russian Association of Endocrinologists. All rights reserved. Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists. The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week.

© 2018, Media Sphera Publishing Group. All rights reserved. Objective. To study the effect of сavinton comforte (CC) on the severity of cognitive impairment and motor awkwardness in patients with chronic brain ischemia (HIGM). Material and methods. There were 30 patients (8 men, 22 women) aged 50—65 years (61.6±4.9 years on average) with AHU with cognitive impairment. We used tests of MINI-Cog, Munsterberg, TMT), ADL). QC appointed 10 mg 3 times a day for 3 months. Results. Against the background of therapy, the improvement of constructive praxis and short-term memory, an increase in the speed of visual search and visual-motor function, an increase in the level of selectivity of attention, an improvement in the reproduction of visual images and perception, an increase in the speed of the motor task (drawing strokes). Conclusion. The obtained data can testify about the improvement of indicators of function of a small motility of brushes on the background of improvement of cognitive functions.

© 2018 Pirogov Russian National Research Medical University. All rights reserved. Mathematical modeling of pharmacokinetic (PK) and pharmacodynamic (PD) parameters essential for establishing correct dosing regimens is an alternative to pharmacokinetic studies (PKS) adopted in the clinical setting. The aim of this work was to compare the values of PK parameters for vancomycin obtained in an actual PKS and through MM in postoperative patients with kidney injury. Our prospective study included 61 patients (47 males and 14 females aged 60.59 ± 12.23 years). During PKS, drug concentrations at steady state Сtrough and Cpeak were measured by high-performance liquid chromatography followed by the calculation of the area under the plasma concentration-time curve AUC24. For mathematical modeling, a single-compartment model was employed; PK parameters were estimated using R 3.4.0. The values of Ctrough measured 48 h after the onset of antibiotic therapy during PKS were significantly lower than those predicted by MM (р = 0.004). In a group of patients with acute kidney injury (AKI), AUC24 measured at the end of treatment was significantly higher than its value predicted by MM (р = 0.011). The probability of achieving the target AUC24 to MIC ratio of over 400 µg•h /ml is higher in the group of patients with Ctrough = 10–15 µg /ml. Our findings confirm that the use of MM in postoperative patients with renal dysfunction is limited and therapeutic drug monitoring should be used instead.

© 2018 Russian Electronic Journal of Radiology.All right reserved. In plastic surgery we often have the need for soft tissue volume restoration of different localization, to close congenital or acquired defects as well as associated with agerelated changes in soft tissue. Autologous adipose tissue in many properties is the ideal filler for the correction of the body contour defects. However, despite its advantages, this minimally invasive technique has been secondary to more complex methods of reconstruction - flap transplantation. The main significant drawback of fat grafting is the unpredictable and ineffective survival of transplanted fat (20 to 60%, according to different authors). Currently, factors that can influence the degree of survival of adipose tissue and make it more predictable are being actively studied, in particular, the effect of Leucocyte and Platelet Rich Plasma (L-PRP). Purpose: To prove the stability of transplanted adipose tissue survival with the addition of L-PRP in breast surgery via multispiral computed tomography (MSCT) with the calculation of resorption rate of adipose tissue before transplantation in the early and in late postoperative stages. Materials and methods: In the period from 2013 to 2016, a total of 48 patients underwent surgery at the plastic surgery clinic in I.M. Sechenov First Moscow State Medical University. All patients complained of dissatisfactory appearance of the breast. Patients underwent breast lipofilling in order to correlate contour deformities. Monitoring of adipose autografts consisted of the following methods: MSCT was performed in 12 cases (5 patients after transplantation of pure adipose tissue and 7 patients after transplantation of adipose tissue enriched with L-PRP). Results: The study of the sample volumes and thickness of soft tissues after the transplantation was performed both with and without the addition of L-PRP. A steady increase in the soft tissue thickness in the breast region was revealed and an increase in volume was noted in the main group. At the same time, in patients of the control group three months after surgery a decrease in the volume and thickness of the breast soft tissues was revealed. Conclusions: The results of the study show that the improvement of breast contour after transplantation of adipose tissue both with and without the addition of L-PRP provides a steady increase in the thickness and volume of breast soft tissues. The average loss of adipose tissue after transplantation ranges from 11.62% to 17.13%. The results also confirm that MSCT is an adequate method of visualization of adipose autografts and volumetric changes in the late postoperative period.