Репозиторий Университета

© 2018 Elsevier Ltd The use of materials based on protein-polymer compositions is a promising method for solving a number of problems in biotechnology and medicine. In our work, we produced multilayer nanofilms based on 4th generation (G4) pyridylphenylene dendrimers with fully pyridine-based periphery containing a protein component. For dairy beta- and kappa-caseins, alpha-lactalbumin, recombinant sheep prion protein, lysozyme, trypsin, and alpha-chymotrypsin the ability to integrate into self-organizing structures about 230–710 nm thick, measured by atomic force microscopy, was found. The formation of nanofilms is dependent on the protein/dendrimer ratio in the initial solution. At the same time, the nanofilms are resistant to pH changes, and the action of detergents. We demonstrated that trypsin and chymotrypsin incorporated into the nanofilms still conserved proteolytic activities and were stable for at least 3 weeks. We have also conducted in silico molecular modeling of the G4 dendrimer interactions with lysozyme. Spatial structure of the dendrimer-protein complex was predicted and most probable variant remained almost intact under 100 ns molecular dynamics simulation conditions. We believe that dendrimer-protein systems are promising tools for possible applications in the development of new stable biomaterials and biosensors.

© 2018 Tkacheva et al. Background: Geriatric syndromes (GSs) are common in older adults and have a significant effect on their quality of life, disability, and use of health care resources. Few studies have assessed the prevalence of GSs in Russia. The aim of this study is to assess the prevalence of GSs among older adults living in the community in Moscow. Methods: A cross-sectional study was conducted in four community clinics in Moscow. A total of 1,220 patients completed a screening questionnaire, and 356 of them also underwent a comprehensive geriatric assessment (CGA). Results: The mean age of the 1,220 participants was 74.9±6.1 years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous year), and 12.2% weight loss. The mean number of GSs per patient was 2.9±1.5. Based on CGA, a decline in Instrumental Activity of Daily Living score was identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional Assessment score, 17–23.5) in 25.8%, probable cognitive impairment (Mini-Mental State Examination score <25) in 8.6%, and symptoms of depression (15-item Geriatric Depression Scale score >5) in 36.2%. On the whole, patients demonstrated good mobility (average walking speed, 1±0.2 m/s) and hand grip strength (23.9±6.4 kg in women and 39.1±8.3 kg in men), but poor balance (only 39.4% were able to maintain their balance on one leg for 10 s or more). Conclusion: The results of this study demonstrate a high prevalence of GSs among community-dwelling people aged 65 years and older in Moscow. The results provide a better understanding of the needs of older adults in Russia and can facilitate planning for medical and social assistance for this population.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The aim of the present work was to study the topographic anatomical characteristics of the intervertebral canal. Studies were performed using 37 anatomical preparations including 185 intervertebral canals in section complexes of the of the cervical segment of the spines of people dying at age 58–78 years. Histological investigations were performed using 32 preparations of ligamentous structures. Five pairs of true intervertebral canals were identified in segments C2–C7. The mean parameters of intervertebral canals were: length 1.46–2.0 mm; outer opening 0.8–1.4 mm; inner opening 0.4–0.8 mm. Histological studies confirmed data showing that the structures observed were ligaments, with diameters ranging from 0.1 to 0.3 mm and length from 0.4 to 0.6 mm. Intervertebral canals could be divided into three groups: those with clearly defined true ligaments (46%), ligaments with additional false ligaments (fibrotic bands) compressing the spinal nerve (43%), and canals without ligaments but with bony and fibrotic protuberances compressing the spinal nerve (11%).

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The possible interchangeability of eye drops was analyzed using glaucoma medicines containing latanoprost as examples. It was shown that the reference and generic drugs could be identical with respect to composition of active ingredients when manufactured from the same pharmaceutical substance but could differ in the excipient composition, in particular, have a different buffer and osmolality that could produce differences in their clinical effects. An analysis of the literature showed that the therapeutic efficacy and safety could vary for pharmaceutically equivalent drugs. The lack of therapeutic equivalence on the background of pharmaceutical equivalence could be caused by the use of different packaging and different dosing systems. Therefore, results from clinical trials must be compared to confirm the interchangeability of eye drops.

© 2018 The Authors. Objective: This study was conducted to evaluate the use of genetic tests, before prescribing drugs to reduce not only the level of side effects but also the costs associated with changing therapy. In this paper, the authors analyze the economic efficiency of HLA*5701 prospective screening of hypersensitivity to abacavir (ABC) in the treatment of HIV-infected patients. Methods: A retrospective study was conducted among HIV-infected patients taking first-line antiretroviral therapy and further, based on the results obtained with the ABC-hypersensitivity reactions, analyzed the costs that affect on healthcare system. Results: In the study group of HIV-infected patients, most of the cases belonged to a young, socially active part of the population. Among the study population of patients (n=637), 171 patients were assigned ABC-containing antiretroviral therapy. An increase in costs was found in 67% of cases when ABC-containing first-line therapy was replaced due to the occurrence of undesirable reactions. Conclusion: The results show that, using this screening, we could reduce the costs associated with replacement therapy.

© 2018 International Pediatric Research Foundation, Inc. BackgroundSurgical treatment for gastroschisis and congenital diaphragmatic hernia (CDH) commonly leads to abdominal compartment syndrome (ACS) associated with hypoxic renal injury. We hypothesized that measurement of urinary and serum concentrations of vascular endothelial growth factor (VEGF), π €-glutathione S-transferase (π €-GST), and monocyte chemoattractant protein-1 (MCP-1) may serve for noninvasive detection of hypoxic renal injury in such patients.MethodsIntra-abdominal pressure (IAP), renal excretory function, and the biomarker levels were analyzed before, 4, and 10 days after surgery. Association between the biomarker levels and renal histology was investigated using an original model of ACS in newborn rats.ResultsFour days after surgery, IAP increased, renal excretory function decreased, and the levels of VEGF, π €-GST, and MCP-1 increased, indicating renal injury. Ten days after surgery, IAP partially decreased, renal excretory function completely restored, but the biomarker levels remained elevated, suggesting the ongoing kidney injury. In the model of ACS, increase in the biomarker levels was associated with progressing kidney morphological alteration.ConclusionSurgical treatment for gastroschisis and CDH is associated with prolonged hypoxic kidney injury despite complete restoration of renal excretory function. Follow-up measurement of VEGF, π €-GST, and MCP-1 levels may provide a better tool for noninvasive assessment of renal parenchyma in newborns with ACS.

© 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.

Copyright © 2017 John Wiley  &  Sons, Ltd. Stress urinary incontinence (SUI) significantly diminishes the quality of patients' lives. Currently available surgical and nonsurgical therapies remain far from ideal. At present, advances in cellular technologies have stirred growing interest in the use of autologous cell treatments aimed to regain urinary control. The objective was to conduct a review of the literature and analyse preclinical and clinical studies dedicated to various cell therapies for SUI, assessing their effectiveness, safety, and future prospects. A systematic literature search in PubMed was conducted using the following key terms: “stem,” “cell,” “stress,” “urinary,” and “incontinence.” A total of 32 preclinical studies and 15 clinical studies published between 1946 and December 2014 were included in the review. Most preclinical trials have used muscle-derived stem cells and adipose-derived stem cells. However, at present, the application of other types of cells, such as human amniotic fluid stem muscle-derived progenitor cells and bone marrow mesenchymal stromal cells, is becoming more extensive. While the evidence shows that these therapies are effective and safe, further work is required to standardize surgical techniques, as well as to identify indications for their use, doses and number of doses. Future research will have to focus on clinical applications of cell therapies; namely, it will have to determine indications for their use, doses of cells, optimal surgical techniques and methods, attractive cell sources, as well as to develop clinically relevant animal models and make inroads into understanding the mechanisms of SUI improvement by cell therapies.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Polyphenolic compounds (flavonoids) of lyophilized aqueous extracts from Caragana jubata (Pall.) Poir. raw material from 2010 and 2015 were studied using modern HPLC-DAD-MS. Primarily mono- and diglycosides of O-hydroxylated (myricetin, quercetin, kaempferol) and O-methylated flavonols (isorhamnetin, laricitrin, syringetin) were identified. Long-term storage of dried raw material under standard conditions had little effect on the quantitative content of polyphenolic compounds. Acute toxicity studies of C. jubata extract showed no toxicity.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Validation results for a spectrophotometric quantitative determination method for ormustine in a lyophilized dosage form are presented. The method is shown to be suitable for quantitative determination of ormustine with respect to parameters such as specificity, linearity, accuracy, repeatability, and intermediate precision.

© 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, Springer Science+Business Media B.V. Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism’s interaction with its environment. Such staggering multilevel diversity in manifestation of senescence precludes (without methodology of systems biology) development of a correct understanding of its primary causes and does not allow for developing approaches capable of postponing ageing or reducing organisms’ ageing rate to attain health preservation. Moreover, it turns out that damage production and damage elimination processes, the misbalance of which results in the ageing process, can to a large extent be regulated by external signals. The purpose of this report is to provide evidence supporting this view and its compatibility with the regularities of mortality statistics, because the main idea is very simple. Even potentially a non-senescent but certainly not immortal body must start to age under inadequate conditions (like a non-melting piece of ice taken out from the deepfreeze inevitably start to melt at the temperatures above zero Celsius). This conclusion is totally consistent with existing patterns of mortality and with agelessness potential of somatic stem cells. Therefore, there is no need to build up and explore too complicated, computational and sophisticated systems models of intrinsic ageing to understand the origin of this mainly extrinsic root cause of natural ageing, which is controlled by environmental signals. In our case, a simple phenomenological black-box approach with Input–Output analysis is ample. Here Input refers to the environmentally dependent initial force of mortality, whereas Output is a rate of age-related increase of mortality force.

© 2017, Springer Science+Business Media, LLC. Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its’ analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2′:6′,2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10−6 and 10−5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2′:6′,2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2′:6′,2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.

© 2018 Astro Ltd. This paper describes a new approach to the fabrication of superconducting nanowire single-photon detectors from ultrathin NbN films on SiO2 substrates. The technology is based on nonlinear femtosecond optical lithography and includes direct formation of the sensitive element of the detector (the meander) through femtosecond laser exposure of the polymethyl methacrylate resist at a wavelength of 525 nm and subsequent removal of NbN using plasma-chemical etching. The nonlinear femtosecond optical lithography method allows the formation of planar structures with a spatial resolution of ∼50 nm. These structures were used to fabricate single-photon superconducting detectors with quantum efficiency no worse than 8% at a wavelength of 1310 nm and dark count rate of 10 s-1 at liquid helium temperature.

© 2018 The Authors. We studied minor variants within two tick-borne encephalitis virus (TBEV) populations with a common ancestor: the mouse brain-adapted variant EK-328c and the tick-adapted variant M. High-throughput sequencing with custom amplicons from RTPCR viral RNA was performed on Illumina MiSeq 2*250 paired-end v2 chemistry. Using the LowFreq program (default settings) and Sanger-sequenced consensus as a reference, variants with an abundance of 1% and above within the studied populations were identified. Using the obtained data in the context of our previous studies, we concluded that TBEV variants, which are different from the major population phenotype and can become a major part of the viral population under favourable environmental conditions, can exist at abundances of less than 1% in the long-term. The comparison of our data with the literature allowed us to conclude that the laboratory variant EK-328c and variant M have similar SNV counts to TBEV variants from natural populations and some fast-evolving RNA viruses.

© Microscopy Society of America 2018. Radiation therapy, widely used in the treatment of a variety of malignancies in the pelvic area, is associated with inevitable damage to the surrounding healthy tissues. We have applied atomic force microscopy (AFM) to track the early damaging effects of ionizing radiation on the collagen structures in the experimental animals' bladder and rectum. The first signs of the low-dose radiation (2 Gy) effect were detected by AFM as early as 1 week postirradiation. The observed changes were consistent with initial radiation destruction of the protein matrix. The alterations in the collagen fibers' packing 1 month postirradiation were indicative of the onset of fibrotic processes. The destructive effect of higher radiation doses was probed 1 day posttreatment. The severity of the radiation damage was proportional to the dose, from relatively minor changes in the collagen packing at 8 Gy to the growing collagen matrix destruction at higher doses and complete three-dimensional collagen network restructuring towards fibrotic-type architecture at the dose of 22 Gy. The AFM study appeared superior to the optical microscopy-based studies in its sensitivity to early radiation damage of tissues, providing valuable additional information on the onset and development of the collagen matrix destruction and remodeling.

© 2018 The Union. BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE : To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity. METHODS : TNFR1/2 levels on peripheral blood mononuclear cells (PBMCs) from 45 patients with aPTB and 150 healthy controls were analysed by flow cytometry using monoclonal antibodies and QuantiBRITE beads. Soluble TNFR1/2 and TNF-α in serum were measured using an enzyme-linked immunosorbent assay. RESULT S : TNFR1 expression in aPTB patients was increased in the main populations of immune cells. Patients who were Mycobacterium tuberculosis culturepositive on bronchoscopy had higher levels of the soluble forms of TNFR1 (sTNFR1) than M. tuberculosisnegative patients. CONCLUS ION: Active TB was shown to cause activation of different immune cell types by increasing TNFR1 expression on cells and reducing sTNFR1 expression compared with healthy controls. M. tuberculosis-positive patients with disseminated infection had the highest sTNFR1 serum level compared with other patients, but did not differ in receptor expression on PBMCs.

© 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 The Authors. Diabetes, Obesity and Metabolism published by John Wiley  &  Sons Ltd. Aim: To investigate determinants of change in glycated haemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM) at 6 months after initiating uninterrupted second-line glucose-lowering therapies. Materials and Methods: This cohort study utilized retrospective data from 10 256 patients with T2DM who initiated second-line glucose-lowering therapy (switch from or add-on to metformin) between 2011 and 2014 in Germany and the UK. Effects of pre-specified patient characteristics on 6-month HbA1c changes were assessed using analysis of covariance. Results: Patients had a mean (standard error [SE]) baseline HbA1c of 8.68% (0.02); 28.5% of patients discontinued metformin and switched to an alternative therapy and the remainder initiated add-on therapy. Mean (SE) unadjusted 6-month HbA1c change was −1.27% (0.02). When adjusted for baseline HbA1c, 6-month changes depended markedly on the magnitude of the baseline HbA1c (HbA1c <9%, −0.45% per unit increase in HbA1c; HbA1c ≥9%, −0.87% per unit increase in HbA1c). Adjusted mean 6-month HbA1c reductions showed slight treatment differences (range, 0.92–1.09%; P <.001). Greater reductions in HbA1c were associated with second-line treatment initiation within 6 months of T2DM diagnosis (1.36% vs 1.03% [P <.001]) and advanced age (≥70 years, 1.13%; <70 years, 1.02% [P <.001]). Conclusions: Many patients with T2DM have very high HbA1c levels when initiating second-line therapy, indicating the need for earlier treatment intensification. Patient-specific factors merit consideration when making treatment decisions.