Репозиторий Университета

© 2018 Elsevier GmbH Anabolic androgenic steroids (AASs) are synthetic analogs of testosterone often used by athletes to increase the skeletal muscle mass. Our goal was to examine the effects of physical activity and physical activity combined with supraphysiological doses of nandrolone on functional morphology of the quadriceps muscle. The study included 32 peripubertal Wistar rats, divided into 4 groups: control (T-N-), nandrolone (T-N+), physical activity (T+N-) and physical activity plus nandrolone (T+N+) groups. The T+N- and T+N+ group swam for 4 weeks, 1 h/day, 5 days/week. The T-N+ and T+N+ groups received nandolone decanoate (20 mg/kg b.w.) once per week, subcutaneously. Subsequently, the rats were sacrificed and muscle specimens were prepared for the processing. Tissue sections were histochemically and immunohistochemically stained, while the image analysis was used for quantification. Longitudinal diameter of quadriceps muscle cells was increased for 21% in T-N+, for 57% in T+N- and for 64% in T+N+ group while cross section muscle cell area was increased in T-N+ for 19%, in T+N- for 47% and in T+N+ group for 59%, compared to the control. Collagen fibers covered area was increased in T-N+ group for 36%, in T+N- for 109% and in T+N+ group for 159%, compared to the control. Erythrocyte depots were decreased in T-N+ group and increased in T+N- and T+N+ group, in comparison with T-N-. VEGF depots were increased in all treated groups. Chronic administration of supraphysiological doses of AASs alone or in combination with physical activity induces hypertrophy and significant changes in the quadriceps muscle tissue structure.

© 2017, Springer-Verlag GmbH Germany, part of Springer Nature. In this article, we present an optimized minimally invasive technique of ETV for children with occlusive hydrocephalus. The study comprises of 64 consecutive pediatric cases (34 boys and 30 girls aged from 1 month to 5 years) of occlusive hydrocephalus from various etiologies, which were treated with a modified technique of ETV. Mean clinical follow-up period after ETV was 24.2 ± 3.8 months. Application of the new technique made it possible to significantly reduce the length of the soft tissue incision for access, and the use of upgraded instruments allowed to perform a twist drill hole in the skull to less than half a usual size. Access to the brain and lateral ventricle was performed by blunt trephination of the dura without the need for significant corticectomy or coagulation, and yielded minimal damage to the brain, which is very important in patients of young age. Continued endoscopic control during the approach down to the lateral ventricle increases safety and decreases risk of injury, and can be performed in cases of pathologies affecting the anatomical relationships of the lateral and third ventricle. Mortality in our cohort was 0%, and there were no postoperative neurological, endocrinological, or infectious complications. Patency rates of the first ETV performed was 78%, with the remaining patients requiring additional surgical procedures for complicated settings. This new technique of minimally invasive ETV placement in pediatric patients is an effective and safe method to treat occlusive hydrocephalus and can be recommended for extensive clinical use.

© 2017 The mitochondrial membrane potential (ΔΨm) generated by proton pumps (Complexes I, III and IV) is an essential component in the process of energy storage during oxidative phosphorylation. Together with the proton gradient (ΔpH), ΔΨm forms the transmembrane potential of hydrogen ions which is harnessed to make ATP. The levels of ΔΨm and ATP in the cell are kept relatively stable although there are limited fluctuations of both these factors that can occur reflecting normal physiological activity. However, sustained changes in both factors may be deleterious. A long-lasting drop or rise of ΔΨm vs normal levels may induce unwanted loss of cell viability and be a cause of various pathologies. Among other factors, ΔΨm plays a key role in mitochondrial homeostasis through selective elimination of dysfunctional mitochondria. It is also a driving force for transport of ions (other than H+) and proteins which are necessary for healthy mitochondrial functioning. We propose additional potential mechanisms for which ΔΨm is essential for maintenance of cellular health and viability and provide recommendations how to accurately measure ΔΨm in a cell and discuss potential sources of artifacts.

© 2018, International Journal of Pharmaceutical Quality Assurance. All rights reserved. Filipendula ulmaria (L.) Maxim. (Meadowsweet) is known in traditional medicine as anti-inflammatory, wound-healing, astringent and antibacterial remedy. However recent studies show that it also has neurotropic activity. In Russia meadowsweet flowers are used as crude herbal drugs (temporary pharmacopoeial monograph 42-1777-87), also leafs and herb are used in the traditional medicine. Objective of the study was to carry out comparative investigation of composition and content of major biologically active compounds (BAC) in Filipendula ulmaria herb, flowers and leafs by thin-layer chromatography, differential spectrophotometry with aluminum chloride reagent (total flavonoids in terms of rutoside), gravimetry (total extractives, extracted by water), permanganatometric titration (total tannins in terms of tannin). Rutoside, tannin, gallic acid and salicylic acid were identified in Filipendula ulmaria herb, flowers and leafs by TLC. Also we analyzed content of substances extracted by water, flavonoids and tannins. Total extractives, extracted by water in F. ulmaria herb is 13.12±0.10%, in leafs - 13.98±0.37%, in flowers - 18.09±0.17%. Total tannins in F. ulmaria herb is 11.87±0.47%, in leafs - 12.06±0.18%, in flowers - 12.26±0.29%. Total flavonoids in F. ulmaria herb 4.34±0.17%, in leafs - 6.98±0.23%, in flowers - 11.75±0.57%. The obtained data will be used for development of a pharmacopoeial monograph project “Filipendula ulmaria (L.) Maxim., herba” for inclusion in the State Pharmacopoeia of the Russian Federation.

© 2018, Allerton Press, Inc. The effect of medium pH and ion strength on the thermal stability of formate dehydrogenases (EC 1.2.1.2, FDH) from model plant Arabidopsis thaliana (AthFDH) and soybean Glycine max (SoyFDH) are studied. The dependence of the residual activity on time is described by the kinetics of the reaction of the first order in all the experimental conditions. The dependence of the first order thermal inactivation constants on phosphate buffer concentration has the form of a bell-shaped curve. It was found that an increase in the pH value resulted in an increase and decrase of inactivation rate constans for SoyFDH and AthFDH, respectively. The activation parameters of the thermal inactivation process, ΔH≠ and ΔS≠ are calculated from the experimental data at different medium pH values and phosphate buffer concentrations.

© 2018, Pleiades Publishing, Ltd. To construct constitutive equations for hyperelastic materials, one increasingly often proposes new strain measures, which result in significant simplifications and error reduction in experimental data processing. One such strain measure is based on the upper triangular (QR) decomposition of the deformation gradient. We describe a finite element method for solving nonlinear elasticity problems in the framework of finite strains for the case in which the constitutive equations are written with the use of the QR-decomposition of the deformation gradient. The method permits developing an efficient, easy-to-implement tool for modeling the stress–strain state of any hyperelastic material.

© 2018, The Author(s). Purpose of Review: The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy. Recent Findings: AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life. Summary: Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.

© 2018 John Wiley  &  Sons Australia, Ltd This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.

© 2017 Wiley Periodicals, Inc. Colorectal cancer (CRC) has become the fourth leading cause of cancer-related death in the worldwide. It is urgent to find more effective therapeutic strategies for it. Reactive oxygen species (ROS) play multiple roles in normal cellular physiology processes. Thus, a certain level of ROS is essential to keep normal cellular function. However, the accumulation of ROS shows dual roles for cells, which is mainly dependent on the concentration of ROS, the origin of the cancer cell and the activated signaling pathways during tumor progression. In general, moderate level of ROS leads to cell damage, DNA mutation and inflammation, which promotes the initiation and development of cancer. Excessive high level of ROS induces cancer cell death, showing an anti-cancer role. ROS are commonly higher in CRC cells than their normal counterpart cells. Therefore, it is possible that ROS induce cell death in cancer cells while not affecting the normal cells, demonstrating lower side effects. Besides, ROS also play a role in tumor microenvironment and drug resistance. These multiple roles of ROS make them a promising therapeutic target for cancer. To explore potential ROS-target therapies against CRC, it is worth to comprehensively understanding the role of ROS in CRC and therapy. In this review, we mainly discuss the strategies of ROS in CRC therapy, including direct CRC cell target and indirect tumor environment target. In addition, the influences of ROS in drug resistance will also been discussed.

© 2017 Elsevier Inc. The mitochondrial set of proteins is a dynamic system, crucial for multiple functions of this organelle. Differential expression of genes in various tissues, alternative splicing, post-translational modifications, turnover and spatial dynamics of proteins are the factors that influence mitochondrial proteomes increasing their versatility. A wide range of high-throughput proteomic approaches are extensively used for identification, quantification and functional assessment of human and other mammalian mitochondrial proteins. This article reviews the methods and approaches which can be utilized for achieving one or another specific goal in mitochondrial investigations, and the recent advances in application of proteomics to study the roles of mitochondria in tumorigenesis and cancer progression.

© The Author(s) 2018. Purpose: To review our experience with peripherally inserted central catheters in pediatric cancer patients. Methods: The analysis included 353 patients (3 months up to 17 years, mean age 11.2 years) with a variety of cancers diseases, which in 2011–2016, 354 peripherally inserted central catheters were placed. All settings are carried out using ultrasound guidance. In 138 (39%) patients, external anatomical landmarks were used and in 216 (61%) intraoperative fluoroscopy. Results: Maximal duration of the line was 1.3 years, the lowest 1.5 months, and average 6.3 months. Among the technical difficulties during placement, most frequently have been the migration of the distal end of the catheter into the internal jugular vein against blood flow—32 (9%) patients. In one (0.3%) case, we were unable to catheterize the patient’s vein. Among the most common complications of operation were marked peripherally inserted central catheter clot occlusion of the lumen—26 (7.3%) cases. Symptomatic catheter-related thrombosis was observed in 16 (4.5%) cases. Catheter-related blood stream infections were not reported. Removal of peripherally inserted central catheters related to the complications was performed in 30 (8.5%) patients who were later implanted venous ports. Conclusion: Peripherally inserted central catheters are recommend to use in the treatment of children with cancer. There should be trained nursing staff to minimize the risk of complications.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Results from experiments conducted for the parameter Residual Organic Solvents during the course of developing a draft regulation for the drug substance of the innovative pharmacological agent thrombaptanib are reported. The structure of the compound is given. Its pharmacological action is described. A list of potential residual organic solvents was compiled by analyzing the synthetic scheme and manufacturing technology. A separate part of the work describes in detail a developed GC-MS procedure for determining residual organic solvents. Validation results of the procedure for Specificity, Linearity, Accuracy, Precision, and Reproducibility are presented. The validation protocol for the procedure at the time of the studies followed domestic guides for validation that were written based on existing international documents because there was no existing GPM for validation in the current edition of the SP RF. A test sample of thrombaptanib was analyzed using the developed procedure for Residual Organic Solvents. The developed procedure was included in the Residual Organic Solvents section of the draft regulation.

© 2018 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim While noninvasive prenatal testing based on cell-free fetal DNA has recently revolutionized the field of aneuploidy screening in pregnancy, it remains limited to aneuploidy and microdeletion screening, and is unable to reliably detect single gene disorders. A number of recent studies have demonstrated the potential of circulating trophoblastic cells in providing cell-based noninvasive diagnosis with sequencing or array-based assays. However, considering the extreme rarity of these cells in blood, efficient, high-throughput, and clinically applicable enrichment technologies are yet to be developed. This study demonstrates for the first time the utility of inertial microfluidics for efficient isolation of trophoblastic cells from maternal peripheral blood. Under optimal operating conditions, high-recovery yields (79%) are obtained using a trophoblastic cell-line, which is subsequently confirmed with analysis of maternal blood. Feasibility of obtaining a diagnosis from cells isolated from a maternal sample is demonstrated in a case of confirmed fetal trisomy 21 in which six fetal cells are found in a 7 mL blood sample using fluorescence in situ hybridization. Finally, it is demonstrated that trophoblastic cells isolated using inertial microfluidics could be picked and subjected to a clinically validated sequencing assay, paving the way for further validation of this technology and larger clinical studies.

© 2018 The Author(s). Stress is integral to tumour evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activates the bioenergetic sensor AMP kinase (AMPK) and, to survive, tumour cells hijack an AMPK-regulated stress response pathway conserved in normal cells. Analysis of The Cancer Genome Atlas data revealed that AMPK isoforms are highly expressed in the lethal human cancer glioblastoma (GBM). We show that AMPK inhibition reduces viability of patient-derived GBM stem cells (GSCs) and tumours. In stressed (exercised) skeletal muscle, AMPK is activated to cooperate with CREB1 (cAMP response element binding protein-1) and promote glucose metabolism. We demonstrate that oncogenic stress chronically activates AMPK in GSCs that coopt the AMPK-CREB1 pathway to coordinate tumour bioenergetics through the transcription factors HIF1α and GABPA. Finally, we show that adult mice tolerate systemic deletion of AMPK, supporting the use of AMPK pharmacological inhibitors in the treatment of GBM.

© 2018 Elsevier B.V. Development of efficient biodegradable, environmentally responsive, biocompatible and non-toxic delivery system is needed for efficient gene delivery. As well known, properties of the vehicle are determined by the structure of carrier components. The aim of the current study was to estimate in vitro transfection efficacy of aliphatic di-, tri- and tetrapeptide-based cationic lipoplexes loaded with siRNA in function of a number of cationic groups using 2D (monolayer culture) and 3D (multicellular tumor spheroids) in vitro models. Physicochemical properties and cytotoxicity of the liposomes were found to be dependent upon a number of amino acid derivatives in an amphiphilic polar head. Uptake of liposomes loaded with nucleic acid (lipoplexes) and their localization in HEK293T cells was studied by confocal microscopy. The liposomes based on lipotripeptides had the highest transfection efficiency which was 20-fold higher than those fabricated from lipotetrapeptides.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature.  New composite materials of collagen with electrical conductivity up to 6.1•10 –4 S cm –1 were obtained using colloidal dispersions of polyvinylpyrrolidone-stabilized graphene.

© 2018 IEEE. In this paper, we propose a computational approach for description of radiation transfer in a quasi-ordered medium and study the impact of scattering on electromagnetic wave propagation and image formation. It combines finite-difference time-domain method, Monte Carlo simulations, and radiative transfer theory. Using, as an example, terahertz (THz) imaging, we analyze the modulation transfer function (MTF) of the imaging system operated at 0.25 THz for scattering material layers placed between the object and the imaging plane. We experimentally study imaging of bar-pattern test objects through a quasi-ordered scattering medium. Both numerical and experimental results are in good agreement and demonstrate an impact of quasi-ordered scatterers on quality of THz images, i.e., particular combination of the electromagnetic wavelength and parameters of scattering materials could enhance MTF compared with ones with random particle structures.

© 2018 Elsevier Ltd  Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca 2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners. All four NCS proteins co-fractionate with caveolin-1 in DRMs, isolated from illuminated bovine rod outer segments. According to pull-down assay, surface plasmon resonance spectroscopy and isothermal titration calorimetry data, they are capable of high-affinity binding to either N-terminal fragment of caveolin-1 (1–101), or its short scaffolding domain (81–101) via a novel structural site. In recoverin this site is localized in C-terminal domain in proximity to the third EF-hand motif and composed of aromatic amino acids conserved among NCS proteins. Remarkably, the binding of NCS proteins to caveolin-1 occurs only in the absence of calcium, which is in agreement with higher accessibility of the caveolin-1 binding site in their Ca 2+ -free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca 2+ -saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca 2+ -free conformation. In addition, the interaction with caveolin-1 decreases cooperativity and augments affinity of Ca2 + binding to recoverin apparently by facilitating exposure of its myristoyl group. We suggest that at low calcium NCS proteins are compartmentalized in photoreceptor rafts via binding to caveolin-1, which may enhance their activity or ensure their faster responses on Ca 2+ -signals thereby maintaining efficient phototransduction recovery and light adaptation.

© 2018, Pleiades Publishing, Ltd. Different methods have been proposed for the incorporation of a dye, vanadyl tetra-5,14,23,32-phenyl-2,3-naphthalocyanine, into the shells of polyelectrolyte capsules. Capsule preparation conditions have been selected to provide efficient incorporation of the dye and stability of capsules to aggregation. A suspension of the capsules has been irradiated with lasers operating at wavelengths belonging to the near-infrared spectral region. It has been found that the capsules can be disrupted under the irradiation. Continuous and pulsed laser radiations have been shown to have different effects on the capsules.