Дослідження морфофункціональних особливостей розвитку експериментальних металонефропатій = The study of morphofunctional features of the development of experimental metallonephropathy

Gozhenko A. I., Lugovskoy S. P., Samokhina N. A. Дослідження морфофункціональних особливостей розвитку експериментальних металонефропатій = The study of morphofunctional features of the development of experimental metallonephropathy. Journal of Education, Health and Sport. 2016;6(4):287-296. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.50201http://ojs.ukw.edu.pl/index.php/johs/article/view/3473 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015).755 Journal of Education, Health and Sport eISSN 2391-8306 7© The Author (s) 2016;This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, PolandOpen Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License(http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercialuse, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 20.03.2016. Revised 17.04.2016. Accepted: 17.04.2016. ДОСЛІДЖЕННЯ МОРФОФУНКЦІОНАЛЬНИХ ОСОБЛИВОСТЕЙ РОЗВИТКУ ЕКСПЕРИМЕНТАЛЬНИХ МЕТАЛОНЕФРОПАТІЙ  А. І. Гоженко, С. П. Луговський, Н. А. Самохіна  Державне підприємство «Український науково-дослідний інститутмедицини транспорту МОЗ України», м. Одеса, Украина РезюмеПроведені експериментальні дослідження щодо тривалого впливу солей кадмію, ртуті, свинцю в дозі 1/50 від DL50 на нирки показали, що важливим аспектом їх дії є зміна показників азотистого обміну, яка проявлялась підвищеним вмістом креатиніну, сечовини та сечової кислоти в сироватці крові, а також високим вмістом білку в сечі. Характерною ознакою ураження нирок є зниження швидкості клубочкової фільтрації, яка визначалась при дії всіх трьох досліджуваних нефротоксикантів: при дії Cd – зниження на 23,6 %, при дії Pb – на 22,1 %, при дії Hg – 28,9 %. Морфологічні дослідження дозволили встановити нові факти, щодо морфологічної характеристики токсичної дії неорганічних сполук Cd, Hg, Pb, які полягають у здатності металів викликати цитопатичну дію на окремі клітини структурних елементів нефрону. Провідним механізмом розвитку експериментальних металонефропатій є ураження епітелію проксимальних канальців нирок, яке зумовлено вибірковим порушенням клітинних мембран, мітохондрій і лізосом епітелію проксимальних канальців нефрону.Ключові слова: важкі метали, нирки, металонефропатії, креатинін, сечовина, білок, швидкість клубочкової фільтрації, гістологічне дослідження нирок, канальцевий апарат, епітеліоцити. THE STUDY OF MORPHOFUNCTIONAL FEATURES OF THE DEVELOPMENT OF EXPERIMENTAL METALLONEPHROPATHY A. I. Gozhenko, S. P. Lugovskoy, N. A. Samokhina  Ukrainian Scientific and Research Institute of Transport Medicine, Odessa SummaryEexperimental studies of prolonged exposure of cadmium salts, mercury, lead in the dose of from 1/50 DL50 on the kidney have shown that an important aspect of their actions is the change of indicators of nitrogen metabolism, which was manifested by increased creatinine, urea and uric acid in serum and high urine protein excretion. A characteristic feature of renal disease is the decline in glomerular filtration rate, which was defined when all three of the studied nephrotoxicants: under the Cd decrease by 23,6 %, under the action of Pb - 22,1 %, under the action of Hg – 28,9 %. Morphological studies revealed new facts concerning the morphological characteristics of toxic action of inorganic compounds of Cd, Hg, Pb, which lies in the ability of metals to cause cytopathic effect on individual cells of the structural elements of the nephron. The main mechanism for the development of experimental metallonephropathy is the damage to the epithelium of the proximal tubules of the kidneys, due to a selective disturbance of cellular membranes, mitochondria and lysosomes in the epithelium of the proximal tubules of the nephron.Key words: heavy metals, kidneys, metallonephropathy, creatinine, urea, protein, glomerular filtration rate, and histological examination of the kidneys, tubular apparatus, the epithelial cells. ИССЛЕДОВАНИЕ МОРФОФУНКЦИОНАЛЬНЫХ ОСОБЕННОСТЕЙ РАЗВИТИЯ ЭКСПЕРИМЕНТАЛЬНЫХ МЕТАЛЛОНЕФРОПАТИЙ  А. И. Гоженко, С. П. Луговской, Н. А. Самохина Украинский НДИ медицины транспорта, г.Одесса РезюмеПроведенные экспериментальные исследования длительного воздействия солей кадмия, ртути, свинца в дозе 1/50 DL50 на почки показали, что важным аспектом их действия является изменение показателей азотистого обмена, которое проявлялось повышенным содержанием креатинина, мочевины и мочевой кислоты в сыворотке крови, а также высоким содержанием белка в моче. Характерным признаком поражения почек является снижение скорости клубочковой фильтрации, которая определялась при действии всех трех исследуемых нефротоксикантов: при действии Cd – снижение на 23,6 %, при действии Pb – на 22,1 %, при действии Hg – 28,9 %. Морфологические исследования позволили установить новые факты, относительно морфологической характеристики токсического действия неорганических соединений Cd, Hg, Pb, которые заключаются в способности металлов вызывать цитопатическое действие на отдельные клетки структурных элементов нефрона. Ведущим механизмом развития экспериментальных металонефропатий является поражение эпителия проксимальных канальцев почек, которое обусловлено выборочным нарушением клеточных мембран, митохондрий и лизосом эпителия проксимальных канальцев нефрона.Ключевые слова: тяжелые металлы, почки, металлонефропатии, креатинин, мочевина, белок, скорость клубочковой фильтрации, гистологическое исследование почек, канальцевый аппарат, эпителиоциты

Інженерна методика визначення параметрів схеми заміщення п`єзоперетворювача

This article presents the simplify method of equivalent scheme piezoelectric transducer parameters finding and analyze accuracy of this methodПриведена упрощенная методика получения параметров эквивалентной схемы замещения пьезопреобразователя и анализ погрешности приведенной методикиНаведена спрощена методика отримання параметрів еквівалентної схеми заміщення п’єзоперетворювача та аналіз похибки наведеної методик

Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event

Positron scattering on atoms and molecules

An overview is given of recent progress in the calculation of positron scattering on atoms and molecules using the convergent close-coupling method. Particular emphasis is given to those cases where positronium formation is one of the reaction channels, as well as the importance of demonstrating convergence with increasing orbital angular momentum of the bases used. Targets considered are atomic hydrogen, lithium, and molecular hydrogen

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Antihydrogen formation in low-energy antiproton collisions with excited-state positronium atoms

© 2018, Springer Nature Switzerland AG. The convergent close-coupling method is used to obtain cross sections for antihydrogen formation in low-energy antiproton collisions with positronium (Ps) atoms in specified initial excited states with principal quantum numbers ni= 5. The threshold behaviour as a function of the Ps kinetic energy, E, is consistent with the 1/E law expected from threshold theory for all initial states. We find that the increase in the cross sections is muted above ni= 3 and that here their scaling is roughly consistent with ni2, rather than the classically expected increase as ni4

Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45

Apoptotic DNA fragmentation is mediated by a caspase-activated DNA fragmentation factor (DFF)40. Expression and folding of DFF40 require the presence of DFF45, which also acts as a nuclease inhibitor before DFF40 activation by execution caspases. The N-terminal domains (NTDs) of both proteins are homologous, and their interaction plays a key role in the proper functioning of this two-component system. Here we report that the NTD of DFF45 alone is unstructured in solution, and its folding is induced upon binding to DFF40 NTD. Therefore, folding of both proteins regulates the formation of the DFF40/DFF45 complex. The solution structure of the heterodimeric complex between NTDs of DFF40 and DFF45 reported here shows that the mutual chaperoning includes the formation of an extensive network of intermolecular interactions that bury a hydrophobic cluster inside the interface, surrounded by intermolecular salt bridges

Finite temperature, magnetic,and many-body effects in Ab initio simulations of alloy thermodynamics

Ab initio electronic structure theory is known as a useful tool for prediction of materials properties. However, majority of simulations still deal with calculations in the framework of density functional theory with local or semi-local functionals carried out at zero temperature. We present new methodological solutions, which go beyond this approach and explicitly take finite temperature, magnetic, and many-body effects into account. Considering Ti-based alloys, we discuss limitations of the quasiharmonic approximation for the treatment of lattice vibrations, and present an accurate and easily extendable method to calculate free energies of strongly anharmonic solids. We underline the necessity to going beyond the state-of-the-art techniques for the determination of effective cluster interactions in systems exhibiting metal-to-insulator transition, and describe a unified cluster expansion approach developed for this class of materials. Finally, we outline a first-principles method, disordered local moments molecular dynamics, for calculations of thermodynamic properties of magnetic alloys, like Cr1-xAl xN, in their high-temperature paramagnetic state. Our results unambiguously demonstrate importance of finite temperature effects in theoretical calculations of thermodynamic properties of materials

Sudden perturbation approximations for interaction of atoms with intense ultrashort electromagnetic pulses

© 2015 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg. The response of an atom to the action of a pulse shorter than the Kepler period of the optically-active electron is often treated analytically using the sudden-perturbation approximation (SPA). It relies on the truncation of the evolution operator expansion in a series over the dimensionless parameter e sys t L, where e sys is the system-dependent characteristic energy and t L is the pulse duration. We examine the SPA with the use of a basis-based solution of the time-dependent Schrödinger equation (TDSE) for the case of a hydrogen atom interacting with two different types of ultrashort pulses, a half-cycle pulse and a few-cycle pulse. The length-gauge form of the electron-field interaction potential is used. The SPA transition probabilities are shown to deviate slightly but systematically from the correct values for the positive-energy states in the region where the sudden-perturbation condition is violated. It is shown that the SPA expectation value of the electron displacement as a function of time differ qualitatively from what follows from the ab initio TDSE solution. Nevertheless, the SPA is shown to be a good approximation for the description of the expectation value of the electron momentum

Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance

Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (IR) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. Thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (HFD) in white rats. Blood samples were collected from 7 control and 14 obese IR rats. Prothrombin time (PT) and partial activated thromboplastin time (APTT) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activa­ting enzymes from snake venoms. Platelet aggregation was measured and their count determined using Aggregometer Solar AP2110. The aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U Test. The haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. PT and APTT demonstrated that blood coagulation time strongly tended to decrease in obese IR rats in comparison to the control group. It was also detec­ted that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese IR rats. A prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese IR rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesity-induced IR compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced IR which we assume indicate early development of atherosclerosis