Поетеса Афінаїда і проблема становлення візантійського героїчного епосу

В статье рассматривается малоизученная проблема возникновения эпических поэм в ранневизантийской литературе ІІІ-IV веков н.э. Главный объект рассмотрения – творчество поэтессы Афинаиды (Евдокии) и ее поэма "О святом Киприане".В статті розглядається маловивчена проблема виникнення епічних поем в ранній візантійській літературі ІІІ-IV століть н.е. Головний об'єкт розгляду – творчість поетеси Афінаїди (Євдокії) і її поема "Про Святого Кіпріана".In the article – the practically non-considered problem of epic appearing of the early Byzantine literature (ІІІ-IV centuries AD). The main subject-matter under consideration is the creative works by Athenais (Eudokia) and her poem "About Saint Cyprian"

A novel hypothesis for an alkaline phosphatase ‘rescue’ mechanism in the hepatic acute phase immune response

AbstractThe liver isoform of the enzyme alkaline phosphatase (AP) has been used classically as a serum biomarker for hepatic disease states such as hepatitis, steatosis, cirrhosis, drug-induced liver injury, and hepatocellular carcinoma. Recent studies have demonstrated a more general anti-inflammatory role for AP, as it is capable of dephosphorylating potentially deleterious molecules such as nucleotide phosphates, the pathogenic endotoxin lipopolysaccharide (LPS), and the contact clotting pathway activator polyphosphate (polyP), thereby reducing inflammation and coagulopathy systemically. Yet the mechanism underlying the observed increase in liver AP levels in circulation during inflammatory insults is largely unknown. This paper hypothesizes an immunological role for AP in the liver and the potential of this system for damping generalized inflammation along with a wide range of ancillary pathologies. Based on the provided framework, a mechanism is proposed in which AP undergoes transcytosis in hepatocytes from the canalicular membrane to the sinusoidal membrane during inflammation and the enzyme's expression is upregulated as a result. Through a tightly controlled, nucleotide-stimulated negative feedback process, AP is transported in this model as an immune complex with immunoglobulin G by the asialoglycoprotein receptor through the cell and secreted into the serum, likely using the receptor's State 1 pathway. The subsequent dephosphorylation of inflammatory stimuli by AP and uptake of the circulating immune complex by endothelial cells and macrophages may lead to decreased inflammation and coagulopathy while providing an early upstream signal for the induction of a number of anti-inflammatory gene products, including AP itself

THE USE OF SANDWICH-CULTURED RAT HEPATOCYTES TO DETERMINE THE INTRINSIC CLEARANCE OF COMPOUNDS WITH DIFFERENT EXTRACTION RATIOS: 7-ETHOXYCOUMARIN AND WARFARIN

ABSTRACT: The application of sandwich-cultured rat hepatocytes for the identification of the hepatic intrinsic clearance of compounds with widely varying extraction ratios was investigated. We previously showed the applicability of this in vitro system, in combination with a model describing molecular diffusion, hepatocyte/medium partition, and nonsaturated metabolism, which resulted in a successful identification of this parameter for tolbutamide. This approach is further validated using the compounds 7-ethoxycoumarin and warfarin, covering a 100-fold range of extraction ratios. Clearance of these two substrates could be reliably determined, but only if the depletion of the parent compound in medium as well as in the hepatocyte sandwich was measured. Sensitivity analyses showed that the time course of depletion of the parent compound in medium, especially for warfarin, is insensitive to the partition and diffusion parameter values, whereas depletion in the hepatocyte sandwich was far more sensitive. When varying the volumes of collagen in the sandwich culture, it appears that the most reliable kinetic parameters could be obtained by fitting the data with the smaller collagen volume and that these parameters obtained from fitting to data of the larger volumes generally cannot be verified satisfactorily with the data of the smaller volumes. The values of hepatic clearance that were obtained after extrapolation of the intrinsic clearance to the hepatic clearance from blood were comparable within a factor of 2 to hepatic clearance data in the literature. This indicates that this sandwich culture and modeling system can be applied for the identification of the hepatic intrinsic clearance rate of the total range from low to high clearance compounds. Predicting the kinetic parameters of compounds in vivo using data from in vitro experiments is a fast developing area of research Recently, we have successfully developed the alternative approach of using sandwich-cultured rat hepatocytes in determining the in vitro intrinsic clearance of the slowly metabolized compound tolbutamide In this alternative approach, the use of data on substrate depletion was chosen rather than the use of data on metabolite formation. Using data on metabolite formation may cause practical problems when analytical methods or standards to study the kinetics of metabolite Article, publication date, and citation information can be found at http://dmd.aspetjournals.org. doi:10.1124/dmd.105.004390. ABBREVIATIONS: CL bile , biliary clearance (ml/min/kg body weight); CL hep , hepatic clearance (ml/min/kg body weight); CL int , intrinsic clearance (ml/min); C m , concentration medium (M); C s , concentration sandwich (M); D m , diffusion coefficient in medium (cm 2 /min); D s , diffusion coefficient in sandwich (cm 2 /min); f a , fraction of cell activity; f m , free fraction medium; f h , free fraction hepatocytes; f n , fraction of cells; f s , free fraction sandwich; f u , free fraction in blood; f v , fraction of viable cells; K h , specific clearance (Ϫ/min); K l , specific intrinsic clearance of the liver (Ϫ/min; Ϫ/h); K m , Michaelis-Menten constant (M); K ow , partition coefficient octanol-water; K s , first-order metabolism (Ϫ/min); L m , medium layer thickness (cm); L s , sandwich layer thickness (cm); PBPK, physiologically based pharmacokinetics; P cm , collagen-medium partition coefficient; P hm , hepatoyctemedium partition coefficient; P sm , sandwich-medium partition coefficient; P, parameter value; Q h , hepatic blood flow (l/h); s, sensitivity; SRW, standard rat body weight (250 g); V c , volume of collagen (ml); V h , volume of hepatocytes (ml); V m , volume of medium (ml); V max , maximum rate of metabolism (M/min); V s , volume sandwich (ml); DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; HPLC, high-performance liquid chromatography

Эпидемиологические исследования в сексологии

Представлены результаты эпидемиологического исследования, позволившие автору на примере обследования 1000 человек популяции из западного региона Украины сформулировать основные закономерности изменения отношения к браку и сексуального поведения мужчин и женщин в современном обществе.The findings of epidemiological study, which allowed the author to formulate main regularities of the changes in the attitude to the marriage and sexual behavior of men and women in the contemporary society on the example of the examination of 1000 persons from the western regions of Ukraine, are presented

The European Registered Toxicologist (ERT) : Current status and prospects for advancement

Acknowledgements We would like to thank the participants of the five workshops in which the issues presented in this paper were discussed and the revised guidelines prepared, as well as the EUROTOX Executive Committee and the societies of toxicology of Sweden, the Netherlands, Switzerland, Austria and France for their support which allowed the workshops to take place.Peer reviewedPostprin

Improving the quality of toxicology and environmental health systematic reviews:What journal editors can do

Systematic reviews are fast increasing in prevalence in the toxicology and environmental health literature. However, how well these complex research projects are being conducted and reported is unclear. Since editors have an essential role in ensuring the scientific quality of manuscripts being published in their journals, a workshop was convened where editors, systematic review practitioners, and research quality control experts could discuss what editors can do to ensure the systematic reviews they publish are of sufficient scientific quality. Interventions were explored along four themes: setting standards; reviewing protocols; optimizing editorial workflows; and measuring the effectiveness of editorial interventions. In total, 58 editorial interventions were proposed. Of these, 26 were shortlisted for being potentially effective, and 5 were prioritized as short-term actions that editors could relatively easily take to improve the quality of published systematic reviews. Recent progress in improving systematic reviews is summarized, and outstanding challenges to further progress are highlighted

Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress

International audience; High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics and metabolomics together with pharmacokinetics for drug testing regimes. Cultured human renal epithelial cells (RPTEC/TERT1) were exposed to the nephrotoxin Cyclosporine A (CsA) at therapeutic and supratherapeutic concentrations for 14 days. CsA was quantified in supernatants and cellular lysates by LC-MS/MS for kinetic modeling. There was a rapid cellular uptake and accumulation of CsA, with a non-linear relationship between intracellular and applied concentrations. CsA at 15 µM induced mitochondrial disturbances and activation of the Nrf2-oxidative-damage and the unfolded protein-response pathways. All three omic streams provided complementary information, especially pertaining to Nrf2 and ATF4 activation. No stress induction was detected with 5 µM CsA; however, both concentrations resulted in a maximal secretion of cyclophilin B. The study demonstrates for the first time that CsA-induced stress is not directly linked to its primary pharmacology. In addition we demonstrate the power of integrated omics for the elucidation of signaling cascades brought about by compound induced cell stress

Die Notverordnungen des kroatischen Präsidenten aus den Jahren 1991 und 1992

U radu se razmatraju uredbe iz nužde koje je donio predsjednik Republike Franjo Tuđman u drugoj polovici 1991. i početkom 1992. godine u vrijeme otvorene agresije na Republiku Hrvatsku. Glavnina uredbi donesena je 10. rujna 1991., a do kraja 1991. godine donesene su gotovo sve uredbe iz nužde. Uredbama su regulirani klasični državni resori poput pravosuđa, unutarnjih poslova i vojske, no velik dio uredbi regulirao je i javne službe te gospodarstvo.At the beginning, this paper gives a brief notional historical overview of emergency decrees, after which follows a reconstruction of events in 1990 that led to the introduction of articles 17 and 101 of the Constitution of the Republic of Croatia as Constitutional decrees relating to states of emergency. The central part of the paper deals with emergency decrees passed by the Croatian President Franjo Tuđman at the time of the open aggression against the Republic of Croatia in the second half of 1991 and the beginning of 1992. In this section, using sources, especially the minutes of the Commission for Constitutional Matters of the Croatian Partliament and the minutes of the plenary sessions of the Croatian Parliament, and also relevant literature, the paper sheds light on the circumstances under which the decrees were passed and approved by the Croatian Parliament, and thus provides a new interpretation of the decrees. After discussing the circumstances under which the decrees were passed, the author deals with various aspects of the decrees\u27 content, first noting the basic characteristics of the decrees, and then classifying them according to fields, such as: internal affairs, defense and justice, and also those covering public services and the economy. While discussing particular decrees the author sets out only the main provisions of the decrees with a view to presenting their basic characteristics, such as the limitation of constitutional rights and the centralisation of public services and of the economy. In the last part of the paper, the author analyzes the constitutionality of the decrees and their lifting. The question of whether the Parliament could convene is paramount in considering the constitutionality of the decrees, since this is important in establishing whether the President of the Republic had the power to pass decrees limiting constitutional rights. The author also considers the decision of the Constitutional Court to approve the constitutionality of the decrees. The lifting of the decrees is analyzed with special consideration given to the circumstances leading to this.Am Anfang dieser Arbeit wird eine kurze begriffshistorische Übersicht über die Notverordnungen präsentiert, wonach rekonstruiert wird, wie die den Ausnahmezustand regelnden Artikel 17 und 101 der Verfassung der Republik Kroatien von 1990 zustande kamen. Der zentrale Teil dieser Arbeit befasst sich mit den Notverordnungen, die der damalige kroatische Staatspräsident Franjo Tuđman während des offenen Angriffskrieges gegen die Republik Kroatien in der zweiten Hälfte des Jahres 1991 und Anfang 1992 erließ. Dabei wird versucht, anhand des Quellenstudiums, vor allem der Niederschriften zur Arbeit der parlamentarischen Kommission für Verfassungsfragen, der Protokolle zu den Plenarsitzungen des Parlaments der Republik Kroatien (Sabor), aber auch unter Rückgriff auf die entsprechende Literatur die Umstände des Erlasses der Notverordnungen sowie ihrer Bestätigung durch den Sabor zu beleuchten und auf diese Weise einen Beitrag zur Reinterpretation der betreffenden Verordnungen zu leisten. Nach einer dementsprechenden Klärung werden die inhaltlichen Aspekte der Verordnungen dargestellt, indem zunächst deren Hauptmerkmale bestimmt werden und danach eine Zuordnung zum Bereich des Inneren, der Verteidigung und der Justiz beziehungsweise zum Bereich der öffentlichen Aufgaben und der Wirtschaft erfolgt. Innerhalb der Darstellung einzelner Verordnungen versuchen wir, lediglich ihre wesentlichen Bestimmungen zu präsentieren, an denen die wichtigsten Merkmale wie die Beschränkung der Verfassungsrechte und die Zentralisierung der öffentlichen Aufgaben und der Wirtschaft deutlich werden. Im letzten Teil der Arbeit werden die Verfassungskonformität der Verordnungen und das Ende ihrer Gültigkeit analysiert. Die Verfassungsmäßigkeit der Verordnungen wird in erster Linie unter dem Aspekt untersucht, ob das Parlament hätte zusammentreten können, wovon schließlich die Zuständigkeit des Präsidenten der Republik für das Erlassen von verfassungsrechtsbeschränkenden Verordnungen abhing. Ebenfalls wird die Entscheidung des Verfassungsgerichts besprochen, in der es den Verordnungen Verfassungsmäßigkeit bescheinigt. Die Aufhebung der Verordnungen wird hinsichtlich der dafür verantwortlichen Umstände analysiert

The long and winding road of progress in the use of in vitro data for risk assessment purposes : From "carnation test" to integrated testing strategies

This paper introduces the special issue on quantitative in vitro-in vivo extrapolations (QIVIVE). It highlights important issues in the development of in vitro toxicology towards its implementation in toxicological risk assessment. (C) 2014 Elsevier Ireland Ltd. All rights reserved