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- 苦労,骨折り / 苦痛,苦脳 / 《古》陣通 / 苦労して働く,骨折る
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/03 22:50:11」(JST)
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- The mitochondrial fluorescent dye rhodamine 123 is a high-affinity substrate for organic cation transporters (OCTs) 1 and 2.
- Jouan E, Le Vee M, Denizot C, Da Violante G, Fardel O.Author information Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043, Rennes, France.AbstractRhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 and OCT2. Intracellular uptake of the dye was demonstrated to be enhanced in both hOCT1- and hOCT2-overexpressing HEK293 cells when compared with control HEK293 cells. This increase of rhodamine 123 influxes was found to be a saturable carrier-mediated process, with low Km values (Km = 0.54 μm and Km = 0.61 μm for transport of the dye in hOCT1- and hOCT2-positive HEK293 cells, respectively). Known inhibitors of hOCT1 and hOCT2 activities such as verapamil, amitriptyline, prazosin, and quinine were next demonstrated to decrease rhodamine 123 accumulation in hOCT1- and hOCT2-overexpressing HEK293 cells. In addition, the dye was found to inhibit hOCT1- and hOCT2-mediated uptake of tetraethylammonium (TEA), a model substrate for both hOCT1 and hOCT2; rhodamine 123 appeared nevertheless to be a more potent inhibitor of hOCT1-mediated TEA transport (IC50 = 0.37 μm) than of that mediated by hOCT2 (IC50 = 61.5 μm). Taken together, these data demonstrate that rhodamine 123 is a high-affinity substrate for both hOCT1 and hOCT2. This dye may be therefore useful for fluorimetrically investigating cellular hOCT1 or hOCT2 activity, knowing, however, that other factors potentially contributing to cellular accumulation of rhodamine 123, including mitochondrial membrane potential or expression of the efflux transporter P-glycoprotein, have also to be considered.
- Fundamental & clinical pharmacology.Fundam Clin Pharmacol.2014 Feb;28(1):65-77. doi: 10.1111/j.1472-8206.2012.01071.x. Epub 2012 Aug 23.
- Rhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 a
- PMID 22913740
- PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessment: Recommendations from a joint EPAA - EURL ECVAM ADME workshop.
- Bessems JG1, Loizou G2, Krishnan K3, Clewell HJ 3rd4, Bernasconi C5, Bois F6, Coecke S5, Collnot EM7, Diembeck W8, Farcal LR5, Geraets L9, Gundert-Remy U10, Kramer N11, Küsters G12, Leite SB13, Pelkonen OR14, Schröder K15, Testai E16, Wilk-Zasadna I5, Zaldívar-Comenges JM5.Author information 1National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. Electronic address: jos.bessems@ec.europa.eu.2Health and Safety Laboratories, Mathematical Sciences Unit, Buxton, UK.3Département de Santé Environnementale et Santé au Travail, Faculté de Médecine, Université de Montréal, Montréal, Canada.4The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.5Systems Toxicology Unit/EURL ECVAM, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy.6Compiegne University of Technology, Chair of Mathematical Modelling for Systems Toxicology, Compiegne & INERIS, DRC/VIVA/METO, Verneuil en Halatte, France.7Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.8Beiersdorf AG, Unnastr. 48, D-20245 Hamburg, Germany.9National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.10Department Clinical Pharmacology and Toxicology, Medical School (Charité), Berlin, Germany.11Institute for Risk Assessment Sciences, Utrecht University, Netherlands.12European Partnership for Alternative Approaches to Animal Testing (EPAA), 15b Avenue Herrmann Debroux, 1160 Bruxelles, Belgium.13Systems Toxicology Unit/EURL ECVAM, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy; Instituto de Biologia Experimental e Tecnológica (IBET)/Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa (ITQB-UNL), Oeiras, Portugal.14Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.15BioMed-zet Life Science GmbH/Centre for Alternative and Complementary Methods to Animal Testing (ZET), Linz, Austria.16Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, Italy.AbstractInformation on toxicokinetics is critical for animal-free human risk assessment. Human external exposure must be translated into human tissue doses and compared with in vitro actual cell exposure associated to effects (in vitro-in vivo comparison). Data on absorption, distribution, metabolism and excretion in humans (ADME) could be generated using in vitro and QSAR tools. Physiologically-based toxicokinetic (PBTK) computer modelling could serve to integrate disparate in vitro and in silico findings. However, there are only few freely-available PBTK platforms currently available. And although some ADME parameters can be reasonably estimated in vitro or in silico, important gaps exist. Examples include unknown or limited applicability domains and lack of (high-throughput) tools to measure penetration of barriers, partitioning between blood and tissues and metabolic clearance. This paper is based on a joint EPAA - EURL ECVAM expert meeting. It provides a state-of-the-art overview of the availability of PBTK platforms as well as the in vitro and in silico methods to parameterise basic (Tier 1) PBTK models. Five high-priority issues are presented that provide the prerequisites for wider use of non-animal based PBTK modelling for animal-free chemical risk assessment.
- Regulatory toxicology and pharmacology : RTP.Regul Toxicol Pharmacol.2014 Feb;68(1):119-39. doi: 10.1016/j.yrtph.2013.11.008. Epub 2013 Nov 26.
- Information on toxicokinetics is critical for animal-free human risk assessment. Human external exposure must be translated into human tissue doses and compared with in vitro actual cell exposure associated to effects (in vitro-in vivo comparison). Data on absorption, distribution, metabolism and ex
- PMID 24287156
- Source contributions of lead in residential floor dust and within-home variability of dust lead loading.
- Lucas JP1, Bellanger L2, Le Strat Y3, Le Tertre A3, Glorennec P4, Le Bot B4, Etchevers A5, Mandin C6, Sébille V7.Author information 1Université Paris Est, CSTB - Centre Scientifique et Technique du Bâtiment, 84 avenue Jean Jaurès, 77447 Marne-la-Vallée Cedex 2, France; Université de Nantes, EA 4275 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, 1 rue Gaston Veil BP 53508, 44035 Nantes Cedex 1, France. Electronic address: jean.paul.lucas@free.fr.2UMR CNRS 6629 Laboratoire de Mathématiques Jean Leray, 2 rue de la Houssinière BP 92208, F-44322 Nantes Cedex, France.3InVS, 12 rue du Val d'Osne, 94415 Saint-Maurice Cedex, France.4EHESP Rennes, Sorbonne Paris Cité, Avenue du Professeur Léon-Bernard, CS 74312, 35043 Rennes Cedex, France; INSERM UMR 1085 Institut de Recherche sur la Santé, l'Environnement et le Travail, Rennes, France.5INSERM UMR 1085 Institut de Recherche sur la Santé, l'Environnement et le Travail, Rennes, France.6Université Paris Est, CSTB - Centre Scientifique et Technique du Bâtiment, 84 avenue Jean Jaurès, 77447 Marne-la-Vallée Cedex 2, France.7Université de Nantes, EA 4275 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, 1 rue Gaston Veil BP 53508, 44035 Nantes Cedex 1, France.AbstractEvidence of the impact of exposure to low levels of lead on children's health is increasing. Residential floor dust is the assumed origin of lead exposure by young children. In this study, we estimate the contribution of different lead sources to household interior floor dust contamination. We also estimate the within-home variability of interior floor dust lead loadings. A multilevel model was developed based on data collected in a French survey in 2008-2009 (484 housing units, 1834 rooms). Missing data were handled by multiple imputation using chained equations. The intra-home correlation between interior floor Log dust lead loadings was approximately 0.6. Dust lead from the landing of an apartment, mostly originating outside the building, was the major contributor to interior floor dust lead. Secondary contributors included the lead-based paint on exterior railings, track-in of the exterior soil of the children's play area into the dwelling, smoking inside the home, demolition of nearby old buildings and sites of pollution in the vicinity. Interior lead-based paint contaminated interior floor dust only in old and non-renovated dwellings. To reduce interior floor dust lead levels in the general population of dwellings, common areas should be maintained, and track-in from the outside should be limited as much as possible.
- The Science of the total environment.Sci Total Environ.2014 Feb 1;470-471:768-79. doi: 10.1016/j.scitotenv.2013.10.028. Epub 2013 Oct 31.
- Evidence of the impact of exposure to low levels of lead on children's health is increasing. Residential floor dust is the assumed origin of lead exposure by young children. In this study, we estimate the contribution of different lead sources to household interior floor dust contamination. We also
- PMID 24184749
Japanese Journal
- Transformation de la vue in situ en signe : le travail de Daniel Buren
- NAKAMURA Yasushi
- Azur (15), 1-19, 2014
- NAID 40020023181
- 塩と銃弾 カミュ『異邦人』における遮断と官能
- 岩切 正一郎
- 人文科学研究 キリスト教と文化 = HUMANITIES Christianity and Culture (44), 2013-10-31
- … D'abord les vis enfoncées dans la bière qui déclenchentle travail de deuil en Meursault tout en le privant de la visibilité de lamort ; …
- NAID 120005416045
- 知覚・労働・科学 : シモーヌ・ヴェイユ「デカルトにおける科学と知覚」から(<特集>科学・技術と宗教)
- 脇坂 真弥
- 宗教研究 87(2), 403-430, 2013-09-30
- 本稿はヴェイユの「科学と知覚」論文を検討し、後の「盲目的メカニズム」としての世界観やそこでの神と人間の関係を読み解くための準備とする。この論文で自らデカルト的懐疑を試みるヴェイユは、《力》を根源的な現象とし、人間と事物を《力》の結節点として理解する。人間は「想像力」においてこの《力》を自覚的に用い(=労働)それによって自分を世界の一部として見出す。ヴェイユによれば、「真の科学」は個人のこのような「 …
- NAID 110009660594
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