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[PMID]:28463416
[Au] Autor:Kaja S; Payne AJ; Naumchuk Y; Koulen P
[Ad] Endereço:Departments of Ophthalmology and Molecular Pharmacology & Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois.
[Ti] Título:Quantification of Lactate Dehydrogenase for Cell Viability Testing Using Cell Lines and Primary Cultured Astrocytes.
[So] Source:Curr Protoc Toxicol;72:2.26.1-2.26.10, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug discovery heavily relies on cell viability studies to assess the potential toxicity of drug candidates. L-Lactate dehydrogenase (LDH) is a cytoplasmic enzyme that catalyzes the concomitant interconversions of pyruvate to L-lactate and NADH to NAD during glycolysis, and the reverse reactions during the Cori cycle. In response to cellular damage, induced by endogenous cellular mechanisms or as a result of exogenously applied insults, LDH is released from the cytoplasm into the extracellular environment. Its stability in cell culture medium makes it a well-suited correlate for the presence of damage and toxicity in tissues and cells. We herein present protocols for a reproducible and validated LDH assay optimized for several cell types. In contrast to commercially available LDH assays, often associated with proprietary formulations and high cost, our protocols provide ample opportunities for experiment-specific optimization with low variability and cost. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Astrócitos/enzimologia
Sobrevivência Celular
L-Lactato Desidrogenase/análise
Toxicologia/métodos
[Mh] Termos MeSH secundário: Animais
Técnicas de Cultura de Células
Linhagem Celular
Linhagem Celular Tumoral
Meios de Cultura/química
Citoplasma/enzimologia
Espaço Extracelular/enzimologia
Glicólise
Seres Humanos
Neurônios/efeitos dos fármacos
Fármacos Neuroprotetores/farmacologia
Nervo Óptico/citologia
Nervo Óptico/efeitos dos fármacos
Cultura Primária de Células
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Neuroprotective Agents); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.21


  2 / 8488 MEDLINE  
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[PMID]:28463417
[Au] Autor:Tolosa L; Gómez-Lechón MJ; Donato MT
[Ad] Endereço:Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe (IIS-La Fe), Valencia, Spain.
[Ti] Título:A Multi-Parametric Fluorescent Assay for the Screening and Mechanistic Study of Drug-Induced Steatosis in Liver Cells in Culture.
[So] Source:Curr Protoc Toxicol;72:14.15.1-14.15.11, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human hepatic cells have been used for drug safety risk evaluations throughout early development phases. They provide rapid, cost-effective early feedback to identify drug candidates with potential hepatotoxicity. This unit presents a cell-based assay to evaluate the risk of liver damage associated with steatogenic drugs. Detailed protocols for cell exposure to test compounds and for the assessment of steatosis-related cell parameters (intracellular lipid content, reactive oxygen species production, mitochondrial impairment, and cell death) are provided. A few representative results that illustrate the utility of this procedure for the screening of drug-induced steatosis are shown. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Fígado Gorduroso/induzido quimicamente
Fígado Gorduroso/patologia
Fígado/citologia
[Mh] Termos MeSH secundário: Morte Celular/efeitos dos fármacos
Células Cultivadas
Doença Hepática Induzida por Substâncias e Drogas
Hepatócitos/metabolismo
Seres Humanos
Metabolismo dos Lipídeos/efeitos dos fármacos
Mitocôndrias Hepáticas/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Toxicologia/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.20


  3 / 8488 MEDLINE  
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[PMID]:28463415
[Au] Autor:McCullough SD; On DM; Bowers EC
[Ad] Endereço:National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
[Ti] Título:Using Chromatin Immunoprecipitation in Toxicology: A Step-by-Step Guide to Increasing Efficiency, Reducing Variability, and Expanding Applications.
[So] Source:Curr Protoc Toxicol;72:3.14.1-3.14.28, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histone modifications work in concert with DNA methylation to regulate cellular structure, function, and response to environmental stimuli. More than 130 unique histone modifications have been described to date, and chromatin immunoprecipitation (ChIP) allows for the exploration of their associations with the regulatory regions of target genes and other DNA/chromatin-associated proteins across the genome. Many variations of ChIP have been developed in the 30 years since its earliest version came into use, which makes it challenging for users to integrate the procedure into their research programs. Furthermore, the differences in ChIP protocols can confound efforts to increase reproducibility across studies. The streamlined ChIP procedure presented here can be readily applied to samples from a wide range of in vitro studies (cell lines and primary cells) and clinical samples (peripheral leukocytes) in toxicology. We also provide detailed guidance on the optimization of critical protocol parameters, such as chromatin fixation, fragmentation, and immunoprecipitation, to increase efficiency and improve reproducibility. Expanding toxicoepigenetic studies to more readily include histone modifications will facilitate a more comprehensive understanding of the role of the epigenome in environmental exposure effects and the integration of epigenetic data in mechanistic toxicology, adverse outcome pathways, and risk assessment. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Imunoprecipitação da Cromatina/métodos
Toxicologia/métodos
[Mh] Termos MeSH secundário: Linhagem Celular
DNA/isolamento & purificação
Epigênese Genética
Redes Reguladoras de Genes
Marcação de Genes
Histonas/metabolismo
Seres Humanos
Leucócitos/química
Peptídeo Hidrolases/química
Reação em Cadeia da Polimerase
Cultura Primária de Células
Reprodutibilidade dos Testes
Sonicação
Toxicologia/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histones); 9007-49-2 (DNA); EC 3.4.- (Peptide Hydrolases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.22


  4 / 8488 MEDLINE  
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[PMID]:29386432
[Au] Autor:Uesawa Y
[Ad] Endereço:Department of Clinical Pharmaceutics, Meiji Pharmaceutical University.
[Ti] Título:[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].
[So] Source:Yakugaku Zasshi;138(2):185-190, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.
[Mh] Termos MeSH primário: Sistemas de Notificação de Reações Adversas a Medicamentos
Computadores
Bases de Dados como Assunto
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Toxicologia/métodos
[Mh] Termos MeSH secundário: Reposicionamento de Medicamentos
Valor Preditivo dos Testes
Vigilância de Produtos Comercializados
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-4


  5 / 8488 MEDLINE  
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[PMID]:29376310
[Au] Autor:Tyshko NV; Sadykova EO; Timonin AN; Shestakova SI; Trebukh MD; Pashorina VA
[Ti] Título:Modification of vitamin-mineral diet composition as a model of adaptive potential reducing in laboratory animals.
[So] Source:Vopr Pitan;85(6):64-71, 2016.
[Is] ISSN:0042-8833
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:This publication presents the results of research that was aimed at elaboration of adaptive potential reducing model, intended for toxicological experiments. Two series of research (with a duration of 70 days each) were conducted on Wistar rats. In the 1st series five groups of animals received diets with 100, 75,50,25 and 0% of vitamins B1, B2, B3, B6 and minerals(Fe3+ and Mg2+); in the 2nd series four groups of animals received diets with 21.37, 9.94, 4.62, 2.15% of this vitamins and minerals. In the 1st series of studies the intervals of maximum, medium and minimum content of essential nutrients in the diet was established; in the 2nd series the range of the lowest possible concentrations of these elements that provided the lowest level of adaptive potential and not causing the pathology development was determined. The certain set of hematological, biochemical, immunological and other indicators were investigated, this article analyzes the results of zoometric studies, mortality of animals, as well as the results of antioxidant status (activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and malondialdehyde content in red blood cells) studies. Based on the evaluation of the data which were obtained in the 1st series, it follows that a dose reduction of relevant essential nutrients to 25% didn't significantly affect the values of the studied indicators, and the complete elimination of these substances resulted in massive death of animals. In the 2nd series a significant differences between the groups were observed from the range of increased mortality (groups with 2.15 and 4.62% content of essential nutrients) to the range of deviations from central tendency of some parameters (group with 21.37% content). The data allowed to trace the dependence of these differences on the levels of vitamins and minerals in the diet. The results were used to determine threshold values of vitamins and minerals that provided the necessary reduction of the adaptive potential level in male and female rats. Taking into account the risk of pathology development, three dosages of essential substances have been established - optimal, marginal and submarginal, which provide consistent decline of adaptive potential of laboratory animals: 75, 30 and 19% for males and 75, 28 and 18% for females, respectively. The modification of vitamin and mineral composition of the diet can be used as a model of adaptive potential reduce in toxicological research.
[Mh] Termos MeSH primário: Adaptação Psicológica/efeitos dos fármacos
Minerais/farmacologia
Complexo Vitamínico B/farmacologia
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Feminino
Masculino
Oxirredutases/sangue
Ratos
Ratos Wistar
Toxicologia/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Minerals); 12001-76-2 (Vitamin B Complex); EC 1.- (Oxidoreductases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  6 / 8488 MEDLINE  
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[PMID]:29048701
[Au] Autor:Food and Drug Administration, HHS
[Ti] Título:Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.
[So] Source:Fed Regist;82(200):48413-5, 2017 Oct 18.
[Is] ISSN:0097-6326
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
[Mh] Termos MeSH primário: Química Clínica/classificação
Química Clínica/instrumentação
Segurança de Equipamentos/classificação
Organofosfatos/urina
Toxicologia/classificação
Toxicologia/instrumentação
[Mh] Termos MeSH secundário: Colinesterases/envenenamento
Aprovação de Equipamentos/legislação & jurisprudência
Seres Humanos
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organophosphates); EC 3.1.1.8 (Cholinesterases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:T
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE


  7 / 8488 MEDLINE  
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[PMID]:28934728
[Au] Autor:Zaunbrecher V; Beryt E; Parodi D; Telesca D; Doherty J; Malloy T; Allard P
[Ad] Endereço:Sustainable Technology and Policy Program, University of California, Los Angeles , Los Angeles, California, USA.
[Ti] Título:Has Toxicity Testing Moved into the 21st Century? A Survey and Analysis of Perceptions in the Field of Toxicology.
[So] Source:Environ Health Perspect;125(8):087024, 2017 08 30.
[Is] ISSN:1552-9924
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ten years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood. OBJECTIVES: We aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology. METHODS: We surveyed 1,381 toxicologists and experts in associated fields regarding the viability and use of ATS and the perceived barriers and drivers of ATS for a range of applications. We performed ranking, hierarchical clustering, and correlation analyses of the survey data. RESULTS: Many respondents indicated that they were already using ATS, or believed that ATS were already viable approaches, for toxicological assessment of one or more end points in their primary area of interest or concern (26-86%, depending on the specific ATS/application pair). However, the proportions of respondents reporting use of ATS in the previous 12 mo were smaller (4.5-41%). Concern about regulatory acceptance was the most commonly cited factor inhibiting the adoption of ATS, and a variety of technical concerns were also cited as significant barriers to ATS viability. The factors most often cited as playing a significant role (currently or in the future) in driving the adoption of ATS were the need for expedited toxicology information, the need for reduced toxicity testing costs, demand by regulatory agencies, and ethical or moral concerns. CONCLUSIONS: Our findings indicate that the transformation of the field of toxicology is partly implemented, but significant barriers to acceptance and adoption remain. https://doi.org/10.1289/EHP1435.
[Mh] Termos MeSH primário: Testes de Toxicidade/tendências
Toxicologia/tendências
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Medição de Risco
Inquéritos e Questionários
Testes de Toxicidade/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1289/EHP1435


  8 / 8488 MEDLINE  
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[PMID]:28771645
[Au] Autor:Davlantes E; Shartar S; Venero J; Steck A; Langston A; Kazzi ZN
[Ad] Endereço:From the Departments of Emergency Medicine and Hematology and Medical Oncology, Emory University School of Medicine, and the Emory University Office of Critical Event Preparedness and Response, Atlanta, Georgia, and the Radiation Injury Treatment Network, Minneapolis, Minnesota.
[Ti] Título:Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.
[So] Source:South Med J;110(8):497-501, 2017 Aug.
[Is] ISSN:1541-8243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. METHODS: We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. RESULTS: The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. CONCLUSIONS: Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.
[Mh] Termos MeSH primário: Prestação Integrada de Cuidados de Saúde
Lesões por Radiação/terapia
Toxicologia
Centros de Traumatologia
[Mh] Termos MeSH secundário: Comportamento Cooperativo
Seres Humanos
Especialização
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.14423/SMJ.0000000000000677


  9 / 8488 MEDLINE  
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[PMID]:28708961
[Au] Autor:Sullivan M
[Ad] Endereço:1 Department of Public Health, William Paterson University, Wayne, NJ, USA.
[Ti] Título:Hamilton and Hardy: Mentoring and Friendship in the Service of Occupational Health.
[So] Source:Public Health Rep;132(5):539-544, 2017 Sep/Oct.
[Is] ISSN:1468-2877
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article explores the mentoring relationship between Alice Hamilton and Harriet Hardy, two female physician-researchers who had a tremendous impact on the development of the field of occupational health in the United States during the 20th century. The article relies on letters the women wrote to each other. Hamilton, the elder, supported and furthered Hardy's career by asking her to coauthor the second edition of a seminal occupational health text. After beginning this intellectual collaboration, Hamilton remained a mentor to Hardy, and a decades-long friendship ensued. The article explores their relationship within the historical, political, and social context in which the women worked and made remarkable contributions to public health.
[Mh] Termos MeSH primário: Tutoria
Saúde do Trabalhador/história
Medicina do Trabalho/história
Toxicologia/história
[Mh] Termos MeSH secundário: História do Século XIX
História do Século XX
Seres Humanos
Estados Unidos
[Pt] Tipo de publicação:BIOGRAPHY; HISTORICAL ARTICLE; JOURNAL ARTICLE
[Ps] Nome de pessoa como assunto:Hamilton A; Hardy H
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1177/0033354917717487


  10 / 8488 MEDLINE  
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[PMID]:28672772
[Au] Autor:Busardò FP; Pacifici R; Pichini S
[Ad] Endereço:.
[Ti] Título:Mass spectrometry vs. immunoassay in clinical and forensic toxicology: qui modus in rebus est?
[So] Source:Clin Chem Lab Med;55(10):e236-e237, 2017 08 28.
[Is] ISSN:1437-4331
[Cp] País de publicação:Germany
[La] Idioma:eng
[Mh] Termos MeSH primário: Toxicologia Forense
Imunoensaio
Espectrometria de Massas
[Mh] Termos MeSH secundário: Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Toxicologia
[Pt] Tipo de publicação:LETTER; COMMENT
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE



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