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[PMID]: 28069453 [Au] Autor: Raykin J; Snider E; Bheri S; Mulvihill J; Ethier CR [Ad] Endereço: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States. [Ti] Título: A modified gelatin zymography technique incorporating total protein normalization. [So] Source: Anal Biochem;521:8-10, 2017 Mar 15. [Is] ISSN: 1096-0309 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Gelatinase zymography is a commonly used laboratory procedure; however, variability in sample loading and concentration reduce the accuracy of quantitative results obtained from this technique. To facilitate normalization of gelatinase activity by loaded protein amount, we developed a protocol using the trihalocompound 2,2,2-trichloroethanol to allow for gelatin zymography and total protein labeling within the same gel. We showed that detected protein levels increased linearly with loading, and describe a loading concentration range over which normalized gelatinase activity was constant. We conclude that in-gel total protein detection is feasible in gelatin zymography and greatly improves comparison of gelatinase activity between samples. [Mh] Termos MeSH primário: Eletroforese em Gel de Poliacrilamida/normas Fibrossarcoma/enzimologia Gelatina/metabolismo Gelatinases/metabolismo Metaloproteinases da Matriz/análise [Mh] Termos MeSH secundário: Etilenocloroidrina/análogos & derivados Etilenocloroidrina/metabolismo Seres Humanos Metaloproteinases da Matriz/metabolismo Células Tumorais Cultivadas [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 753N66IHAN (Ethylene Chlorohydrin); 9000-70-8 (Gelatin); AW835AJ62N (2,2,2-trichloroethanol); EC 3.4.24.- (Gelatinases); EC 3.4.24.- (Matrix Metalloproteinases) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170508 [Lr] Data última revisão: 170508 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170111 [St] Status: MEDLINE

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[PMID]: 26153352 [Au] Autor: Ness TL; Robinson RL; Mojadedi W; Peavy L; Weiland MH [Ad] Endereço: Department of Biology, Armstrong State University, Savannah, Georgia, 31419. [Ti] Título: A streamlined Western blot exercise: An efficient and greener approach in the laboratory classroom. [So] Source: Biochem Mol Biol Educ;43(5):358-65, 2015 Sep-Oct. [Is] ISSN: 1539-3429 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: SDS-PAGE and western blotting are two commonly taught protein detection techniques in biochemistry and molecular biology laboratory classrooms. A pitfall associated with incorporating these techniques into the laboratory is the significant wait times that do not allow students to obtain timely results. The waiting associated with SDS-PAGE comes from staining and destaining, whereas with western blotting it is the times required for antibody incubations and the numerous wash steps. This laboratory exercise incorporates 2,2,2-trichloroethanol (TCE) into the SDS-PAGE gel allowing for visualization of migrated proteins in a matter of minutes, saving both the time and chemical waste associated with traditional Coomassie staining. Additionally, TCE staining does not affect protein transfer eliminating the requirement for duplicated gels for total protein and western analyses. Protein transfer can be confirmed immediately without the use of Ponceau S staining. Lastly, this western blot procedure has been further shortened by using an HRP-conjugated primary antibody, which eliminates the secondary antibody incubation and washes, and uses a colorimetric detection to allow for visualization by students without the need for specialized equipment. [Mh] Termos MeSH primário: Western Blotting/métodos Educação/métodos Biologia Molecular/educação [Mh] Termos MeSH secundário: Currículo Eletroforese em Gel de Poliacrilamida/métodos Etilenocloroidrina/análogos & derivados Etilenocloroidrina/química Peroxidase do Rábano Silvestre/química Seres Humanos Laboratórios Biologia Molecular/métodos Estudantes Universidades [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S. [Nm] Nome de substância: 753N66IHAN (Ethylene Chlorohydrin); AW835AJ62N (2,2,2-trichloroethanol); EC 1.11.1.- (Horseradish Peroxidase) [Em] Mês de entrada: 1607 [Cu] Atualização por classe: 150916 [Lr] Data última revisão: 150916 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150709 [St] Status: MEDLINE [do] DOI: 10.1002/bmb.20876

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[PMID]: 26039745 [Au] Autor: Rouhou MC; Charest-Tardif G; Haddad S [Ad] Endereço: a Sciences Biologiques , Université du Québec à Montréal , Montréal , Quebec , Canada. [Ti] Título: In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats. [So] Source: J Toxicol Environ Health A;78(11):671-84, 2015. [Is] ISSN: 1528-7394 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure. [Mh] Termos MeSH primário: Etilenocloroidrina/análogos & derivados Naproxeno/metabolismo Ácido Salicílico/metabolismo Solventes/metabolismo Ácido Tricloroacético/metabolismo Tricloroetileno/metabolismo Ácido Valproico/metabolismo [Mh] Termos MeSH secundário: Analgésicos/metabolismo Animais Anti-Inflamatórios não Esteroides/metabolismo Anticonvulsivantes/metabolismo Etilenocloroidrina/sangue Etilenocloroidrina/metabolismo Etilenocloroidrina/farmacocinética Etilenocloroidrina/urina Masculino Modelos Teóricos Ratos Ratos Sprague-Dawley Medição de Risco Solventes/farmacocinética Ácido Tricloroacético/sangue Ácido Tricloroacético/farmacocinética Ácido Tricloroacético/urina Tricloroetileno/sangue Tricloroetileno/farmacocinética Tricloroetileno/urina [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Analgesics); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Anticonvulsants); 0 (Solvents); 290YE8AR51 (Trichloroethylene); 57Y76R9ATQ (Naproxen); 5V2JDO056X (Trichloroacetic Acid); 614OI1Z5WI (Valproic Acid); 753N66IHAN (Ethylene Chlorohydrin); AW835AJ62N (2,2,2-trichloroethanol); O414PZ4LPZ (Salicylic Acid) [Em] Mês de entrada: 1508 [Cu] Atualização por classe: 150604 [Lr] Data última revisão: 150604 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150604 [St] Status: MEDLINE [do] DOI: 10.1080/15287394.2015.1020977

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[PMID]: 26020840 [Au] Autor: Nasr AT; Alexander K; Schreiner LJ; McAuley KB [Ad] Endereço: Department Chemical Engineering, Queen's University, Kingston, Ontario K7L 3N6, Canada. [Ti] Título: Leuco-crystal-violet micelle gel dosimeters: I. Influence of recipe components and potential sensitizers. [So] Source: Phys Med Biol;60(12):4665-83, 2015 Jun 21. [Is] ISSN: 1361-6560 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Radiochromic leuco crystal violet (LCV) micelle gel dosimeters are promising three-dimensional radiation dosimeters because of their spatial stability and suitability for optical readout. The effects of surfactant type and surfactant concentration on dose sensitivity of LCV micelle gels are tested, demonstrating that dose sensitivity and initial colour of the gel increases with increasing Triton x-100 (Tx100) concentration. Using Cetyl Trimethyl Ammonium Bromide (CTAB) in place of Tx100 produces gels that are nearly colourless prior to irradiation, but reduces the dose sensitivity. The separate effects of Tri-chloro acetic acid concentration and pH are investigated, revealing that controlling the pH near 3.6 is crucial for achieving high dose sensitivity. The sensitizing effect of chlorinated species on dose sensitivity is tested using 2,2,2-trichloroethanol (TCE), chloroform, and 1,1,1-trichloro-2-methyl-2-propanol hemihydrate. TCE gives the largest improvement in dose sensitivity and is recommended for use in micelle gel dosimeters because it is less volatile and safer to use than chloroform. Preliminary experiments on a new gel containing CTAB as the surfactant and TCE show that this new gel gives a dose sensitivity that is 24% higher than that of previous LCV micelle gels and is nearly colourless prior to irradiation. [Mh] Termos MeSH primário: Géis/química Violeta de Genciana/química Radiometria/métodos Corantes de Rosanilina/química Tensoativos/química [Mh] Termos MeSH secundário: Compostos de Cetrimônio/química Relação Dose-Resposta à Radiação Etilenocloroidrina/análogos & derivados Etilenocloroidrina/química Concentração de Íons de Hidrogênio Micelas Octoxinol/química Ácido Tricloroacético/química [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cetrimonium Compounds); 0 (Gels); 0 (Micelles); 0 (Rosaniline Dyes); 0 (Surface-Active Agents); 5V2JDO056X (Trichloroacetic Acid); 753N66IHAN (Ethylene Chlorohydrin); 8U61G37Z20 (leucomalachite green); 9002-93-1 (Octoxynol); AW835AJ62N (2,2,2-trichloroethanol); J4Z741D6O5 (Gentian Violet); Z7FF1XKL7A (cetrimonium) [Em] Mês de entrada: 1601 [Cu] Atualização por classe: 150610 [Lr] Data última revisão: 150610 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150529 [St] Status: MEDLINE [do] DOI: 10.1088/0031-9155/60/12/4665

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[PMID]: 26020119 [Au] Autor: Nasr AT; Alexander KM; Olding T; Schreiner LJ; McAuley KB [Ad] Endereço: Department Chemical Engineering, Queen's University, Kingston, K7L 3N6, Canada. [Ti] Título: Leuco-crystal-violet micelle gel dosimeters: II. Recipe optimization and testing. [So] Source: Phys Med Biol;60(12):4685-704, 2015 Jun 21. [Is] ISSN: 1361-6560 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In this study, recipe optimization of Leuco Crystal Violet (LCV) micelle gels made with the surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and the chemical sensitizer 2,2,2-trichloroethanol (TCE) was aided by a two-level three-factor designed experiment. The optimized recipe contains 0.75 mM LCV, 17.0 mM CTAB, 120 mM TCE, 25.0 mM tri-chloro acetic acid (TCAA), 4 wt% gelatin and ~96 wt% water. Dose sensitivity of the optimized gel is 1.5 times higher than that of Jordan's standard LCV micelle gel. Spatial integrity of the 3D dose distribution information in 1L phantoms filled with this recipe is maintained for >120 d. Unfortunately, phantoms made using the optimized recipe showed dose-rate dependence (14% difference in optical attenuation at the peak dose using electron beam irradiations at 100 and 400 MU min(-1)). Further testing suggests that the surfactant CTAB is the cause of this dose rate behaviour. [Mh] Termos MeSH primário: Géis/química Violeta de Genciana/química Imagens de Fantasmas Radiometria/métodos Radiometria/normas Tensoativos/química Água/química [Mh] Termos MeSH secundário: Compostos de Cetrimônio/química Relação Dose-Resposta à Radiação Etilenocloroidrina/análogos & derivados Etilenocloroidrina/química Micelas [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cetrimonium Compounds); 0 (Gels); 0 (Micelles); 0 (Surface-Active Agents); 059QF0KO0R (Water); 753N66IHAN (Ethylene Chlorohydrin); AW835AJ62N (2,2,2-trichloroethanol); J4Z741D6O5 (Gentian Violet); Z7FF1XKL7A (cetrimonium) [Em] Mês de entrada: 1601 [Cu] Atualização por classe: 150610 [Lr] Data última revisão: 150610 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150529 [St] Status: MEDLINE [do] DOI: 10.1088/0031-9155/60/12/4685

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[PMID]: 25956065 [Au] Autor: Gao J; Yang C; Ding H; Zhang Y; Xue J; Cai Y [Ad] Endereço: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Parkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, PR China. [Ti] Título: 2,2,2-Trichloroethanol lengthens the circadian period of Bmal1-driven circadian bioluminescence rhythms in U2OS cells. [So] Source: Biochem Biophys Res Commun;462(3):239-44, 2015 Jul 03. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: 2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human exposure to TCOH is known to be increasing. Recently, it was reported that TCOH causes a significant phase delay of Per2 expression in mouse liver when injected daily over the course of several days. However, it is not clear whether TCOH directly modulates the molecular clock. In the present study we used a cell-based assay system to test this possibility. We found that the daily oscillation period of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal. Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period, suggesting that exposure to anesthesia should be taken into consideration for circadian rhythm studies. In summary, our study reveals a direct regulation of TCOH on molecular clock. [Mh] Termos MeSH primário: Fatores de Transcrição ARNTL/genética Ritmo Circadiano/efeitos dos fármacos Ritmo Circadiano/genética Etilenocloroidrina/análogos & derivados [Mh] Termos MeSH secundário: Animais Proteínas CLOCK/genética Linhagem Celular Hidrato de Cloral/farmacologia Hidrato de Cloral/toxicidade Etilenocloroidrina/farmacologia Etilenocloroidrina/toxicidade Seres Humanos Hipnóticos e Sedativos/farmacologia Hipnóticos e Sedativos/toxicidade Medições Luminescentes Masculino Camundongos Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética Proteínas Circadianas Period/genética Ratos Ratos Endogâmicos F344 [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (ARNTL Transcription Factors); 0 (ARNTL protein, human); 0 (Hypnotics and Sedatives); 0 (NR1D1 protein, human); 0 (Nuclear Receptor Subfamily 1, Group D, Member 1); 0 (PER2 protein, human); 0 (Period Circadian Proteins); 418M5916WG (Chloral Hydrate); 753N66IHAN (Ethylene Chlorohydrin); AW835AJ62N (2,2,2-trichloroethanol); EC 2.3.1.48 (CLOCK Proteins) [Em] Mês de entrada: 1508 [Cu] Atualização por classe: 150606 [Lr] Data última revisão: 150606 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150510 [St] Status: MEDLINE

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[PMID]: 25941891 [Au] Autor: Liu X; Sun S; Meng Z; Lou H; Liu L [Ad] Endereço: Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. [Ti] Título: Organocatalytic asymmetric C-H vinylation and arylation of N-acyl tetrahydroisoquinolines. [So] Source: Org Lett;17(10):2396-9, 2015 May 15. [Is] ISSN: 1523-7052 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The first organocatalytic enantioselective oxidative C-H functionalization of N-acyl tetrahydroisoquinolines with vinyl and aryl boronates promoted by a chiral Brønsted acid is described. This metal-free process tolerates a wide range of electronically varied N-acyl tetrahydroisoquinolines and structurally diverse boronates with good to excellent enantioselectivities. [Mh] Termos MeSH primário: Ácidos Borônicos/química Etilenocloroidrina/análogos & derivados Tetra-Hidroisoquinolinas/química Trifluoretanol/química [Mh] Termos MeSH secundário: Catálise Etilenocloroidrina/química Estrutura Molecular Estereoisomerismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Boronic Acids); 0 (Tetrahydroisoquinolines); 75-89-8 (Trifluoroethanol); 753N66IHAN (Ethylene Chlorohydrin); AW835AJ62N (2,2,2-trichloroethanol) [Em] Mês de entrada: 1510 [Cu] Atualização por classe: 150515 [Lr] Data última revisão: 150515 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150506 [St] Status: MEDLINE [do] DOI: 10.1021/acs.orglett.5b00909

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[PMID]: 25424545 [Au] Autor: Yoo HS; Bradford BU; Kosyk O; Uehara T; Shymonyak S; Collins LB; Bodnar WM; Ball LM; Gold A; Rusyn I [Ad] Endereço: a Department of Environmental Sciences and Engineering , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA. [Ti] Título: Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. [So] Source: J Toxicol Environ Health A;78(1):32-49, 2015. [Is] ISSN: 1528-7394 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal-cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, interspecies and interindividual differences, and the mode of action for kidney carcinogenicity. It was postulated that TCE renal metabolite levels are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In subacute study, interstrain differences in renal TCE metabolite levels were observed. In addition, data showed that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In subchronic study, peroxisome proliferator-marker gene induction and renal toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ but not C57BL/6J mice. Overall, data demonstrated that renal TCE metabolite levels are associated with kidney-specific toxicity and that these effects are strain dependent. [Mh] Termos MeSH primário: Rim/efeitos dos fármacos Tricloroetileno/farmacocinética Tricloroetileno/toxicidade [Mh] Termos MeSH secundário: Animais Carcinógenos/farmacocinética Carcinógenos/toxicidade Proliferação Celular/efeitos dos fármacos Cisteína/análogos & derivados Cisteína/metabolismo Sistema Enzimático do Citocromo P-450/genética Sistema Enzimático do Citocromo P-450/metabolismo Ácido Dicloroacético/metabolismo Etilenocloroidrina/análogos & derivados Etilenocloroidrina/metabolismo Glutationa/análogos & derivados Glutationa/metabolismo Receptor Celular 1 do Vírus da Hepatite A Rim/citologia Rim/metabolismo Masculino Proteínas de Membrana/genética Proteínas de Membrana/metabolismo Camundongos Camundongos Endogâmicos C57BL Camundongos Endogâmicos Oxirredução/efeitos dos fármacos PPAR alfa/genética PPAR alfa/metabolismo Ácido Tricloroacético/metabolismo [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Carcinogens); 0 (Cyp4a10 protein, mouse); 0 (Havcr1 protein, mouse); 0 (Hepatitis A Virus Cellular Receptor 1); 0 (Membrane Proteins); 0 (PPAR alpha); 290YE8AR51 (Trichloroethylene); 5V2JDO056X (Trichloroacetic Acid); 627-72-5 (S-(1,2-dichlorovinyl)cysteine); 753N66IHAN (Ethylene Chlorohydrin); 9035-51-2 (Cytochrome P-450 Enzyme System); 96614-59-4 (S-(1,2-dichlorovinyl)glutathione); 9LSH52S3LQ (Dichloroacetic Acid); AW835AJ62N (2,2,2-trichloroethanol); GAN16C9B8O (Glutathione); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1501 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141127 [St] Status: MEDLINE [do] DOI: 10.1080/15287394.2015.958418

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[PMID]: 25424544 [Au] Autor: Yoo HS; Bradford BU; Kosyk O; Shymonyak S; Uehara T; Collins LB; Bodnar WM; Ball LM; Gold A; Rusyn I [Ad] Endereço: a Department of Environmental Sciences and Engineering , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA. [Ti] Título: Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: liver effects. [So] Source: J Toxicol Environ Health A;78(1):15-31, 2015. [Is] ISSN: 1528-7394 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of interindividual variability in TCE metabolism and toxicity, especially in the liver. A hypothesis was tested that amounts of oxidative metabolites of TCE in mouse liver are associated with hepatic-specific toxicity. Oral dosing with TCE was conducted in subacute (600 mg/kg/d; 5 d; 7 inbred mouse strains) and subchronic (100 or 400 mg/kg/d; 1, 2, or 4 wk; 2 inbred mouse strains) designs. The quantitative relationship was evaluated between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P-450-mediated oxidation (trichloroacetic acid [TCA], dichloroacetic acid [DCA], and trichloroethanol) and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various hepatic toxicity phenotypes. In subacute study, interstrain variability in TCE metabolite amounts was observed in serum and liver. No marked induction of Cyp2e1 protein levels in liver was detected. Serum and hepatic levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1 but not with degree of induction in hepatocellular proliferation. In subchronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Hepatic protein levels of CYP2E1, ADH, and ALDH2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. [Mh] Termos MeSH primário: Fígado/efeitos dos fármacos Tricloroetileno/farmacocinética Tricloroetileno/toxicidade [Mh] Termos MeSH secundário: Administração Oral Animais Carcinógenos/farmacocinética Carcinógenos/toxicidade Proliferação Celular Cisteína/análogos & derivados Cisteína/sangue Sistema Enzimático do Citocromo P-450/genética Sistema Enzimático do Citocromo P-450/metabolismo Ácido Dicloroacético/sangue Relação Dose-Resposta a Droga Etilenocloroidrina/análogos & derivados Etilenocloroidrina/metabolismo Expressão Gênica Glutationa/análogos & derivados Glutationa/sangue Hepatócitos/efeitos dos fármacos Hepatócitos/metabolismo Fígado/citologia Fígado/metabolismo Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Endogâmicos Oxirredução/efeitos dos fármacos Estresse Oxidativo/efeitos dos fármacos Reação em Cadeia da Polimerase em Tempo Real Solventes/farmacocinética Solventes/toxicidade Ácido Tricloroacético/sangue [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Carcinogens); 0 (Cyp4a10 protein, mouse); 0 (Solvents); 290YE8AR51 (Trichloroethylene); 5V2JDO056X (Trichloroacetic Acid); 627-72-5 (S-(1,2-dichlorovinyl)cysteine); 753N66IHAN (Ethylene Chlorohydrin); 9035-51-2 (Cytochrome P-450 Enzyme System); 96614-59-4 (S-(1,2-dichlorovinyl)glutathione); 9LSH52S3LQ (Dichloroacetic Acid); AW835AJ62N (2,2,2-trichloroethanol); GAN16C9B8O (Glutathione); K848JZ4886 (Cysteine) [Em] Mês de entrada: 1501 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141127 [St] Status: MEDLINE [do] DOI: 10.1080/15287394.2015.958417

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[PMID]: 25345596 [Au] Autor: Yang R; Lao QC; Yu HP; Zhang Y; Liu HC; Luan L; Sun HM; Li CQ [Ad] Endereço: National Institutes for Food and Drug Control, China Food and Drug Administration (CFDA), No. 2 Tiantan Xili, Dongcheng District, Beijing, 100050, China. [Ti] Título: Tween-80 and impurity induce anaphylactoid reaction in zebrafish. [So] Source: J Appl Toxicol;35(3):295-301, 2015 Mar. [Is] ISSN: 1099-1263 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: A number of recent reports suspected that Tween-80 in injectable medicines, including traditional Chinese medicine injections could cause life-threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug-induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate-based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N-benzoyl-dl-arginine p-nitroanilide as a substrate. We assessed 10 batches of Tween-80 solutions from various national and international suppliers and three Tween-80 impurities (ethylene glycol, 2-chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween-80 (nos 2, 20080709 and 20080616) and one Tween-80 impurity, hydrogen peroxide (H2 O2 ), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H2 O2 residue and peroxide value were much higher in Tween-80 samples 2, 20080709 and 20080616. These findings suggest that H2 O2 residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween-80 samples, but not Tween-80 itself, may induce anaphylactoid reaction. High-throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween-80-containing injectable medicines and potentially for screening novel mast cell-modulating drugs. [Mh] Termos MeSH primário: Anafilaxia/induzido quimicamente Contaminação de Medicamentos Excipientes/toxicidade Polissorbatos/toxicidade Peixe-Zebra/imunologia [Mh] Termos MeSH secundário: Anafilaxia/enzimologia Anafilaxia/imunologia Animais Medicamentos de Ervas Chinesas/administração & dosagem Etilenocloroidrina/química Etilenocloroidrina/toxicidade Etilenoglicol/química Etilenoglicol/toxicidade Excipientes/química Ensaios de Triagem em Larga Escala Peróxido de Hidrogênio/química Peróxido de Hidrogênio/toxicidade Intestinos/efeitos dos fármacos Mastócitos/efeitos dos fármacos Polissorbatos/química Triptases/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Drugs, Chinese Herbal); 0 (Excipients); 0 (Polysorbates); 753N66IHAN (Ethylene Chlorohydrin); BBX060AN9V (Hydrogen Peroxide); EC 3.4.21.59 (Tryptases); FC72KVT52F (Ethylene Glycol) [Em] Mês de entrada: 1510 [Cu] Atualização por classe: 150128 [Lr] Data última revisão: 150128 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141028 [St] Status: MEDLINE [do] DOI: 10.1002/jat.3069

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