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  1 / 1135 MEDLINE  
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[PMID]:28844238
[Au] Autor:Ono Y; Tomimori N; Hori H; Kitagawa Y; Shibata H
[Ad] Endereço:Suntory Wellness Limited, 8-1-1 Seikadai, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan. Electronic address: Yoshiko_Toyoda@suntory.co.jp.
[Ti] Título:Mechanisms of chromosomal aberrations induced by sesamin metabolites in Chinese hamster lung cells.
[So] Source:Mutat Res;822:19-26, 2017 Oct.
[Is] ISSN:1873-135X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sesamin is a major lignan in sesame seeds and oil. We previously demonstrated that sesamin induces chromosomal aberrations (CA) in Chinese hamster lung (CHL/IU) cells in the presence of a metabolic activation system (S9 mix), although no genotoxicity was detected in vivo. To clarify the mechanism of CA induction by sesamin, we identified its principal active metabolite. A mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (SC-1)], was previously identified in culture medium when sesamin was incubated with S9 mix. In the present study, we show that SC-1 induces CA in CHL/IU cells but not in human hepatoblastoma (HepG2) cells. SC-1 was unstable in culture medium. Addition of glutathione (GSH) to the incubation mixture decreased the rate of decomposition and also suppressed induction of CA in CHL/IU cells. These results indicate that SC-1 itself may not contribute to the induction of CA. Two GSH adducts of SC-1 were identified when SC-1 was incubated with GSH, suggesting that SC-1 was converted to the semiquinone/quinone form and then conjugated with GSH in the culture medium. Sodium sulfite (a quinone-responsive compound) also suppressed CA induction by SC-1. These findings strongly suggest that SC-1 is oxidized to semiquinone/quinone derivatives extracellularly in culture medium, that these derivatives are responsible for the induction of CA in CHL/IU cells, and therefore that the positive results obtained with sesamin in in vitro CA tests using CHL/IU cells may not be relevant to the assessment of in vivo activity.
[Mh] Termos MeSH primário: Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade
Aberrações Cromossômicas/induzido quimicamente
Ciclo-Octanos/toxicidade
Dioxóis/toxicidade
Lignanas/toxicidade
[Mh] Termos MeSH secundário: Animais
Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo
Técnicas de Cultura de Células
Cricetinae
Ciclo-Octanos/metabolismo
Dioxóis/metabolismo
Relação Dose-Resposta a Droga
Glutationa/metabolismo
Células Hep G2
Seres Humanos
Lignanas/metabolismo
Fígado/metabolismo
Extratos Hepáticos
Pulmão/citologia
Pulmão/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Cyclooctanes); 0 (Dioxoles); 0 (Lignans); 0 (Liver Extracts); GAN16C9B8O (Glutathione); S7946O4P76 (sesamin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


  2 / 1135 MEDLINE  
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[PMID]:27487575
[Au] Autor:Fay KA; Fitzsimmons PN; Hoffman AD; Nichols JW
[Ad] Endereço:National Health and Environmental Effects Research Laboratory, Office of Research and Development, Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA.
[Ti] Título:Comparison of trout hepatocytes and liver S9 fractions as in vitro models for predicting hepatic clearance in fish.
[So] Source:Environ Toxicol Chem;36(2):463-471, 2017 Feb.
[Is] ISSN:1552-8618
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Isolated hepatocytes and liver S9 fractions have been used to collect in vitro biotransformation data for fish as a means of improving modeled estimates of chemical bioaccumulation. To date, however, there have been few direct comparisons of these 2 methods. In the present study, cryopreserved trout hepatocytes were used to measure in vitro intrinsic clearance rates for 6 polycyclic aromatic hydrocarbons (PAHs). These rates were extrapolated to estimates of in vivo intrinsic clearance and used as inputs to a well stirred liver model to predict hepatic clearance. Predicted rates of hepatic clearance were then evaluated by comparison with measured rates determined previously using isolated perfused livers. Hepatic clearance rates predicted using hepatocytes were in good agreement with measured values (<2.1-fold difference for 5 of 6 compounds) under 2 competing binding assumptions. These findings, which may be attributed in part to high rates of PAH metabolism, are similar to those obtained previously using data from liver S9 fractions. For 1 compound (benzo[a]pyrene), the in vivo intrinsic clearance rate calculated using S9 data was 10-fold higher than that determined using hepatocytes, possibly due to a diffusion limitation on cellular uptake. Generally, however, there was good agreement between calculated in vivo intrinsic clearance rates obtained using either in vitro test system. These results suggest that both systems can be used to improve bioaccumulation assessments for fish, particularly when vitro rates of activity are relatively high, although additional work is needed to determine if the chemical domain of applicability for each system differs. Environ Toxicol Chem 2017;36:463-471. Published 2016 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
[Mh] Termos MeSH primário: Hepatócitos/metabolismo
Extratos Hepáticos/metabolismo
Fígado/metabolismo
Modelos Biológicos
Oncorhynchus mykiss/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzo(a)pireno/farmacocinética
Biotransformação
Células Cultivadas
Cinética
Taxa de Depuração Metabólica
Hidrocarbonetos Aromáticos Policíclicos/farmacocinética
Cultura Primária de Células
Poluentes Químicos da Água/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liver Extracts); 0 (Polycyclic Aromatic Hydrocarbons); 0 (Water Pollutants, Chemical); 3417WMA06D (Benzo(a)pyrene)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1002/etc.3572


  3 / 1135 MEDLINE  
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[PMID]:27934284
[Au] Autor:Chen Y; Hermens JL; Jonker MT; Arnot JA; Armitage JM; Brown T; Nichols JW; Fay KA; Droge ST
[Ad] Endereço:Institute for Risk Assessment Sciences, Utrecht University , Utrecht, 3508 TD, The Netherlands.
[Ti] Título:Which Molecular Features Affect the Intrinsic Hepatic Clearance Rate of Ionizable Organic Chemicals in Fish?
[So] Source:Environ Sci Technol;50(23):12722-12731, 2016 Dec 06.
[Is] ISSN:1520-5851
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Greater knowledge of biotransformation rates for ionizable organic compounds (IOCs) in fish is required to properly assess the bioaccumulation potential of many environmentally relevant contaminants. In this study, we measured in vitro hepatic clearance rates for 50 IOCs using a pooled batch of liver S9 fractions isolated from rainbow trout (Oncorhynchus mykiss). The IOCs included four types of strongly ionized acids (carboxylates, phenolates, sulfonates, and sulfates), three types of strongly ionized bases (primary, secondary, tertiary amines), and a pair of quaternary ammonium compounds (QACs). Included in this test set were several surfactants and a series of beta-blockers. For linear alkyl chain IOC analogues, biotransformation enzymes appeared to act directly on the charged terminal group, with the highest clearance rates for tertiary amines and sulfates and no clearance of QACs. Clearance rates for C -IOCs were higher than those for C -IOC analogues. Several analogue series with multiple alkyl chains, branched alkyl chains, aromatic rings, and nonaromatic rings were evaluated. The likelihood of multiple reaction pathways made it difficult to relate all differences in clearance to specific molecular features the tested IOCs. Future analysis of primary metabolites in the S9 assay is recommended to further elucidate biotransformation pathways for IOCs in fish.
[Mh] Termos MeSH primário: Fígado/metabolismo
Oncorhynchus mykiss/metabolismo
[Mh] Termos MeSH secundário: Animais
Biotransformação
Extratos Hepáticos/metabolismo
Compostos Orgânicos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liver Extracts); 0 (Organic Chemicals)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE


  4 / 1135 MEDLINE  
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[PMID]:26947351
[Au] Autor:Ladd MA; Fitzsimmons PN; Nichols JW
[Ad] Endereço:a United States Environmental Protection Agency (US EPA), ORD, NHEERL, Mid-Continent Ecology Division , Duluth , MN , USA.
[Ti] Título:Optimization of a UDP-glucuronosyltransferase assay for trout liver S9 fractions: activity enhancement by alamethicin, a pore-forming peptide.
[So] Source:Xenobiotica;46(12):1066-1075, 2016 Dec.
[Is] ISSN:1366-5928
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. An existing assay for UDP-glucuronosyltransferase (UGT) activity in trout liver microsomes was optimized using trout liver S9 fractions. Individual experiments were conducted to determine the time dependence of UGT activity as well as optimal levels of S9 protein, uridine 5'-diphosphoglucuronic acid (UDPGA), substrate (p-nitrophenol) and alamethicin, a pore-forming agent added to eliminate latency. 2. Addition of Mg (to 1 mM) or bovine serum albumin (BSA; to 2% w/v) had variable effects on activity, but these effects were minor. Eliminating alamethicin from the system resulted in very low levels of activity. A portion of this activity could be recovered by adding Triton X-100 or Brij 58; however, the optimal concentration range for either detergent was very narrow. 3. When expressed on a pmol/min/g liver basis, UGT activities determined using this updated assay were substantially higher than those reported previously for uninduced trout. 4. These results clearly demonstrate the advantages of using alamethicin for the removal of latency in UGT activity studies with trout and may have broad implications for the study of UGTs in other fish species.
[Mh] Termos MeSH primário: Alameticina/farmacologia
Bioensaio/métodos
Glucuronosiltransferase/metabolismo
Ionóforos/farmacologia
Extratos Hepáticos/metabolismo
[Mh] Termos MeSH secundário: Animais
Fígado
Truta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ionophores); 0 (Liver Extracts); 27061-78-5 (Alamethicin); EC 2.4.1.17 (Glucuronosyltransferase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170214
[Lr] Data última revisão:
170214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160308
[St] Status:MEDLINE


  5 / 1135 MEDLINE  
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[PMID]:26668056
[Au] Autor:Li Y; Zong Y; Xiao Z; Zhu M; Xiao H; Qi J; Liu K; Wang H
[Ad] Endereço:Department of Molecular Biology, Hebei Key Lab of Laboratory Animal, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
[Ti] Título:Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation.
[So] Source:Dig Dis Sci;61(4):1098-106, 2016 Apr.
[Is] ISSN:1573-2568
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood. AIM: The developmental stage-specific embryonic induction of tumor cell differentiation was investigated. METHODS: Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4α RNA interference was used to verify the role of HNF-4α. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice. RESULTS: The 9-11-days chick liver extracts and 13.5-14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4α, HNF-1α, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4α RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4α, confirming this embryonic induction effect in vivo. CONCLUSIONS: This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis.
[Mh] Termos MeSH primário: Indução Embrionária
Células Hep G2/fisiologia
[Mh] Termos MeSH secundário: Animais
Embrião de Galinha
Fator 4 Nuclear de Hepatócito/metabolismo
Seres Humanos
Extratos Hepáticos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HNF4A protein, human); 0 (Hepatocyte Nuclear Factor 4); 0 (Liver Extracts)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:151216
[St] Status:MEDLINE
[do] DOI:10.1007/s10620-015-3966-4


  6 / 1135 MEDLINE  
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[PMID]:26540984
[Au] Autor:Yan C; Xue G; Wu L; Liu J; Hou Y
[Ti] Título:[DIFFERENTIATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS INTO HEPATOCYTES INDUCED BY RAT FIBROTIC LIVER TISSUE EXTRACTS].
[So] Source:Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi;29(7):878-83, 2015 Jul.
[Is] ISSN:1002-1892
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To investigate the differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes induced by rat fibrotic liver tissue extracts. METHODS: Liver fibrosis was induced in the Sprague Dawley rats (weighting, 180-220 g) by repeated intraperitoneal injections of 3% thioacetamide-saline at a dose of 200 mg/kg twice a week for 4 weeks; fibrotic liver tissues were used to prepare liver homogenate supernatants. The HUCMSCs at passage 3 were cultured in DMEM/F12 with 10% fetal bovine serum (FBS) (control group) and in DMEM/F12 with 10% FBS and 50 g/L liver homogenate supernatants (experimental group) for 7 days. The morphological changes of the cells were recorded; the protein levels of cytokeratin 18 (CK18), alpha fetoprotein (AFP), and CYP3A4 were measured using Western blot. The glycogen storing ability of the cells was detected by periodic acid-schiff (PAS) staining. Furthermore, the synthesis of albumin (ALB) and blood urea nitrogen (BUN) was measured. RESULTS: In experimental group, after 1 day of induction, the stem cells of fusiform shape began to lose sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with round and irregular shape at 7 days. Positive expressions of AFP, CK18, and CYP3A4 were observed in the experimental group, but negative expression in the control group. The concentrations of BUN and ALB were (0.43 ± 0.07) mmol/L and (8.08 ± 0.41) µg/mL in the control group and were (2.52 ± 0.20) mmol/L and (41.48 ± 4.11) µg/mL in the experimental group, showing significant differences (t=24.160, P = 0.000; t = 19.810, P = 0.000). PAS staining results showed navy blue nucleus and lavender cytoplasm in the control group, but dark purple cell body and visible nucleus in the experimental group. CONCLUSION: HUCMSCs could differentiate into hepatocyte-like cells induced by rat fibrotic liver tissue extracts, which have hepatocyte biomarkers (AFP, CK18, and CYP3A4) and hepatocyte-specific functions of glycogen storage, urea production and ALB secretion, so they could partially replace the function of hepatocytes, that may be one of the therapeutic mechanisms of stem cell transplantation.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Sangue Fetal/citologia
Fator de Crescimento de Hepatócito/farmacologia
Hepatócitos/citologia
Extratos Hepáticos/farmacologia
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/fisiologia
Células Cultivadas
Transplante de Células-Tronco de Sangue do Cordão Umbilical
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Seres Humanos
Queratina-18/biossíntese
Fígado/embriologia
Células Mesenquimais Estromais/efeitos dos fármacos
Células Mesenquimais Estromais/metabolismo
Ratos
Ratos Sprague-Dawley
Células-Tronco/citologia
Células-Tronco/efeitos dos fármacos
Extratos de Tecidos
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Keratin-18); 0 (Liver Extracts); 0 (Tissue Extracts); 67256-21-7 (Hepatocyte Growth Factor)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:151106
[Lr] Data última revisão:
151106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151107
[St] Status:MEDLINE


  7 / 1135 MEDLINE  
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[PMID]:26349651
[Au] Autor:dos Santos GA; Ferreira MS; de Oliveira DN; de Oliveira V; Siqueira-Santos ES; Cintra DE; Castilho RF; Velloso LA; Catharino RR
[Ad] Endereço:INNOVARE Biomarkers Laboratory, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
[Ti] Título:Identification of compounds from high-fat and extra virgin olive oil-supplemented diets in whole mouse liver extracts and isolated mitochondria using mass spectrometry.
[So] Source:J Mass Spectrom;50(7):951-8, 2015 Jul.
[Is] ISSN:1096-9888
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nonalcoholic steatohepatitis (NASH) is a fatty liver disorder that could be improved with extra virgin olive oil (EVOO) supplementation in diet. We propose the monitoring, in whole mouse liver extracts and in isolated mitochondria, of the absorption of compounds from three different diets: standard (CT), high-fat (HFD) and high-fat supplemented with EVOO (HFSO). Male mice were submitted to one of the following three diets: CT or HFD for 16 weeks or HFD for 8 weeks followed by additional 8 weeks with HFSO. Following this period, liver was extracted for histological evaluation, mitochondria isolation and mass spectrometry analyses. Diets, liver extracts and Percoll-purified mitochondria were analyzed using ESI-MS and the lipidomics approach. Morphological, histological and spectrometric results indicated a decrease in NASH severity with EVOO supplementation in comparison with animals maintained with HFD. Spectrometric data also demonstrated that some compounds presented on the diets are absorbed by the mitochondria. EVOO was shown to be a potential therapeutic alternative in food for NASH. Our results are in accordance with the proposition that the major factor that influences different responses to diets is their composition - and not only calories - especially when it comes to studies on obesity.
[Mh] Termos MeSH primário: Dieta Hiperlipídica
Extratos Hepáticos/química
Mitocôndrias/química
Azeite de Oliva/metabolismo
Espectrometria de Massas por Ionização por Electrospray/métodos
[Mh] Termos MeSH secundário: Animais
Fígado/química
Fígado/efeitos dos fármacos
Fígado/metabolismo
Fígado/patologia
Masculino
Camundongos
Hepatopatia Gordurosa não Alcoólica/metabolismo
Obesidade
Azeite de Oliva/farmacologia
Análise de Componente Principal
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Liver Extracts); 0 (Olive Oil)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150909
[Lr] Data última revisão:
150909
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150910
[St] Status:MEDLINE
[do] DOI:10.1002/jms.3609


  8 / 1135 MEDLINE  
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[PMID]:26321157
[Au] Autor:Misaki K; Suzuki G; Tue NM; Takahashi S; Someya M; Takigami H; Tajima Y; Yamada TK; Amano M; Isobe T; Tanabe S
[Ad] Endereço:Center for Marine Environmental Studies (CMES), Ehime University , Bunkyo-cho 2-5, Matsuyama 790-8577, Ehime, Japan.
[Ti] Título:Toxic Identification and Evaluation of Androgen Receptor Antagonistic Activities in Acid-Treated Liver Extracts of High-Trophic Level Wild Animals from Japan.
[So] Source:Environ Sci Technol;49(19):11840-8, 2015 Oct 06.
[Is] ISSN:1520-5851
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sulfuric acid-treated liver extracts of representative high-trophic level Japanese animals were analyzed by toxic identification and evaluation (TIE) with chemically activated luciferase expression (CALUX) and chemical analysis to elucidate androgen receptor (AR) antagonistic activities and potential contributions of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). The activities were detected in striped dolphins (n = 5), Stejneger's beaked whales (n = 6), golden eagle (n = 1), and Steller's sea eagle (n = 1) with CALUX-flutamide equivalents (FluEQs) as follow: 38 (20-52), 47 (21-96), 5.0, and 80 µg FluEQ/g-lipid, respectively. The AR antagonism was detected in limited number of specimens at lower levels for finless porpoise, raccoon dog, and common cormorant. Theoretical activities (Theo-FluEQs) were calculated using the concentration of OCPs and PCBs and their IC25-based relative potency (REP) values. These total contribution to CALUX-FluEQ was 126%, 84%, 53%, 55%, and 44% for striped dolphin, Steller's sea eagle, Stejneger's beaked whale, finless porpoise, and golden eagle, respectively, and the main contributor was p,p'-DDE. However, most of the activities for raccoon dog (7.6%) and common cormorant (17%) could not be explained by OCPs and PCBs. This suggests other unknown compounds could function as AR antagonists in these terrestrial species.
[Mh] Termos MeSH primário: Antagonistas de Receptores de Andrógenos/análise
Ecotoxicologia/métodos
Extratos Hepáticos/análise
Praguicidas/análise
[Mh] Termos MeSH secundário: Antagonistas de Receptores de Andrógenos/metabolismo
Animais
Animais Selvagens/metabolismo
Aves
Diclorodifenil Dicloroetileno/análise
Águias
Monitoramento Ambiental/métodos
Cadeia Alimentar
Hidrocarbonetos Clorados/análise
Hidrocarbonetos Clorados/toxicidade
Japão
Extratos Hepáticos/metabolismo
Praguicidas/toxicidade
Bifenilos Policlorados/análise
Bifenilos Policlorados/toxicidade
Toninhas
Cães Guaxinins
Receptores Androgênicos/metabolismo
Poluentes Químicos da Água/análise
Poluentes Químicos da Água/metabolismo
Poluentes Químicos da Água/toxicidade
Baleias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Androgen Receptor Antagonists); 0 (Hydrocarbons, Chlorinated); 0 (Liver Extracts); 0 (Pesticides); 0 (Receptors, Androgen); 0 (Water Pollutants, Chemical); 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene); DFC2HB4I0K (Polychlorinated Biphenyls)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:151007
[Lr] Data última revisão:
151007
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150901
[St] Status:MEDLINE
[do] DOI:10.1021/acs.est.5b02288


  9 / 1135 MEDLINE  
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[PMID]:26275888
[Au] Autor:Nhung TH; Nam NH; Nguyen NT; Nghia H; Van Thanh N; Ngoc PK; Van Pham P
[Ad] Endereço:Laboratory of Stem Cell Research and Application, University of Science, VNU-HCM, HCM City, Vietnam. thnhung@hcmus.edu.vn.
[Ti] Título:A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells.
[So] Source:In Vitro Cell Dev Biol Anim;51(10):1085-92, 2015 Nov.
[Is] ISSN:1543-706X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 µg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte-like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Hepatopatias/terapia
Extratos Hepáticos/farmacologia
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Tecido Adiposo/citologia
Albuminas/biossíntese
Animais
Terapia Baseada em Transplante de Células e Tecidos/métodos
Células Cultivadas
Fatores de Crescimento de Fibroblastos/farmacologia
Glicogênio/metabolismo
Fator de Crescimento de Hepatócito/farmacologia
Seres Humanos
Camundongos
Oncostatina M/farmacologia
alfa 1-Antitripsina/biossíntese
alfa-Fetoproteínas/biossíntese
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Albumins); 0 (HGF protein, human); 0 (Liver Extracts); 0 (alpha 1-Antitrypsin); 0 (alpha-Fetoproteins); 106956-32-5 (Oncostatin M); 62031-54-3 (Fibroblast Growth Factors); 67256-21-7 (Hepatocyte Growth Factor); 9005-79-2 (Glycogen)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171105
[Lr] Data última revisão:
171105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150816
[St] Status:MEDLINE
[do] DOI:10.1007/s11626-015-9939-2


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[PMID]:26077187
[Au] Autor:Lo JC; Allard GN; Otton SV; Campbell DA; Gobas FA
[Ad] Endereço:Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
[Ti] Título:Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.
[So] Source:Environ Toxicol Chem;34(12):2782-90, 2015 Dec.
[Is] ISSN:1552-8618
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 µM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances.
[Mh] Termos MeSH primário: Poluentes Ambientais/análise
Poluentes Ambientais/metabolismo
Fígado/metabolismo
Modelos Biológicos
Oncorhynchus mykiss/metabolismo
[Mh] Termos MeSH secundário: Animais
Antracenos/análise
Antracenos/metabolismo
Benzo(a)pireno/análise
Benzo(a)pireno/metabolismo
Biotransformação
Crisenos/análise
Crisenos/metabolismo
Interações Hidrofóbicas e Hidrofílicas
Cinética
Extratos Hepáticos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthracenes); 0 (Chrysenes); 0 (Environmental Pollutants); 0 (Liver Extracts); 084HCM49PT (chrysene); 3417WMA06D (Benzo(a)pyrene); 65NK4CIN03 (9-methylanthracene)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150617
[St] Status:MEDLINE
[do] DOI:10.1002/etc.3117



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