Base de dados : MEDLINE
Pesquisa : E01.370.225.843 [Categoria DeCS]
Referências encontradas : 22508 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 2251 ir para página                         

  1 / 22508 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28463419
[Au] Autor:Lin C; Khetani SR
[Ad] Endereço:School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado.
[Ti] Título:Micropatterned Co-Cultures of Human Hepatocytes and Stromal Cells for the Assessment of Drug Clearance and Drug-Drug Interactions.
[So] Source:Curr Protoc Toxicol;72:14.17.1-14.17.23, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug clearance rates from the body can determine drug exposure that can affect efficacy or toxicity. Thus, accurate prediction of drug clearance during preclinical development can help guide dose selection in humans, but animal testing is not always predictive of human outcomes. Because hepatic drug metabolism is a rate-limiting step in the overall clearance of many drugs, primary human hepatocytes (PHHs) in suspension cultures or monolayers are used for drug clearance predictions. Yet, the precipitous decline in drug metabolism capacity can lead to significant underestimation of clearance rates, particularly for low turnover compounds that have desirable one-pill-a-day dosing regimens. In contrast, micropatterned co-cultures (MPCCs) of PHHs and fibroblasts display phenotypic stability for several weeks and can help mitigate the limitations of conventional cultures. Here, we describe protocols to create and use MPCCs for drug clearance predictions, and for modeling clinically-relevant drug-drug interactions that can affect drug clearance. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Técnicas de Cocultura/métodos
Interações Medicamentosas
Hepatócitos/metabolismo
Preparações Farmacêuticas/metabolismo
Células Estromais/metabolismo
[Mh] Termos MeSH secundário: Células 3T3
Animais
Técnicas de Cultura de Células
Meios de Cultura
Fibroblastos/metabolismo
Hepatócitos/ultraestrutura
Seres Humanos
Taxa de Depuração Metabólica
Camundongos
Fenótipo
Células Estromais/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Pharmaceutical Preparations)
[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.23


  2 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28468837
[Au] Autor:Lu W; Rettenmeier E; Paszek M; Yueh MF; Tukey RH; Trottier J; Barbier O; Chen S
[Ad] Endereço:Laboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, California (W.L., E.R., M.P., M-F.Y., R.H.T., S.C.); and Laboratory of Molecular Pharmacology, CHU de Quebec Research Centre and Faculty of Pharmacy, Laval University, Québec (Québec),
[Ti] Título:Crypt Organoid Culture as an in Vitro Model in Drug Metabolism and Cytotoxicity Studies.
[So] Source:Drug Metab Dispos;45(7):748-754, 2017 Jul.
[Is] ISSN:1521-009X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The gastrointestinal tract is enriched with xenobiotic processing proteins that play important roles in xenobiotic bioactivation, metabolism, and detoxification. The application of genetically modified mouse models has been instrumental in characterizing the function of xenobiotic processing genes (XPG) and their proteins in drug metabolism. Here, we report the utilization of three-dimensional crypt organoid cultures from these animal models to study intestinal drug metabolism and toxicity. With the successful culturing of crypt organoids, we profiled the abundance of Phase I and Phase II XPG expression, drug transporter gene expression, and xenobiotic nuclear receptor (XNR) gene expression. Functions of XNRs were examined by treating crypt cells with XNR prototypical agonists. Real-time quantitative polymerase chain reaction demonstrated that the representative downstream target genes were induced. These findings were validated from cultures developed from XNR-null mice. In crypt cultures isolated from mice, pregnenolone 16 -carbonitrile failed to induce gene expression; similarly, WY14643 failed to induce in the crypts. Crypt cultures from control ( ) and intestinal epithelial cell (IEC) specific null mice ( ) were treated with camptothecin-11, an anticancer prodrug with severe intestinal toxicity that originates from insufficient UGT1A1-dependent glucuronidation of its active metabolite SN-38. In the absence of gene expression, crypt cultures exhibit very limited production of SN-38 glucuronide, concordant with increased apoptosis in comparison with crypt cultures. This study suggests crypt organoid cultures as an effective in vitro model for studying intestinal drug metabolism and toxicity.
[Mh] Termos MeSH primário: Camptotecina/análogos & derivados
Inativação Metabólica/fisiologia
Organoides/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Camptotecina/metabolismo
Técnicas de Cultura de Células/métodos
Citocromo P-450 CYP3A/metabolismo
Expressão Gênica/fisiologia
Intestinos/metabolismo
Taxa de Depuração Metabólica/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Xenobióticos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Xenobiotics); 7673326042 (irinotecan); EC 1.14.14.1 (Cytochrome P-450 CYP3A); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1124/dmd.117.075945


  3 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27778050
[Au] Autor:Sörgel F; Höhl R; Glaser R; Stelzer C; Munz M; Vormittag M; Kinzig M; Bulitta J; Landersdorfer C; Junger A; Christ M; Wilhelm M; Holzgrabe U
[Ad] Endereço:IBMP - Institut für Biomedizinische und Pharmazeutische Forschung, Paul-Ehrlich-Straße 19, 90562, Nürnberg-Heroldsberg, Deutschland. ibmp@osn.de.
[Ti] Título:[Pharmacokinetics and pharmacodynamics of antibiotics in intensive care].
[Ti] Título:Pharmakokinetik und Pharmakodynamik von Antibiotika in der Intensivmedizin..
[So] Source:Med Klin Intensivmed Notfmed;112(1):11-23, 2017 Feb.
[Is] ISSN:2193-6226
[Cp] País de publicação:Germany
[La] Idioma:ger
[Ab] Resumo:Optimized dosage regimens of antibiotics have remained obscure since their introduction. During the last two decades pharmacokinetic(PK)-pharmacodynamic(PD) relationships, originally established in animal experiments, have been increasingly used in patients. The action of betalactams is believed to be governed by the time the plasma concentration is above the minimum inhibitory concentration (MIC). Aminoglycosides act as planned when the peak concentration is a multiple of the MIC and vancomycin seems to work best when the area under the plasma vs. time curve (AUC) to MIC has a certain ratio. Clinicians should be aware that these relationships can only be an indication in which direction dosing should go. Larger studies with sufficiently high numbers of patients and particularly severely sick patients are needed to prove the concepts. In times where all antibiotics can be measured with new technologies, the introduction of therapeutic drug monitoring (TDM) is suggested for ICUs (Intensive Care Unit). The idea of a central lab for TDM of antibiotics such as PEAK (Paul Ehrlich Antibiotika Konzentrationsmessung) is supported.
[Mh] Termos MeSH primário: Antibacterianos/farmacocinética
Cuidados Críticos
[Mh] Termos MeSH secundário: Antibacterianos/uso terapêutico
Monitoramento de Medicamentos
Feminino
Meia-Vida
Seres Humanos
Unidades de Terapia Intensiva
Masculino
Espectrometria de Massas
Taxa de Depuração Metabólica/fisiologia
Testes de Sensibilidade Microbiana
Penicilinas/farmacocinética
Penicilinas/uso terapêutico
Ligação Proteica/fisiologia
Valores de Referência
Vancomicina/farmacocinética
Vancomicina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Penicillins); 6Q205EH1VU (Vancomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00063-016-0185-5


  4 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29384603
[Au] Autor:Tan LW; Ma BY; Zhao Q; Zhang L; Chen LJ; Peng JR; Qian ZY
[Ti] Título:Toxicity Evaluation and Anti-Tumor Study of Docetaxel Loaded mPEG-Polyester Micelles for Breast Cancer Therapy.
[So] Source:J Biomed Nanotechnol;13(4):393-408, 2017 Apr.
[Is] ISSN:1550-7033
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.
[Mh] Termos MeSH primário: Nanocápsulas/administração & dosagem
Nanocápsulas/toxicidade
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/metabolismo
Taxoides/administração & dosagem
Taxoides/farmacocinética
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/farmacocinética
Apoptose/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Células MCF-7
Taxa de Depuração Metabólica
Camundongos
Micelas
Nanocápsulas/ultraestrutura
Neoplasias Experimentais/patologia
Especificidade de Órgãos
Tamanho da Partícula
Taxoides/toxicidade
Distribuição Tecidual
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Micelles); 0 (Nanocapsules); 0 (Taxoids); 15H5577CQD (docetaxel)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE


  5 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29177262
[Au] Autor:Pietrzak A; Czepczynski R; Wierzchoslawska E; Cholewinski W
[Ad] Endereço:Nuclear Medicine Department, Greater Poland Cancer Centre, Garbary 15 Street, 60-101 Poznan, Poland. Agata.pietrzakk@gmail.com.
[Ti] Título:Metabolic activity in bone metastases of breast and prostate cancer were similar as studied by F-FDG PET/CT. The role of Tc-MDP.
[So] Source:Hell J Nucl Med;20(3):237-240, 2017 Sep-Dec.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to compare the metabolic activity of metastatic foci from breast and prostate cancer patients as scanned by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( F-FDG PET/CT) and by technetium-99m methyl diphosphonate ( Tc-MDP) bone scan (BS). SUBJECTS AND METHODS: Forty one patients were studied, divided into 2 groups based on histologically confirmed diagnosis: a) Breast cancer group, 23 women, mean age: 61±12 years, range: 37-79 years and, b) Prostate cancer group, 18 men, mean age 68±8 years, range: 52-82 years. Another group of 17 non cancer atherosclerotic subjects 9 women and 8 men, of mean age and age range similar to the above were also studied for comparison. The R index (the total count rate in bone metastases divided by the total count rate in a contralateral area), the maximum semi-quantitative standardized uptake value (SUVmax) of BS lesions and the mean number of metastases were evaluated. For the metastatic findings in the PET/CT scans the automatic method of contouring with 50% background cut-off was used, while for the Tc-MDP BS metastases were delineated manually. RESULTS: The mean R index of the bone metastatic foci studied by F-FDG PET/CT was 1.89±0.69 for Groups I and II patients. There was no significant difference of the R index between prostate cancer and breast cancer metastases (1.95±0.86 vs 1.83±0.52). The average SUVmax value was significantly higher in breast cancer patients than in prostate cancer patients (5.15±2.54 vs 4.01±1.71; P<0.05). There was no significant correlation in both cancer groups between R index and SUVmax values. The number of metastatic foci diagnosed by the Tc-MDP BS scan was much less than by the F-FDG PET/CT. CONCLUSION: No significant correlation was noticed in the metabolic activity-glucose utilization of metastatic bone foci between breast and prostate cancer cases. This observation validates the independent value of analyzed diagnostic methods and suggests negligible influence of glucose utilization in bone re-modeling in the above metastatic cancer cells. The F-FDG PET/CT bone scan was much better in diagnosing metastases compared to the Tc-MDP scan.
[Mh] Termos MeSH primário: Neoplasias Ósseas/metabolismo
Neoplasias Ósseas/secundário
Neoplasias da Mama/metabolismo
Fluordesoxiglucose F18/farmacocinética
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
Neoplasias da Próstata/metabolismo
Medronato de Tecnécio Tc 99m/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Neoplasias Ósseas/diagnóstico por imagem
Neoplasias da Mama/diagnóstico por imagem
Feminino
Seres Humanos
Masculino
Taxa de Depuração Metabólica
Meia-Idade
Neoplasias da Próstata/diagnóstico por imagem
Neoplasias da Próstata/patologia
Compostos Radiofarmacêuticos/farmacocinética
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Distribuição Tecidual
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18); X89XV46R07 (Technetium Tc 99m Medronate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1967/s002449910608


  6 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29177259
[Au] Autor:Yoo ID; Lee SM; Lee JW; Oh JE; Cho YJ; Shin HS
[Ad] Endereço:Department of Nuclear Medicine, Soonchunhyang University, Cheonan Hospital, 6-31 Soonchunhyang-gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea. gareen@naver.com.
[Ti] Título:The influence of adipose tissue volume can significantly affect the metabolic activity of reference organs in F-FDG PET/CT studies of a normal healthy population.
[So] Source:Hell J Nucl Med;20(3):211-216, 2017 Sep-Dec.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: This study investigated whether fluorine-18-fluorodeoxyglucose ( F-FDG) uptake of reference organs can be affected by subjects' factors in positron emission tomography/computed tomography (PET/CT) in a healthy population. SUBJECTS AND METHODS: A total of 208 normal healthy subjects without diabetes or dyslipidemia were included. Adipose tissue volume was measured by CT images from a dedicated PET/CT scan. Uptake of F-FDG of reference organs was measured from liver, blood pool, and muscle, and was normalized by lean body anthropometric data and adipose tissue volume. RESULTS: Of 208 participants, 118 were metabolically healthy lean (MHL); with body mass index (BMI) <25kg/m and 90 were metabolically healthy obese (MHO) with; BMI≥25kg/m . These subjects had significantly higher values of liver, blood pool, and muscle than did the MHL subjects (P<0.001 for both). Among subjects' factors, adipose tissue volume revealed strongest correlation with standardized uptake value multiplied by lean body weight divided by body weight (SUL) of liver (r=0.754, P<0.001), of blood pool (r=0.756, P<0.001) and of muscle (r=0.635, P<0.001). On regression analysis, adipose tissue volume was determined to be a common independent predictor for SUL of liver, blood pool and muscle (P<0.001) and furthermore was serum C-reactive protein level for SUL of the liver and also age and serum insulin level for SUL of blood pool. CONCLUSION: Adipose tissue volume can significantly affect SUL of liver, blood pool, and muscle in a healthy population. Liver and blood pool may have limited roles as reference organs for normalization of F-FDG uptake of the lesion.
[Mh] Termos MeSH primário: Tecido Adiposo/fisiologia
Artefatos
Fluordesoxiglucose F18/farmacocinética
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas
Vísceras/metabolismo
[Mh] Termos MeSH secundário: Tecido Adiposo/anatomia & histologia
Adulto
Feminino
Seres Humanos
Masculino
Taxa de Depuração Metabólica/fisiologia
Tamanho do Órgão
Especificidade de Órgãos/fisiologia
Compostos Radiofarmacêuticos/farmacocinética
Valores de Referência
Reprodutibilidade dos Testes
República da Coreia
Sensibilidade e Especificidade
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1967/s002449910605


  7 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29177256
[Au] Autor:Chen Y; Huang J; Wang Y; Xie S; He F
[Ad] Endereço:Nuclear medicine department of Quanzhou, East Road 248#, Licheng District, Quanzhou City, China, 362000. 1526797743@qq.com.
[Ti] Título:Errors in the absorbed and the administered I therapeutic dose in patients with Graves' disease. A suggested more precise technique.
[So] Source:Hell J Nucl Med;20(3):217-221, 2017 Sep-Dec.
[Is] ISSN:1790-5427
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to evaluate the relative error (RE) in the thyroid absorbed dose (TD) of iodine-131 ( I) in patients with Graves' disease comparing the simplified Quimby-Marinelli-Hine formula method (sQMHF) and the Standard Operational Procedures for dosimetry (SOPD) recommended by the European Association of Nuclear Medicine. PATIENTS AND METHODS: This study included 45 patients with Graves' disease 12 men and 33 women; age 44.1±12.8 years. Thyroid mass (TM) was measured using ultrasound. Uptake of I (RAIU) was tested at 2, 4-6, 24, 48-72, and 96-168h after its administration and the half-life (T ) and resident time (RT) of I were computed. According to the sQMHF, a prescribed TD of 75Gy required 3.7MBq/g of I, correction based on the RAIU and T . Subsequently, the therapeutic TD was computed according to the SOPD and the RE was recorded. The data were analyzed using t-tests. RESULTS: The TM, RAIU , therapeutic TD, and RE were 36.5±23.9g, 0.54±0.14, 89.4±9.4Gy, and -0.01±0.02, respectively. There was a significant difference (t-value 9.84, P<0.01) between the prescribed and therapeutic TD because the sQMHF ignores the absorbed dose deposited in the thyroid during the first 24h, which is included in the SOPD. In addition, the RE was significantly smaller than the variable coefficient (VC) of the therapeutic TD (t=-39.6, P<0.01). CONCLUSION: When the activity of I was calculated using the simplified Q-M-H formula, the therapeutic absorbed thyroid dose was significantly higher than what was expected for the prescribed dose. Precision of the individualized therapeutic absorbed dose could be improved by computing the activity of I using the standard operational procedures for dosimetry of the EANM.
[Mh] Termos MeSH primário: Absorção Fisico-Química
Esquema de Medicação
Doença de Graves/metabolismo
Doença de Graves/radioterapia
Radioisótopos do Iodo/administração & dosagem
Radioisótopos do Iodo/farmacocinética
Erros de Medicação/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Taxa de Depuração Metabólica
Compostos Radiofarmacêuticos/administração & dosagem
Compostos Radiofarmacêuticos/farmacocinética
Dosagem Radioterapêutica
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iodine Radioisotopes); 0 (Iodine-131); 0 (Radiopharmaceuticals)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1967/s002449910602


  8 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29277574
[Au] Autor:Caspar AT; Meyer MR; Maurer HH
[Ad] Endereço:Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg, Germany.
[Ti] Título:Human cytochrome P450 kinetic studies on six N-2-methoxybenzyl (NBOMe)-derived new psychoactive substances using the substrate depletion approach.
[So] Source:Toxicol Lett;285:1-8, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A huge number of new chemical derivatives of known drugs of abuse, so-called new psychoactive substances (NPS), are sold and consumed without prior preclinical and clinical testing. For assessing the elimination behaviors, determination of the kinetic constants K and V of the cytochrome P450 (CYP) isoforms involved in the hepatic metabolism of NPS could help to predict their contributions to hepatic clearance, drug-drug interactions and polymorphisms. Therefore, the aims of the present study were to determine the K and V values for CYP isoforms using the substrate depletion approach for the six N-2-methoxybenzyl (NBOMe)-derived NPS 25B-NBOMe, 25C-NBOMe, 25I-NBOMe, 3,4-DMA-NBOMe, 4-EA-NBOMe, and 4-MMA-NBOMe. Furthermore, the contributions of each CYP isozyme to the hepatic net clearance were elucidated using the relative activity factor approach. Several CYPs including CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 were identified to be involved in the metabolism of the investigated compounds. The determined K values ranged from 0.010 µM (CYP2D6, 4-MMA-NBOMe) to 13 µM (CYP2B6, 4-EA-NBOMe). All NBOMes were good substrates of CYP2C19 and CYP2D6 resulting in very low K values in the nanomolar range. The main contributors to hepatic net clearance were CYP2D6 for 25B-NBOMe (69%), 25C-NBOMe (83%), 25I-NBOMe (61%), 3,4-DMA-NBOMe (89%) as well as for 4-EA-NBOMe (62%) and CYP2C19 for 4-MMA-NBOMe (64%). As more than one isoform was involved in the particular steps, the risk of harm associated with drug-drug interactions might be considered low. However, in cases where substances with high contributions from polymorphically expressed CYP2C19 and CYP2D6 are encountered, inter-individual variations in metabolism and excretion cannot be excluded.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacocinética
Sistema Enzimático do Citocromo P-450/metabolismo
Microssomos Hepáticos/enzimologia
Psicotrópicos/farmacocinética
Drogas Ilícitas/farmacocinética
[Mh] Termos MeSH secundário: Animais
Compostos de Benzil/química
Sistema Enzimático do Citocromo P-450/genética
Interações Medicamentosas
Seres Humanos
Técnicas In Vitro
Cinética
Taxa de Depuração Metabólica
Microssomos Hepáticos/metabolismo
Modelos Biológicos
Psicotrópicos/química
Drogas Ilícitas/química
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Psychotropic Drugs); 0 (Street Drugs); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  9 / 22508 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29307833
[Au] Autor:Irie M; Hayakawa E; Fujimura Y; Honda Y; Setoyama D; Wariishi H; Hyodo F; Miura D
[Ad] Endereço:Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
[Ti] Título:Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.
[So] Source:Biochem Biophys Res Commun;496(1):140-146, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method.
[Mh] Termos MeSH primário: Lesão Renal Aguda/induzido quimicamente
Lesão Renal Aguda/metabolismo
Cisplatino/efeitos adversos
Rim/efeitos dos fármacos
Rim/metabolismo
Metaboloma
Análise Espaço-Temporal
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida/métodos
Cisplatino/administração & dosagem
Relação Dose-Resposta a Droga
Masculino
Espectrometria de Massas/métodos
Taxa de Depuração Metabólica
Camundongos
Camundongos Endogâmicos C57BL
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  10 / 22508 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29247645
[Au] Autor:Qin C; Yang L; Zheng W; Yan X; Lu R; Xie D; Nie G
[Ad] Endereço:Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, College of Fisheries, Henan Normal University, No. 46 Jianshe Road, Xinxiang 453007, PR China.
[Ti] Título:Effects of dietary glucose and sodium chloride on intestinal glucose absorption of common carp (Cyprinus carpio L.).
[So] Source:Biochem Biophys Res Commun;495(2):1948-1955, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a.m.. Then we designed iso-nitrogenous and iso-energetic diets with graded levels of glucose (10%, 20%, 30%, 40% and 50%) and NaCl (0%, 1%, 3% and 5%), and submitted to feeding trial for 10 weeks. The expressions of SGLT1 and GLUT2, brush border membrane vesicles (BBMVs) glucose transport and intestinal villus height were determined after the feeding trial. Increasing levels of dietary glucose and NaCl up-regulated mRNA and protein levels of SGLT1 and GLUT2, enhanced BBMVs glucose transport in the proximal, mid and distal intestine. As for histological adaptive response, however, high-glucose diet prolonged while high-NaCl diet shrank intestinal villus height. Furthermore, we also found that higher mRNA levels of SGLT1 and GLUT2, higher glucose transport capacity of BBMVs, and higher intestinal villus were detected in the proximal and mid intestine, compared to the distal part. Taken together, our study indicated that intestinal glucose absorption in carp was primarily occurred in the proximal and mid intestine, and increasing levels of dietary glucose and NaCl enhanced intestinal glucose absorption in carp.
[Mh] Termos MeSH primário: Carpas/metabolismo
Açúcares da Dieta/metabolismo
Ingestão de Alimentos/fisiologia
Glucose/metabolismo
Absorção Intestinal/fisiologia
Cloreto de Sódio na Dieta/metabolismo
[Mh] Termos MeSH secundário: Animais
Taxa de Depuração Metabólica
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dietary Sugars); 0 (Sodium Chloride, Dietary); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE



página 1 de 2251 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde