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[PMID]:23850400
[Au] Autor:Shi X; Yu S
[Ad] Endereço:Department of Geriatric Neurology, Chinese PLA General Hospital, Haidian District, Beijing, China.
[Ti] Título:Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity.
[So] Source:J Clin Neurosci;20(10):1387-9, 2013 Oct.
[Is] ISSN:1532-2653
[Cp] País de publicação:Scotland
[La] Idioma:eng
[Ab] Resumo:Trichloropropane (TCP) and dichlorohydrin are widely used in industrial production; however, TCP and dichlorohydrin poisoning are rarely encountered in clinical practice. There have been no cases of peripheral neurotoxicity previously reported. A cluster of 23 patients who had been exposed to high levels of TCP and dichlorohydrin presented with painful peripheral neuropathy, and the pain was assessed using a visual analogue scale (VAS). Nerve conduction studies (NCS) were performed in all patients. All patients demonstrated symmetrical pin-prick pain in a stocking distribution in the lower limbs, with VAS scores between 3 and 10, with an average score of 6.8. NCS showed a mild mixture of axonal and demyelinating sensorimotor polyneuropathy in 14 of the 23 patients. After administration of standard neuropathic pain medication, pain was relieved in most patients. Painful peripheral neuropathy was the primary symptom observed in our patients, which differs from clinical and animal model reports of TCP or dichlorohydrin poisoning. However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves.
[Mh] Termos MeSH primário: Neuralgia/sangue
Neuralgia/induzido quimicamente
Síndromes Neurotóxicas/sangue
Síndromes Neurotóxicas/etiologia
Tricloroepoxipropano/envenenamento
[Mh] Termos MeSH secundário: Adulto
Alanina Transaminase/sangue
Aspartato Aminotransferases/sangue
Creatina Quinase/sangue
Feminino
Seguimentos
Seres Humanos
L-Lactato Desidrogenase/sangue
Masculino
Condução Nervosa
Neuralgia/complicações
Síndromes Neurotóxicas/complicações
Medição da Dor
Tricloroepoxipropano/análogos & derivados
Tricloroepoxipropano/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
3083-23-6 (Trichloroepoxypropane); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 2.7.3.2 (Creatine Kinase)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:131009
[Lr] Data última revisão:
131009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130716
[St] Status:MEDLINE


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[PMID]:22804946
[Au] Autor:Liu X; Qiu ZW; Shen W; Peng XB
[Ad] Endereço:Department of Emergency, Chinese PLA Postgraduate Medical School, Beijing 100853,China.
[Ti] Título:[The clinical analysis of 18 cases with acute trichloropropane poisoning].
[So] Source:Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi;30(4):307-9, 2012 Apr.
[Is] ISSN:1001-9391
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To summarise the clinical features of 18 cases with acute trichloropropane (TCP) poisoning for improving the diagnosis and treatment of the disease. METHODS: Exposure history, clinical manifestations, laboratorial examinations, poisoning causes and treatment were retrospectively reviewed in 18 cases with acute TCP poisoning. The results of peripheral lymphocyte micronucleus tests were compared with the healthy control group (n = 33). RESULTS: The common clinical symptoms were as following: respiratory symptoms were the earlier one set, such as chest tightness in 13, dry and sore throat in 7, cough and runny nose in 2. Gastrointestinal symptoms were more common, such as abdominal pain in 18, nausea and vomit in 14. Only 1 out of 18 patients was found with liver injury. The major manifestation was the increase in ALT and AST, which was returned to normal after treatment. ALL of the 18 patients were found TCP in their serum which concentration was from 39.0 to 310.0 ng/ml, and the average was (68.9 ± 42.1) ng/ml. The symptoms of toxic peripheral neuropathy were typical in all the patients, such as fatigue and numb limb in 18, burning pain of the distal lower limbs in 14, the symmetrical sock-like sensory dysfunction of pain, touch and vibration of the lower limbs in 13, muscle strength reduced in 7, hyporeflexia knee-jerks in 4, hyporeflexia ankle-jerks in 3. The peripheral nerve conduction velocity (NCV) examinations were as followed: the (sensore-nerve conduction velocity) SCV of peroneus super nerve in 18 and the (motor-nerve conduction velocity) MCV of tibial nerve in 8 was slowed down and the distal latency in 18 was prolonged. Micronucleus were found in all 18 cases. The micronucleus rate was 10.06‰ ± 2.80‰ and 8.24‰ ± 2.67‰ in acute TCP poisoning group and healthy control group, respectively. The difference was significant (P < 0.05). CONCLUSION: The common clinical manifestations of respiratory exposure of TCP poisoning patients were respiratory symptoms, gastrointestinal symptoms and the symptoms of toxic peripheral neuropathy. Liver injury in those 18 cases was not obvious. Lymphocyte micronucleus of peripheral blood were found in all 18 cases.
[Mh] Termos MeSH primário: Gastroenteropatias/induzido quimicamente
Doenças do Sistema Nervoso Periférico/induzido quimicamente
Doenças Respiratórias/induzido quimicamente
Tricloroepoxipropano/envenenamento
[Mh] Termos MeSH secundário: Adolescente
Adulto
Estudos de Casos e Controles
Feminino
Gastroenteropatias/diagnóstico
Gastroenteropatias/terapia
Seres Humanos
Masculino
Condução Nervosa
Doenças do Sistema Nervoso Periférico/diagnóstico
Doenças do Sistema Nervoso Periférico/terapia
Doenças Respiratórias/diagnóstico
Doenças Respiratórias/terapia
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
3083-23-6 (Trichloroepoxypropane)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:120718
[Lr] Data última revisão:
120718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120719
[St] Status:MEDLINE


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[PMID]:18397838
[Au] Autor:Zhao S; Zhao E; Shen P; Zhao M; Sun J
[Ad] Endereço:Department of Chemistry, Xinzhou Teachers University, Xinzhou 034000, China. sanhuzhao@yahoo.cn
[Ti] Título:An atom-efficient and practical synthesis of new pyridinium ionic liquids and application in Morita-Baylis-Hillman reaction.
[So] Source:Ultrason Sonochem;15(6):955-9, 2008 Sep.
[Is] ISSN:1350-4177
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:New ionic liquids containing (3-chloro-2-hydroxypropyl)-functionalized pyridinium cations have been synthesized by the ultrasound-assisted, atom-efficient, room temperature reaction of pyridine with acid and 3-chloro-propylene oxide, the acid providing the anionic component of the resultant ionic liquids, and under the ultrasound, a clear yield increase results and a dramatic reduction of the reaction time accompanied by an improved quality of the products occurs. Furthermore, the application of new ionic liquids were tested as solvents in Morita-Baylis-Hillman reaction, in some cases, good results were obtained.
[Mh] Termos MeSH primário: Compostos de Piridínio/síntese química
[Mh] Termos MeSH secundário: Alquilantes/química
Catálise
Cromatografia em Camada Delgada
Indicadores e Reagentes
Espectroscopia de Ressonância Magnética
Compostos de Piridínio/química
Tricloroepoxipropano/química
Ultrassom
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Alkylating Agents); 0 (Indicators and Reagents); 0 (Pyridinium Compounds); 3083-23-6 (Trichloroepoxypropane)
[Em] Mês de entrada:0809
[Cu] Atualização por classe:080609
[Lr] Data última revisão:
080609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080410
[St] Status:MEDLINE
[do] DOI:10.1016/j.ultsonch.2008.02.011


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[PMID]:14663952
[Au] Autor:Shi KH; Zhang X; Zhang JF
[Ad] Endereço:Department of Cardiovasic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P. R. China 510080.
[Ti] Título:[Experimental study of xenogeneic heart valve material].
[So] Source:Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi;17(6):496-500, 2003 Nov.
[Is] ISSN:1002-1892
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To explore the possibility of improving the performance of tissue engineering valve by means of preendothelialization with cultured human umbilical vein endothelial cell(hUVEC) and to develop a new xenogenic bioprosthesis valve material. METHODS: The porcine aortic valves treated by use of glutaraldehyde(GA), epoxychloropropane(EC), L-glutamic acid(L-GA) and cellular extraction(CE) respectively were divided into four groups; group 1(GA), group 2(EC), group 3(EC + L-GA), and group 4(EC + L-GA + CE). The cultured hUVECs were seeded onto the treated porcine aortic valve, then that stuff were examined by means of EC VIII factor staining, living cells counting and microscopy. RESULTS: The cultured hUVEC could adhere to culturing bottle wall an hour later, and propagated to two passages after seven days. The cells increased with serial passage at a 7-day interval. But the hUVEC grew slowly when seeded onto the treated valve material except group 4. The cells in group 4 covered the surface of valve completely seven days later, which could also be seen in group 3 but not completely. There was no cell growing in group 1, and only fewer in group 2. The living cell in groups 3 and 4 were significantly more than in groups 1 and 2 on the 3rd, 7th and 14th days (P < 0.01), meanwhile, the number of cells in group 4 were also significantly more than that in group 3 (P < 0.05). The covering area of cultured cell on the valve material in groups 3 and 4 was significantly larger than that in groups 1 and 2. The covering area of cell in group 4 was over 95%, and higher than that in group 3(60%-70%). The hUVEC of group 4 arranged in pattern of three dimension. So it could resist rising of foreign power from the cardiac cavity of high pressure and flowing volume. There was no cell on the leaflet surface in group 1, and only a few pinch of cells could be seen in group 2. CONCLUSION: The porcine aortic valve can be used to be an ideal xenogeneic valve scaffold; the scaffold of porcine aortic valve should be treated by use of epoxy-chloropropane, L-glutamic acid and cellular extraction, so that a best growing environment to the hUVEC would be given; the cultured hUVECs used to be source of seed living cell had a boundless prospects; the growing velocity of cultured hUVEC was controllable, which facilitated clinical application; and the endothelial cells of xenogeneic valve material which grew compactly onto the scaffold can resist rising of foreign power from the cardiac cavity itself.
[Mh] Termos MeSH primário: Bioprótese
Endotélio Vascular/citologia
Próteses Valvulares Cardíacas
Engenharia Tecidual/métodos
[Mh] Termos MeSH secundário: Animais
Valva Aórtica
Adesão Celular
Contagem de Células
Células Cultivadas
Endotélio Vascular/ultraestrutura
Ácido Glutâmico/farmacologia
Glutaral/farmacologia
Seres Humanos
Desenho de Prótese
Suínos
Tricloroepoxipropano/farmacologia
Veias Umbilicais/citologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
3083-23-6 (Trichloroepoxypropane); 3KX376GY7L (Glutamic Acid); T3C89M417N (Glutaral)
[Em] Mês de entrada:0407
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:031211
[St] Status:MEDLINE


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[PMID]:10426800
[Au] Autor:Lovern MR; Maris ME; Schlosser PM
[Ad] Endereço:Chemical Industry Institute of Toxicology, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
[Ti] Título:Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data.
[So] Source:Carcinogenesis;20(8):1511-20, 1999 Aug.
[Is] ISSN:0143-3334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Benzene, a ubiquitous environmental pollutant, is known to cause leukemia and aplastic anemia in humans and hematotoxicity and myelotoxicity in rodents. Toxicity is thought to be exerted through oxidative metabolites formed in the liver, primarily via pathways mediated by cytochrome P450 2E1 (CYP2E1). Phenol, hydroquinone and trans-trans-muconaldehyde have all been hypothesized to be involved in benzene-induced toxicity. Recent reports indicate that benzene oxide is produced in vitro and in vivo and may be sufficiently stable to reach the bone marrow. Our goal was to improve existing mathematical models of microsomal benzene metabolism by including time course data for benzene oxide, by obtaining better parameter estimates and by determining if enzymes other than CYP2E1 are involved. Microsomes from male B6C3F1 mice and F344 rats were incubated with [(14)C]benzene (14 microM), [(14)C]phenol (303 microM) and [(14)C]hydroquinone (8 microM). Benzene and phenol were also incubated with mouse microsomes in the presence of trans-dichloroethylene, a CYP2E1 inhibitor, and benzene was incubated with trichloropropene oxide, an epoxide hydrolase inhibitor. These experiments did not indicate significant contributions of enzymes other than CYP2E1. Mathematical model parameters were fitted to rodent data and the model was validated by predicting human data. Model simulations predicted the qualitative behavior of three human time course data sets and explained up to 81% of the total variation in data from incubations of benzene for 16 min with microsomes from nine human individuals. While model predictions did deviate systematically from the data for benzene oxide and trihydroxybenzene, overall model performance in predicting the human data was good. The model should be useful in quantifying human risk due to benzene exposure and explicitly accounts for interindividual variation in CYP2E1 activity.
[Mh] Termos MeSH primário: Benzeno/metabolismo
Carcinógenos/metabolismo
Citocromo P-450 CYP2E1/metabolismo
Microssomos Hepáticos/metabolismo
Modelos Biológicos
[Mh] Termos MeSH secundário: Animais
Inibidores do Citocromo P-450 CYP2E1
Inibidores Enzimáticos/farmacologia
Seres Humanos
Masculino
Camundongos
Microssomos Hepáticos/efeitos dos fármacos
Compostos de Amônio Quaternário/farmacologia
Ratos
Ratos Endogâmicos F344
Tricloroepoxipropano/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carcinogens); 0 (Cytochrome P-450 CYP2E1 Inhibitors); 0 (Enzyme Inhibitors); 0 (Quaternary Ammonium Compounds); 3083-23-6 (Trichloroepoxypropane); CBU2X6BBJR (tetrabutylammonium); EC 1.14.13.- (Cytochrome P-450 CYP2E1); J64922108F (Benzene)
[Em] Mês de entrada:9909
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:990730
[St] Status:MEDLINE


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[PMID]:9483718
[Au] Autor:Morel JG; Neerchal NK
[Ad] Endereço:Procter & Gamble Company, Biostatistics & Medical Surveillance Department, Mason, Ohio 45040-9462, USA.
[Ti] Título:Clustered binary logistic regression in teratology data using a finite mixture distribution.
[So] Source:Stat Med;16(24):2843-53, 1997 Dec 30.
[Is] ISSN:0277-6715
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The beta-binomial distribution introduced by Skellam has been applied in many teratology problems for modelling the litter effect. Recently, Morel and Nagaraj proposed a new distribution for modelling cluster multinomial data when the clustering is believed to be caused by clumped sampling. It turns out that the distribution is a mixture of two binomial distributions and accommodates the estimation of an additional parameter to account for intra-litter effect. The new distribution arises from a cluster mechanism in which some individuals within a cluster exhibit the same behaviour while the remaining individuals from the cluster react independently of each other. Such a mechanism is a natural model in teratology problems, where typically a genetic trait is passed with a certain probability to the foetuses of the same litter. In this article, we use the new distribution to model binary responses with logistic regression. We analyse data from a teratology experiment to demonstrate that the new model provides a useful addition to current methodology. The experiment investigates the synergistic effect of the anticonvulsant phenytoin and trichloropopene oxide on the prenatal development of inbred mice. In a simulation study we investigate the type I error rate and the power of the maximum likelihood ratio test when the data follow a finite mixture distribution.
[Mh] Termos MeSH primário: Análise por Conglomerados
Modelos Logísticos
Teratologia/estatística & dados numéricos
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/toxicidade
Desenvolvimento Ósseo/efeitos dos fármacos
Simulação por Computador
Sinergismo Farmacológico
Inibidores Enzimáticos/toxicidade
Feminino
Funções Verossimilhança
Camundongos
Camundongos Endogâmicos
Razão de Chances
Fenitoína/toxicidade
Gravidez
Tricloroepoxipropano/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Enzyme Inhibitors); 3083-23-6 (Trichloroepoxypropane); 6158TKW0C5 (Phenytoin)
[Em] Mês de entrada:9804
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:980304
[St] Status:MEDLINE


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[PMID]:8961944
[Au] Autor:Shou M; Gonzalez FJ; Gelboin HV
[Ad] Endereço:Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
[Ti] Título:Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase.
[So] Source:Biochemistry;35(49):15807-13, 1996 Dec 10.
[Is] ISSN:0006-2960
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stereoselective epoxidation by cytochrome P450s (P450s) and regioselective hydration by epoxide hydrolase determine the carcinogenic potency of some polycyclic aromatic hydrocarbons (PAHs). In this report, cDNA-expressed human and mouse P450s 1A1 and 1A2 and epoxide hydrolase were used to characterize the stereoselective epoxidation and regioselective hydration at the K-region of benz[a]-anthracene (BA), 7,12-dimethylbenz[a]anthracene (DMBA), chrysene (CR), benzo[a]pyrene (B[a]P), dibenz[a,h]anthracene (DB[a,h]A), and benzo[c]phenanthrene (B[c]Ph) by direct chiral stationary-phase HPLC (CSP-HPLC) analyses. Our results indicated that all P450 isoforms preferentially produced major K-region, S,R-epoxides of BA (95-98%), DMBA (94-97%), B[a]P (91-96%), DB[a,h]A (94-98%), and B[c]Ph (87-92%), and major R,S-epoxide of CR (74-85%) in the presence of 3,3,3-trichloropropylene 1,2-oxide (TCPO), an inhibitor of epoxide hydrolase, suggesting that P450 enzymes exhibited the high stereoselectivity toward one of two stereoheterotopic faces of K-region double bond of the PAHs. Epoxide hydrolase either expressed from recombinant vaccinia virus or contained in human hepatoma G2 cells (HepG2) hydrated the C-O bond of epoxy-ring at the S-carbon of major metabolically-formed K-region epoxide enantiomers of BA, CR, DMBA, B[a]P, and DB[a,h]A to yield 80-98% dihydrodiols enriched in R,R-form and that at the R-carbon of B[c]Ph epoxide to yield 77-92% dihydrodiol enriched in S,S-form, suggesting that epoxide hydrolase was highly regioselective. The various enantiomeric components of dihydrodiol products in the metabolism of PAHs were apparently due to the combined effect of stereoselectivity of the P450s and regioselectivity of epoxide hydrolase. Our results provide a clear understanding of how these enzymes catalyze overall stereoselective metabolism at the K-region of the PAHs.
[Mh] Termos MeSH primário: Citocromo P-450 CYP1A1/metabolismo
Citocromo P-450 CYP1A2/metabolismo
Epóxido Hidrolases/metabolismo
Compostos de Epóxi/metabolismo
Hidrocarbonetos Aromáticos Policíclicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Antracenos/metabolismo
Baculoviridae/genética
Crisenos/metabolismo
Citocromo P-450 CYP1A1/genética
Citocromo P-450 CYP1A2/genética
Di-Hidroxi-Di-Hidrobenzopirenos/metabolismo
Inibidores Enzimáticos/farmacologia
Epóxido Hidrolases/antagonistas & inibidores
Expressão Gênica/genética
Seres Humanos
Camundongos
Modelos Químicos
Conformação Molecular
Estrutura Molecular
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Tricloroepoxipropano/farmacologia
Vírus Vaccinia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthracenes); 0 (Chrysenes); 0 (Dihydroxydihydrobenzopyrenes); 0 (Enzyme Inhibitors); 0 (Epoxy Compounds); 0 (Polycyclic Aromatic Hydrocarbons); 0 (Recombinant Proteins); 084HCM49PT (chrysene); 3083-23-6 (Trichloroepoxypropane); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); EC 3.3.2.- (Epoxide Hydrolases)
[Em] Mês de entrada:9701
[Cu] Atualização por classe:161124
[Lr] Data última revisão:
161124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:961210
[St] Status:MEDLINE


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[PMID]:8870989
[Au] Autor:Sahali-Sahly Y; Balani SK; Lin JH; Baillie TA
[Ad] Endereço:Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
[Ti] Título:In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4.
[So] Source:Chem Res Toxicol;9(6):1007-12, 1996 Sep.
[Is] ISSN:0893-228X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:L-754,394, a furanopyridine derivative, is an experimental anti-HIV agent which has been shown to be an unusually potent and selective inhibitor of cytochrome P450 3A enzymes in a number of mammalian species. In the present studies, L-754,394 was demonstrated to undergo NADPH-dependent metabolic activation in hepatic microsomal preparations from rats, dogs, rhesus monkeys, and humans to electrophilic intermediates which became bound covalently to cellular proteins. The extent of binding was species-dependent, the highest levels being observed with liver microsomes from rhesus monkeys. Inclusion in incubation media of the nucleophilic trapping agents glutathione, cysteine, or methoxyamine led to a modest (15-25%) decrease in the covalent binding, while trichloropropylene oxide, an inhibitor of epoxide hydrolase, had no effect. When L-754,394 was incubated with monkey liver microsomes, the corresponding dihydrofurandiol was identified as a metabolite by liquid chromatography-tandem mass spectrometry. In contrast, when incubations were carried out in the presence of methoxyamine, the O-methyloxime derivative of the ring-opened dihydrodiol tautomer was formed, while inclusion of glutathione or N-acetylcysteine led to the formation of S-linked conjugates of a putative furan epoxide. Collectively, these results are taken to indicate that L-754,394 undergoes cytochrome P450-dependent oxidation of the fused furan ring system, leading to the formation of chemically-reactive intermediates. One or more of these electrophilic species may be responsible for the autocatalytic destruction of cytochrome P450 enzymes which accompanies L-754,394 metabolism in vitro and in vivo.
[Mh] Termos MeSH primário: Inibidores das Enzimas do Citocromo P-450
Inibidores Enzimáticos/metabolismo
Indanos/metabolismo
Microssomos Hepáticos/metabolismo
Oxigenases de Função Mista/antagonistas & inibidores
Piperazinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Biotransformação
Citocromo P-450 CYP3A
Sistema Enzimático do Citocromo P-450/metabolismo
Cães
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Hidroxilaminas/farmacologia
Técnicas In Vitro
Indanos/química
Macaca mulatta
Masculino
Microssomos Hepáticos/enzimologia
Oxigenases de Função Mista/metabolismo
NADP/metabolismo
Oxirredução
Piperazinas/química
Ligação Proteica
Ratos
Ratos Sprague-Dawley
Especificidade da Espécie
Tricloroepoxipropano/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 Enzyme Inhibitors); 0 (Enzyme Inhibitors); 0 (Hydroxylamines); 0 (Indans); 0 (L 754394); 0 (Piperazines); 3083-23-6 (Trichloroepoxypropane); 53-59-8 (NADP); 9035-51-2 (Cytochrome P-450 Enzyme System); 9TZH4WY30J (methoxyamine); EC 1.- (Mixed Function Oxygenases); EC 1.14.14.1 (CYP3A protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A)
[Em] Mês de entrada:9701
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:960901
[St] Status:MEDLINE


  9 / 62 MEDLINE  
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[PMID]:8765137
[Au] Autor:Moghaddam M; Motoba K; Borhan B; Pinot F; Hammock BD
[Ad] Endereço:Department of Entomology, University of California, Davis 95616, USA.
[Ti] Título:Novel metabolic pathways for linoleic and arachidonic acid metabolism.
[So] Source:Biochim Biophys Acta;1290(3):327-39, 1996 Aug 13.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mouse liver microsomes oxidized linoleic acid to form 9,10- or 12,13-epoxyoctadecenoate. These monoepoxides were subsequently hydrolyzed to their corresponding diols in the absence of the microsomal epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropane. Furthermore, both 9,10- and 12,13-epoxyoctadecenoates were oxidized to diepoxyoctadecanoate at apparently identical rates by mouse liver microsomal P-450 epoxidation. Both epoxyoctadecanoates and diepoxyoctadecanoates were converted to tetrahydrofuran-diols by microsomes. Tetrahydroxides of linoleate were produced as minor metabolites. Arachidonic acid was metabolized to epoxyeicosatrienoates, dihydroxyeicosatrienoates, and monohydroxyeicosatetraenoates by the microsomes. Microsomes prepared from clofibrate (but not phenobarbital) -treated mice exhibited much higher production rates for epoxyeicosatrienoates and vic-dihydroxyeicosatrienoates. This indicated an induction of P-450 epoxygenase(s) and microsomal epoxide hydrolase in mice by clofibrate and not by phenobarbital. Incubation of synthetic epoxyeicosatrienoates with microsomes led to the production of diepoxyeicosadienoates. Among chemically generated diepoxyeicosadienoate isomers, three of them possessing adjacent diepoxides were hydrolyzed to their diol epoxides which cyclized to the corresponding tetrahydrofuran-diols by microsomes as well as soluble epoxide hydrolase at a much higher rate. Larger cyclic products from non-adjacent diepoxides were not observed. The results of our in vitro experiments suggest that linoleic and arachidonic acid can be metabolized to their tetrahydrofuran-diols by two consecutive microsomal cytochrome P-450 epoxidations followed by microsomal or soluble epoxide hydrolase catalyzed hydrolysis of the epoxides. Incubation experiments with the S-9 fractions indicate that the soluble epoxide hydrolase is more important in this conversion. This manuscript is the first report of techniques for the separation and identification of regio and geometrical isomer of an interesting class of oxylipins and their metabolism by liver microsomes and S-9 fractions to THF-diols.
[Mh] Termos MeSH primário: Ácido Araquidônico/metabolismo
Compostos de Epóxi/metabolismo
Ácidos Linoleicos/metabolismo
Microssomos Hepáticos/metabolismo
[Mh] Termos MeSH secundário: Animais
Clofibrato/farmacologia
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos
Indução Enzimática
Inibidores Enzimáticos/farmacologia
Epóxido Hidrolases/antagonistas & inibidores
Compostos de Epóxi/química
Ácido Linoleico
Masculino
Camundongos
Oxirredução
Fenobarbital/farmacologia
Tricloroepoxipropano/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Epoxy Compounds); 0 (Linoleic Acids); 27YG812J1I (Arachidonic Acid); 3083-23-6 (Trichloroepoxypropane); 9035-51-2 (Cytochrome P-450 Enzyme System); 9KJL21T0QJ (Linoleic Acid); EC 3.3.2.- (Epoxide Hydrolases); HPN91K7FU3 (Clofibrate); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:9609
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:960813
[St] Status:MEDLINE


  10 / 62 MEDLINE  
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Fotocópia
[PMID]:8656450
[Au] Autor:Gadberry MG; DeNicola DB; Carlson GP
[Ad] Endereço:Department of Pharmacology and Toxicology, Purdue University, West Lafayette, Indiana 47907-1334, USA.
[Ti] Título:Pneumotoxicity and hepatotoxicity of styrene and styrene oxide.
[So] Source:J Toxicol Environ Health;48(3):273-94, 1996 Jun 28.
[Is] ISSN:0098-4108
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to investigate the toxicity of styrene and styrene oxide in the lung in comparison to the toxicity in the liver. Pneumotoxicity caused by styrene or styrene oxide was measured by elevations in the release of gamma-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) into bronchoalveolar lavage fluid (BALF), while hepatotoxicity was measured by increases in serum sorbitol dehydrogenase (SDH) in non-Swiss Albino (Hsd:NSA) mice. Intraperitoneal administration of styrene at doses of 500-1000 mg/kg caused consistent dose-dependent increases in both sets of biomarkers with the hepatic effect appearing earlier than the pulmonary effect. Pyridine, phenobarbital, and beta-naphthoflavone, inducers of CYP2E1, CYP2B, and CYP1A, respectively, increased the toxicity of styrene. Pyridine and phenobarbital treatments increased mortality due to styrene. Styrene oxide exists in two enantiomeric forms: (R)- and (S)-styrene oxide, and the differential toxicities of the two enantiomers and racemic styrene oxide were compared. In all studies, (R)-styrene oxide caused greater toxicity than the (S) enantiomer, especially in the liver. Trichloropropene oxide, an epoxide hydrolase inhibitor, was used to inhibit styrene oxide detoxification and increased its hepatotoxicity, while buthionine sulfoxamine, a glutathione depletor, did not. These results demonstrated the greater role of epoxide hydrolase in styrene oxide detoxification.
[Mh] Termos MeSH primário: Carcinógenos/toxicidade
Doença Hepática Induzida por Substâncias e Drogas
Compostos de Epóxi/toxicidade
Pneumopatias/induzido quimicamente
Estirenos/toxicidade
[Mh] Termos MeSH secundário: Animais
Benzoflavonas/farmacologia
Líquido da Lavagem Broncoalveolar/química
Butionina Sulfoximina
Carcinógenos/administração & dosagem
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos
Sistema Enzimático do Citocromo P-450/metabolismo
Compostos de Epóxi/administração & dosagem
Injeções Intraperitoneais
L-Iditol 2-Desidrogenase/sangue
L-Iditol 2-Desidrogenase/metabolismo
L-Lactato Desidrogenase/metabolismo
Fígado/enzimologia
Fígado/patologia
Hepatopatias/patologia
Masculino
Metionina Sulfoximina/análogos & derivados
Metionina Sulfoximina/farmacologia
Camundongos
Fenobarbital/farmacologia
Piridinas/farmacologia
Estireno
Estirenos/administração & dosagem
Tricloroepoxipropano/farmacologia
beta-Naftoflavona
gama-Glutamiltransferase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Benzoflavones); 0 (Carcinogens); 0 (Epoxy Compounds); 0 (Pyridines); 0 (Styrenes); 1982-67-8 (Methionine Sulfoximine); 3083-23-6 (Trichloroepoxypropane); 44LJ2U959V (Styrene); 5072-26-4 (Buthionine Sulfoximine); 6051-87-2 (beta-Naphthoflavone); 9035-51-2 (Cytochrome P-450 Enzyme System); 9QH06NGT6O (styrene oxide); EC 1.1.1.14 (L-Iditol 2-Dehydrogenase); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.3.2.2 (gamma-Glutamyltransferase); NH9L3PP67S (pyridine); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:9607
[Cu] Atualização por classe:161123
[Lr] Data última revisão:
161123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:960628
[St] Status:MEDLINE



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