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[PMID]:29339251
[Au] Autor:Carta A; Sanna G; Briguglio I; Madeddu S; Vitale G; Piras S; Corona P; Peana AT; Laurini E; Fermeglia M; Pricl S; Serra A; Carta E; Loddo R; Giliberti G
[Ad] Endereço:Department of Chemistry and Pharmacy, University of Sassari, Via Muroni 23, 07100 Sassari, Italy. Electronic address: acarta@uniss.it.
[Ti] Título:Quinoxaline derivatives as new inhibitors of coxsackievirus B5.
[So] Source:Eur J Med Chem;145:559-569, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses. Promisingly, three compounds showed a very potent and selective antiviral activity against coxsackievirus B5, with EC in the sub-micromolar range (0.3-0.06 µM). A combination of experimental techniques (i.e. virucidal activity, time of drug addition and adsorption assays) and in silico modeling studies were further performed, aiming to understand the mode of action of the most active, selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6-yl)methylthio]benzoate (6).
[Mh] Termos MeSH primário: Antivirais/farmacologia
Enterovirus Humano B/efeitos dos fármacos
Quinoxalinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antivirais/síntese química
Antivirais/química
Bovinos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Cricetinae
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Testes de Sensibilidade Microbiana
Modelos Moleculares
Estrutura Molecular
Quinoxalinas/síntese química
Quinoxalinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Quinoxalines)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  2 / 41685 MEDLINE  
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[PMID]:29324347
[Au] Autor:He L; Pei H; Zhang C; Shao M; Li D; Tang M; Wang T; Chen X; Xiang M; Chen L
[Ad] Endereço:State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China.
[Ti] Título:Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis.
[So] Source:Eur J Med Chem;145:96-112, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC = 21.70 ±â€¯0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC values over 30 µM. Moreover, B16 showed very weak potential to block the hERG channel (IC = 11.10 µM) in comparison to ibrutinib (IC = 0.97 µM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis.
[Mh] Termos MeSH primário: Artrite Reumatoide/tratamento farmacológico
Desenho de Drogas
Inibidores de Proteínas Quinases/farmacologia
Proteínas Tirosina Quinases/antagonistas & inibidores
Pirimidinas/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Animais
Artrite Reumatoide/metabolismo
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Cães
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Camundongos
Microssomos Hepáticos/química
Microssomos Hepáticos/metabolismo
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Tirosina Quinases/metabolismo
Pirimidinas/síntese química
Pirimidinas/química
Pirróis/síntese química
Pirróis/química
Ratos
Ratos Sprague-Dawley
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (7H-pyrrolo(2,3-d)pyrimidin-4-amine); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 0 (Pyrroles); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


  3 / 41685 MEDLINE  
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[PMID]:29297217
[Au] Autor:Musajo-Somma L; Musajo-Somma A
[Ti] Título:Medical Rejuvenation in Georgia in the past: the Sukhumi Station.
[So] Source:Vesalius;22(2 Suppl):59-66, 2016 Dec.
[Is] ISSN:1373-4857
[Cp] País de publicação:Belgium
[La] Idioma:eng
[Ab] Resumo:If youth and body appearance enhancement is as old as Homo Sapiens, reliable medical technology for such activities is only about 100 years old. At the dawn of the 20th century, surgical operations performed under the Voronoff's treatment plan (monkey gonads' tissue grafting into humans) or the Steinach's technique (vasoligation) offered a promise of longevity, beauty and therefore youth restoration. The many links with a newly recognized discipline, endocrinology, offer a critical insight on the strong interactions between medicine and surgery in the promise of successful antiaging. On the front-line of scientific research, the Institute of Experimental Endocrinology's primate station in Sukhumi (West Georgia, now Abkhazia, on the Black Sea coast) developed a leadership role in the medical research, including rejuvenation with testis' tissues. Authors focus their attention to the everlasting commitment to experimental and clinical research as developed by Sukhumi scholars and the related moral, practical and ideological implications.
[Mh] Termos MeSH primário: Fisiologia/história
Rejuvenescimento
[Mh] Termos MeSH secundário: Animais
Endocrinologia/história
República da Geórgia
Gônadas/cirurgia
Gônadas/transplante
Haplorrinos/cirurgia
História do Século XX
História do Século XXI
Seres Humanos
Masculino
Primatas/fisiologia
Primatas/cirurgia
Testículo/fisiologia
Testículo/cirurgia
U.R.S.S.
Vasectomia/história
[Pt] Tipo de publicação:BIOGRAPHY; HISTORICAL ARTICLE; JOURNAL ARTICLE; PORTRAITS
[Ps] Nome de pessoa como assunto:Ivanov I; Koltsov NK
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:QIS
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE


  4 / 41685 MEDLINE  
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[PMID]:29240774
[Au] Autor:DeWind NK; Peng J; Luo A; Brannon EM; Platt ML
[Ad] Endereço:Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
[Ti] Título:Pharmacological inactivation does not support a unique causal role for intraparietal sulcus in the discrimination of visual number.
[So] Source:PLoS One;12(12):e0188820, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The "number sense" describes the intuitive ability to quantify without counting. Single neuron recordings in non-human primates and functional imaging in humans suggest the intraparietal sulcus is an important neuroanatomical locus of numerical estimation. Other lines of inquiry implicate the IPS in numerous other functions, including attention and decision making. Here we provide a direct test of whether IPS has functional specificity for numerosity judgments. We used muscimol to reversibly and independently inactivate the ventral and lateral intraparietal areas in two monkeys performing a numerical discrimination task and a color discrimination task, roughly equilibrated for difficulty. Inactivation of either area caused parallel impairments in both tasks and no evidence of a selective deficit in numerical processing. These findings do not support a causal role for the IPS in numerical discrimination, except insofar as it also has a role in the discrimination of color. We discuss our findings in light of several alternative hypotheses of IPS function, including a role in orienting responses, a general cognitive role in attention and decision making processes and a more specific role in ordinal comparison that encompasses both number and color judgments.
[Mh] Termos MeSH primário: Lobo Parietal/fisiologia
Visão Ocular
[Mh] Termos MeSH secundário: Animais
Comportamento Animal
Agonistas de Receptores de GABA-A/administração & dosagem
Haplorrinos
Seres Humanos
Masculino
Muscimol/administração & dosagem
Estimulação Luminosa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA-A Receptor Agonists); 2763-96-4 (Muscimol)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188820


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[PMID]:29203142
[Au] Autor:Kinoshita A; Higashino M; Yoshida K; Aratani Y; Kakuuchi A; Hanada K; Takeda H; Naganawa A; Matsuya H; Ohmoto K
[Ad] Endereço:Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan. Electronic address: ak.kinoshita@ono.co.jp.
[Ti] Título:Synthesis and evaluation of a potent, well-balanced EP /EP dual agonist.
[So] Source:Bioorg Med Chem;26(1):200-214, 2018 01 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A highly potent and well-balanced dual agonist for the EP and EP receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC EP = 1.1 nM, EP = 1.0 nM) with acceptable selectivity over the EP and EP subtypes (>2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB.
[Mh] Termos MeSH primário: Receptores de Prostaglandina E Subtipo EP2/agonistas
Receptores de Prostaglandina E Subtipo EP3/agonistas
Tiazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CACO-2
Permeabilidade da Membrana Celular/efeitos dos fármacos
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Masculino
Modelos Moleculares
Estrutura Molecular
Ratos
Relação Estrutura-Atividade
Tiazóis/síntese química
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ONO-8055); 0 (Receptors, Prostaglandin E, EP2 Subtype); 0 (Receptors, Prostaglandin E, EP3 Subtype); 0 (Thiazoles)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180106
[Lr] Data última revisão:
180106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


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[PMID]:28454849
[Au] Autor:Aikawa K; Asano M; Ono K; Habuka N; Yano J; Wilson K; Fujita H; Kandori H; Hara T; Morimoto M; Santou T; Yamaoka M; Nakayama M; Hasuoka A
[Ad] Endereço:Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1 Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: katsuji.aikawa@takeda.com.
[Ti] Título:Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2f as a clinical candidate.
[So] Source:Bioorg Med Chem;25(13):3330-3349, 2017 07 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We previously reported that 4-(pyrrolidin-1-yl)benzonitrile derivative 1b was a selective androgen receptor modulator (SARM) that exhibited anabolic effects on organs such as muscles and the central nervous system (CNS), but neutral effects on the prostate. From further modification, we identified that 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2a showed strong AR binding affinity with improved metabolic stabilities. Based on these results, we tried to enhance the AR agonistic activities by modifying the substituents of the 5-oxopyrrolidine ring. As a consequence, we found that 4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile (2f) had ideal SARM profiles in Hershberger assay and sexual behavior induction assay. Furthermore, 2f showed good pharmacokinetic profiles in rats, dogs, monkeys, excellent nuclear selectivity and acceptable toxicological profiles. We also determined its binding mode by obtaining the co-crystal structures with AR.
[Mh] Termos MeSH primário: Androgênios/farmacologia
Descoberta de Drogas
Nitrilos/farmacologia
Receptores Androgênicos/metabolismo
[Mh] Termos MeSH secundário: Androgênios/síntese química
Androgênios/química
Animais
Células COS
Cercopithecus aethiops
Cães
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Masculino
Camundongos
Microssomos Hepáticos/química
Microssomos Hepáticos/metabolismo
Estrutura Molecular
Nitrilos/síntese química
Nitrilos/química
Ratos
Ratos Sprague-Dawley
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Nitriles); 0 (Receptors, Androgen); 9V9APP5H5S (benzonitrile)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28743932
[Au] Autor:Orhan AE; Ma WJ
[Ad] Endereço:Center for Neural Science, New York University, New York, NY, 10003, USA. aeminorhan@gmail.com.
[Ti] Título:Efficient probabilistic inference in generic neural networks trained with non-probabilistic feedback.
[So] Source:Nat Commun;8(1):138, 2017 07 26.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Animals perform near-optimal probabilistic inference in a wide range of psychophysical tasks. Probabilistic inference requires trial-to-trial representation of the uncertainties associated with task variables and subsequent use of this representation. Previous work has implemented such computations using neural networks with hand-crafted and task-dependent operations. We show that generic neural networks trained with a simple error-based learning rule perform near-optimal probabilistic inference in nine common psychophysical tasks. In a probabilistic categorization task, error-based learning in a generic network simultaneously explains a monkey's learning curve and the evolution of qualitative aspects of its choice behavior. In all tasks, the number of neurons required for a given level of performance grows sublinearly with the input population size, a substantial improvement on previous implementations of probabilistic inference. The trained networks develop a novel sparsity-based probabilistic population code. Our results suggest that probabilistic inference emerges naturally in generic neural networks trained with error-based learning rules.Behavioural tasks often require probability distributions to be inferred about task specific variables. Here, the authors demonstrate that generic neural networks can be trained using a simple error-based learning rule to perform such probabilistic computations efficiently without any need for task specific operations.
[Mh] Termos MeSH primário: Retroalimentação Fisiológica/fisiologia
Retroalimentação Psicológica/fisiologia
Rede Nervosa/fisiologia
Probabilidade
[Mh] Termos MeSH secundário: Algoritmos
Animais
Comportamento de Escolha/fisiologia
Haplorrinos
Seres Humanos
Aprendizagem/fisiologia
Modelos Neurológicos
Modelos Psicológicos
Neurônios/fisiologia
Desempenho Psicomotor/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00181-8


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[PMID]:29024651
[Au] Autor:Chafee MV; Crowe DA
[Ad] Endereço:Associate Professor, Department of Neuroscience, University of Minnesota, 321 Church Street SE, Minneapolis, MN 55455, USA. Electronic address: chafe001@umn.edu.
[Ti] Título:Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.
[So] Source:Neuron;96(2):256-258, 2017 Oct 11.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this issue, Loonis et al. (2017) provide the first description of unique synchrony patterns differentiating implicit and explicit forms of learning in monkey prefrontal networks. Their results have broad implications for how prefrontal networks integrate the two learning mechanisms to control behavior.
[Mh] Termos MeSH primário: Haplorrinos
Aprendizagem
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Córtex Pré-Frontal
Tempo de Reação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE


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[PMID]:28934219
[Au] Autor:Zimmermann F; Köhler SM; Nowak K; Dupke S; Barduhn A; Düx A; Lang A; De Nys HM; Gogarten JF; Grunow R; Couacy-Hymann E; Wittig RM; Klee SR; Leendertz FH
[Ad] Endereço:Robert Koch Institute, P3: "Epidemiology of Highly Pathogenic Microorganisms", Seestraße 10, Berlin, Germany.
[Ti] Título:Low antibody prevalence against Bacillus cereus biovar anthracis in Taï National Park, Côte d'Ivoire, indicates high rate of lethal infections in wildlife.
[So] Source:PLoS Negl Trop Dis;11(9):e0005960, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bacillus cereus biovar anthracis (Bcbva) is a member of the B. cereus group which carries both B. anthracis virulence plasmids, causes anthrax-like disease in various wildlife species and was described in several sub-Saharan African rainforests. Long-term monitoring of carcasses in Taï National Park, Côte d'Ivoire, revealed continuous wildlife mortality due to Bcbva in a broad range of mammalian species. While non-lethal anthrax infections in wildlife have been described for B. anthracis, nothing is known about the odds of survival following an anthrax infection caused by Bcbva. To address this gap, we present the results of a serological study of anthrax in five wildlife species known to succumb to Bcbva in this ecosystem. Specific antibodies were only detected in two out of 15 wild red colobus monkeys (Procolobus badius) and one out of 10 black-and-white colobus monkeys (Colobus polykomos), but in none of 16 sooty mangabeys (Cercocebus atys), 9 chimpanzees (Pan troglodytes verus) and 9 Maxwell's duikers (Cephalophus maxwellii). The combination of high mortality and low antibody detection rates indicates high virulence of this disease across these different mammalian species.
[Mh] Termos MeSH primário: Antraz/imunologia
Antraz/mortalidade
Anticorpos Antibacterianos/sangue
Bacillus cereus/imunologia
Bacillus cereus/patogenicidade
[Mh] Termos MeSH secundário: Animais
Costa do Marfim/epidemiologia
Haplorrinos
Parques Recreativos
Prevalência
Ruminantes
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bacterial)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005960


  10 / 41685 MEDLINE  
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[PMID]:28915417
[Au] Autor:Kang L; Connolly TM; Weng N; Jian W
[Ad] Endereço:Janssen Research & Development, Johnson & Johnson, 1400 McKean Road, Spring House, PA, 19477, USA.
[Ti] Título:LC-MS/MS quantification of 7α-hydroxy-4-cholesten-3-one (C4) in rat and monkey plasma.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1064:49-55, 2017 Oct 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:7α-hydroxy-4-cholesten-3-one (C4) is an oxidative enzymatic product of cholesterol metabolism via cholesterol 7α-hydroxylase, an enzyme also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1). C4 is a stable intermediate in the rate limiting pathway of bile acid biosynthesis. Previous studies showed that plasma C4 levels correlated with CYP7A1 enzymatic activity and could serve as a biomarker for bile acid synthesis. Here we developed and qualified a simple and robust high-throughput method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to quantify C4 in rat and monkey plasma. As C4 being an endogenous compound, this method used calibration standards in 50/50: acetonitrile/water (v/v). In order to mimic the incurred samples, quality control samples were prepared in the authentic plasma. Stable isotope labeled C4 (C4-d ) was used as the internal standard. The sample volume for analysis was 20µL and the sample preparation method was protein precipitation with acetonitrile. The average endogenous C4 concentrations, from 10 different lots of rat and monkey plasma, were 53.0±16.5ng/mL and 6.8±5.6ng/mL, respectively. Based on these observed endogenous C4 levels, the calibration curve ranges were established at 1-200ng/mL and 0.5-100ng/mL for rat assay and monkey assay, respectively. The method was qualified with acceptable accuracy, precision, linearity, and specificity. Matrix effect, recovery, and plasma stability of bench-top, freeze-thaw, and long-term frozen storage were also evaluated. The method has been successfully applied to pre-clinical studies.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Colestenonas/sangue
Cromatografia Líquida/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Haplorrinos
Modelos Lineares
Ratos
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cholestenones); 3862-25-7 (7 alpha-hydroxy-4-cholesten-3-one)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE



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