Base de dados : MEDLINE
Pesquisa : D08.244.453.491 [Categoria DeCS]
Referências encontradas : 1172 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 118 ir para página                         

  1 / 1172 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28454738
[Au] Autor:Miksys S; Wadji FB; Tolledo EC; Remington G; Nobrega JN; Tyndale RF
[Ad] Endereço:Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Canada. Electronic address: s.miksys@utoronto.ca.
[Ti] Título:Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.
[So] Source:Prog Neuropsychopharmacol Biol Psychiatry;78:140-148, 2017 Aug 01.
[Is] ISSN:1878-4216
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Encéfalo/enzimologia
Família 2 do Citocromo P450/metabolismo
Haloperidol/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Catalepsia/induzido quimicamente
Haloperidol/sangue
Fígado/enzimologia
Masculino
Microinjeções
Nicotina/administração & dosagem
Nicotina/farmacologia
Propranolol/administração & dosagem
Propranolol/farmacologia
Ratos
Discinesia Tardia/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
6M3C89ZY6R (Nicotine); 9Y8NXQ24VQ (Propranolol); EC 1.14.14.1 (Cytochrome P450 Family 2); J6292F8L3D (Haloperidol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  2 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28951217
[Au] Autor:Andersen ME; Cruzan G; Black MB; Pendse SN; Dodd D; Bus JS; Sarang SS; Banton MI; Waites R; McMullen PD
[Ad] Endereço:ScitoVation LLC, Six Davis Drive, PO Box 12878, Research Triangle Park, NC 27709, United States.
[Ti] Título:Assessing molecular initiating events (MIEs), key events (KEs) and modulating factors (MFs) for styrene responses in mouse lungs using whole genome gene expression profiling following 1-day and multi-week exposures.
[So] Source:Toxicol Appl Pharmacol;335:28-40, 2017 Nov 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm. Enrichment for 1-day and 1-week exposures included cell cycle, mitotic M-M/G1 phases, DNA-synthesis and metabolism of lipids and lipoproteins pathways. The numbers of DEGs decreased steadily over time with no DEGs meeting both statistical significance and fold-change criteria at 26weeks. At 4 and 26weeks, some key transcription factors (TFs) - Nr1d1, Nr1d2, Dbp, Tef, Hlf, Per3, Per2 and Bhlhe40 - were upregulated (|FC|>1.5), while others - Npas, Arntl, Nfil3, Nr4a1, Nr4a2, and Nr4a3 - were down-regulated. At all times, consistent changes in gene expression only occurred in the parental strain. Our results support a MIE for styrene of direct mitogenicity from mouse-specific CYP2F2-mediated metabolites activating Nr4a signaling. Longer-term MFs include down-regulation of Nr4a genes and shifts in both circadian clock TFs and other TFs, linking circadian clock to cellular metabolism. We found no gene expression changes indicative of cytotoxicity or activation of p53-mediated DNA-damage pathways.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica/métodos
Pulmão/efeitos dos fármacos
Estirenos/toxicidade
Toxicogenética/métodos
Transcriptoma/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Hidrocarboneto de Aril Hidroxilases/genética
Hidrocarboneto de Aril Hidroxilases/metabolismo
Ritmo Circadiano/efeitos dos fármacos
Ritmo Circadiano/genética
Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética
Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo
Citocromo P-450 CYP2B6/genética
Citocromo P-450 CYP2B6/metabolismo
Sistema Enzimático do Citocromo P-450/deficiência
Sistema Enzimático do Citocromo P-450/genética
Família 2 do Citocromo P450/genética
Família 2 do Citocromo P450/metabolismo
Relação Dose-Resposta a Droga
Redes Reguladoras de Genes/efeitos dos fármacos
Genótipo
Exposição por Inalação/efeitos adversos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Pulmão/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Modelos Animais
Fenótipo
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
Estirenos/metabolismo
Fatores de Tempo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Circadian Rhythm Signaling Peptides and Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (Styrenes); 0 (Transcription Factors); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.14.- (Cyp2f2 protein, mouse); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (CYP2A13 protein, human); EC 1.14.14.1 (CYP2B6 protein, human); EC 1.14.14.1 (CYP2F1 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2B6); EC 1.14.14.1 (Cytochrome P450 Family 2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE


  3 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28757204
[Au] Autor:Manousaki D; Dudding T; Haworth S; Hsu YH; Liu CT; Medina-Gómez C; Voortman T; van der Velde N; Melhus H; Robinson-Cohen C; Cousminer DL; Nethander M; Vandenput L; Noordam R; Forgetta V; Greenwood CMT; Biggs ML; Psaty BM; Rotter JI; Zemel BS; Mitchell JA; Taylor B; Lorentzon M; Karlsson M; Jaddoe VVW; Tiemeier H; Campos-Obando N; Franco OH; Utterlinden AG; Broer L; van Schoor NM; Ham AC; Ikram MA; Karasik D; de Mutsert R; Rosendaal FR; den Heijer M; Wang TJ; Lind L; Orwoll ES; Mook-Kanamori DO; Michaëlsson K; Kestenbaum B; Ohlsson C; Mellström D; de Groot LCPGM; Grant SFA; Kiel DP; Zillikens MC; Rivadeneira F
[Ad] Endereço:Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada.
[Ti] Título:Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis.
[So] Source:Am J Hum Genet;101(2):227-238, 2017 Aug 03.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10 ). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 × 10 ). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 × 10 ) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
[Mh] Termos MeSH primário: Colestanotriol 26-Mono-Oxigenase/genética
Família 2 do Citocromo P450/genética
Predisposição Genética para Doença/genética
Esclerose Múltipla/genética
Deficiência de Vitamina D/diagnóstico
Deficiência de Vitamina D/genética
Vitamina D/análogos & derivados
[Mh] Termos MeSH secundário: Frequência do Gene
Genoma Humano/genética
Estudo de Associação Genômica Ampla
Seres Humanos
Esclerose Múltipla/etiologia
Polimorfismo de Nucleotídeo Único
Fatores de Risco
Vitamina D/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
1406-16-2 (Vitamin D); 64719-49-9 (25-hydroxyvitamin D); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 1.14.14.24 (CYP2R1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170909
[Lr] Data última revisão:
170909
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


  4 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28599267
[Au] Autor:Li L; Carratt S; Hartog M; Kovalchik N; Jia K; Wang Y; Zhang QY; Edwards P; Winkle LV; Ding X
[Ad] Endereço:Wadsworth Center, New York State Department of Health, Albany, New York, USA
[Ti] Título:Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice.
[So] Source:Environ Health Perspect;125(6):067004, 2017 06 08.
[Is] ISSN:1552-9924
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The potential carcinogenicity of naphthalene (NA), a ubiquitous environmental pollutant, in human respiratory tract is a subject of intense debate. Chief among the uncertainties in risk assessment for NA is whether human lung CYP2A13 and CYP2F1 can mediate NA's respiratory tract toxicity. OBJECTIVES: We aimed to assess the function of CYP2A13 and CYP2F1 in NA bioactivation and NA-induced respiratory tract toxicity in mouse models. METHODS: Rates of microsomal NA bioactivation and the effects of an anti-CYP2A antibody were determined for lung and nasal olfactory mucosa (OM) from -null, CYP2A13-humanized, and CYP2A13/2F1-humanized mice. The extent of NA respiratory toxicity was compared among wild-type, -null, and CYP2A13/2F1-humanized mice following inhalation exposure at an occupationally relevant dose (10 ppm for 4 hr). RESULTS: studies indicated that the NA bioactivation activities in OM and lung of the CYP2A13/2F1-humanized mice were primarily contributed by, respectively, CYP2A13 and CYP2F1. CYP2A13/2F1-humanized mice showed greater sensitivity to NA than -null mice, with greater depletion of nonprotein sulfhydryl and occurrence of cytotoxicity (observable by routine histology) in the OM, at 2 or 20 hr after termination of NA exposure, in humanized mice. Focal, rather than gross, lung toxicity was observed in -null and CYP2A13/2F1-humanized mice; however, the extent of NA-induced lung injury (shown as volume fraction of damaged cells) was significantly greater in the terminal bronchioles of CYP2A13/2F1-humanized mice than in -null mice. CONCLUSION: CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. https://doi.org/10.1289/EHP844.
[Mh] Termos MeSH primário: Família 2 do Citocromo P450/metabolismo
Naftalenos/toxicidade
Testes de Toxicidade
[Mh] Termos MeSH secundário: Animais
Carcinógenos/toxicidade
Seres Humanos
Pulmão/metabolismo
Camundongos
Camundongos Knockout
Mucosa Nasal/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinogens); 0 (Naphthalenes); EC 1.14.14.1 (Cytochrome P450 Family 2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE
[do] DOI:10.1289/EHP844


  5 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28590769
[Au] Autor:Zhang Y; Wang Z; Ma T
[Ad] Endereço:1 Department of Neonatal Intensive Care Unit, The First People's Hospital of Shangqiu , Shangqiu City, China .
[Ti] Título:Associations of Genetic Polymorphisms Relevant to Metabolic Pathway of Vitamin D3 with Development and Prognosis of Childhood Bronchial Asthma.
[So] Source:DNA Cell Biol;36(8):682-692, 2017 Aug.
[Is] ISSN:1557-7430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study was aimed at investigating the correlation between genetic polymorphisms relevant to metabolic pathway of vitamin D3 (VD ) and susceptibility to childhood bronchial asthma. Altogether 143 childhood patients with bronchial asthma and 143 healthy children of Chinese Han ethnicity were enrolled in this study. The key single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software and selected from previous investigations. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios and corresponding 95% confidence intervals were calculated to evaluate the association between SNPs and susceptibility to bronchial asthma. Statistical analyses were conducted by using SPSS 13.0 software. Rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR were shown to be significantly associated with increased risk of bronchial asthma. Besides, prognosis of childhood bronchial asthma, which was represented as Saint George Respiratory Questionnaire (SGRQ) scoring, was closely linked with CYP2R1 rs10766197, CYP27B1 rs4646536, VDR rs7975232, VDR rs1544410, PPAR rs1805192, and PPAR rs10865710. The haplotype analysis suggested that TA and CG of CG rs7041/rs4588, CA and AG of VDR rs7975232/rs1544410, and CC of PPAR rs1805192/rs10865710 were, respectively, correlated with levels of VD, IL-4, and IL-5. And only haplotypes of VDR showed associations with risk of bronchial asthma during childhood, whereas hardly any significance could be observed between the haplotypes and behavior of quality-of-life (SGRQ) scoring. Significant associations were found between rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR and susceptibility to and prognosis of childhood bronchial asthma, providing novel targets for treating the disorder.
[Mh] Termos MeSH primário: Asma/diagnóstico
Asma/genética
Colecalciferol/genética
Predisposição Genética para Doença
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética
Biomarcadores/sangue
Criança
Pré-Escolar
China
Colecalciferol/deficiência
Colestanotriol 26-Mono-Oxigenase/genética
Família 2 do Citocromo P450/genética
Feminino
Genótipo
Haplótipos/genética
Seres Humanos
Interferon gama/biossíntese
Interferon gama/sangue
Interleucina-4/biossíntese
Interleucina-4/sangue
Interleucina-5/biossíntese
Interleucina-5/sangue
Masculino
Subunidade 1 do Complexo Mediador
Redes e Vias Metabólicas/genética
Razão de Chances
Prognóstico
Receptores de Calcitriol/genética
Inquéritos e Questionários
Deficiência de Vitamina D/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Interleukin-5); 0 (Mediator Complex Subunit 1); 0 (Receptors, Calcitriol); 0 (VDR protein, human); 1C6V77QF41 (Cholecalciferol); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma); EC 1.14.13.13 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase); EC 1.14.13.13 (CYP27B1 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 1.14.14.24 (CYP2R1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1089/dna.2017.3730


  6 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28575224
[Au] Autor:Moon RJ; Harvey NC; Cooper C; D'Angelo S; Curtis EM; Crozier SR; Barton SJ; Robinson SM; Godfrey KM; Graham NJ; Holloway JW; Bishop NJ; Kennedy S; Papageorghiou AT; Schoenmakers I; Fraser R; Gandhi SV; Prentice A; Inskip HM; Javaid MK; Maternal Vitamin D Osteoporosis Study Trial Group
[Ad] Endereço:Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, United Kingdom.
[Ti] Título:Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.
[So] Source:J Clin Endocrinol Metab;102(8):2941-2949, 2017 Aug 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [ß represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [ß = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (ß = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (ß = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity.
[Mh] Termos MeSH primário: Colecalciferol/uso terapêutico
Deficiência de Vitamina D/prevenção & controle
Vitaminas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Alelos
Colestanotriol 26-Mono-Oxigenase/genética
Família 2 do Citocromo P450/genética
Suplementos Nutricionais
Método Duplo-Cego
Feminino
Genótipo
Seres Humanos
Modelos Lineares
Análise Multivariada
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Polimorfismo de Nucleotídeo Único
Gravidez
Resultado do Tratamento
Vitamina D/análogos & derivados
Vitamina D/sangue
Proteína de Ligação a Vitamina D/genética
Vitamina D3 24-Hidroxilase/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Vitamin D-Binding Protein); 0 (Vitamins); 1406-16-2 (Vitamin D); 1C6V77QF41 (Cholecalciferol); 64719-49-9 (25-hydroxyvitamin D); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 1.14.14.24 (CYP2R1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase); EC 1.14.15.16 (CYP24A1 protein, human); EC 1.14.15.16 (Vitamin D3 24-Hydroxylase); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00682


  7 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28560658
[Au] Autor:Ding Y; Zhang H; Li X; Li C; Chen G; Chen H; Wu M; Niu J
[Ad] Endereço:Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, No. 71 Xinmin Street, Changchun, 130021, China.
[Ti] Título:Safety, pharmacokinetics and pharmacogenetics of a single ascending dose of pradefovir, a novel liver-targeting, anti-hepatitis B virus drug, in healthy Chinese subjects.
[So] Source:Hepatol Int;11(4):390-400, 2017 Jul.
[Is] ISSN:1936-0541
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pradefovir is efficiently converted to adefovir [9-(2-phosphonylmethoxyethyl) adenine (PMEA)], producing high hepatic PMEA concentration but low levels in the systemic circulation and kidney. The aim of this study is to evaluate the tolerability, adverse effect (AEs), pharmacokinetics and pharmacogenetics of a single ascending dose of pradefovir. METHODS: Fifty healthy subjects were divided into five groups and randomized within each group at a ratio of 3:1:1 to receive a single ascending dose of pradefovir (10, 30, 60, 90, or 120 mg), and 10 mg adefovir dipivoxil (ADP) or placebo. Blood and urine samples were collected and analyzed. A total of 1930 polymorphic loci were analyzed in 6 blood samples collected from the 90 mg pradefovir group. RESULTS: The single oral dose of pradefovir up to 120 mg was well tolerated. A total of 29 dose-limited mild AEs were reported in 17 subjects. The peak plasma concentration (C ) and area under the curve (AUC) of serum pradefovir ranged from (21.41 ± 12.98) to (447.33 ± 79.34) ng/mL and (46.10 ± 29.45) to (748.18 ± 134.15) ng h/mL across the dose range, respectively. The C and AUC of serum PMEA ranged from 18.10 ± 4.96 to 312.33 ± 114.19 ng/mL and 72.65 ± 28.25 to 1095.48 ± 248.47 ng h/mL. Generally, no kidney impairment was observed. Pharmacogenetic analysis identified three metabolism-related single nucleotide polymorphism (SNP) locis, P450 (cytochrome) oxidoreductase [POR (rs6965343)], arylamine N-acetyltransferases [NAT1 (rs4986993)] and CYP2F1 (rs305968)], and one distribution-related loci, orosomucoid 2 [ORM2 (rs12685968)]. CONCLUSIONS: The single oral dose of pradefovir 10-120 mg was well tolerated. SNPs may be associated with variable rates of adverse events. TRIAL REGISTRATION NUMBER: CTR20140341.
[Mh] Termos MeSH primário: Adenina/análogos & derivados
Arilamina N-Acetiltransferase/genética
Sistema Enzimático do Citocromo P-450/genética
Família 2 do Citocromo P450/genética
Isoenzimas/genética
Compostos Organofosforados/administração & dosagem
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adenina/administração & dosagem
Adenina/efeitos adversos
Adenina/farmacocinética
Adulto
Esquema de Medicação
Feminino
Voluntários Saudáveis
Seres Humanos
Masculino
Compostos Organofosforados/efeitos adversos
Compostos Organofosforados/farmacocinética
Variantes Farmacogenômicos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Organophosphorus Compounds); 0 (POR protein, human); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.14.1 (CYP2F1 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 2.3.1.5 (Arylamine N-Acetyltransferase); EC 2.3.1.5 (N-acetyltransferase 1); GZE85Q9Q61 (pradefovir); JAC85A2161 (Adenine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE
[do] DOI:10.1007/s12072-017-9797-y


  8 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28550179
[Au] Autor:Hashimoto R; Joshi SR; Jiang H; Capdevila JH; McMurtry IF; Laniado Schwartzman M; Gupte SA
[Ad] Endereço:Department of Pharmacology, and Translation Cardiovascular Institute, School of Medicine, New York Medical College, Valhalla, New York.
[Ti] Título: gene disruption is associated with increased hematopoietic stem cells: implication in chronic hypoxia-induced pulmonary hypertension.
[So] Source:Am J Physiol Heart Circ Physiol;313(2):H293-H303, 2017 Aug 01.
[Is] ISSN:1522-1539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have recently demonstrated that disruption of the murine cytochrome -450 2c44 gene ( exacerbates chronic hypoxia-induced pulmonary artery remodeling and hypertension in mice. Subsequently, we serendipitously found that gene disruption also increases hematopoietic stem cell (HSC) numbers in bone marrow and blood. Therefore, the objective of the present study was to investigate whether CYP2C44-derived eicosanoids regulate HSC proliferation/cell growth and whether increased HSCs contribute to chronic hypoxia-induced remodeling of pulmonary arteries in knockout mice. Our findings demonstrated that lack of CYP2C44 epoxygenase, which catalyzed the oxidation of arachidonic acid to epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETE) acids, increases the numbers of ) HSCs (CD34 , CD117 , and CD133 ), ) proangiogenic (CD34 CD133 and CD34 CD117 CD133 ) cells, and ) immunogenic/inflammatory (CD34 CD11b , CD133 CD11b , F4/80 , CD11b , and F4/80 CD11b ) macrophages in bone marrow and blood compared with wild-type mice. Among the various CYP2C44-derived arachidonic acids, only 15-HETE decreased CD117 cell numbers when applied to bone marrow cell cultures. Interestingly, CD133 and von Willebrand factor-positive cells, which are derived from proangiogenic stem cells, are increased in the bone marrow, blood, and lungs of mice exposed to chronic hypoxia and in remodeled and occluded pulmonary arteries of CYP2C44-deficient mice. In conclusion, our results demonstrate that CYP2C44-derived 15-HETE plays a critical role in downregulating HSC proliferation and growth, because disruption of the gene increased HSCs that potentially contribute to chronic hypoxia-induced pulmonary arterial remodeling and occlusion. This study demonstrates that cytochrome -450 2C44 plays a critical role in controlling the phenotype of hematopoietic stem cells and that when this enzyme is knocked out, stem cells are differentiated. These stem cells give rise to increased circulating monocytes and macrophages and contribute to the pathogenesis of chronic hypoxia-induced pulmonary artery remodeling and hypertension.
[Mh] Termos MeSH primário: Proliferação Celular
Família 2 do Citocromo P450/deficiência
Células-Tronco Hematopoéticas/enzimologia
Ácidos Hidroxieicosatetraenoicos/metabolismo
Hipertensão Pulmonar/enzimologia
Hipóxia/complicações
Artéria Pulmonar/enzimologia
Remodelação Vascular
[Mh] Termos MeSH secundário: Antígeno AC133/metabolismo
Animais
Antígenos CD34/metabolismo
Antígenos de Diferenciação/metabolismo
Antígeno CD11b/metabolismo
Diferenciação Celular
Células Cultivadas
Doença Crônica
Família 2 do Citocromo P450/genética
Modelos Animais de Doenças
Feminino
Predisposição Genética para Doença
Hipertensão Pulmonar/genética
Hipertensão Pulmonar/patologia
Hipertensão Pulmonar/fisiopatologia
Macrófagos/enzimologia
Masculino
Camundongos da Linhagem 129
Camundongos Knockout
Monócitos/enzimologia
Fenótipo
Proteínas Proto-Oncogênicas c-kit/metabolismo
Artéria Pulmonar/patologia
Artéria Pulmonar/fisiopatologia
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AC133 Antigen); 0 (Antigens, CD34); 0 (Antigens, Differentiation); 0 (CD11b Antigen); 0 (Hydroxyeicosatetraenoic Acids); 0 (Prom1 protein, mouse); 0 (monocyte-macrophage differentiation antigen); 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid); EC 1.14.14.1 (Cyp2c44 protein, mouse); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170528
[St] Status:MEDLINE
[do] DOI:10.1152/ajpheart.00785.2016


  9 / 1172 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28406212
[Au] Autor:Saleheen D; Natarajan P; Armean IM; Zhao W; Rasheed A; Khetarpal SA; Won HH; Karczewski KJ; O'Donnell-Luria AH; Samocha KE; Weisburd B; Gupta N; Zaidi M; Samuel M; Imran A; Abbas S; Majeed F; Ishaq M; Akhtar S; Trindade K; Mucksavage M; Qamar N; Zaman KS; Yaqoob Z; Saghir T; Rizvi SNH; Memon A; Hayyat Mallick N; Ishaq M; Rasheed SZ; Memon FU; Mahmood K; Ahmed N; Do R; Krauss RM; MacArthur DG; Gabriel S; Lander ES; Daly MJ; Frossard P; Danesh J; Rader DJ; Kathiresan S
[Ad] Endereço:Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.
[So] Source:Nature;544(7649):235-239, 2017 04 12.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.
[Mh] Termos MeSH primário: Consanguinidade
Análise Mutacional de DNA
Deleção de Genes
Genes/genética
Estudos de Associação Genética/métodos
Homozigoto
Fenótipo
[Mh] Termos MeSH secundário: 1-Alquil-2-acetilglicerofosfocolina Esterase/deficiência
1-Alquil-2-acetilglicerofosfocolina Esterase/genética
Apolipoproteína C-III/deficiência
Apolipoproteína C-III/genética
Estudos de Coortes
Doença das Coronárias/sangue
Doença das Coronárias/genética
Família 2 do Citocromo P450/genética
Gorduras na Dieta/farmacologia
Exoma/genética
Jejum/sangue
Feminino
Frequência do Gene
Seres Humanos
Interleucina-8/sangue
Masculino
Meia-Idade
Infarto do Miocárdio/sangue
Infarto do Miocárdio/genética
Neurregulinas/genética
Paquistão
Linhagem
Fosfoproteínas/genética
Período Pós-Prandial
Sítios de Splice de RNA/genética
Genética Reversa/métodos
Trocadores de Sódio-Hidrogênio/genética
Triglicerídeos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Apolipoprotein C-III); 0 (Dietary Fats); 0 (IL8 protein, human); 0 (Interleukin-8); 0 (Neuregulins); 0 (Phosphoproteins); 0 (RNA Splice Sites); 0 (Sodium-Hydrogen Exchangers); 0 (Triglycerides); 0 (neuregulin-4); 0 (sodium-hydrogen exchanger regulatory factor); EC 1.14.14.1 (CYP2F1 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase); EC 3.1.1.47 (PLA2G7 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1038/nature22034


  10 / 1172 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28382877
[Au] Autor:Petersen RA; Larsen LH; Damsgaard CT; Sørensen LB; Hjorth MF; Andersen R; Tetens I; Krarup H; Ritz C; Astrup A; Michaelsen KF; Mølgaard C
[Ad] Endereço:1University College Lillebaelt,Denmark,Niels Bohrs Allé 1,DK-5230 Odense M,Denmark.
[Ti] Título:Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes.
[So] Source:Br J Nutr;117(6):829-838, 2017 Mar.
[Is] ISSN:1475-2662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of -5·8 to -10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (P interaction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.
[Mh] Termos MeSH primário: Alelos
Genótipo
Polimorfismo de Nucleotídeo Único
Estações do Ano
Raios Ultravioleta
Deficiência de Vitamina D/genética
Vitamina D/análogos & derivados
[Mh] Termos MeSH secundário: Criança
Colestanotriol 26-Mono-Oxigenase/genética
Família 2 do Citocromo P450/genética
Dinamarca
Feminino
Predisposição Genética para Doença
Seres Humanos
Masculino
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Receptores de Calcitriol/genética
Instituições Acadêmicas
Vitamina D/sangue
Deficiência de Vitamina D/sangue
Proteína de Ligação a Vitamina D/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Calcitriol); 0 (VDR protein, human); 0 (Vitamin D-Binding Protein); 1406-16-2 (Vitamin D); 64719-49-9 (25-hydroxyvitamin D); EC 1.14.14.1 (Cytochrome P450 Family 2); EC 1.14.14.24 (CYP2R1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1017/S0007114517000538



página 1 de 118 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