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  1 / 4522 MEDLINE  
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[PMID]:29211347
[Au] Autor:Tanuma J; Matsumoto S; Haneuse S; Cuong DD; Vu TV; Thuy PTT; Dung NT; Dung NTH; Trung NV; Kinh NV; Oka S
[Ad] Endereço:AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
[Ti] Título:Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.
[So] Source:J Int AIDS Soc;20(4), 2017 Dec.
[Is] ISSN:1758-2652
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. METHODS: We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm in CD4 counts at 24 months) were further analysed. RESULTS: From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. CONCLUSION: Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Infecções por HIV/tratamento farmacológico
Carga Viral
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Benzoxazinas/uso terapêutico
Contagem de Linfócito CD4
Estudos de Coortes
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Meia-Idade
Nevirapina/uso terapêutico
Estavudina/uso terapêutico
Fatores de Tempo
Vietnã
Adulto Jovem
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); 4B9XT59T7S (Zidovudine); 99DK7FVK1H (Nevirapine); BO9LE4QFZF (Stavudine); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1002/jia2.25030


  2 / 4522 MEDLINE  
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[PMID]:29384848
[Au] Autor:Tierrablanca LE; Ochalek J; Ford D; Babiker A; Gibb D; Butler K; Turkova A; Griffin S; Revill P; BREATHER (PENTA 16) Trial Group
[Ad] Endereço:Tecnología e Información para la Salud, Mexico City, Mexico.
[Ti] Título:Economic evaluation of weekends-off antiretroviral therapy for young people in 11 countries.
[So] Source:Medicine (Baltimore);97(5):e9698, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To analyze the cost effectiveness of short-cycle therapy (SCT), where patients take antiretroviral (ARV) drugs 5 consecutive days a week and have 2 days off, as an alternative to continuous ARV therapy for young people infected with human immunodeficiency virus (HIV) and taking efavirenz-based first-line ARV drugs. METHODS: We conduct a hierarchical cost-effectiveness analysis based on data on clinical outcomes and resource use from the BREATHER trial. BREATHER is a randomized trial investigating the effectiveness of SCT and continuous therapy in 199 participants aged 8 to 24 years and taking efavirenz-based first-line ARV drugs in 11 countries worldwide. Alongside nationally representative unit costs/prices, these data were used to estimate costs and quality adjusted life years (QALYs). An incremental cost-effectiveness comparison was performed using a multilevel bivariate regression approach for total costs and QALYs. Further analyses explored cost-effectiveness in low- and middle-income countries with access to low-cost generic ARV drugs and high-income countries purchasing branded ARV drugs, respectively. RESULTS: At 48 weeks, SCT offered significant total cost savings over continuous therapy of US dollar (USD) 41 per patient in countries using generic drugs and USD 4346 per patient in countries using branded ARV drugs, while accruing nonsignificant total health benefits of 0.008 and 0.009 QALYs, respectively. Cost-effectiveness estimates were similar across settings with access to generic ARV drugs but showed significant variation among high-income countries where branded ARV drugs are purchased. CONCLUSION: SCT is a cost-effective treatment alternative to continuous therapy for young people infected with HIV in countries where viral load monitoring is available.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/economia
Análise Custo-Benefício
Infecções por HIV/tratamento farmacológico
Infecções por HIV/economia
[Mh] Termos MeSH secundário: Adolescente
Benzoxazinas/administração & dosagem
Benzoxazinas/economia
Criança
Esquema de Medicação
Medicamentos Genéricos/administração & dosagem
Medicamentos Genéricos/economia
Seguimentos
Custos de Cuidados de Saúde
Seres Humanos
Internacionalidade
Anos de Vida Ajustados por Qualidade de Vida
Análise de Regressão
Resultado do Tratamento
Carga Viral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); 0 (Drugs, Generic); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009698


  3 / 4522 MEDLINE  
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[PMID]:28466599
[Au] Autor:Barwe S; Andronescu C; Masa J; Ventosa E; Klink S; Genç A; Arbiol J; Schuhmann W
[Ad] Endereço:Analytical Chemistry, Center for Electrochemical Sciences (CES), Ruhr-Universität Bochum, 44780, Bochum, Germany.
[Ti] Título:Polybenzoxazine-Derived N-doped Carbon as Matrix for Powder-Based Electrocatalysts.
[So] Source:ChemSusChem;10(12):2653-2659, 2017 06 22.
[Is] ISSN:1864-564X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In addition to catalytic activity, intrinsic stability, tight immobilization on a suitable electrode surface, and sufficient electronic conductivity are fundamental prerequisites for the long-term operation of particle- and especially powder-based electrocatalysts. We present a novel approach to concurrently address these challenges by using the unique properties of polybenzoxazine (pBO) polymers, namely near-zero shrinkage and high residual-char yield even after pyrolysis at high temperatures. Pyrolysis of a nanocubic prussian blue analogue precursor (K Mn [Co(CN) ] ⋅n H O) embedded in a bisphenol A and aniline-based pBO led to the formation of a N-doped carbon matrix modified with Mn Co O nanocubes. The obtained electrocatalyst exhibits high efficiency toward the oxygen evolution reaction (OER) and more importantly a stable performance for at least 65 h.
[Mh] Termos MeSH primário: Benzoxazinas/química
Carbono/química
Nitrogênio/química
Polímeros/química
[Mh] Termos MeSH secundário: Catálise
Cobalto/química
Eletroquímica
Manganês/química
Nanoestruturas/química
Pós
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzoxazines); 0 (Polymers); 0 (Powders); 3G0H8C9362 (Cobalt); 42Z2K6ZL8P (Manganese); 7440-44-0 (Carbon); N762921K75 (Nitrogen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1002/cssc.201700593


  4 / 4522 MEDLINE  
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[PMID]:29267335
[Au] Autor:Milczarski P; Masojc P; Krajewski P; Stochmal A; Kowalczyk M; Angelov M; Ivanova V; Schollenberger M; Wakulinski W; Banaszak Z; Banaszak K; Rakoczy-Trojanowska M
[Ad] Endereço:West Pomeranian University of Technology, Szczecin, Poland.
[Ti] Título:QTL mapping for benzoxazinoid content, preharvest sprouting, α-amylase activity, and leaf rust resistance in rye (Secale cereale L.).
[So] Source:PLoS One;12(12):e0189912, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mapping population of recombinant inbred lines (RILs) representing 541 × Ot1-3 cross exhibited wide variations of benzoxazinoid (BX) content in leaves and roots, brown rust resistance, α-amylase activity in the grain, and resistance to preharvest sprouting. QTL mapping of major BX species using a DArT-based map revealed a complex genetic architecture underlying the production of these main secondary metabolites engaged in stress and allelopathy responses. The synthesis of BX in leaves and roots was found to be regulated by different QTL. The QTL for the BX content, rust resistance, α-amylase activity, and preharvest sprouting partially overlapped; this points to their common genetic regulation by a definite subset of genes. Only one QTL for BX located on chromosome 7R coincided with the loci of the ScBx genes, which were mapped as two clusters on chromosomes 5RS (Bx3-Bx5) and 7R (Bx1-Bx2). The QTL common for several BX species, rust resistance, preharvest sprouting, and α-amylase activity are interesting objects for further exploration aimed at developing common markers for these important agronomic traits.
[Mh] Termos MeSH primário: Basidiomycota/patogenicidade
Benzoxazinas/metabolismo
Folhas de Planta/microbiologia
Locos de Características Quantitativas
Secale/microbiologia
alfa-Amilases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzoxazines); EC 3.2.1.1 (alpha-Amylases)
[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:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189912


  5 / 4522 MEDLINE  
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[PMID]:29190729
[Au] Autor:Tan Z; Jia X; Ma F; Feng Y; Lu H; Jin JO; Wu D; Yin L; Liu L; Zhang L
[Ad] Endereço:Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
[Ti] Título:Increased MMAB level in mitochondria as a novel biomarker of hepatotoxicity induced by Efavirenz.
[So] Source:PLoS One;12(11):e0188366, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), has been widely used in the therapy of human immunodeficiency virus (HIV) infection. Some of its toxic effects on hepatic cells have been reported to display features of mitochondrial dysfunction through bioenergetic stress and autophagy, etc. However, alteration of protein levels, especially mitochondrial protein levels, in hepatic cells during treatment of EFV has not been fully investigated. METHODS: We built a cell model of EFV-induced liver toxicity through treating Huh-7 cells with different concentrations of EFV for different time followed by the analysis of cell viability using cell counting kit -8 (CCK8) and reactive oxygen species (ROS) using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSox dye. Proteomic profiles in the mitochondria of Huh-7 cells stimulated by EFV were analyzed. Four differentially expressed proteins were quantified by real time RT-PCR. We also detected the expression of mitochondrial precursor Cob(I)yrinic acid a,c-diamide adenosyltransferase (MMAB) by immunohistochemistry analysis in clinical samples. The expression levels of MMAB and ROS were detected in EFV-treated Huh-7 cells with and without shRNA used to knock down MMAB, and in primary hepatocytes (PHC). The effects of other anti-HIV drugs (nevirapine (NVP) and tenofovirdisoproxil (TDF)), and hydrogen peroxide (H2O2) were also tested. Amino acid analysis and fatty aldehyde dehydrogenase (ALDH3A2) expression after MMAB expression knock-down with shRNA was used to investigate the metabolic effect of MMAB in Huh-7 cells. RESULTS: EFV treatment inhibited cell viability and increased ROS production with time- and concentration-dependence. Proteomic study was performed at 2 hours after EFV treatment. After treated Huh-7 cells with EFV (2.5mg/L or 10 mg/L) for 2 h, fifteen differentially expressed protein spots from purified mitochondrion that included four mitochondria proteins were detected in EFV-treated Huh-7 cells compared to controls. Consistent with protein expression levels, mRNA expression levels of mitochondrial protein MMAB were also increased by EFV treatment. In addition, the liver of EFV-treated HIV infected patients showed substantially higher levels of MMAB expression compared to the livers of untreated or protease inhibitor (PI)-treated HIV-infected patients. Furthermore, ROS were found to be decreased in Huh-7 cells treated with shMMAB compared with empty plasmid treated with EFV at the concentration of 2.5 or 10 mg/L. MMAB was increased in EFV-treated Huh-7 cells and primary hepatocytes. However, no change in MMAB expression was detected after treatment of Huh-7 cells and primary hepatocytes with anti-HIV drugs nevirapine (NVP) and tenofovirdisoproxil (TDF), or hydrogen peroxide (H2O2), although ROS was increased in these cells. Finally, knockdown of MMAB by shRNA induced increases in the ß-Alanine (ß-Ala) production levels and decrease in ALDH3A2 expression. CONCLUSIONS: A mitochondrial proteomic study was performed to study the proteins related to EFV-inducted liver toxicity. MMAB might be a target and potential biomarker of hepatotoxicity in EFV-induced liver toxicity.
[Mh] Termos MeSH primário: Alquil e Aril Transferases/metabolismo
Benzoxazinas/toxicidade
Mitocôndrias/enzimologia
Inibidores da Transcriptase Reversa/farmacologia
[Mh] Termos MeSH secundário: Aldeído Desidrogenase/genética
Alquil e Aril Transferases/genética
Western Blotting
Linhagem Celular
Perfilação da Expressão Gênica
Técnicas de Silenciamento de Genes
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/metabolismo
Proteínas Mitocondriais/genética
Estresse Oxidativo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transcrição Genética
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoxazines); 0 (Mitochondrial Proteins); 0 (Reverse Transcriptase Inhibitors); EC 1.2.1.3 (Aldehyde Dehydrogenase); EC 2.5.- (Alkyl and Aryl Transferases); EC 2.5.1.17 (cob(I)alamin adenosyltransferase); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188366


  6 / 4522 MEDLINE  
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[PMID]:29061818
[Au] Autor:Müller L; Radtke A; Decker J; Koch M; Belge G
[Ad] Endereço:Faculty of Biology and Chemistry, University of Bremen, Bremen, Germany.
[Ti] Título:The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.
[So] Source:Anticancer Res;37(11):6341-6345, 2017 11.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients. MATERIALS AND METHODS: Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis. RESULTS: Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells. CONCLUSION: The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Benzoxazinas/farmacologia
Neoplasias Pulmonares/genética
Morfolinas/farmacologia
Naftalenos/farmacologia
Neuroblastoma/genética
Neoplasias Testiculares/genética
[Mh] Termos MeSH secundário: Células A549
Apoptose
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Fragmentação do DNA
Relação Dose-Resposta a Droga
Seres Humanos
Neoplasias Pulmonares/tratamento farmacológico
Masculino
Neuroblastoma/tratamento farmacológico
Neoplasias Testiculares/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzoxazines); 0 (Morpholines); 0 (Naphthalenes); 5H31GI9502 (Win 55212-2)
[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:171025
[St] Status:MEDLINE


  7 / 4522 MEDLINE  
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[PMID]:28931220
[Au] Autor:Mollan KR; Tierney C; Hellwege JN; Eron JJ; Hudgens MG; Gulick RM; Haubrich R; Sax PE; Campbell TB; Daar ES; Robertson KR; Ventura D; Ma Q; Edwards DRV; Haas DW; AIDS Clinical Trials Group
[Ad] Endereço:Center for AIDS Research.
[Ti] Título:Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.
[So] Source:J Infect Dis;216(5):554-564, 2017 Sep 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. Methods: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. Results: Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96-1.27) and on-treatment 1.16; 1.01-1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. Conclusions: Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/efeitos adversos
Benzoxazinas/efeitos adversos
Infecções por HIV/tratamento farmacológico
Farmacogenética
Suicídio/etnologia
[Mh] Termos MeSH secundário: Adulto
Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/sangue
Benzoxazinas/administração & dosagem
Benzoxazinas/sangue
Grupos de Populações Continentais
Citocromo P-450 CYP2A6/genética
Citocromo P-450 CYP2B6/genética
Grupos Étnicos
Feminino
Frequência do Gene
Genótipo
Seres Humanos
Masculino
Polimorfismo de Nucleotídeo Único
Modelos de Riscos Proporcionais
Fatores de Risco
Ideação Suicida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); EC 1.14.14.1 (CYP2A6 protein, human); EC 1.14.14.1 (CYP2B6 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2A6); EC 1.14.14.1 (Cytochrome P-450 CYP2B6); JE6H2O27P8 (efavirenz)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix248


  8 / 4522 MEDLINE  
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[PMID]:28892388
[Au] Autor:Pearce LV; Ann J; Jung A; Thorat SA; Herold BKA; Habtemichael AD; Blumberg PM; Lee J
[Ad] Endereço:Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, Maryland 20892-4255, United States.
[Ti] Título:Novel Radiolabeled Vanilloid with Enhanced Specificity for Human Transient Receptor Potential Vanilloid 1 (TRPV1).
[So] Source:J Med Chem;60(19):8246-8252, 2017 Oct 12.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transient receptor potential vanilloid 1 (TRPV1) has emerged as a promising therapeutic target. While radiolabeled resiniferatoxin (RTX) has provided a powerful tool for characterization of vanilloid binding to TRPV1, TRPV1 shows 20-fold weaker binding to the human TRPV1 than to the rodent TRPV1. We now describe a tritium radiolabeled synthetic vanilloid antagonist, 1-((2-(4-(methyl-[ H])piperidin-1-yl-4-[ H])-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)urea ([ H]MPOU), that embodies improved absolute affinity for human TRPV1 and improved synthetic accessibility.
[Mh] Termos MeSH primário: Benzoxazinas/farmacologia
Canais de Cátion TRPV/efeitos dos fármacos
Ureia/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Benzoxazinas/síntese química
Sítios de Ligação/efeitos dos fármacos
Seres Humanos
Ligação Proteica
Ratos
Relação Estrutura-Atividade
Especificidade por Substrato
Ureia/síntese química
Ureia/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(3-oxo-3,4-dihydro-2H-benzo(b)(1,4)oxazin-8-yl)urea); 0 (Benzoxazines); 0 (TRPV Cation Channels); 0 (TRPV1 protein, human); 8W8T17847W (Urea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00859


  9 / 4522 MEDLINE  
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[PMID]:28886044
[Au] Autor:Soeria-Atmadja S; Österberg E; Gustafsson LL; Dahl ML; Eriksen J; Rubin J; Navér L
[Ad] Endereço:Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
[Ti] Título:Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin.
[So] Source:PLoS One;12(9):e0181316, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Approximately 2.6 million children live with HIV globally, and efavirenz (EFV) is one of the most widely used antiretroviral agents for HIV treatment in children and adults. There are concerns about the appropriateness of current EFV dosing and it has been discussed whether EFV dosing should be adapted according to genotype in children as suggested for adults. AIM: To investigate if pediatric EFV dosing should be guided by genetic variation in drug metabolizing enzymes rather than by body weight. METHOD: EFV plasma concentrations measured for clinical purposes from all children less than 18 years old at Karolinska University Hospital, Stockholm, Sweden, treated with EFV were collected retrospectively. They were genotyped for eleven polymorphisms in genes coding for drug-metabolizing enzymes and P-glycoprotein, of potential importance for EFV disposition. Data on country of origin, sex, age, weight, HIV RNA, viral resistance patterns, CD4 cells, adherence to treatment, subjective health status and adverse events were collected from their medical records. RESULTS: Thirty-six patients and 182 (mean 5 samples/patient) EFV plasma concentration measurements from children of African, Asian and Latin American origin were included. EFV plasma concentration varied 21-fold between measurements (n = 182) (0.85-19.3 mg/L) and 9-fold measured as mean EFV plasma concentration across the subjects (1.55-13.4 mg/L). A multivariate mixed-effects restricted maximum likelihood regression model, including multiple gene polymorphisms, identified CYP2B6*6 T/T (p < 0.0005), CYP2B6*11 G/G (p < 0.0005), CYP2A6*9 A/C (p = 0.001) genotypes, age at treatment initiation (p = 0.002) and time from treatment initiation (p < 0.0005) as independent factors significantly related to loge concentration/(dose/weight). The contribution of the model to the intra- and interindividual variation were 6 and 75%, respectively (Bryk/Raudenbush R-squared level). CONCLUSION: Genetic polymorphisms in CYP2B6 and CYP2A6 explained a significant proportion of variability in EFV plasma concentration in HIV-infected children in a multi-ethnic outpatient clinic. Knowledge about individual variants in key drug metabolizing enzyme genes could improve clinical safety and genotype directed dosing could achieve more predictable EFV plasma concentrations in HIV-infected children.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacocinética
Benzoxazinas/farmacocinética
Citocromo P-450 CYP2A6/genética
Citocromo P-450 CYP2B6/genética
Grupos Étnicos/genética
Infecções por HIV/genética
HIV/efeitos dos fármacos
Variantes Farmacogenômicos
[Mh] Termos MeSH secundário: Fatores Etários
Alelos
Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/efeitos adversos
Benzoxazinas/administração & dosagem
Benzoxazinas/efeitos adversos
Contagem de Linfócito CD4
Criança
Feminino
Frequência do Gene
Genótipo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
Seres Humanos
Masculino
Polimorfismo de Nucleotídeo Único
Fatores Sexuais
Suécia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Benzoxazines); EC 1.14.14.1 (Cytochrome P-450 CYP2A6); EC 1.14.14.1 (Cytochrome P-450 CYP2B6); JE6H2O27P8 (efavirenz)
[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:170909
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181316


  10 / 4522 MEDLINE  
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[PMID]:28838830
[Au] Autor:Saifuzzaman M; Morrison R; Zheng Z; Orive S; Hamilton J; Thompson PE; Al-Rawi JMA
[Ad] Endereço:Pharmacy and Applied Science, La Trobe Institute for Molecular Science, La Trobe University, P.O. Box 199 Bendigo, VIC 3552, Australia. Electronic address: M.Saifuzzaman@latrobe.edu.au.
[Ti] Título:Synthesis and biological evaluation of 8-aryl-2-morpholino-7-O-substituted benzo[e][1,3]oxazin-4-ones against DNA-PK, PI3K, PDE3A enzymes and platelet aggregation.
[So] Source:Bioorg Med Chem;25(20):5531-5536, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of 40 7-(O-substituted)-2-morpholino-8-aryl-4H-benzo[e][1,3]oxazin-4-one derivatives was synthesized. They were prepared via synthesis of a key precursor, 8-bromo-7-hydroxy-2-morpholino-4H-benzo[e][1,3]oxazin-4-one 13 which was amenable to ether synthesis at the 7-position and Suzuki coupling at the 8-position. The 2 protons of 7-OCH in compounds 18g, 18h, 18i, 18l and 18m prove to be magnetically non-equivalent, atropisomerism (axial chirality), as result of sterically hindered rotation of the bulky 8-aryl-substituent. The products were evaluated for their activities against PI3K isoforms, DNA-PK and PDE3. The results showed that this substitution pattern has a deleterious effect on PI3K activities, which may arise from steric hindrance in the active site. PI3Kδ was somewhat more tolerant of this substitution particularly where 8-(4-methoxylphenyl) substituents were present (IC s∼2-3µM). Good activities against PDE3 were also obtained for compounds, with particular members of the 7-(2-pyridinyl) methoxy series 19 showing good inhibition (IC s∼2-3µM), comparable to previously described analogues. A piperazinyl derivative 26a effectively inhibited ADP-induced platelet aggregation with an IC of 8µM.
[Mh] Termos MeSH primário: Benzoxazinas/farmacologia
Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo
Proteína Quinase Ativada por DNA/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Inibidores da Agregação de Plaquetas/farmacologia
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Benzoxazinas/síntese química
Benzoxazinas/química
Proteína Quinase Ativada por DNA/metabolismo
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Fosfatidilinositol 3-Quinases/metabolismo
Agregação Plaquetária/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/síntese química
Inibidores da Agregação de Plaquetas/química
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoxazines); 0 (Platelet Aggregation Inhibitors); 0 (Protein Kinase Inhibitors); 0 (benzo(e)(1,3)oxazin-4-one); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3); EC 3.1.4.17 (PDE3A protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE



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