Base de dados : MEDLINE
Pesquisa : D02.241.081.337.540 [Categoria DeCS]
Referências encontradas : 3711 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 372 ir para página                         

  1 / 3711 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29311556
[Au] Autor:Springsteen G; Yerabolu JR; Nelson J; Rhea CJ; Krishnamurthy R
[Ad] Endereço:Department of Chemistry, Furman University, Greenville, SC, 29613, USA.
[Ti] Título:Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle.
[So] Source:Nat Commun;9(1):91, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The development of metabolic approaches towards understanding the origins of life, which have focused mainly on the citric acid (TCA) cycle, have languished-primarily due to a lack of experimentally demonstrable and sustainable cycle(s) of reactions. We show here the existence of a protometabolic analog of the TCA involving two linked cycles, which convert glyoxylate into CO and produce aspartic acid in the presence of ammonia. The reactions proceed from either pyruvate, oxaloacetate or malonate in the presence of glyoxylate as the carbon source and hydrogen peroxide as the oxidant under neutral aqueous conditions and at mild temperatures. The reaction pathway demonstrates turnover under controlled conditions. These results indicate that simpler versions of metabolic cycles could have emerged under potential prebiotic conditions, laying the foundation for the appearance of more sophisticated metabolic pathways once control by (polymeric) catalysts became available.
[Mh] Termos MeSH primário: Dióxido de Carbono/química
Glioxilatos/química
Modelos Químicos
Origem da Vida
Ácido Oxaloacético/química
Ácido Pirúvico/química
[Mh] Termos MeSH secundário: Amônia/química
Ácido Aspártico/química
Descarboxilação
Peróxido de Hidrogênio/química
Concentração de Íons de Hidrogênio
Cinética
Malonatos/química
Redes e Vias Metabólicas
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Glyoxylates); 0 (Malonates); 142M471B3J (Carbon Dioxide); 2F399MM81J (Oxaloacetic Acid); 30KYC7MIAI (Aspartic Acid); 7664-41-7 (Ammonia); 8558G7RUTR (Pyruvic Acid); 9KX7ZMG0MK (malonic acid); BBX060AN9V (Hydrogen Peroxide); JQ39C92HH6 (glyoxylic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02591-0


  2 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28652730
[Au] Autor:Chen WL; Li F; Tang Y; Yang SD; Li JZ; Yuan ZQ; Liu Y; Zhou XF; Liu C; Zhang XN
[Ad] Endereço:Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou.
[Ti] Título:Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin.
[So] Source:Int J Nanomedicine;12:4241-4256, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/administração & dosagem
Doxorrubicina/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Nanopartículas/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/química
Antibióticos Antineoplásicos/farmacocinética
Linhagem Celular Tumoral
Quitosana/química
Doxorrubicina/química
Doxorrubicina/farmacocinética
Portadores de Fármacos/química
Avaliação Pré-Clínica de Medicamentos/métodos
Liberação Controlada de Fármacos
Feminino
Concentração de Íons de Hidrogênio
Malonatos/química
Camundongos Endogâmicos BALB C
Nanopartículas/química
Tamanho da Partícula
Distribuição Tecidual
Ácido Urocânico/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Drug Carriers); 0 (Malonates); 80168379AG (Doxorubicin); 9012-76-4 (Chitosan); EM8Y79998C (methyl malonate); G8D26XJJ3B (Urocanic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S129748


  3 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28644952
[Au] Autor:Lombard DB; Zhao Y
[Ad] Endereço:Department of Pathology and Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: davidlom@med.umich.edu.
[Ti] Título:ACSF3 and Mal(onate)-Adapted Mitochondria.
[So] Source:Cell Chem Biol;24(6):649-650, 2017 Jun 22.
[Is] ISSN:2451-9456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this issue of Cell Chemical Biology, Bowman and colleagues show that the mitochondrial enzyme ACSF3 generates malonyl-CoA from malonate, in turn regulating metabolic flux and mitochondrial protein malonylation (Bowman et al., 2017). The study reveals a mechanism to generate mitochondrial malonyl-CoA and how this molecule impacts mitochondrial biology.
[Mh] Termos MeSH primário: Coenzima A Ligases/metabolismo
Malonatos/metabolismo
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Malonil Coenzima A/metabolismo
Camundongos
Proteínas Mitocondriais/metabolismo
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Malonates); 0 (Mitochondrial Proteins); 524-14-1 (Malonyl Coenzyme A); 9KX7ZMG0MK (malonic acid); EC 6.2.1.- (ACSF3 protein, human); EC 6.2.1.- (Coenzyme A Ligases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE


  4 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28499743
[Au] Autor:Huddleston JP; Wang SC; Johnson KA; Whitman CP
[Ad] Endereço:Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, TX 78712, United States.
[Ti] Título:Resolution of the uncertainty in the kinetic mechanism for the trans-3-Chloroacrylic acid dehalogenase-catalyzed reaction.
[So] Source:Arch Biochem Biophys;623-624:9-19, 2017 Jun 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:trans- and cis-3-Chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively) catalyze the hydrolytic dehalogenation of their respective isomers and represent key steps in the bacterial conversion of 1,3-dichloropropene to acetaldehyde. In prior work, a kinetic mechanism for the CaaD-catalyzed reaction could not be unequivocally determined because (1) the order of product release could not be determined and (2) the fluorescence factor for the enzyme species, E*PQ (where P = bromide and Q = malonate semialdehyde, the two products of the reaction) could not be assigned. The ambiguities in the model have now been resolved by stopped-flow experiments following the reaction using an active site fluorescent probe, αY60W-CaaD and 3-bromopropiolate, previously shown to be a mechanism-based inhibitor of CaaD, coupled with the rate of bromide release in the course of CaaD inactivation. A global fit of the combined datasets provides a complete minimal model for the reaction of αY60W-CaaD and 3-bromoacrylate. In addition, the global fit produces kinetic constants for CaaD inactivation by 3-bromopropiolate and implicates the acyl bromide as the inactivating species. Finally, a comparison of the model with that for cis-CaaD shows that for both enzymes turnover is limited by product release and not chemistry.
[Mh] Termos MeSH primário: Hidrolases/metabolismo
Pseudomonas/enzimologia
[Mh] Termos MeSH secundário: Brometos/metabolismo
Domínio Catalítico
Ativação Enzimática
Seres Humanos
Hidrolases/química
Hidrólise
Cinética
Malonatos/metabolismo
Simulação de Acoplamento Molecular
Pseudomonas/química
Pseudomonas/metabolismo
Infecções por Pseudomonas/microbiologia
Incerteza
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bromides); 0 (Malonates); 9KX7ZMG0MK (malonic acid); EC 3.- (Hydrolases); EC 3.8.1.- (trans-3-chloroacrylic acid dehalogenase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170514
[St] Status:MEDLINE


  5 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28498354
[Au] Autor:Yang Z; Abdellaoui H; He W; Xu J
[Ad] Endereço:State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, China. zhyang_2008a@163.com.
[Ti] Título:Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and Staudinger Cycloadditions.
[So] Source:Molecules;22(5), 2017 May 12.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The -nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an -nitro group is present at the -aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver -ß-sultams in considerable amounts, together with the predominant -ß-sultams. In other cases, the above sulfa-Staudinger cycloadditions give rise to -ß-sultams exclusively. Further mechanistic rationalization discloses that the -nitro effect is attributed to its strong electron-withdrawing inductive effect. Similarly, the -nitro effect also exists in Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current research provides further insights into the diastereoselective control in sulfa-Staudinger and Staudinger cycloadditions.
[Mh] Termos MeSH primário: Reação de Cicloadição
Ésteres/química
Iminas/química
Cetonas/química
Sulfonamidas/química
Sulfonas/química
[Mh] Termos MeSH secundário: Espectroscopia de Ressonância Magnética
Malonatos/química
Espectrometria de Massas
Estereoisomerismo
Ácidos Sulfínicos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Esters); 0 (Imines); 0 (Ketones); 0 (Malonates); 0 (Sulfinic Acids); 0 (Sulfonamides); 0 (Sulfones); 0 (beta-sultam); 0 (ethyl malonyl chloride); 7791-25-5 (sulfonyl chloride)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE


  6 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28479296
[Au] Autor:Bowman CE; Rodriguez S; Selen Alpergin ES; Acoba MG; Zhao L; Hartung T; Claypool SM; Watkins PA; Wolfgang MJ
[Ad] Endereço:Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
[Ti] Título:The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency.
[So] Source:Cell Chem Biol;24(6):673-684.e4, 2017 Jun 22.
[Is] ISSN:2451-9456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry generated and utilized in the cytoplasm; however, little is known about noncanonical organelle-specific malonyl-CoA metabolism. Intramitochondrial malonyl-CoA is generated by a malonyl-CoA synthetase, ACSF3, which produces malonyl-CoA from malonate, an endogenous competitive inhibitor of succinate dehydrogenase. To determine the metabolic requirement for mitochondrial malonyl-CoA, ACSF3 knockout (KO) cells were generated by CRISPR/Cas-mediated genome editing. ACSF3 KO cells exhibited elevated malonate and impaired mitochondrial metabolism. Unbiased and targeted metabolomics analysis of KO and control cells in the presence or absence of exogenous malonate revealed metabolic changes dependent on either malonate or malonyl-CoA. While ACSF3 was required for the metabolism and therefore detoxification of malonate, ACSF3-derived malonyl-CoA was specifically required for lysine malonylation of mitochondrial proteins. Together, these data describe an essential role for ACSF3 in dictating the metabolic fate of mitochondrial malonate and malonyl-CoA in mammalian metabolism.
[Mh] Termos MeSH primário: Coenzima A Ligases/metabolismo
Malonatos/metabolismo
Mitocôndrias/metabolismo
Proteínas Mitocondriais/metabolismo
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: Acilação
Animais
Linhagem Celular
Coenzima A Ligases/deficiência
Coenzima A Ligases/genética
Técnicas de Inativação de Genes
Seres Humanos
Lipogênese
Camundongos
Mutação
Especificidade de Órgãos
Oxirredução
Engenharia de Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Malonates); 0 (Mitochondrial Proteins); 9KX7ZMG0MK (malonic acid); EC 6.2.1.- (ACSF3 protein, human); EC 6.2.1.- (Coenzyme A Ligases)
[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:170509
[St] Status:MEDLINE


  7 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28175948
[Au] Autor:Wang J; Liu H; Huang D; Jin L; Wang C; Wen J
[Ad] Endereço:Key Laboratory of System Bioengineering (Tianjin University), Ministry of Education, Tianjin, 300072, People's Republic of China.
[Ti] Título:Comparative proteomic and metabolomic analysis of Streptomyces tsukubaensis reveals the metabolic mechanism of FK506 overproduction by feeding soybean oil.
[So] Source:Appl Microbiol Biotechnol;101(6):2447-2465, 2017 Mar.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:FK506 (tacrolimus) is a 23-membered polyketide macrolide that possesses powerful immunosuppressant activity. In this study, feeding soybean oil into the fermentation culture of Streptomyces tsukubaensis improved FK506 production by 88.8%. To decipher the overproduction mechanism, comparative proteomic and metabolomic analysis was carried out. A total of 72 protein spots with differential expression in the two-dimensional gel electrophoresis (2-DE) were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), and 66 intracellular metabolites were measured by gas chromatography-mass spectrometer (GC-MS). The analysis of proteome and metabolome indicated that feeding soybean oil as a supplementary carbon source could not only strengthen the FK506 precursor metabolism and energy metabolism but also tune the pathways related to transcriptional regulation, translation, and stress response, suggesting a better intracellular metabolic environment for the synthesis of FK506. Based on these analyses, 20 key metabolites and precursors of FK506 were supplemented into the soybean oil medium. Among them, lysine, citric acid, shikimic acid, and malonic acid performed excellently for promoting the FK506 production and biomass. Especially, the addition of malonic acid achieved the highest FK506 production, which was 1.56-fold of that in soybean oil medium and 3.05-fold of that in initial medium. This report represented the first comprehensive study on the comparative proteomics and metabolomics applied in S. tsukubaensis, and it would be a rational guidance to further strengthen the FK506 production.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Regulação Bacteriana da Expressão Gênica
Imunossupressores/metabolismo
Óleo de Soja/metabolismo
Streptomyces/genética
Tacrolimo/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Reatores Biológicos
Ácido Cítrico/metabolismo
Eletroforese em Gel Bidimensional
Fermentação
Cromatografia Gasosa-Espectrometria de Massas
Perfilação da Expressão Gênica
Ontologia Genética
Lisina/metabolismo
Malonatos/metabolismo
Redes e Vias Metabólicas/genética
Metabolômica
Anotação de Sequência Molecular
Proteômica
Ácido Chiquímico/metabolismo
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Streptomyces/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Immunosuppressive Agents); 0 (Malonates); 2968PHW8QP (Citric Acid); 29MS2WI2NU (Shikimic Acid); 8001-22-7 (Soybean Oil); 9KX7ZMG0MK (malonic acid); K3Z4F929H6 (Lysine); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170307
[Lr] Data última revisão:
170307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-017-8136-5


  8 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28152053
[Au] Autor:Kassouf N; Syed S; Larner J; Amlôt R; Chilcott RP
[Ad] Endereço:Research Centre for Topical Drug Delivery and Toxicology, School of Pharmacy, University of Hertfordshire, Hatfield, United Kingdom.
[Ti] Título:Evaluation of absorbent materials for use as ad hoc dry decontaminants during mass casualty incidents as part of the UK's Initial Operational Response (IOR).
[So] Source:PLoS One;12(2):e0170966, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The UK's Initial Operational Response (IOR) is a revised process for the medical management of mass casualties potentially contaminated with hazardous materials. A critical element of the IOR is the introduction of immediate, on-scene disrobing and decontamination of casualties to limit the adverse health effects of exposure. Ad hoc cleansing of the skin with dry absorbent materials has previously been identified as a potential means of facilitating emergency decontamination. The purpose of this study was to evaluate the in vitro oil and water absorbency of a range of materials commonly found in the domestic and clinical environments and to determine the effectiveness of a small, but representative selection of such materials in skin decontamination, using an established ex vivo model. Five contaminants were used in the study: methyl salicylate, parathion, diethyl malonate, phorate and potassium cyanide. In vitro measurements of water and oil absorbency did not correlate with ex vivo measurements of skin decontamination. When measured ex vivo, dry decontamination was consistently more effective than a standard wet decontamination method ("rinse-wipe-rinse") for removing liquid contaminants. However, dry decontamination was ineffective against particulate contamination. Collectively, these data confirm that absorbent materials such as wound dressings and tissue paper provide an effective, generic capability for emergency removal of liquid contaminants from the skin surface, but that wet decontamination should be used for non-liquid contaminants.
[Mh] Termos MeSH primário: Descontaminação/métodos
Incidentes com Feridos em Massa
Absorção Cutânea/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Feminino
Malonatos/toxicidade
Paration/toxicidade
Forato/toxicidade
Cianeto de Potássio/toxicidade
Salicilatos/toxicidade
Suínos
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Malonates); 0 (Salicylates); 3W54X3W9IV (Phorate); 53A58PA183 (diethyl malonate); 61G466064D (Parathion); LAV5U5022Y (methyl salicylate); MQD255M2ZO (Potassium Cyanide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170966


  9 / 3711 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28134976
[Au] Autor:Chadha R; Sharma M; Haneef J
[Ad] Endereço:University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, India.
[Ti] Título:Multicomponent solid forms of felodipine: preparation, characterisation, physicochemical and in-vivo studies.
[So] Source:J Pharm Pharmacol;69(3):254-264, 2017 Mar.
[Is] ISSN:2042-7158
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This study aimed to improve biopharmaceutical parameters of the poorly soluble antihypertensive drug, felodipine, by preparing multicomponent solid forms using three coformers, viz. imidazole, nicotinamide and malonic acid. METHODS: The multicomponent solid forms were prepared by mechanochemical synthesis and characterised by various analytical techniques. These solid forms were further assessed for their physicochemical parameters. Pharmacokinetic and in-vivo antihypertensive activity was performed in rats. KEY FINDINGS: Felodipine (FEL) was found to be cocrystallised with imidazole (FEL-IM) while it formed eutectic with nicotinamide (FEL-NCT) and malonic acid (FEL-MA). Cocrystal was sustained by NH…N and NH….O hydrogen-bonded network. Solubility and intrinsic dissolution studies in 0.1 N HCl (pH 1.2) revealed that eutectics exhibited higher solubility and release rate than cocrystal vis-a-vis pure drug and were found to be stable under accelerated storage condition. Significant enhancement of bioavailability was observed in eutectics (3.5- to twofold) and cocrystal (1.3-fold) compared with the pure drug. Antihypertensive activity of new solid forms in an animal model showed a marked decrease in systolic blood pressure. CONCLUSIONS: Mechanochemical approach was successful to prepare multicomponent solid forms that have the potential to improve biopharmaceutical parameters of the poorly soluble drug, FEL.
[Mh] Termos MeSH primário: Anti-Hipertensivos/química
Anti-Hipertensivos/farmacologia
Felodipino/química
Felodipino/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Hipertensivos/metabolismo
Disponibilidade Biológica
Química Farmacêutica/métodos
Cristalização/métodos
Composição de Medicamentos/métodos
Estabilidade de Medicamentos
Felodipino/metabolismo
Masculino
Malonatos/química
Ratos
Ratos Wistar
Solubilidade
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Malonates); 9KX7ZMG0MK (malonic acid); OL961R6O2C (Felodipine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170131
[St] Status:MEDLINE
[do] DOI:10.1111/jphp.12685


  10 / 3711 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28119202
[Au] Autor:Schettgen T; Bertram J; Kraus T
[Ad] Endereço:Institute for Occupational and Social Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, D-52074, Aachen, Germany. Electronic address: tschettgen@ukaachen.de.
[Ti] Título:Quantification of N-methylmalonamic acid in urine as metabolite of the biocides methylisothiazolinone and chloromethylisothiazolinone using gas chromatography-tandem mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1044-1045:185-193, 2017 Feb 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Methylisothiazolinone and the mixture of chloromethylisothiazolinone/methylisothiazolinone (MCI/MI, 3:1) are widespread biocides used in cosmetic and household products. Due to their skin permeability, they might be taken up by the general population via use of products containing these biocides. As both compounds are known skin sensitizers, the use of these products is under discussion by regulatory agencies. In order to evaluate the possible uptake of MI and/or MCI/MI by human biomonitoring, we have developed and validated a highly sensitive and specific GC/MS/MS-method for the quantification of N-methylmalonamic acid (NMMA), a known metabolite of MI and MCI in urine of rats. After freeze-drying of urine, the analyte is derivatised with pentafluorobenzyl bromide in anhydrous solution and the PFB-derivative is extracted into n-hexane. After concentration, the derivative is finally quantified by GC/MS/MS in EI-mode using C -NMMA as internal standard. The limit of quantification for NMMA was 0.5ngmL urine. Precision within and between-series was determined to range between 3.7-10.9% using native and spiked quality control samples. Accuracy ranged between 89 and 114%. In a pilot study we applied this method to spot urine samples of 63 persons not knowingly exposed to MI and/or MCI/MI. NMMA was quantifiable in every urine sample analysed, with no significant difference in urinary levels between male and female participants. The median (95th percentile) levels for urinary NMMA were 3.6 (7.4) ngmg creatinine and 2.9 (9.1) ngmg creatinine for males (n=32) and females (n=31), respectively. In a volunteer experiment, a relation of exposure to MI and/or MCI/MI and subsequent NMMA-excretion was shown. Our method is the first to report human urinary background levels of NMMA. However, the possibility of formation and urinary excretion of NMMA within physiological processes cannot be ruled out.
[Mh] Termos MeSH primário: Desinfetantes/urina
Cromatografia Gasosa-Espectrometria de Massas/métodos
Malonatos/urina
Espectrometria de Massas em Tandem/métodos
Tiazóis/urina
[Mh] Termos MeSH secundário: Adulto
Animais
Feminino
Seres Humanos
Modelos Lineares
Masculino
Meia-Idade
Ratos
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disinfectants); 0 (Malonates); 0 (Thiazoles); 229D0E1QFA (2-methyl-4-isothiazolin-3-one); 42105-98-6 (N-methylmalonamic acid)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170324
[Lr] Data última revisão:
170324
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE



página 1 de 372 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