Base de dados : MEDLINE
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[PMID]:28291959
[Au] Autor:Liang W; Chen M; Zheng D; Li J; Song M; Zhang W; Feng J; Lan J
[Ti] Título:The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway.
[So] Source:Cell Physiol Biochem;41(3):1020-1034, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. METHODS: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. RESULTS: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. CONCLUSION: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Glucose/toxicidade
Miócitos Cardíacos/efeitos dos fármacos
Canais de Potássio/genética
Espécies Reativas de Oxigênio/antagonistas & inibidores
Receptor 4 Toll-Like/genética
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Animais
Linhagem Celular
Ácidos Decanoicos/farmacologia
Diazóxido/farmacologia
Regulação da Expressão Gênica
Glibureto/farmacologia
Hidroxiácidos/farmacologia
Imidazóis/farmacologia
Indóis/farmacologia
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Necrose/genética
Necrose/metabolismo
Necrose/prevenção & controle
Estresse Oxidativo
Pinacidil/farmacologia
Canais de Potássio/agonistas
Canais de Potássio/metabolismo
Ratos
Espécies Reativas de Oxigênio/metabolismo
Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores
Proteína Serina-Treonina Quinases de Interação com Receptores/genética
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Transdução de Sinais
Sulfonamidas/farmacologia
Receptor 4 Toll-Like/antagonistas & inibidores
Receptor 4 Toll-Like/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Decanoic Acids); 0 (Hydroxy Acids); 0 (Imidazoles); 0 (Indoles); 0 (Potassium Channels); 0 (Reactive Oxygen Species); 0 (Sulfonamides); 0 (Tlr4 protein, rat); 0 (Toll-Like Receptor 4); 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate); 0 (mitochondrial K(ATP) channel); 0 (necrostatin-1); 624-00-0 (5-hydroxydecanoic acid); 7B0ZZH8P2W (Pinacidil); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 2.7.11.1 (receptor-interacting protein 3, rat); IY9XDZ35W2 (Glucose); O5CB12L4FN (Diazoxide); SX6K58TVWC (Glyburide); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1159/000461391


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[PMID]:28256825
[Au] Autor:Lancelot A; González-Pastor R; Concellón A; Sierra T; Martín-Duque P; Serrano JL
[Ad] Endereço:Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Nanociencia de Aragón, Universidad de Zaragoza , Zaragoza 50009, Spain.
[Ti] Título:DNA Transfection to Mesenchymal Stem Cells Using a Novel Type of Pseudodendrimer Based on 2,2-Bis(hydroxymethyl)propionic Acid.
[So] Source:Bioconjug Chem;28(4):1135-1150, 2017 Apr 19.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the search for effective vehicles to carry genetic material into cells, we present here new pseudodendrimers that consist of a hyperbranched polyester core surrounded by amino-terminated 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) dendrons. The pseudodendrimers are readily synthesized from commercial hyperbranched bis-MPA polyesters of the second, third, and fourth generations and third-generation bis-MPA dendrons, bearing eight peripheral glycine moieties, coupled by the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). This approach provides globular macromolecular structures bearing 128, 256, and 512 terminal amino groups, and these can complex pDNA. The toxicity of the three pseudodendrimers was studied on two cell lines, mesenchymal stem cells, and HeLa, and it was demonstrated that these compounds do not affect negatively cell viability up to 72 h. The complexation with DNA was investigated in terms of N-to-P ratio and dendriplex stability. The three generations were found to promote internalizing of pDNA into mesenchymal stem cells (MSCs), and their transfection capacity was compared with two nonviral commercial transfection agents, Lipofectamine and TransIT-X2. The highest generations were able to transfect these cells at levels comparable to both commercial reagents.
[Mh] Termos MeSH primário: Dendrímeros/química
Hidroxiácidos/farmacologia
Células Mesenquimais Estromais/metabolismo
Propionatos/farmacologia
Transfecção/métodos
[Mh] Termos MeSH secundário: Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Plasmídeos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dendrimers); 0 (Hydroxy Acids); 0 (Propionates); 4NHI8V17MN (2,2-bis(hydroxymethyl)-propionic acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.7b00037


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[PMID]:28139228
[Au] Autor:Calderón C; Lämmerhofer M
[Ad] Endereço:Institute of Pharmaceutical Sciences, Pharmaceutical (Bio-)Analysis, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
[Ti] Título:Chiral separation of short chain aliphatic hydroxycarboxylic acids on cinchonan carbamate-based weak chiral anion exchangers and zwitterionic chiral ion exchangers.
[So] Source:J Chromatogr A;1487:194-200, 2017 Mar 03.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chiral short chain aliphatic hydrocarboxylic acids (HCAs) are common compounds being part of different biological processes. In order to control and understand these processes is of pivotal importance to determine the identity of the involved enantiomer or their enantiomeric ratio. In this study the capacity of quinine- and quinidine-derived chiral stationary phases to perform the enantioseparation of eight chiral HCAs (tartaric acid, isocitric acid, malic acid, glyceric acid, 2-hydroxyglutaric acid, 2-hydroxybutyric acid, lactic acid and 3-hydroxybutyric acid) was evaluated. MS-compatible conditions consisting of ACN/MeOH mixtures as eluents with formic acid, acetic acid and/or their ammonium salts as additives, temperatures between 10 and 25°C (except for -20°C for 3-hydroxybutyric acid) and a flow rate of 1.00mL/min yielded full baseline resolution for all studied HCAs. Elution order for the HCA enantiomers was determined revealing different behaviors between the studied compounds.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Cromatografia por Troca Iônica/métodos
Hidroxiácidos/isolamento & purificação
Resinas de Troca Iônica/química
[Mh] Termos MeSH secundário: Ácido 3-Hidroxibutírico/isolamento & purificação
Resinas de Troca de Ânions/química
Carbamatos/química
Ácidos Graxos/química
Ácidos Graxos/isolamento & purificação
Hidroxiácidos/química
Quinidina/química
Quinina/química
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Exchange Resins); 0 (Carbamates); 0 (Fatty Acids); 0 (Hydroxy Acids); 0 (Ion Exchange Resins); A7V27PHC7A (Quinine); ITX08688JL (Quinidine); TZP1275679 (3-Hydroxybutyric Acid)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170314
[Lr] Data última revisão:
170314
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE


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[PMID]:28126559
[Au] Autor:Dobricic V; Savic J; Nikolic K; Vladimirov S; Vujic Z; Brboric J
[Ad] Endereço:Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia. Electronic address: vladimir@pharmacy.bg.ac.rs.
[Ti] Título:Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel ß-hydroxy-ß-arylalkanoic acids.
[So] Source:Eur J Pharm Sci;100:280-284, 2017 Mar 30.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Gastrointestinal absorption of thirteen novel ß-hydroxy-ß-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors (k) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN(k) model was selected as optimal. Descriptors which form this model (nBM, P_VSA_LogP_8 and Eta_L) indicate that replacement of phenyl ring with a saturated or partially unsaturated one, as well as presence of halogens and nitro group should positively affect k values. On the basis of these conclusions, six novel HAA were designed and selected QSRR model was used for the prediction of their k values.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacocinética
Absorção Gastrointestinal
Hidroxiácidos/farmacocinética
Modelos Moleculares
[Mh] Termos MeSH secundário: Anti-Inflamatórios/química
Cromatografia/métodos
Desenho de Drogas
Hidroxiácidos/química
Micelas
Redes Neurais (Computação)
Relação Quantitativa Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Hydroxy Acids); 0 (Micelles)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE


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[PMID]:28077276
[Au] Autor:Savic J; Dobricic V; Nikolic K; Vladimirov S; Dilber S; Brboric J
[Ad] Endereço:Department of Pharmaceutical Chemistry, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
[Ti] Título:In vitro prediction of gastrointestinal absorption of novel ß-hydroxy-ß-arylalkanoic acids using PAMPA technique.
[So] Source:Eur J Pharm Sci;100:36-41, 2017 Mar 30.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Prediction of gastrointestinal absorption of thirteen newly synthesized ß-hydroxy-ß-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test. The highest values of PAMPA parameters (%T and P ) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %T and -logP and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %T and -logP were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.
[Mh] Termos MeSH primário: Absorção Gastrointestinal
Hidroxiácidos/química
Ibuprofeno/química
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/química
Anti-Inflamatórios não Esteroides/metabolismo
Hidroxiácidos/metabolismo
Ibuprofeno/metabolismo
Membranas Artificiais
Redes Neurais (Computação)
Permeabilidade
Relação Quantitativa Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Hydroxy Acids); 0 (Membranes, Artificial); WK2XYI10QM (Ibuprofen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170113
[St] Status:MEDLINE


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[PMID]:28029240
[Au] Autor:Christenson JK; Richman JE; Jensen MR; Neufeld JY; Wilmot CM; Wackett LP
[Ad] Endereço:Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
[Ti] Título:ß-Lactone Synthetase Found in the Olefin Biosynthesis Pathway.
[So] Source:Biochemistry;56(2):348-351, 2017 Jan 17.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The first ß-lactone synthetase enzyme is reported, creating an unexpected link between the biosynthesis of olefinic hydrocarbons and highly functionalized natural products. The enzyme OleC, involved in the microbial biosynthesis of long-chain olefinic hydrocarbons, reacts with syn- and anti-ß-hydroxy acid substrates to yield cis- and trans-ß-lactones, respectively. Protein sequence comparisons reveal that enzymes homologous to OleC are encoded in natural product gene clusters that generate ß-lactone rings, suggesting a common mechanism of biosynthesis.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Coenzima A Ligases/genética
Regulação Bacteriana da Expressão Gênica
Lactonas/metabolismo
Micrococcus luteus/genética
Stenotrophomonas maltophilia/genética
Streptomyces/genética
[Mh] Termos MeSH secundário: Alcenos/metabolismo
Sequência de Aminoácidos
Proteínas de Bactérias/metabolismo
Produtos Biológicos/metabolismo
Coenzima A Ligases/metabolismo
Hidroxiácidos
Micrococcus luteus/enzimologia
Família Multigênica
Óperon
Homologia de Sequência de Aminoácidos
Stenotrophomonas maltophilia/enzimologia
Streptomyces/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkenes); 0 (Bacterial Proteins); 0 (Biological Products); 0 (Hydroxy Acids); 0 (Lactones); EC 6.2.1.- (Coenzyme A Ligases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161229
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b01199


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[PMID]:27197623
[Au] Autor:Weber N; Zupanc V; Jakopic J; Veberic R; Mikulic-Petkovsek M; Stampar F
[Ad] Endereço:Agronomy Department, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000, Ljubljana, Slovenia.
[Ti] Título:Influence of deficit irrigation on strawberry (Fragaria × ananassa Duch.) fruit quality.
[So] Source:J Sci Food Agric;97(3):849-857, 2017 Feb.
[Is] ISSN:1097-0010
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Three different irrigation regimes - upper limit of field capacity (UFC), -12 kPa); lower limit of field capacity (LFC), -33 kPa; and deficit irrigation (DI), -70 kPa) were established on silty-loam soil and monitored with tensiometers. Yield and fruit quality of 'Flamenco' and 'Eva's Delight' ever-bearing strawberry cultivars were monitored. The aim of the study was to evaluate the effect of different irrigation regimes on the content of sugars, organic acids and phenolic compounds using high-performance liquid chromatography-mass spectrometry HPLC/HPLC-MS. RESULTS: Deficit irrigation significantly increased the content of sugars (from 1.1- to 1.3 fold), organic acids (from 1.1- to 1.3-fold), their ratio (from 1.1- to 1.2-fold) and the content of most identified phenolics in cv. 'Flamenco'. Conversely, higher amounts of total sugars and organic acids (1.7- to 1.8-fold) were detected in 'Eva's Delight' strawberries at UFC and LFC irrigation. Deficit irrigation generally decreased strawberry yield of cv. 'Eva's Delight'. CONCLUSION: The results suggest superior fruit quality and taste of strawberries grown under minor deficit irrigation for cv. 'Flamenco'. © 2016 Society of Chemical Industry.
[Mh] Termos MeSH primário: Irrigação Agrícola
Conservação dos Recursos Naturais
Produção Agrícola
Produtos Agrícolas/química
Qualidade dos Alimentos
Fragaria/química
Frutas/química
[Mh] Termos MeSH secundário: Ácidos Acíclicos/análise
Ácidos Acíclicos/metabolismo
Antioxidantes/análise
Antioxidantes/metabolismo
Cinamatos/análise
Cinamatos/metabolismo
Produtos Agrícolas/crescimento & desenvolvimento
Produtos Agrícolas/metabolismo
Cruzamentos Genéticos
Carboidratos da Dieta/análise
Flavonoides/análise
Flavonoides/biossíntese
Fragaria/crescimento & desenvolvimento
Fragaria/metabolismo
Frutas/crescimento & desenvolvimento
Frutas/metabolismo
Seres Humanos
Hidroxiácidos/análise
Hidroxiácidos/metabolismo
Fenômenos Mecânicos
Valor Nutritivo
Fenóis/análise
Fenóis/metabolismo
Melhoramento Vegetal
Sensação
Eslovênia
Especificidade da Espécie
Paladar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acids, Acyclic); 0 (Antioxidants); 0 (Cinnamates); 0 (Dietary Carbohydrates); 0 (Flavonoids); 0 (Hydroxy Acids); 0 (Phenols)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160521
[St] Status:MEDLINE
[do] DOI:10.1002/jsfa.7806


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[PMID]:27959901
[Au] Autor:Rickert E; Wahl M; Link H; Richter H; Pohnert G
[Ad] Endereço:Department of Marine Ecology, Division of Benthic Ecology, Helmholtz Centre for Ocean Research Kiel GEOMAR, Kiel, Germany.
[Ti] Título:Seasonal Variations in Surface Metabolite Composition of Fucus vesiculosus and Fucus serratus from the Baltic Sea.
[So] Source:PLoS One;11(12):e0168196, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Perennial macroalgae within the genus Fucus are known to exude metabolites through their outer thallus surface. Some of these metabolites have pro- and/or antifouling properties. Seasonal fluctuations of natural fouling pressure and chemical fouling control strength against micro- and macrofoulers have previously been observed in Fucus, suggesting that control strength varies with threat. To date, a study on the seasonal composition of surface associated metabolites, responsible for much of the fouling control, has not been done. We sampled individuals of the two co-occurring species F. vesiculosus and F. serratus at monthly intervals (six per species and month) during a one-year field study. We analysed the chemical composition of surface associated metabolites of both Fucus species by means of gas chromatography-mass spectrometry (GC-MS) to describe temporal patterns in chemical surface composition. Additionally, we correlated abiotic and biotic parameters recorded monthly within the sampled habitat with the variation in the chemical surface landscape of Fucus. Our study revealed that the chemical surface composition of both Fucus species exhibits substantial seasonal differences between spring/summer and autumn/winter months. Light and temperature explained most of the seasonal variability in surface metabolite composition of both Fucus species. A strong summerly up-regulation of eighteen saccharides and two hydroxy acids in F. vesiculosus as well as of four fatty acids and two saccharides in F. serratus was observed. We discuss how these up-regulated molecules may have a complex effect on associated microfoulers, both promoting or decreasing fouling depending on metabolite and bacterial identity. These seasonal shifts in the surface metabolome seem to exert a compound control of density and composition of the Fucus associated biofilm.
[Mh] Termos MeSH primário: Fucus/metabolismo
Estações do Ano
[Mh] Termos MeSH secundário: Biofilmes
Ecossistema
Ácidos Graxos/química
Cromatografia Gasosa-Espectrometria de Massas
Hidroxiácidos/química
Luz
Modelos Lineares
Oceanos e Mares
Polissacarídeos/química
Alga Marinha/metabolismo
Temperatura Ambiente
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Hydroxy Acids); 0 (Polysaccharides)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0168196


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[PMID]:27914476
[Au] Autor:Arsyad A; Dobson GP
[Ad] Endereço:Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, 1 James Cook Drive, 4811, Queensland, Australia.
[Ti] Título:Lidocaine relaxation in isolated rat aortic rings is enhanced by endothelial removal: possible role of K , K channels and A receptor crosstalk.
[So] Source:BMC Anesthesiol;16(1):121, 2016 Dec 03.
[Is] ISSN:1471-2253
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine's vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent K and K channels, membrane Na /K pump, and A and A receptors. METHODS: Aortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7.4, 37 °C. The rings were pre-contracted sub-maximally with 0.3 µM norepinephrine (NE), and the effect of increasing lidocaine concentrations was examined. Rings were tested for viability after each experiment with maximally dilating 100 µM papaverine. The drugs 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined. RESULTS: All drugs tested had no significant effect on basal tension. Lidocaine relaxation in intact rings was biphasic between 1 and 10 µM (Phase 1) and 10 and 1000 µM (Phase 2). Mechanical removal of the endothelium resulted in further relaxation, and at lower concentrations ring sensitivity (% relaxation per µM lidocaine) significantly increased 3.5 times compared to intact rings. The relaxing factor(s) responsible for enhancing ring relaxation did not appear to be NO- or prostacyclin-dependent, as L-NAME and indomethacin had little or no effect on intact ring relaxation. In denuded rings, lidocaine relaxation was completely abolished by K channel inhibition and significantly reduced by antagonists of the MitoK channel, and to a lesser extent the SarcK channel. Curiously, A subtype receptor antagonism significantly inhibited lidocaine relaxation above 100 µM, but not the A receptor. CONCLUSIONS: We show that lidocaine relaxation in rat thoracic aorta was biphasic and significantly enhanced by endothelial removal, which did not appear to be NO or prostacyclin dependent. The unknown factor(s) responsible for enhanced relaxation was significantly reduced by K inhibition, 5-HD inhibition, and A subtype inhibition indicating a potential role for crosstalk in lidocaine's vasoreactivity.
[Mh] Termos MeSH primário: Aorta Torácica/efeitos dos fármacos
Canais KATP/antagonistas & inibidores
Lidocaína/farmacologia
Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores
Vasodilatação/efeitos dos fármacos
[Mh] Termos MeSH secundário: 4-Aminopiridina/farmacologia
Antagonistas do Receptor A2 de Adenosina/farmacologia
Animais
Cafeína/análogos & derivados
Cafeína/farmacologia
Ácidos Decanoicos/farmacologia
Relação Dose-Resposta a Droga
Epoprostenol/antagonistas & inibidores
Glibureto/farmacologia
Hidroxiácidos/farmacologia
Técnicas In Vitro
Indometacina/farmacologia
Lidocaína/antagonistas & inibidores
Masculino
NG-Nitroarginina Metil Éster/farmacologia
Óxido Nítrico/antagonistas & inibidores
Norepinefrina/farmacologia
Ouabaína/farmacologia
Papaverina/farmacologia
Ratos
Receptor Cross-Talk/efeitos dos fármacos
Receptor A2A de Adenosina/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenosine A2 Receptor Antagonists); 0 (Decanoic Acids); 0 (Hydroxy Acids); 0 (KATP Channels); 0 (Potassium Channels, Voltage-Gated); 0 (Receptor, Adenosine A2A); 148589-13-3 (8-(3-chlorostyryl)caffeine); 31C4KY9ESH (Nitric Oxide); 3G6A5W338E (Caffeine); 5ACL011P69 (Ouabain); 624-00-0 (5-hydroxydecanoic acid); 98PI200987 (Lidocaine); BH3B64OKL9 (4-Aminopyridine); DAA13NKG2Q (Papaverine); DCR9Z582X0 (Epoprostenol); SX6K58TVWC (Glyburide); V55S2QJN2X (NG-Nitroarginine Methyl Ester); X4W3ENH1CV (Norepinephrine); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161205
[St] Status:MEDLINE


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[PMID]:27535111
[Au] Autor:Waseem M; Tabassum H; Parvez S
[Ad] Endereço:School of Medicine, University of Alabama at Birmingham, Birmingham, AL-35294 USA.
[Ti] Título:Melatonin modulates permeability transition pore and 5-hydroxydecanoate induced K channel inhibition in isolated brain mitochondria.
[So] Source:Mitochondrion;31:1-8, 2016 Nov.
[Is] ISSN:1872-8278
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:There is increasing recognition of the magnitude of mitochondria in neurodegenerative disorders. Mitochondria play a key role in apoptotic and necrotic cell death. Melatonin (Mel), an indoleamine produced in several organs including the pineal gland has been known for its neuroprotective actions. In our study, we have investigated whether the mitochondrial ATP sensitive potassium (mtK ) channel blocker 5-hydroxydecanoate (5-HD) and calcium (Ca ) affects permeability transition pore (PTP) alterations in isolated brain mitochondria treated with melatonin (Mel) and cyclosporin A (CsA). Mitochondrial swelling, mitochondrial membrane potential (Δψ ), ROS measurement and mitochondrial respiration were evaluated in isolated brain mitochondria. In our results, mitochondrial swelling stimulated by exposing Ca ions and 5-HD associated by mPTP opening as depicted by modulation of CsA and Mel. In addition, Ca and 5-HD decreased Δψ , depleted intracellular ROS, and inhibition of mitochondrial respiration (state 3 and state 4) in isolated brain mitochondria. Addition of Mel and CsA has shown significant restoration in mitochondrial swelling, Δψ , intracellular ROS measurement and mitochondrial respiration in isolated brain mitochondria. Therefore, we speculate the modulatory effect of Mel and CsA in mitochondria treated with 5-HD and Ca hinders the mPTP-mediated mitochondrial dysfunction and cellular oxidative stress. We conclude that inhibition of mPT is one likely mechanism of CsA's and its neuroprotective actions. Development of neuroprotective agents including Mel targeting the mPTP therefore bears hope for future treatment of severe neurodegenerative diseases.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Ácidos Decanoicos/metabolismo
Hidroxiácidos/metabolismo
Canais KATP/efeitos dos fármacos
Melatonina/metabolismo
Mitocôndrias/efeitos dos fármacos
Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacos
Fármacos Neuroprotetores/metabolismo
[Mh] Termos MeSH secundário: Animais
Antiarrítmicos/metabolismo
Ciclosporina/metabolismo
Masculino
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Mitocôndrias/patologia
Membranas Mitocondriais/fisiologia
Ratos Wistar
Espécies Reativas de Oxigênio/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Decanoic Acids); 0 (Hydroxy Acids); 0 (KATP Channels); 0 (Mitochondrial Membrane Transport Proteins); 0 (Neuroprotective Agents); 0 (Reactive Oxygen Species); 0 (mitochondrial permeability transition pore); 624-00-0 (5-hydroxydecanoic acid); 83HN0GTJ6D (Cyclosporine); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE



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