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[PMID]:28465084
[Au] Autor:Jensen TP; Zheng K; Tyurikova O; Reynolds JP; Rusakov DA
[Ad] Endereço:UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. Electronic address: t.jensen@ucl.ac.uk.
[Ti] Título:Monitoring single-synapse glutamate release and presynaptic calcium concentration in organised brain tissue.
[So] Source:Cell Calcium;64:102-108, 2017 Jun.
[Is] ISSN:1532-1991
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Brain function relies in large part on Ca -dependent release of the excitatory neurotransmitter glutamate from neuronal axons. Establishing the causal relationship between presynaptic Ca dynamics and probabilistic glutamate release is therefore a fundamental quest across neurosciences. Its progress, however, has hitherto depended primarily on the exploration of either cultured nerve cells or giant central synapses accessible to direct experimental probing in situ. Here we show that combining patch-clamp with time-resolved imaging of Ca -sensitive fluorescence lifetime of Oregon Green BAPTA-1 (Tornado-FLIM) enables readout of single spike-evoked presynaptic Ca concentration dynamics, with nanomolar sensitivity, in individual neuronal axons in acute brain slices. In parallel, intensity Tornado imaging of a locally expressed extracellular optical glutamate sensor iGluSnFr provides direct monitoring of single-quantum, single-synapse glutamate releases in situ. These two methods pave the way for simultaneous registration of presynaptic Ca dynamics and transmitter release in an intact brain at the level of individual synapses.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Cálcio/metabolismo
Ácido Glutâmico/metabolismo
Terminações Pré-Sinápticas/metabolismo
Sinapses/metabolismo
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Compostos de Anilina/metabolismo
Animais
Axônios/metabolismo
Fluoresceínas/metabolismo
Hipocampo/metabolismo
Camundongos Endogâmicos C57BL
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Fluoresceins); 0 (Oregon green 488 BAPTA-1); 3KX376GY7L (Glutamic Acid); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  2 / 14308 MEDLINE  
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[PMID]:29215269
[Au] Autor:Yang SP; Zhao W; Hu PP; Wu KY; Jiang ZH; Bai LP; Li MM; Chen JX
[Ad] Endereço:Guangdong Provincial Key Laboratory of New Drug Screening and Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou 510515, People's Republic of China.
[Ti] Título:Lanthanum-Based Metal-Organic Frameworks for Specific Detection of Sudan Virus RNA Conservative Sequences down to Single-Base Mismatch.
[So] Source:Inorg Chem;56(24):14880-14887, 2017 Dec 18.
[Is] ISSN:1520-510X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reactions of La(NO ) ·6H O with the polar, tritopic quaternized carboxylate ligands N-carboxymethyl-3,5-dicarboxylpyridinium bromide (H CmdcpBr) and N-(4-carboxybenzyl)-3,5-dicarboxylpyridinium bromide (H CbdcpBr) afford two water-stable metal-organic frameworks (MOFs) of {[La (Cmdcp) (H O) ]} (1, 3D) and {[La (Cbdcp) (H O) ]} (2, 2D). MOFs 1 and 2 absorb the carboxyfluorescein (FAM)-tagged probe DNA (P-DNA) and quench the fluorescence of FAM via a photoinduced electron transfer (PET) process. The nonemissive P-DNA@MOF hybrids thus formed in turn function as sensing platforms to distinguish conservative linear, single-stranded RNA sequences of Sudan virus with high selectivity and low detection limits of 112 and 67 pM, respectively (at a signal-to-noise ratio of 3). These hybrids also exhibit high specificity and discriminate down to single-base mismatch RNA sequences.
[Mh] Termos MeSH primário: Ebolavirus/isolamento & purificação
Doença pelo Vírus Ebola/virologia
Lantânio/química
Estruturas Metalorgânicas/química
RNA Viral/análise
[Mh] Termos MeSH secundário: Sequência de Bases
Cristalografia por Raios X
Fluoresceínas/química
Corantes Fluorescentes/química
Doença pelo Vírus Ebola/diagnóstico
Seres Humanos
Limite de Detecção
Modelos Moleculares
Espectrometria de Fluorescência/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluoresceins); 0 (Fluorescent Dyes); 0 (Metal-Organic Frameworks); 0 (RNA, Viral); 3301-79-9 (6-carboxyfluorescein); 6I3K30563S (Lanthanum)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1021/acs.inorgchem.7b02107


  3 / 14308 MEDLINE  
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[PMID]:29239411
[Au] Autor:Ogasawara H; Grzybowski M; Hosokawa R; Sato Y; Taki M; Yamaguchi S
[Ad] Endereço:Department of Chemistry, Graduate School of Science and Integrated Research Consortium on Chemical Sciences (IRCCS), Nagoya University, Furo, Chikusa, Nagoya 464-8602, Japan.
[Ti] Título:A far-red fluorescent probe based on a phospha-fluorescein scaffold for cytosolic calcium imaging.
[So] Source:Chem Commun (Camb);54(3):299-302, 2018 Jan 02.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The far-red emissive fluorescent probe CaPF-1 based on a phospha-fluorescein scaffold enables the detection of cytosolic calcium ions in living cells. The probe can be excited in the red region (λ = 636 nm) and exhibits a sufficiently high fluorescence turn-on response in the far-red region (λ = 663 nm) upon complexation with calcium ions. The hydrophilic and anionic characteristics of this phospha-fluorescein fluorophore allowed the cytosolic localization of CaPF-1. Moreover, it was possible to visualize histamine-induced calcium oscillation in HeLa cells using CaPF-1.
[Mh] Termos MeSH primário: Cálcio/análise
Óxidos P-Cíclicos/farmacologia
Fluoresceínas/farmacologia
Corantes Fluorescentes/farmacologia
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Óxidos P-Cíclicos/síntese química
Óxidos P-Cíclicos/química
Fluoresceínas/síntese química
Fluoresceínas/química
Fluorescência
Corantes Fluorescentes/síntese química
Corantes Fluorescentes/química
Células HeLa
Histamina/metabolismo
Seres Humanos
Concentração de Íons de Hidrogênio
Microscopia Confocal
Imagem Molecular
Imagem Óptica
Receptores Histamínicos H1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic P-Oxides); 0 (Fluoresceins); 0 (Fluorescent Dyes); 0 (Receptors, Histamine H1); 820484N8I3 (Histamine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1039/c7cc07344e


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[PMID]:29174985
[Au] Autor:Ivanova L; Fæste CK; Solhaug A
[Ad] Endereço:Section for Chemistry, Norwegian Veterinary Institute, P.O. Box 750, Sentrum, 0106 Oslo, Norway. Electronic address: lada.ivanova@vetinst.no.
[Ti] Título:Role of P-glycoprotein in deoxynivalenol-mediated in vitro toxicity.
[So] Source:Toxicol Lett;284:21-28, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Deoxynivalenol (DON) is the most prevalent mycotoxin produced by grain-infecting Fusarium strains and frequently occurs in small cereals all over the world. After ingestion, DON is absorbed in the gut, which leads dose-dependently to critical health effects. In the present study, we have further investigated DON's previously reported affinity to the efflux transporter P-glycoprotein (Pgp) in the apical enterocyte membrane. Interaction with Pgp was studied in human colorectal adenocarcinoma (Caco-2) cells and Madin-Darby Canine Kidney wild-type (MDCKII-wt) and Pgp-overexpressing (MDCKII-MDR1) cells in different transport and cytotoxicity experiments. We found that DON was exported by Pgp and was less cytotoxic in Pgp-overexpressing cells. In the fluorometric calcein-acetoxymethylester (Calcein AM) assay DON reduced intracellular calcein retention, indicating a stimulation of Pgp-mediated efflux. In the presence of the selective Pgp inhibitors verapamil (Ver) and valspodar (PSC 833) the effect was, respectively, distinctive and significant. Verrucarol, a structural analogue of DON, was much less effective indicating the importance of the α, ß-conjugated carbonyl group in the DON molecule for Pgp interaction. Our results confirmed that Pgp might have the potential to reduce intestinal absorption of DON in vivo. Furthermore, we were able to show that DON can modulate Pgp activity in vitro.
[Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Tricotecenos/metabolismo
Tricotecenos/toxicidade
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Animais
Transporte Biológico
Células CACO-2
Sobrevivência Celular/efeitos dos fármacos
Citosol/metabolismo
Cães
Relação Dose-Resposta a Droga
Citometria de Fluxo
Fluoresceínas/metabolismo
Seres Humanos
Absorção Intestinal
Células Madin Darby de Rim Canino
Modelos Biológicos
Permeabilidade
Ligação Proteica
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Fluoresceins); 0 (Trichothecenes); JT37HYP23V (deoxynivalenol); V0YM2B16TS (fluorexon)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  5 / 14308 MEDLINE  
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[PMID]:28448884
[Au] Autor:Clericuzio M; Burlando B; Borghesi B; Salis A; Damonte G; Ribulla S; Cornara L
[Ad] Endereço:Department of Sciences and Technological Innovation, University of Eastern Piedmont, Viale T. Michel 11, 15121 Alessandria, Italy.
[Ti] Título:Antiproliferative hydroxy-fatty acids from the fodder legume Stylosanthes guianensis.
[So] Source:J Pharm Biomed Anal;141:157-164, 2017 Jul 15.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Stylosanthes guianensis is a fodder legume native from South America and widely grown worldwide. Dried plant material was purchased on the web and taxonomically identified by light and SEM microscopy, and morphological analysis of plants germinated from seeds. The plant was extracted with dichloromethane:2-propanol (9:1). Bioguided fractionation using calcein-AM cytotoxicity assay on HeLa and A431 tumor cells allowed to isolate a lipophilic fraction, endowed with strong cytotoxicity. By means of 1- and 2-D NMR, HPLC-MS, and HR-ESIMS it could be seen that the fraction was an inseparable mixture of complex lipids, mainly consisting of esterified 3-hydroxy fatty acids. Acidic methanolysis of the mixture yielded 3-OH C10 and C12 carboxylic acids, together with palmitic, stearic, and arachidonic acids. Mass values indicate the presence of dimeric and trimeric combinations of 3-hydroxy, C10/C12 acids, and C16/C18/C20 acids, linked via ester bond. Monomeric hydroxyl-fatty acids were also observed, in particular derivatives of mono-hydroxy and di-hydroxy linolenic, linoleic, and oleic acids. 3-O-acylated, esterified fatty acids are unusual in higher plants, and recall motifs of Gram-negative endotoxin lipid A. These oxylipins are likely to be responsible for the antiproliferative activity of S. guianensis, suggesting possible use of the plant in the development of antitumor drugs.
[Mh] Termos MeSH primário: Fabaceae
[Mh] Termos MeSH secundário: Ração Animal
Ácidos Graxos
Fluoresceínas
Lipídeos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Fluoresceins); 0 (Lipids); 148504-34-1 (calcein AM)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


  6 / 14308 MEDLINE  
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[PMID]:29227077
[Au] Autor:Franskevych DV; Grynyuk II; Prylutska SV; Matyshevs ka OP
[Ti] Título:Modulation of cisplatin-induced reactive oxygen species production by fullerene C(60) in normal and transformed lymphoid cells
[So] Source:Ukr Biochem J;88(1):44-50, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The early response of normal (Wistar rat thymocytes) and transformed (mice lymphoid leukemia L1210) cells to treatment with anticancer drug cisplatin or to combined treatment with cisplatin and carbon nanostructure fullerene C60 was studied. We demonstrated with fluorescent probes DCFH-DA and TMRE that cisplatin at concentration 1 µg/ml induced reactive oxygen species (ROS) production and decreased the value of mitochondrial membrane potential in both cell types. The combined treatment with cisplatin (1 µg/ml) and fullerene C60 (7.2 µg/ml) was shown to be followed by oppositely directed modulation of ROS production in thymocytes and L1210 cells. Cisplatin-induced ROS production was intensified in L1210 cells, while in thymocytes it was decreased. It is supposed that the different effects of combined treatment are associated with peculiarities of fullerene C60 accumulation and localization in normal and cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Cisplatino/farmacologia
Fulerenos/farmacologia
Linfócitos/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Timócitos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Combinação de Medicamentos
Interações Medicamentosas
Fluoresceínas/química
Corantes Fluorescentes/química
Linfócitos/metabolismo
Linfócitos/patologia
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Especificidade de Órgãos
Compostos Organometálicos/química
Cultura Primária de Células
Ratos
Ratos Wistar
Espécies Reativas de Oxigênio/agonistas
Espécies Reativas de Oxigênio/antagonistas & inibidores
Timócitos/citologia
Timócitos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Fluoresceins); 0 (Fluorescent Dyes); 0 (Fullerenes); 0 (Organometallic Compounds); 0 (Reactive Oxygen Species); 0 (tetramethyl rhodamine ethyl ester); 2044-85-1 (diacetyldichlorofluorescein); NP9U26B839 (fullerene C60); Q20Q21Q62J (Cisplatin)
[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:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.044


  7 / 14308 MEDLINE  
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[PMID]:29244817
[Au] Autor:Montiel-Dávalos A; Silva Sánchez GJ; Huerta-García E; Rueda-Romero C; Soca Chafre G; Mitre-Aguilar IB; Alfaro-Moreno E; Pedraza-Chaverri J; López-Marure R
[Ad] Endereço:Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, México.
[Ti] Título:Curcumin inhibits activation induced by urban particulate material or titanium dioxide nanoparticles in primary human endothelial cells.
[So] Source:PLoS One;12(12):e0188169, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Curcumin has protective effects against toxic agents and shows preventive properties for various diseases. Particulate material with an aerodynamic diameter of ≤10 µm (PM10) and titanium dioxide nanoparticles (TiO2-NPs) induce endothelial dysfunction and activation. We explored whether curcumin is able to attenuate different events related to endothelial activation. This includes adhesion, expression of adhesion molecules and oxidative stress induced by PM10 and TiO2-NPs. Human umbilical vein endothelial cells (HUVEC) were treated with 1, 10 and 100 µM curcumin for 1 h and then exposed to PM10 at 3 µg/cm2 or TiO2-NPs at 10 µg/cm2. Cell adhesion was evaluated by co-culture with U937 human myelomonocytic cells. Adhesion molecules expression was measured by flow cytometry after 3 or 24 h of exposure. Oxidative stress was determined by 2,7-dichlorodihydrofluorescein (H2DCF) oxidation. PM10 and TiO2-NPs induced the adhesion of U937 cells and the expression of E- and P-selectins, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1). The expression of E- and P-selectins matched the adhesion of monocytes to HUVEC after 3 h. In HUVEC treated with 1 or 10 µM curcumin, the expression of adhesion molecules and monocytes adhesion was significantly diminished. Curcumin also partially reduced the H2DCF oxidation induced by PM10 and TiO2-NPs. Our results suggest an anti-inflammatory and antioxidant role by curcumin attenuating the activation caused on endothelial cells by exposure to particles. Therefore, curcumin could be useful in the treatment of diseases where an inflammatory process and endothelial activation are involved.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Curcumina/farmacologia
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Nanopartículas/toxicidade
Material Particulado/antagonistas & inibidores
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Adesão Celular/efeitos dos fármacos
Cidades
Técnicas de Cocultura
Selectina E/genética
Selectina E/metabolismo
Fluoresceínas/química
Expressão Gênica
Células Endoteliais da Veia Umbilical Humana/citologia
Células Endoteliais da Veia Umbilical Humana/metabolismo
Seres Humanos
Molécula 1 de Adesão Intercelular/genética
Molécula 1 de Adesão Intercelular/metabolismo
México
Estresse Oxidativo/efeitos dos fármacos
Selectina-P/genética
Selectina-P/metabolismo
Material Particulado/farmacologia
Molécula-1 de Adesão Celular Endotelial de Plaquetas/genética
Molécula-1 de Adesão Celular Endotelial de Plaquetas/metabolismo
Titânio/farmacologia
Células U937
Molécula 1 de Adesão de Célula Vascular/genética
Molécula 1 de Adesão de Célula Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biomarkers); 0 (E-Selectin); 0 (Fluoresceins); 0 (ICAM1 protein, human); 0 (P-Selectin); 0 (Particulate Matter); 0 (Platelet Endothelial Cell Adhesion Molecule-1); 0 (SELE protein, human); 0 (Vascular Cell Adhesion Molecule-1); 106070-31-9 (2',7'-dichlorodihydrofluorescein); 126547-89-5 (Intercellular Adhesion Molecule-1); 15FIX9V2JP (titanium dioxide); D1JT611TNE (Titanium); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188169


  8 / 14308 MEDLINE  
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[PMID]:29186162
[Au] Autor:Efimova SS; Tevyashova AN; Olsufyeva EN; Bykov EE; Ostroumova OS
[Ad] Endereço:Group of Ion Channel Modeling, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, Russia.
[Ti] Título:Pore-forming activity of new conjugate antibiotics based on amphotericin B.
[So] Source:PLoS One;12(11):e0188573, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A series of amides of the antifungal antibiotic amphotericin B (AmB) and its conjugates with benzoxaboroles was tested to determine whether they form pores in lipid bilayers and to compare their channel characteristics. The tested derivatives produced pores of larger amplitude and shorter lifetime than those of the parent antibiotic. The pore conductance was related to changes in the partial charge of the hydrogens of the hydroxyl groups in the lactone ring that determined the anion coordination in the channel. Neutralization of one of the polar group charges in the AmB head during chemical modification produced a pronounced effect by diminishing the dwell time of the polyene channel compared to modification of both groups. In this study, compounds that had a modification of one carboxyl or amino group were less effective in initializing phase separation in POPC-membranes compared to derivatives that had modifications of both polar groups as well as the parent antibiotic. The effects were attributed to the restriction of the aggregation process by electrical repulsion between charged derivatives in contrast to neutral compounds. The significant correlation between the ability of derivatives to increase the permeability of model membranes-causing the appearance of single channels in lipid bilayers or inducing calcein leakage from unilamellar vesicles-and the minimal inhibitory concentration indicated that the antifungal effect of the conjugates was due to pore formation in the membranes of target cells.
[Mh] Termos MeSH primário: Anfotericina B/farmacologia
Antibacterianos/farmacologia
[Mh] Termos MeSH secundário: Anfotericina B/química
Antibacterianos/química
Fluoresceínas/química
Bicamadas Lipídicas/química
Microscopia de Fluorescência
Fosfatidilcolinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoresceins); 0 (Lipid Bilayers); 0 (Phosphatidylcholines); 7XU7A7DROE (Amphotericin B); V0YM2B16TS (fluorexon)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188573


  9 / 14308 MEDLINE  
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[PMID]:29214974
[Au] Autor:Cavalcante CSP; de Aguiar FLL; Fontenelle ROS; de Menezes RRPPB; Martins AMC; Falcão CB; Andreu D; Rádis-Baptista G
[Ad] Endereço:1​Post-graduate Program in Pharmaceutical Sciences, Federal University of Ceará, 60740-000, Fortaleza, CE, Brazil.
[Ti] Título:Insights into the candidacidal mechanism of Ctn[15-34] - a carboxyl-terminal, crotalicidin-derived peptide related to cathelicidins.
[So] Source:J Med Microbiol;67(1):129-138, 2018 Jan.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Ctn[15-34], a carboxyl-terminal fragment of crotalicidin (a cathelicidin from the venom gland of a South American rattlesnake), has shown antifungal activity against clinical and standard strains of Candida species. The aim of the present work was to investigate the underlying mechanisms of the candidicidal activity of Ctn[15-34]. METHODOLOGY: The time-kill profile and drug synergism were evaluated by means of a microdilution assay and multi-parametric flow cytometry. The presumptive interaction of Ctn[15-34] with lipid membranes was estimated in vitro with a lipid-mimic compound, the chromogenic substance 4-nitro-3-(octanoyloxy)benzoic acid (4N3OBA).Results/Key findings. The absorbance increment (at 425 nm) indicated a concentration- and time-dependent in-solution association between Ctn[15-34] and 4N3OBA. The interaction of Ctn[15-34] with Candida cells was confirmed by flow cytometric measurements with the 5(6)-carboxyfluorescein-labelled peptide (CF-Ctn[15-34]). Analysis of the killing time of Candida exposed to Ctn[15-34] and amphotericin B (AMB) showed that both the peptide and polyene drug reduce the number of c.f.u. but in mechanistically different ways. The Ctn[15-34] peptide alone caused yeast cell membrane disruption, which was confirmed by lactate dehydrogenase leakage and biomarkers of cell death mediated by necrosis. CONCLUSION: Overall, Ctn[15-34] displays a synergistic antifungal activity with AMB, an effect that can be further developed into a multi-target therapeutic option with other antimycotics currently in use.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Candida/efeitos dos fármacos
Catelicidinas/farmacologia
Fragmentos de Peptídeos/farmacologia
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Candidíase/tratamento farmacológico
Sinergismo Farmacológico
Fluoresceínas/farmacologia
Seres Humanos
Testes de Sensibilidade Microbiana/métodos
Nitrobenzoatos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-nitro-3-(octanoyloxy)benzoic acid); 0 (Antifungal Agents); 0 (Cathelicidins); 0 (Fluoresceins); 0 (Nitrobenzoates); 0 (Peptide Fragments); 0 (Peptides); 0 (crotalicidin); 3301-79-9 (6-carboxyfluorescein); 7XU7A7DROE (Amphotericin B)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000652


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Fotocópia
Chiari, Egler
Texto completo
[PMID]:29176759
[Au] Autor:Magalhães LMD; Viana A; de Jesus AC; Chiari E; Galvão L; Gomes JA; Gollob KJ; Dutra WO
[Ad] Endereço:Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
[Ti] Título:Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human neutrophils.
[So] Source:PLoS One;12(11):e0188083, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neutrophils are critical players in the first line of defense against pathogens and in the activation of subsequent cellular responses. We aimed to determine the effects of the interaction of Trypanosoma cruzi with human neutrophils, using isolates of the two major discrete type units (DTUs) associated with Chagas' disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II, respectively). Thus, we used CFSE-stained trypomastigotes to measure neutrophil-T. cruzi interaction, neutrophil activation, cytokine expression and death, after infection with Col1.7G2 and Y strain. Our results show that the frequency of CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per-cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL-12 expression, although at different levels between the two strains. No change in IL-10 expression was observed after interaction of neutrophils with either strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil death. This was specific to neutrophils, since interaction of either strain with monocytes did not cause death. Our further analysis showed that neutrophil death was a result of apoptosis, which was associated with an upregulation of TNF-receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated neutrophil apoptosis by the different T. cruzi isolates may act as an effective common mechanism to decrease the host's immune response and favor parasite survival.
[Mh] Termos MeSH primário: Apoptose
Ativação de Neutrófilo
Neutrófilos/citologia
Trypanosoma cruzi/isolamento & purificação
[Mh] Termos MeSH secundário: Adulto
Antígenos CD/metabolismo
Sobrevivência Celular
Proteína Ligante Fas/metabolismo
Fluoresceínas/metabolismo
Seres Humanos
Interleucina-10/metabolismo
Interleucina-12/metabolismo
Neutrófilos/metabolismo
Receptores do Fator de Necrose Tumoral/metabolismo
Succinimidas/metabolismo
Receptor 2 Toll-Like/metabolismo
Receptor 4 Toll-Like/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
Adulto Jovem
Receptor fas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-(6)-carboxyfluorescein diacetate succinimidyl ester); 0 (Antigens, CD); 0 (FAS protein, human); 0 (Fas Ligand Protein); 0 (Fluoresceins); 0 (Receptors, Tumor Necrosis Factor); 0 (Succinimides); 0 (Toll-Like Receptor 2); 0 (Toll-Like Receptor 4); 0 (Tumor Necrosis Factor-alpha); 0 (fas Receptor); 130068-27-8 (Interleukin-10); 187348-17-0 (Interleukin-12)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188083



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