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[PMID]:29206032
[Au] Autor:Rajendran K; Anwar A; Khan NA; Siddiqui R
[Ad] Endereço:Department of Biological Sciences, School of Science and Technology, Sunway University , Bandar Sunway 47500, Malaysia.
[Ti] Título:Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri.
[So] Source:ACS Chem Neurosci;8(12):2626-2630, 2017 12 20.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.
[Mh] Termos MeSH primário: Amebicidas/administração & dosagem
Nanopartículas Metálicas/administração & dosagem
Naegleria fowleri/efeitos dos fármacos
Naegleria fowleri/fisiologia
Nanoconjugados/administração & dosagem
Nanoconjugados/química
Prata/administração & dosagem
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Sinergismo Farmacológico
Fluconazol/administração & dosagem
Nanopartículas Metálicas/química
Nanopartículas Metálicas/ultraestrutura
Naegleria fowleri/citologia
Nanocápsulas/administração & dosagem
Nanocápsulas/química
Nanocápsulas/ultraestrutura
Nanoconjugados/ultraestrutura
Nistatina/administração & dosagem
Tamanho da Partícula
Prata/química
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amebicides); 0 (Drug Combinations); 0 (Nanocapsules); 0 (Nanoconjugates); 1400-61-9 (Nystatin); 3M4G523W1G (Silver); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00430


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[PMID]:28763970
[Au] Autor:Zhang D; Park JA; Abd El-Aty AM; Kim SK; Cho SH; Wang Y; Shim JH; Jeong JH; Shin SC; Kim JS; Chang BJ; Shin HC
[Ad] Endereço:Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
[Ti] Título:Residual detection of buparvaquone, nystatin, and etomidate in animal-derived food products in a single chromatographic run using liquid chromatography-tandem mass spectrometry.
[So] Source:Food Chem;237:1202-1208, 2017 Dec 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A reliable and highly sensitive screening method based on liquid chromatography coupled withtriple-quadrupoleelectrospray tandemmass spectrometry (LC-MS/MS) analysis has been developed for the detection and quantification of three veterinary drugs, including buparvaquone, nystatin, and etomidate impurity B CRS. The tested drugs were extracted from samples of porcine muscle, pasteurized whole milk, and eggs using 10mM ammonium formate in acetonitrile followed by liquid-liquid purification with n-hexane. Chromatographic separation was achieved on a Phenomenex Luna C18 analytical column using 0.1% formic acid in ultrapure water (A) and acetonitrile (B) as mobile phases. All the matrix-matched calibration curves were linear (R ≥0.9756) over the concentration levels of the drugs tested. Recovery at two spiking levels (equivalent to the limit of quantification (LOQ)=5ng/g and 2×LOQ) ranged from 72.88% to 92.59% with intra- and inter-day precisions <17%, except for porcine muscle spiked with 5ng/g nystatin (RSD=25.15%). Samples collected from markets located in Seoul, Republic of Korea, tested negative for all the drugs analyzed. In summary, this method is suitable for screening and quantifying the selected drugs in a single chromatographic run and with high selectivity in animal-derived food products meant for human consumption.
[Mh] Termos MeSH primário: Etomidato/análise
Naftoquinonas/análise
Nistatina/análise
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida de Alta Pressão
Suínos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Naphthoquinones); 0354RT7LG4 (buparvaquone); 1400-61-9 (Nystatin); Z22628B598 (Etomidate)
[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:170803
[St] Status:MEDLINE


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[PMID]:28630013
[Au] Autor:Kunz D; Oliveira GB; Uchôa AF; Samuels RI; Macedo MLR; Silva CP
[Ad] Endereço:Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, C.P. 476, 88040-900 Florianópolis, SC, Brazil.
[Ti] Título:Receptor mediated endocytosis of vicilin in Callosobruchus maculatus (Coleoptera: Chrysomelidae) larval midgut epithelial cells.
[So] Source:Comp Biochem Physiol B Biochem Mol Biol;210:39-47, 2017 Aug.
[Is] ISSN:1879-1107
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The transport of proteins across the intestinal epithelium of insects is still not well understood. There is evidence that vicilin, a major storage protein of cowpea seeds (Vigna unguiculata), is internalized in larvae of the seed-beetle Callosobruchus maculatus. It has been reported that this vicilin interacts with proteins present in the microvillar membranes of columnar cells along the digestive tract of the larvae. In the present work, we studied the cellular pathway involved in endocytosis of vicilin in larval C. maculatus by employing ex vivo experiments. In the ex vivo approach, we incubated FITC-labelled vicilin with isolated midgut wholemounts in the absence or in the presence of endocytosis inhibitors. The fate of labelled or non-labelled globulins was monitored by confocal microscopy and fluorescence measurement. Our results suggest that the internalization of vicilins is due to receptor-mediated endocytosis. Here we report the identity of a microvillar vicilin-binding protein that was purified using affinity chromatography on a vicilin-sepharose column. The putative vicilin receptor showed high homology to proteins with the CRAL-TRIO domain, specifically the Sec14 superfamily member α-tocopherol transfer protein. The precise mechanism involved in vicilin internalization was defined through the use of specific inhibitors of the endocytosis pathway. The inhibitors filipin III and nystatin significantly inhibited the endocytosis of vicilin, while chlorpromazine and phenylarsine oxide had a much lower effect on endocytosis, suggesting that the endocytic pathway is predominantly mediated by caveolin.
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Coleópteros/metabolismo
Células Epiteliais/metabolismo
Proteínas de Insetos/metabolismo
Larva/metabolismo
Proteínas de Armazenamento de Sementes/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Arsenicais/farmacologia
Transporte Biológico
Proteínas de Transporte/genética
Clorpromazina/farmacologia
Coleópteros/efeitos dos fármacos
Coleópteros/genética
Sistema Digestório/efeitos dos fármacos
Sistema Digestório/metabolismo
Sistema Digestório/ultraestrutura
Endocitose/efeitos dos fármacos
Endocitose/genética
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/ultraestrutura
Filipina/farmacologia
Fluoresceína-5-Isotiocianato/química
Corantes Fluorescentes/química
Expressão Gênica
Proteínas de Insetos/genética
Larva/efeitos dos fármacos
Larva/genética
Nistatina/farmacologia
Proteínas de Armazenamento de Sementes/genética
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Coloração e Rotulagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arsenicals); 0 (Carrier Proteins); 0 (Fluorescent Dyes); 0 (Insect Proteins); 0 (Seed Storage Proteins); 0 (alpha-tocopherol transfer protein); 0HUR2WY345 (oxophenylarsine); 1400-61-9 (Nystatin); 87Z59R7D14 (Filipin); 9067-60-1 (vicilin protein, plant); I223NX31W9 (Fluorescein-5-isothiocyanate); U42B7VYA4P (Chlorpromazine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE


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[PMID]:28615098
[Au] Autor:Xu Y; Liu Q; Zhang Z
[Ad] Endereço:Department of Infectious Disease, Children's Hospital Affiliated to Chongqing Medical University, Ministry-of-Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
[Ti] Título:[Human EV71 invades human neuroblastoma SK-N-SH cells by clathrin-mediated endocytosis].
[So] Source:Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi;33(6):761-766, 2017 Jun.
[Is] ISSN:1007-8738
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:Objective To study the mechanism ofhuman enterovirus 71 (EV71) entering human neuroblastoma SK-N-SH cells. Methods After the SK-N-SH cells were pretreated with chlorpromazine (CPZ) or nystatin (NT), real-time quantitative PCR (qRT-PCR) was employed to measure EV71 mRNA level, and indirect immunofluorescence microscopy was used to detect the expression level of viral protein 1 (VP1) in the target cells. In order to reveal the colocalization of EV71 with clathrin, laser confocal microscopy was performed on the infected cells. Results CPZ could significantly inhibit EV71 mRNA level and the expression of VP1 in the target cells, while NT had no effect on EV71 infection. Confocal microscopy showed that EV71 was colocalize with clathrin. Conclusion EV71 infects human neuroblastoma SK-N-SH cells by the clathrin-mediated endocytosis.
[Mh] Termos MeSH primário: Clatrina/fisiologia
Endocitose
Enterovirus Humano A/genética
Neuroblastoma/virologia
[Mh] Termos MeSH secundário: Proteínas do Capsídeo/análise
Linhagem Celular Tumoral
Clorpromazina/farmacologia
Seres Humanos
Neuroblastoma/patologia
Nistatina/farmacologia
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (Clathrin); 1400-61-9 (Nystatin); U42B7VYA4P (Chlorpromazine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE


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[PMID]:28438376
[Au] Autor:Wheat CM; Bickley RJ; Hsueh YH; Cohen BA
[Ad] Endereço:Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: cwheat1@jhmi.edu.
[Ti] Título:Current Trends in the Use of Two Combination Antifungal/Corticosteroid Creams.
[So] Source:J Pediatr;186:192-195.e1, 2017 Jul.
[Is] ISSN:1097-6833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Superficial fungal infections are among the most commonly managed skin problems by general practitioners. Although evidence shows combination antifungal/corticosteroid topicals are more expensive and less effective than single-agent antifungals, practitioners continue to prescribe combination agents. We examined current prescription trends of 2 combination antifungal/corticosteroid medications, Lotrisone and Mycolog-II.
[Mh] Termos MeSH primário: Anti-Inflamatórios/uso terapêutico
Antifúngicos/uso terapêutico
Betametasona/uso terapêutico
Clotrimazol/uso terapêutico
Dermatomicoses/tratamento farmacológico
Glucocorticoides/uso terapêutico
Gramicidina/uso terapêutico
Neomicina/uso terapêutico
Nistatina/uso terapêutico
Triancinolona Acetonida/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Combinação de Medicamentos
Seres Humanos
Lactente
Recém-Nascido
Padrões de Prática Médica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antifungal Agents); 0 (Drug Combinations); 0 (Glucocorticoids); 0 (Gramicidin, Neomycin Sulfate, Nystatin, Triamcinolone Acetonide Drug Combination); 0 (Lotrisone); 1400-61-9 (Nystatin); 1404-04-2 (Neomycin); 1405-97-6 (Gramicidin); 9842X06Q6M (Betamethasone); F446C597KA (Triamcinolone Acetonide); G07GZ97H65 (Clotrimazole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE


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Rosalen, Pedro Luiz
Texto completo
[PMID]:28259673
[Au] Autor:Sardi JC; Freires IA; Lazarini JG; Infante J; de Alencar SM; Rosalen PL
[Ad] Endereço:Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil.
[Ti] Título:Unexplored endemic fruit species from Brazil: Antibiofilm properties, insights into mode of action, and systemic toxicity of four Eugenia spp.
[So] Source:Microb Pathog;105:280-287, 2017 Apr.
[Is] ISSN:1096-1208
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Brazilian endemic fruit species have aroused attention due to their highly valuable, yet unexplored, agro-industrial, food and therapeutic potential. Herein, we describe the antifungal activity of four Eugenia spp. against Candida albicans biofilms, and further demonstrate insights into their potential mode(s) of action and toxicity in vitro and in vivo. Extracts from different parts (seeds, pulps, leaves) of E. leitonii (EL), E. brasiliensis (EB), E. myrcianthes (EM) and E. involucrata (EI) were obtained (S23°23',W45°39') and chemically characterized by GC/MS. The active extracts were tested against C. albicans biofilm viability and architecture, as well as mode of action, and toxicology using RAW 264.7 macrophages and Galleria mellonella larvae. The MIC values ranged from 15.62 to >2000 µg/mL. The most active extracts were EL (seed, 15.62 µg/mL) and EB (leaf and seeds, 31.25 and 15.62 µg/mL, respectively). Treatment with these extracts at 10xMIC reduced biofilm viability by 54-55% (P < 0.0001) as compared to 42% by nystatin. At 10xMIC, all extracts caused damages to biofilm architecture and integrity, and fewer hyphae remained attached to treated biofilms. None of them was found to interfere with cell wall biosynthesis or complexation with ergosterol. The extracts had low toxicity against macrophages in vitro (P > 0.05) and G. mellonella larvae, with mean in vivo LD of 1500 mg/kg (EL, seeds); 2500 mg/kg (EB, seeds); and 1250 mg/kg (EB, leaf). The phenolic compounds epicatechin and gallic acid were the major constituents in the extracts. Our findings may open avenues for the application of these yet unexplored native fruits in the food and pharmaceutical industry.
[Mh] Termos MeSH primário: Biofilmes/efeitos dos fármacos
Eugenia/química
Frutas/química
Extratos Vegetais/farmacologia
Extratos Vegetais/toxicidade
Plantas Tóxicas/química
[Mh] Termos MeSH secundário: Animais
Antifúngicos/química
Antifúngicos/farmacologia
Brasil
Candida albicans/efeitos dos fármacos
Parede Celular/metabolismo
Ergosterol/metabolismo
Ácido Gálico/química
Camundongos
Testes de Sensibilidade Microbiana
Nistatina/farmacologia
Fenóis/química
Extratos Vegetais/química
Folhas de Planta/química
Plantas Medicinais/química
Células RAW 264.7
Sementes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Phenols); 0 (Plant Extracts); 1400-61-9 (Nystatin); 632XD903SP (Gallic Acid); Z30RAY509F (Ergosterol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170306
[St] Status:MEDLINE


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[PMID]:28114370
[Au] Autor:Ono J; Gerstein AC; Otto SP
[Ad] Endereço:Department of Zoology & Biodiversity Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Título:Widespread Genetic Incompatibilities between First-Step Mutations during Parallel Adaptation of Saccharomyces cerevisiae to a Common Environment.
[So] Source:PLoS Biol;15(1):e1002591, 2017 Jan.
[Is] ISSN:1545-7885
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Independently evolving populations may adapt to similar selection pressures via different genetic changes. The interactions between such changes, such as in a hybrid individual, can inform us about what course adaptation may follow and allow us to determine whether gene flow would be facilitated or hampered following secondary contact. We used Saccharomyces cerevisiae to measure the genetic interactions between first-step mutations that independently evolved in the same biosynthetic pathway following exposure to the fungicide nystatin. We found that genetic interactions are prevalent and predominantly negative, with the majority of mutations causing lower growth when combined in a double mutant than when alone as a single mutant (sign epistasis). The prevalence of sign epistasis is surprising given the small number of mutations tested and runs counter to expectations for mutations arising in a single biosynthetic pathway in the face of a simple selective pressure. Furthermore, in one third of pairwise interactions, the double mutant grew less well than either single mutant (reciprocal sign epistasis). The observation of reciprocal sign epistasis among these first adaptive mutations arising in the same genetic background indicates that partial postzygotic reproductive isolation could evolve rapidly between populations under similar selective pressures, even with only a single genetic change in each. The nature of the epistatic relationships was sensitive, however, to the level of drug stress in the assay conditions, as many double mutants became fitter than the single mutants at higher concentrations of nystatin. We discuss the implications of these results both for our understanding of epistatic interactions among beneficial mutations in the same biochemical pathway and for speciation.
[Mh] Termos MeSH primário: Adaptação Fisiológica/genética
Meio Ambiente
Mutação/genética
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Adaptação Fisiológica/efeitos dos fármacos
Evolução Biológica
Diploide
Epistasia Genética/efeitos dos fármacos
Ergosterol/biossíntese
Genes Fúngicos
Haploidia
Modelos Biológicos
Nistatina/farmacologia
Fenótipo
Reprodução/efeitos dos fármacos
Reprodução/genética
Saccharomyces cerevisiae/efeitos dos fármacos
Saccharomyces cerevisiae/crescimento & desenvolvimento
Espectrofotometria
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
1400-61-9 (Nystatin); Z30RAY509F (Ergosterol)
[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:170124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pbio.1002591


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[PMID]:28041915
[Au] Autor:Girotra P; Thakur A; Kumar A; Singh SK
[Ad] Endereço:Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar 125001, India. Electronic address: ph.arora13@gmail.com.
[Ti] Título:Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.
[So] Source:Int J Biol Macromol;96:687-696, 2017 Mar.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (ß adrenoceptor, Dopamine D , 5HT , TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), ß adrenoceptor (3NYA) and Dopamine D (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Quitosana/química
Portadores de Fármacos/química
Transtornos de Enxaqueca/tratamento farmacológico
Nanopartículas/química
Nistatina/química
Nistatina/farmacologia
[Mh] Termos MeSH secundário: Animais
Bradicinina/farmacologia
Encéfalo/metabolismo
Avaliação Pré-Clínica de Medicamentos
Liberação Controlada de Fármacos
Asseio Animal/efeitos dos fármacos
Hiperalgesia/complicações
Masculino
Camundongos
Transtornos de Enxaqueca/complicações
Transtornos de Enxaqueca/metabolismo
Simulação de Acoplamento Molecular
Terapia de Alvo Molecular
Nistatina/metabolismo
Nistatina/uso terapêutico
Tamanho da Partícula
Fotofobia/induzido quimicamente
Fotofobia/complicações
Conformação Proteica
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 1400-61-9 (Nystatin); 9012-76-4 (Chitosan); S8TIM42R2W (Bradykinin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


  9 / 2782 MEDLINE  
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[PMID]:27901310
[Au] Autor:Hellfritzsch M; Pottegård A; Pedersen AJ; Burghle A; Mouaanaki F; Hallas J; Grove EL; Damkier P
[Ad] Endereço:Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
[Ti] Título:Topical Antimycotics for Oral Candidiasis in Warfarin Users.
[So] Source:Basic Clin Pharmacol Toxicol;120(4):368-372, 2017 Apr.
[Is] ISSN:1742-7843
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis.
[Mh] Termos MeSH primário: Antifúngicos/efeitos adversos
Coagulação Sanguínea/efeitos dos fármacos
Candidíase Bucal/tratamento farmacológico
Miconazol/efeitos adversos
Nistatina/efeitos adversos
Varfarina/efeitos adversos
[Mh] Termos MeSH secundário: Administração Oral
Idoso
Antifúngicos/administração & dosagem
Antifúngicos/uso terapêutico
Candidíase Bucal/sangue
Estudos de Coortes
Estudos Cross-Over
Interações Medicamentosas
Feminino
Géis
Seres Humanos
Coeficiente Internacional Normatizado
Masculino
Miconazol/administração & dosagem
Miconazol/uso terapêutico
Meia-Idade
Nistatina/administração & dosagem
Nistatina/uso terapêutico
Soluções
Varfarina/administração & dosagem
Varfarina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Gels); 0 (Solutions); 1400-61-9 (Nystatin); 5Q7ZVV76EI (Warfarin); 7NNO0D7S5M (Miconazole)
[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:161201
[St] Status:MEDLINE
[do] DOI:10.1111/bcpt.12722


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[PMID]:27858138
[Au] Autor:Walmsley S; De Poire E; Rawlings B; Caffrey P
[Ad] Endereço:Department of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
[Ti] Título:Engineered biosynthesis and characterisation of disaccharide-modified 8-deoxyamphoteronolides.
[So] Source:Appl Microbiol Biotechnol;101(5):1899-1905, 2017 Mar.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Several polyene macrolides are potent antifungal agents that have severe side effects. Increased glycosylation of these compounds can improve water solubility and reduce toxicity. Three extending glycosyltransferases are known to add hexoses to the mycosaminyl sugar residues of polyenes. The Actinoplanes caeruleus PegA enzyme catalyses attachment of a D-mannosyl residue in a ß-1,4 linkage to the mycosamine of the aromatic heptaene 67-121A to form 67-121C. NppY from Pseudonocardia autotrophica adds an N-acetyl-D-glucosamine to the mycosamine of 10-deoxynystatin. NypY from Pseudonocardia sp. P1 adds an extra hexose to a nystatin, but the identity of the sugar is unknown. Here, we express the nypY gene in Streptomyces nodosus amphL and show that NypY modifies 8-deoxyamphotericins more efficiently than C-8 hydroxylated forms. The modified heptaene was purified and shown to be mannosyl-8-deoxyamphotericin B. This had the same antifungal activity as amphotericin B but was slightly less haemolytic. Chemical modification of this new disaccharide polyene could give better antifungal antibiotics.
[Mh] Termos MeSH primário: Anfotericina B/química
Antifúngicos/química
Candida albicans/efeitos dos fármacos
Leishmania/efeitos dos fármacos
Macrolídeos/metabolismo
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Acetilglucosamina/química
Actinobacteria/genética
Actinobacteria/metabolismo
Anfotericina B/efeitos adversos
Anfotericina B/farmacologia
Antifúngicos/efeitos adversos
Antifúngicos/farmacologia
Glicosiltransferases
Hexosaminas/química
Leishmaniose/tratamento farmacológico
Macrolídeos/química
Micoses/tratamento farmacológico
Nistatina/química
Streptomyces/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Hexosamines); 0 (Macrolides); 1400-61-9 (Nystatin); 1KHW2634R4 (mycosamine); 7XU7A7DROE (Amphotericin B); EC 2.4.- (Glycosyltransferases); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170227
[Lr] Data última revisão:
170227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-016-7986-6



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