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[PMID]:29376594
[Au] Autor:Kadyrov ZA; Suleymanov SI; Ramishvili VS; Istratov VG
[Ad] Endereço:Faculty of Postgraduate Education of the RUDN University, Moscow, Russia.
[Ti] Título:[Clinical and biochemical aspects of pathogenesis of urolithiasis].
[So] Source:Urologiia;(6):43-49, 2017 Dec.
[Is] ISSN:1728-2985
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: To investigate the role of infection in the pathogenesis of urolithiasis using chromatography mass spectrometry analysis. MATERIALS AND METHODS: The study analyzed clinical and laboratory data of 316 urolithiasis patients hospitalized between February 2005 and January 2015. All patients underwent a comprehensive clinical examination, including laboratory tests (hematological and biochemical blood tests, clinical and bacteriological tests of urine) and chromatography mass spectrometry analysis urine and blood. The laboratory testing was carried out both during the patients hospital stay and outpatient follow-up. RESULTS: We analyzed the biological material for the presence of characteristic ions. Urine samples of 316 urolithiasis patients were found to contain activators of "cooperative sensitivity." Moreover, there was a significant increase in the concentration of signaling compounds of the "cooperative sensitivity" of microorganisms in patients with complicated urolithiasis in comparison with the control indices (lactones-0.006 plus/minus 0.0004 mmol/L, normal values less than 0.002, quinolones 0.004 plus/minus 0.0003 mmol/l, normal values - less than 0.002 and furan esters - 0.005 plus/minus 0.0004, normal values less than 0.002). Threshold values of the activators of "cooperative sensitivity" demonstrated the readiness of the microbial community to initiate an inflammatory process. The presence of activators such as lactones, quinolones and furan esters in the samples of urolithiasis patients predisposes to the activation of pathogenic genes in a large group of microorganisms, including gram positive and gram negative species. DISCUSSION: In our opinion, to improve the quality of diagnostic, treatment and preventive measures in patients with different types of stone formation, it is advisable to use chromatography mass spectrometry analysis, which allows determination of priority clinical and laboratory indicators. CONCLUSION: The data on the role of infection in the pathogenesis of urolithiasis obtained by chromatographic methods suggest the possibility of using the indicators of the activators of the "cooperative sensitivity" of microbes in patients with various forms of urolithiasis to assess the disease severity.
[Mh] Termos MeSH primário: Lactonas/sangue
Lactonas/urina
Quinolonas/sangue
Quinolonas/urina
Urolitíase/sangue
Urolitíase/urina
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lactones); 0 (Quinolones)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


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[PMID]:29458676
[Au] Autor:Gorla MC; Cassiolato AP; Pinhata JMW; de Moraes C; Corso A; Gagetti P; Lemos AP
[Ad] Endereço:1​Bacteriology Department, Adolfo Lutz Institute, Av. Dr. Arnaldo 351, São Paulo, CEP 01246-902, SP, Brazil.
[Ti] Título:Emergence of resistance to ciprofloxacin in Neisseria meningitidis in Brazil.
[So] Source:J Med Microbiol;67(3):286-288, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To prevent secondary invasive meningococcal disease (IMD) cases and outbreaks, antimicrobial prophylaxis of high-risk contacts is indicated. This study reports two ciprofloxacin-resistant Neisseria meningitidis strains in Brazil. The 3523 N. meningitidis isolates collected throughout Brazil from 2009 to 2016 were evaluated for antimicrobial resistance. Meningococcal isolates showing minimal inhibitory concentrations, MICs≥0.125µg ml to ciprofloxacin, were analysed to determine the presence of mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes. Two ciprofloxacin-resistant N. meningitidis isolates were found, both presenting a single mutation in the quinolone resistance-determining region of the gyrA gene. These results confirmed that ciprofloxacin is still a first-line drug for chemoprophylaxis. However, we highlight the importance of continued surveillance to monitor the trends of N. meningitidis susceptibility profiles to the antimicrobials recommended for chemoprophylaxis and IMD treatment.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Ciprofloxacino/farmacologia
Farmacorresistência Bacteriana/genética
Infecções Meningocócicas/microbiologia
Neisseria meningitidis/efeitos dos fármacos
Neisseria meningitidis/genética
[Mh] Termos MeSH secundário: Brasil/epidemiologia
DNA Girase/genética
DNA Topoisomerase IV/genética
Fluoroquinolonas/farmacologia
Seres Humanos
Infecções Meningocócicas/epidemiologia
Testes de Sensibilidade Microbiana
Tipagem de Sequências Multilocus
Mutação
Neisseria gonorrhoeae/isolamento & purificação
Quinolonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoroquinolones); 0 (Quinolones); 5E8K9I0O4U (Ciprofloxacin); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000685


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[PMID]:28460066
[Au] Autor:Kim HR; Kang HN; Shim HS; Kim EY; Kim J; Kim DJ; Lee JG; Lee CY; Hong MH; Kim SM; Kim H; Pyo KH; Yun MR; Park HJ; Han JY; Youn HA; Ahn MJ; Paik S; Kim TM; Cho BC
[Ad] Endereço:Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul.
[Ti] Título:Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma.
[So] Source:Ann Oncol;28(6):1250-1259, 2017 Jun 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). Methods: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. Results: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. Conclusions: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.
[Mh] Termos MeSH primário: Benzimidazóis/uso terapêutico
Biomarcadores/sangue
Carcinoma de Células Escamosas/tratamento farmacológico
Ensaios Clínicos como Assunto
Neoplasias Pulmonares/tratamento farmacológico
Quinolonas/uso terapêutico
Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/genética
Seres Humanos
Neoplasias Pulmonares/genética
Mutação
Receptores de Fatores de Crescimento de Fibroblastos/metabolismo
Transdução de Sinais
Sequenciamento Completo do Exoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one); 0 (Benzimidazoles); 0 (Biomarkers); 0 (Quinolones); 0 (Receptors, Fibroblast Growth Factor)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx098


  4 / 10395 MEDLINE  
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[PMID]:29363539
[Au] Autor:Pirmohamed M
[Ad] Endereço:Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
[Ti] Título:Nucleic acid based therapies: developing frontier for precision medicine.
[So] Source:BMJ;360:k223, 2018 01 23.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Terapia Genética/utilização
Terapia de Alvo Molecular/utilização
Ácidos Nucleicos/uso terapêutico
Medicina de Precisão/métodos
[Mh] Termos MeSH secundário: Adenoviridae/genética
Aminofenóis/uso terapêutico
Agonistas dos Canais de Cloreto/uso terapêutico
Fibrose Cística/tratamento farmacológico
Fibrose Cística/genética
Regulador de Condutância Transmembrana em Fibrose Cística/efeitos dos fármacos
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Terapia Genética/economia
Genômica
Hemofilia A/classificação
Hemofilia A/tratamento farmacológico
Hemofilia A/genética
Seres Humanos
Doença dos Neurônios Motores/tratamento farmacológico
Doença dos Neurônios Motores/genética
Mutação
Oligonucleotídeos Antissenso/economia
Oligonucleotídeos Antissenso/uso terapêutico
Quinolonas/uso terapêutico
Reino Unido/epidemiologia
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Aminophenols); 0 (CFTR protein, human); 0 (Chloride Channel Agonists); 0 (Nucleic Acids); 0 (Oligonucleotides, Antisense); 0 (Quinolones); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1Y740ILL1Z (ivacaftor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k223


  5 / 10395 MEDLINE  
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[PMID]:29386430
[Au] Autor:Hanawa T; Kawano Y; Satoh M
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Tokyo University of Science.
[Ti] Título:[Development of "Patient Friendly Formulations" to Counter the Side Effects of Cancer Chemotherapy].
[So] Source:Yakugaku Zasshi;138(2):169-175, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit. Irsogladine maleate (IM) is a drug with gastric mucosal protective properties. IM increases intracellular cAMP levels in the gastric mucosa and activates communication between cells. It has been reported that the oral administration of IM reduces the incidence of 5-FU-based chemotherapy-induced stomatitis. However, there have been no reports on the effect of the direct use of IM in treating stomatitis. Therefore, we studied the development of an IM oral spray for stomatitis treatment, and obtained evidence of a direct effect in an animal experiment using a stomatitis model. Next, rebamipide mouthwash was administered to patients who had stomatitis caused by cancer chemotherapy. The total scores were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). When comparing SES and changes in the stomatitis area in patients, gradual reductions in the extent of stomatitis were observed, even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Antineoplásicos/efeitos adversos
Composição de Medicamentos
Quinolonas/administração & dosagem
Estomatite/induzido quimicamente
Estomatite/tratamento farmacológico
Triazinas/administração & dosagem
Triazinas/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Alanina/administração & dosagem
Animais
Comunicação Celular/efeitos dos fármacos
AMP Cíclico/metabolismo
Modelos Animais de Doenças
Medicina Baseada em Evidências
Mucosa Gástrica/citologia
Mucosa Gástrica/metabolismo
Seres Humanos
Antissépticos Bucais
Estomatite/prevenção & controle
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Mouthwashes); 0 (Quinolones); 0 (Triazines); E0399OZS9N (Cyclic AMP); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine); QBX79NZC1D (irsogladine)
[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:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-2


  6 / 10395 MEDLINE  
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[PMID]:28459323
[Au] Autor:Ramsey BW; Welsh MJ
[Ad] Endereço:1 Department of Pediatrics University of Washington School of Medicine Seattle, Washington.
[Ti] Título:AJRCCM: 100-Year Anniversary. Progress along the Pathway of Discovery Leading to Treatment and Cure of Cystic Fibrosis.
[So] Source:Am J Respir Crit Care Med;195(9):1092-1099, 2017 05 01.
[Is] ISSN:1535-4970
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Aminofenóis/uso terapêutico
Aminopiridinas/uso terapêutico
Antibacterianos/uso terapêutico
Benzodioxóis/uso terapêutico
Agonistas dos Canais de Cloreto/uso terapêutico
Fibrose Cística/tratamento farmacológico
Publicações Periódicas como Assunto/história
Pneumologia/história
Quinolonas/uso terapêutico
[Mh] Termos MeSH secundário: Aniversários e Eventos Especiais
Fibrose Cística/genética
Fibrose Cística/história
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Combinação de Medicamentos
Terapia de Reposição de Enzimas
História do Século XX
História do Século XXI
Mutação
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminophenols); 0 (Aminopyridines); 0 (Anti-Bacterial Agents); 0 (Benzodioxoles); 0 (CFTR protein, human); 0 (Chloride Channel Agonists); 0 (Drug Combinations); 0 (Quinolones); 0 (lumacaftor, ivacaftor drug combination); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1Y740ILL1Z (ivacaftor)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1164/rccm.201702-0266ED


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[PMID]:28458352
[Au] Autor:Matsuda T; Hiraoka S; Urashima H; Ogura A; Ishida T
[Ad] Endereço:Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University.
[Ti] Título:Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency.
[So] Source:Biol Pharm Bull;40(5):665-674, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A 2% commercially available, milky-white, rebamipide micro-particle suspension is used to treat dry eyes, and it causes short-term blurring of the patient's vision. In the current study, to improve the transparency of a rebamipide suspension, we attempted to obtain a clear rebamipide suspension by transforming the rebamipide particles to an ultrafine state. In the initial few efforts, various rebamipide suspensions were prepared using a neutralizing crystallization method with additives, but the suspensions retained their opaque quality. However, as a consequence of several critical improvements in the neutralizing crystallization methods such as selection of additives for crystallization, process parameters during crystallization, the dispersion method, and dialysis, we obtained an ultrafine rebamipide suspension (2%) that was highly transparent (transmittance at 640 nm: 59%). The particle size and transparency demonstrated the fewest level of changes at 25°C after 3 years, compared to initial levels. During that period, no obvious particle sedimentation was observed. The administration of this ultrafine rebamipide suspension (2%) increased the conjunctival mucin, which was comparable to the commercially available micro-particle suspension (2%). The corneal and conjunctival concentration of rebamipide following ocular administration of the ultrafine suspension was slightly higher than that of the micro-particle suspension. The ultrafine rebamipide suspension (eye-drop formulation) with a highly transparent ophthalmic clearness should improve a patient's QOL by preventing even a shortened period of blurred vision.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Antiulcerosos/administração & dosagem
Antiulcerosos/química
Soluções Oftálmicas/química
Quinolonas/administração & dosagem
Quinolonas/química
[Mh] Termos MeSH secundário: Administração Oftálmica
Alanina/administração & dosagem
Alanina/química
Animais
Túnica Conjuntiva/efeitos dos fármacos
Túnica Conjuntiva/metabolismo
Córnea/efeitos dos fármacos
Córnea/metabolismo
Cristalização
Diálise
Masculino
Mucinas/metabolismo
Tamanho da Partícula
Coelhos
Suspensões
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Ulcer Agents); 0 (Mucins); 0 (Ophthalmic Solutions); 0 (Quinolones); 0 (Suspensions); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00962


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[PMID]:29197729
[Au] Autor:Bortolozzi R; Mattiuzzo E; Dal Pra M; Sturlese M; Moro S; Hamel E; Carta D; Viola G; Ferlin MG
[Ad] Endereço:Department of Woman's and Child's Health, University of Padova, Laboratory of Oncohematology, 35128 Padova, Italy.
[Ti] Título:Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs.
[So] Source:Eur J Med Chem;143:244-258, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of ß-tubulin.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Quinolonas/farmacologia
Tubulina (Proteína)/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Células HeLa
Seres Humanos
Leucócitos Mononucleares/efeitos dos fármacos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Estrutura Molecular
Polimerização/efeitos dos fármacos
Quinolonas/síntese química
Quinolonas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Quinolones); 0 (Tubulin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171204
[St] Status:MEDLINE


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[PMID]:29300775
[Au] Autor:Varughese LR; Rajpoot M; Goyal S; Mehra R; Chhokar V; Beniwal V
[Ad] Endereço:Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, India.
[Ti] Título:Analytical profiling of mutations in quinolone resistance determining region of gyrA gene among UPEC.
[So] Source:PLoS One;13(1):e0190729, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in gyrA are the primary cause of quinolone resistance encountered in gram-negative clinical isolates. The prospect of this work was to analyze the role of gyrA mutations in eliciting high quinolone resistance in uropathogenic E.coli (UPEC) through molecular docking studies. Quinolone susceptibility testing of 18 E.coli strains isolated from UTI patients revealed unusually high resistance level to all the quinolones used; especially norfloxacin and ciprofloxacin. The QRDR of gyrA was amplified and sequenced. Mutations identified in gyrA of E.coli included Ser83Leu, Asp87Asn and Ala93Gly/Glu. Contrasting previous reports, we found Ser83Leu substitution in sensitive strains. Strains with S83L, D87N and A93E (A15 and A26) demonstrated norfloxacin MICs ≥1024mg/L which could be proof that Asp87Asn is necessary for resistance phenotype. Resistance to levofloxacin was comparatively lower in all the isolates. Docking of 4 quinolones (ciprofloxacin, ofloxacin, levofloxacin and norfloxacin) to normal and mutated E.coli gyrase A protein demonstrated lower binding energies for the latter, with significant displacement of norfloxacin in the mutated GyrA complex and least displacement in case of levofloxacin.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
DNA Girase/genética
Farmacorresistência Bacteriana/genética
Proteínas de Escherichia coli/genética
Quinolonas/farmacologia
Escherichia coli Uropatogênica/genética
[Mh] Termos MeSH secundário: DNA Girase/metabolismo
Infecções por Escherichia coli/microbiologia
Proteínas de Escherichia coli/metabolismo
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Mutação
Homologia de Sequência do Ácido Nucleico
Infecções Urinárias/microbiologia
Escherichia coli Uropatogênica/efeitos dos fármacos
Escherichia coli Uropatogênica/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Escherichia coli Proteins); 0 (Quinolones); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190729


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[PMID]:29241892
[Au] Autor:Dilokthornsakul P; Patidar M; Campbell JD
[Ad] Endereço:Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. Electronic address: piyamethd@nu.ac.th.
[Ti] Título:Forecasting the Long-Term Clinical and Economic Outcomes of Lumacaftor/Ivacaftor in Cystic Fibrosis Patients with Homozygous phe508del Mutation.
[So] Source:Value Health;20(10):1329-1335, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To forecast lifetime outcomes and cost of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis (CF) with homozygous phe508del mutation from the US payer perspective. METHODS: A lifetime Markov model was developed from a US payer perspective. The model included five health states: 1) mild lung disease (percent predicted forced expiratory volume in 1 second [FEV ] >70%), 2) moderate lung disease (40% ≤ FEV ≤ 70%), 3) severe lung disease (FEV < 40%), 4) lung transplantation, and 5) death. All inputs were derived from published literature. We estimated lumacaftor/ivacaftor's improvement in outcomes compared with a non-CF referent population as well as CF-specific mortality estimates. RESULTS: Lumacaftor/ivacaftor was associated with additional 2.91 life-years (95% credible interval 2.55-3.56) and additional 2.42 quality-adjusted life-years (QALYs) (95% credible interval 2.10-2.98). Lumacaftor/ivacaftor was associated with improvements in survival and QALYs equivalent to 27.6% and 20.7%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $2,632,249. CONCLUSIONS: Lumacaftor/ivacaftor increased life-years and QALYs in CF patients with the homozygous phe508del mutation and moved morbidity and mortality closer to that of their non-CF peers but it came with higher cost.
[Mh] Termos MeSH primário: Aminofenóis/administração & dosagem
Aminopiridinas/administração & dosagem
Benzodioxóis/administração & dosagem
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Fibrose Cística/tratamento farmacológico
Anos de Vida Ajustados por Qualidade de Vida
Quinolonas/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Aminofenóis/economia
Aminopiridinas/economia
Benzodioxóis/economia
Fibrose Cística/genética
Fibrose Cística/fisiopatologia
Combinação de Medicamentos
Volume Expiratório Forçado
Homozigoto
Seres Humanos
Cadeias de Markov
Mutação
Quinolonas/economia
Índice de Gravidade de Doença
Resultado do Tratamento
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminophenols); 0 (Aminopyridines); 0 (Benzodioxoles); 0 (Drug Combinations); 0 (Quinolones); 0 (cystic fibrosis transmembrane conductance regulator delta F508); 0 (lumacaftor, ivacaftor drug combination); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE



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