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[PMID]:29324337
[Au] Autor:Ullah A; Iftikhar F; Arfan M; Batool Kazmi ST; Anjum MN; Haq IU; Ayaz M; Farooq S; Rashid U
[Ad] Endereço:Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
[Ti] Título:Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity relationship, antibacterial and urease inhibition activity.
[So] Source:Eur J Med Chem;145:140-153, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 µM (2 µg/mL) for S. aureus and 1.1 µM (0.66 µg/mL) for E. coli. The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC = 6.23 ±â€¯0.09 µM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP) were carried out.
[Mh] Termos MeSH primário: Aminoácidos/farmacologia
Antibacterianos/farmacologia
Inibidores Enzimáticos/farmacologia
Isoniazida/farmacologia
Metronidazol/farmacologia
Trimetoprima/farmacologia
[Mh] Termos MeSH secundário: Aminoácidos/química
Antibacterianos/síntese química
Antibacterianos/química
Bacillus/efeitos dos fármacos
Bacillus/enzimologia
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Escherichia coli/efeitos dos fármacos
Interações Hidrofóbicas e Hidrofílicas
Isoniazida/síntese química
Isoniazida/química
Metronidazol/síntese química
Metronidazol/química
Testes de Sensibilidade Microbiana
Estrutura Molecular
Pseudomonas aeruginosa/efeitos dos fármacos
Salmonella typhi/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
Relação Estrutura-Atividade
Trimetoprima/síntese química
Trimetoprima/química
Urease/antagonistas & inibidores
Urease/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Anti-Bacterial Agents); 0 (Enzyme Inhibitors); 140QMO216E (Metronidazole); AN164J8Y0X (Trimethoprim); EC 3.5.1.5 (Urease); V83O1VOZ8L (Isoniazid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


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[PMID]:29216620
[Au] Autor:Graves RA; Phan KV; Bostanian LA; Mandal TK; Pramar YV
[Ad] Endereço:College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana.
[Ti] Título:Physicochemical Stability of an Oral Suspension of Trimethoprim 20 mg/mL in Combination with Sulfadiazine 200 mg/mL in PCCA Base SuspendIt.
[So] Source:Int J Pharm Compd;21(5):430-435, 2017 Sep-Oct.
[Is] ISSN:1092-4221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trimethoprim is a diaminopyrimidine antibacterial agent that, like sulfonamides, inhibits bacterial folic acid synthesis, but at a different stage in the metabolic pathway. It has a similar spectrum of activity to the sulfonamides and is given by mouth or by injection, either alone or in conjunction with a sulfonamide, such as sulfadiazine. Sulfadiazine is a bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. The combination of the two drugs produces a synergistic effect against both Gram-positive and Gram-negative aerobic bacteria, by inhibiting enzymes in the folic acid pathways, which in turn inhibits bacterial thymidine synthesis. There are no published studies of the stability of the combination of trimethoprim and sulfadiazine in a liquid dosage form. An extemporaneously compounded suspension from pure drug powders or commercial tablets would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of trimethoprim combined with sulfadiazine in PCCA base SuspendIt. PCCA base SuspendIt is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating high-performance liquid chromatographic assay for the simultaneous determination of trimethoprim and sulfadiazine in SuspendIt was developed and validated. This assay was used to determine the chemical stability of both drugs in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, 40°C), and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 0, 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated temperature. Physical data such as pH, viscosity, appearance, and average particle size were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at room temperature and in the refrigerator. The pH values also did not change significantly. There was some variability in viscosity and average particle size. This study demonstrates that trimethoprim and sulfadiazine are physically and chemically stable in combination in SuspendIt for 182 days at room temperature and in the refrigerator, thus providing a viable, compounded alternative for both drugs in a liquid dosage form, with an extended beyond-use-date to meet patient needs.
[Mh] Termos MeSH primário: Sulfadiazina/química
Trimetoprima/química
[Mh] Termos MeSH secundário: Administração Oral
Cromatografia Líquida de Alta Pressão
Combinação de Medicamentos
Estabilidade de Medicamentos
Concentração de Íons de Hidrogênio
Sulfadiazina/administração & dosagem
Sulfadiazina/análise
Suspensões
Trimetoprima/administração & dosagem
Trimetoprima/análise
Viscosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Suspensions); 0N7609K889 (Sulfadiazine); AN164J8Y0X (Trimethoprim)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


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[PMID]:29293328
[Au] Autor:Bhalsod GD; Chuang YH; Jeon S; Gui W; Li H; Ryser ET; Guber AK; Zhang W
[Ad] Endereço:Cook County Unit, University of Illinois Extension , Arlington Heights, Illinois 60004, United States.
[Ti] Título:Uptake and Accumulation of Pharmaceuticals in Overhead- and Surface-Irrigated Greenhouse Lettuce.
[So] Source:J Agric Food Chem;66(4):822-830, 2018 Jan 31.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the uptake and accumulation of pharmaceuticals in vegetables under typical irrigation practices is critical to risk assessment of crop irrigation with reclaimed water. This study investigated the pharmaceutical residues in greenhouse lettuce under overhead and soil-surface irrigations using pharmaceutical-contaminated water. Compared to soil-surface irrigation, overhead irrigation substantially increased the pharmaceutical residues in lettuce shoots. The increased residue levels persisted even after washing for trimethoprim, monensin sodium, and tylosin, indicating their strong sorption to the shoots. The postwashing concentrations in fresh shoots varied from 0.05 ± 0.04 µg/kg for sulfadiazine to 345 ± 139 µg/kg for carbamazepine. Root concentration factors ranged from 0.04 ± 0.14 for tylosin to 19.2 ± 15.7 for sulfamethoxazole. Translocation factors in surface-irrigated lettuce were low for sulfamethoxalzole, trimethoprim, monensin sodium, and tylosin (0.07-0.15), but high for caffeine (4.28 ± 3.01) and carbamazepine (8.15 ± 2.87). Carbamazepine was persistent in soil and hyperaccumulated in shoots.
[Mh] Termos MeSH primário: Irrigação Agrícola/métodos
Resíduos de Drogas/análise
Alface/metabolismo
Preparações Farmacêuticas/metabolismo
Poluentes Químicos da Água/metabolismo
[Mh] Termos MeSH secundário: Carbamazepina/análise
Contaminação de Alimentos
Alface/química
Monensin/análise
Preparações Farmacêuticas/análise
Folhas de Planta/química
Raízes de Plantas/química
Solo/química
Poluentes do Solo/análise
Poluentes do Solo/metabolismo
Sulfametoxazol/análise
Trimetoprima/análise
Tilosina/análise
Verduras
Poluentes Químicos da Água/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations); 0 (Soil); 0 (Soil Pollutants); 0 (Water Pollutants, Chemical); 33CM23913M (Carbamazepine); 906O0YJ6ZP (Monensin); AN164J8Y0X (Trimethoprim); JE42381TNV (Sulfamethoxazole); YEF4JXN031 (Tylosin)
[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:180103
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04355


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[PMID]:29102867
[Au] Autor:Murillo-Sierra JC; Sirés I; Brillas E; Ruiz-Ruiz EJ; Hernández-Ramírez A
[Ad] Endereço:Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Av. Universidad, Ciudad Universitaria, San Nicolás de los Garza, Nuevo León, Mexico.
[Ti] Título:Advanced oxidation of real sulfamethoxazole + trimethoprim formulations using different anodes and electrolytes.
[So] Source:Chemosphere;192:225-233, 2018 Feb.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A commercial sulfamethoxazole + trimethoprim formulation has been degraded in 0.050 M Na SO at pH 3.0 by electrochemical oxidation with electrogenerated H O (EO-H O ), electro-Fenton (EF), photoelectro-Fenton with a 6-W UVA lamp (PEF) and solar photoelectro-Fenton (SPEF). The tests were performed in an undivided cell with an IrO -based, Pt or boron-doped diamond (BDD) anode and an air-diffusion cathode for H O electrogeneration. The anode material had little effect on the accumulated H O concentration. Both drugs always obeyed a pseudo-first-order decay with low apparent rate constant in EO-H O . Much higher values were found in EF, PEF and SPEF, showing no difference because the main oxidant was always OH formed from Fenton's reaction between H O and added Fe . The solution mineralization increased in the sequence EO-H O < EF < PEF < SPEF regardless of the anode. The IrO -based and Pt anodes behaved similarly but BDD was always more powerful. In SPEF, similar mineralization profiles were found for all anodes because of the rapid removal of photoactive intermediates by sunlight. About 87% mineralization was obtained as maximum for the powerful SPEF with BDD anode. Addition of Cl enhanced the decay of both drugs due to their quicker reaction with generated active chlorine, but the formation of persistent chloroderivatives decelerated the mineralization process. Final carboxylic acids like oxalic and oxamic were detected, yielding Fe(III) complexes that remained stable in EF with BDD but were rapidly photolyzed in SPEF with BDD, explaining its superior mineralization ability.
[Mh] Termos MeSH primário: Anti-Infecciosos/química
Água Doce/química
Sulfametoxazol/química
Trimetoprima/química
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Boro/química
Diamante/química
Eletroquímica
Eletrodos
Compostos Férricos/química
Água Doce/análise
Peróxido de Hidrogênio/química
Oxirredução
Fotólise
Luz Solar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Ferric Compounds); 0 (Water Pollutants, Chemical); 7782-40-3 (Diamond); AN164J8Y0X (Trimethoprim); BBX060AN9V (Hydrogen Peroxide); JE42381TNV (Sulfamethoxazole); N9E3X5056Q (Boron)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171106
[St] Status:MEDLINE


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[PMID]:28958376
[Au] Autor:Yarmohammadi H; Cunningham-Rundles C
[Ad] Endereço:Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: hale.yar@mssm.edu.
[Ti] Título:Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies.
[So] Source:Ann Allergy Asthma Immunol;119(4):374-378, 2017 Oct.
[Is] ISSN:1534-4436
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. OBJECTIVE: To describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. METHODS: In a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. RESULTS: Twenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7-76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm (range 4-294/mm ) and 219 ± 258/mm (range 7-630/mm ), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. CONCLUSION: The pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Doenças Desmielinizantes/tratamento farmacológico
Neoplasias/tratamento farmacológico
Infecções Oportunistas/tratamento farmacológico
T-Linfocitopenia Idiopática CD4-Positiva/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Contagem de Linfócito CD4
Linfócitos T CD4-Positivos/efeitos dos fármacos
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD4-Positivos/patologia
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/patologia
Criança
Doenças Desmielinizantes/complicações
Doenças Desmielinizantes/diagnóstico
Doenças Desmielinizantes/imunologia
Gerenciamento Clínico
Feminino
Seres Humanos
Masculino
Meia-Idade
Neoplasias/complicações
Neoplasias/diagnóstico
Neoplasias/imunologia
Infecções Oportunistas/complicações
Infecções Oportunistas/diagnóstico
Infecções Oportunistas/imunologia
Estudos Retrospectivos
Sulfametoxazol/uso terapêutico
T-Linfocitopenia Idiopática CD4-Positiva/complicações
T-Linfocitopenia Idiopática CD4-Positiva/diagnóstico
T-Linfocitopenia Idiopática CD4-Positiva/imunologia
Trimetoprima/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); AN164J8Y0X (Trimethoprim); JE42381TNV (Sulfamethoxazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE


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[PMID]:28847075
[Au] Autor:Kong Q; He X; Ma SS; Feng Y; Miao MS; Du YD; Xu F; Wang Q
[Ad] Endereço:College of Geography and Environment, Shandong Normal University, 88 Wenhua Donglu, Jinan 250014, Shandong, PR China; College of Life Science, Shandong Normal University, 88 Wenhua Donglu, Jinan 250014, Shandong, PR China; Institute of Environment and Ecology, Shandong Normal University, 88 Wenhua D
[Ti] Título:The performance and evolution of bacterial community of activated sludge exposed to trimethoprim in a sequencing batch reactor.
[So] Source:Bioresour Technol;244(Pt 1):872-879, 2017 Nov.
[Is] ISSN:1873-2976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The performance and microbial community changes of an activated sludge sequencing batch reactor were evaluated after exposure to trimethoprim for 51days. The average chemical oxygen demand, ammonia nitrogen, phosphorus efficiencies were 88.6%±0.56%, 90.47%±0.29% and 64.25%±1.12%, respectively. The protein and polysaccharide contents increased with increasing trimethoprim concentration to protect the cells from the unfavorable conditions. The chemical composition of extracellular polymeric substances increased. For denitrifying bacteria, the read numbers of Pseudomonas, Flavobacterium and Bacillus were both significantly increased from Day 1 to 25 and sharply decreased by Day 50 (p<0.05), which is consistent with the tendency of Planctomyces (Anammox). The read number of Paracoccus displayed an increasing trend, whereas Nitrospirales, Nitrospira (nitrite oxidizer) and Nitrosomonadaceae (ammonia oxidizer) were significantly decreased (p<0.05). The read number of Rhodocyclaceae (phosphorus oxidizer) was significantly decreased from Day 1 to 25 and sharply increased by Day 50 (p<0.05).
[Mh] Termos MeSH primário: Reatores Biológicos
Esgotos
Trimetoprima
[Mh] Termos MeSH secundário: Nitrogênio
Eliminação de Resíduos Líquidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sewage); AN164J8Y0X (Trimethoprim); N762921K75 (Nitrogen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE


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[PMID]:28829844
[Au] Autor:Vu KT; Zhang F; Hulleman JD
[Ad] Endereço:Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
[Ti] Título:Conditional, Genetically Encoded, Small Molecule-Regulated Inhibition of NFκB Signaling in RPE Cells.
[So] Source:Invest Ophthalmol Vis Sci;58(10):4126-4137, 2017 Aug 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Nuclear factor κB (NFκB) is a ubiquitously expressed, proinflammatory transcription factor that controls the expression of genes involved in cell survival, angiogenesis, complement activation, and inflammation. Studies have implicated NFκB-dependent cytokines or complement-related factors as being detrimentally involved in retinal diseases, thus making inhibition of NFκB signaling a potential therapeutic target. We sought to develop a conditional and reversible method that could regulate pathogenic NFκB signaling by the addition of a small molecule. Methods: We developed a genetically based, trimethoprim (TMP)-regulated approach that conditionally inhibits NFκB signaling by fusing a destabilized dihydrofolate reductase (DHFR) domain to an inhibitor of NFκB, IκBα, in ARPE-19 cells. We then challenged ARPE-19 cells with a number of stimuli that have been demonstrated to trigger NFκB signaling, including LPS, TNFα, IL-1α, and A2E. Western blotting, electrophoretic mobility shift assay, quantitative PCR, ELISA, and NFκB reporter assays were used to evaluate the effectiveness of this DHFR-IκBα approach. Results: This destabilized domain approach, coupled with doxycycline-inducibility, allowed for accurate control over the abundance of DHFR-IκBα. Stabilization of DHFR-IκBα with TMP prevented IL-1α-, A2E-, LPS-, and TNFα-induced NFκB-mediated upregulation and release of the proinflammatory cytokines IL-1ß and IL-6 from ARPE-19 cells (by as much as 93%). This strategy is dosable, completely reversible, and can be cycled "on" or "off" within the same cell population repeatedly to confer protection at desired time points. Conclusions: These studies lay the groundwork for the use of destabilized domains in retinal pigment epithelium (RPE) cells in vivo and in this context, demonstrate their utility for preventing inflammatory signaling.
[Mh] Termos MeSH primário: Inibidores do Citocromo P-450 CYP2C8/farmacologia
NF-kappa B/antagonistas & inibidores
Epitélio Pigmentado da Retina/metabolismo
Tetra-Hidrofolato Desidrogenase/farmacologia
Trimetoprima/farmacologia
[Mh] Termos MeSH secundário: Western Blotting
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Inibidores do Citocromo P-450 CYP2C8/química
Ensaio de Desvio de Mobilidade Eletroforética
Ensaio de Imunoadsorção Enzimática
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
NF-kappa B/metabolismo
Domínios Proteicos/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Tetra-Hidrofolato Desidrogenase/química
Trimetoprima/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP2C8 Inhibitors); 0 (NF-kappa B); AN164J8Y0X (Trimethoprim); EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22133


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[PMID]:28771141
[Au] Autor:Herrera-Heredia SA; Pezina-Cantú C; Garza-González E; Bocanegra-Ibarias P; Mendoza-Olazarán S; Morfín-Otero R; Camacho-Ortiz A; Villarreal-Treviño L; Rodríguez-Noriega E; Paláu-Davila L; Maldonado-Garza HJ; Flores-Treviño S
[Ad] Endereço:1​Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
[Ti] Título:Risk factors and molecular mechanisms associated with trimethoprim-sulfamethoxazole resistance in Stenotrophomonas maltophilia in Mexico.
[So] Source:J Med Microbiol;66(8):1102-1109, 2017 Aug.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing an increasing number of nosocomial infections. Our aim was to evaluate the risk factors and mechanisms associated with trimethoprim-sulfamethoxazole (SXT) resistance in S. maltophilia infections in Mexico. METHODOLOGY: Clinical isolates and patients' demographic and clinical data were collected from February 2007 to August 2015 in two tertiary-care hospitals in Mexico. Antimicrobial susceptibility and analysis of sul and SmeABC and SmeDEF efflux pump overexpression were performed in all isolates.Results/Key findings. In the 9-year period, 196 patients infected with S. maltophilia were identified. Most patients were male, and the mean age was 46.2 years. The mean Charlson score was 1.42, and the most frequent comorbidities were arterial hypertension (26.7 %), type 2 diabetes (21.2 %) and cerebral infarction (11.6 %). High drug resistance to meropenem (93.4 %), gentamicin (55.1 %), ceftazidime (52.3 %), cefotaxime (51.5 %), amikacin (42.3 %) and cefepime (32.1 %), and lower resistance to ciprofloxacin (26.0 %), SXT (25.0 %), chloramphenicol (14.3 %) and levofloxacin (2.6 %) were detected. SXT resistance was not associated with the sul genes. SmeABC overexpression was associated with gentamicin (P=0.001) and levofloxacin resistance (P=0.041), whereas SmeDEF overexpression was associated with ceftazidime resistance (P=0.003). Prolonged hospitalization (≥15 days) was an independent risk factor for SXT-resistant S. maltophilia infections (OR=3.05; 95 % CI=1.12-8.86; P=0.029). CONCLUSION: Given the high SXT resistance rate, SXT is not an effective first-line therapy for our patients; instead, levofloxacin could be used as an appropriate therapeutic option against S. maltophilia infections.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana Múltipla
Infecções por Bactérias Gram-Negativas/microbiologia
Stenotrophomonas maltophilia/efeitos dos fármacos
Sulfametoxazol/farmacologia
Trimetoprima/farmacologia
[Mh] Termos MeSH secundário: Adulto
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Infecção Hospitalar
Feminino
Infecções por Bactérias Gram-Negativas/tratamento farmacológico
Seres Humanos
Masculino
México
Testes de Sensibilidade Microbiana
Meia-Idade
Stenotrophomonas maltophilia/classificação
Stenotrophomonas maltophilia/genética
Stenotrophomonas maltophilia/isolamento & purificação
Combinação Trimetoprima e Sulfametoxazol
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination); AN164J8Y0X (Trimethoprim); JE42381TNV (Sulfamethoxazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000550


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[PMID]:28763485
[Au] Autor:Jee J; Mourya R; Shivakumar P; Fei L; Wagner M; Bezerra JA
[Ad] Endereço:Divisions of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
[Ti] Título:Cxcr2 signaling and the microbiome suppress inflammation, bile duct injury, and the phenotype of experimental biliary atresia.
[So] Source:PLoS One;12(8):e0182089, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biliary atresia is progressive fibro-inflammatory cholangiopathy of young children. Central to pathogenic mechanisms of injury is the tissue targeting by the innate and adaptive immune cells. Among these cells, neutrophils and the IL-8/Cxcl-8 signaling via its Cxcr2 receptor have been linked to bile duct injury. Here, we aimed to investigate whether the intestinal microbiome modulates Cxcr2-dependent bile duct injury and obstruction. Adult wild-type (WT) and Cxcr2-/- mice were fed a diet supplemented with sulfamethoxazole/trimethoprim (SMZ/TMP) during pregnancy and lactation, and their pups were injected intraperitoneally with rhesus rotavirus (RRV) within 24 hours of life to induce experimental biliary atresia. The maternal exposure to SMZ/TMP significantly lowered the incidence of jaundice and bile duct obstruction and resulted in improved survival, especially in Cxcr2-/- mice. Analyses of the microbiome by deep sequencing of 16S rRNA of the neonatal colon showed a delay in bacterial colonization of WT mice induced by SMZ/TMP, with a notable switch from Proteobacteria to Firmicutes. Interestingly, the genetic inactivation of Cxcr2 alone produced a similar bacterial shift. When treated with SMZ/TMP, Cxcr2-/- mice infected with RRV to induce experimental biliary atresia showed further enrichment of Corynebacterium, Anaerococcus and Streptococcus. Among these, Anaerococcus lactolyticus was significantly associated with a suppression of biliary injury, cholestasis, and survivability. These results suggest that the postnatal development of the intestinal microbiota is an important susceptibility factor for experimental biliary atresia.
[Mh] Termos MeSH primário: Ductos Biliares/lesões
Atresia Biliar/metabolismo
Inflamação/metabolismo
Microbiota
Receptores de Interleucina-8B/metabolismo
[Mh] Termos MeSH secundário: Animais
Atresia Biliar/microbiologia
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Lactação
Modelos Lineares
Macaca mulatta
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Fenótipo
Reação em Cadeia da Polimerase
Gravidez
Prenhez
RNA Ribossômico 16S/genética
Receptores de Interleucina-8B/genética
Rotavirus
Transdução de Sinais
Sulfametoxazol/administração & dosagem
Trimetoprima/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Ribosomal, 16S); 0 (Receptors, Interleukin-8B); AN164J8Y0X (Trimethoprim); JE42381TNV (Sulfamethoxazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182089


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[PMID]:28719270
[Au] Autor:Bitan O; Wiener-Well Y; Segal R; Schwartz E
[Ad] Endereço:Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
[Ti] Título:Mycetoma (Madura Foot) in Israel: Recent Cases and a Systematic Review of the Literature.
[So] Source:Am J Trop Med Hyg;96(6):1355-1361, 2017 Jun.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AbstractMycetoma is a chronic soft tissue infection caused by fungal or bacterial pathogens, and is endemic in tropical and subtropical regions. Cases in developed countries outside the mycetoma belt are rare and usually imported by immigrants. Sporadic cases have been reported in Israel. Unpublished cases in the participating medical centers are reported. In addition, a systematic review of the literature was performed. All published mycetoma cases diagnosed in Israel were included with relevant variables collected. Twenty-one cases of mycetoma were diagnosed in Israel between 1942 and 2015, including four unpublished cases and 17 published cases. The mean age at diagnosis was 42 years (range 23-73), and 16 of the patients were male. The foot was the primary involved organ. Fifteen patients were immigrants from Yemen, Ethiopia, and Sudan. Five cases were autochthonous. One case was travel related. Among patients who developed symptoms after immigration, the mean time from exposure to symptom onset was 5.6 years (range 1-10 years). The mean time from symptom onset to diagnosis was 6.6 years (range 0.2-35 years). The autochthonous cases demonstrate that Israel is endemic of mycetoma. The immigrant population represents two distinct waves of immigration to Israel in the past century. Two unpublished cases of Ethiopian immigrants are the first reported cases of mycetoma acquired in Ethiopia. The diagnostic and therapeutic challenges along with the epidemiological data emphasize the need of raising the awareness of physicians to this devastating condition even in developed countries.
[Mh] Termos MeSH primário: Emigrantes e Imigrantes
Micetoma/diagnóstico
Micetoma/etnologia
[Mh] Termos MeSH secundário: Adulto
Amicacina/uso terapêutico
Anti-Infecciosos/uso terapêutico
Bases de Dados Factuais
Etiópia/etnologia
Feminino
Seguimentos
Seres Humanos
Israel/epidemiologia
Masculino
Meia-Idade
Micetoma/tratamento farmacológico
Rifampina/uso terapêutico
Sudão/etnologia
Sulfametoxazol/uso terapêutico
Resultado do Tratamento
Trimetoprima/uso terapêutico
Iêmen/etnologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Infective Agents); 84319SGC3C (Amikacin); AN164J8Y0X (Trimethoprim); JE42381TNV (Sulfamethoxazole); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0710



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