Base de dados : MEDLINE
Pesquisa : D09.408.051 [Categoria DeCS]
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  1 / 9912 MEDLINE  
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[PMID]:27778478
[Au] Autor:Hoang NH; Huong NL; Kim B; Sohng JK; Yoon YJ; Park JW
[Ad] Endereço:Department of Biotechnology Convergent Pharmaceutical Engineering, SunMoon University, Chungnam, Republic of Korea.
[Ti] Título:Istamycin aminoglycosides profiling and their characterization in Streptomyces tenjimariensis ATCC 31603 culture using high-performance liquid chromatography with tandem mass spectrometry.
[So] Source:J Sep Sci;39(24):4712-4722, 2016 Dec.
[Is] ISSN:1615-9314
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A high-performance liquid chromatography with electrospray ionization ion trap tandem mass spectrometry method was developed and validated for the robust profiling and characterization of biosynthetic congeners in the 2-deoxy-aminocyclitol istamycin pathway, from the fermentation broth of Streptomyces tenjimariensis ATCC 31603. Gradient elution on an Acquity CSH C column was performed with a gradient of 5 mM aqueous pentafluoropropionic acid and 50% acetonitrile. Sixteen natural istamycin congeners were profiled and quantified in descending order; istamycin A, istamycin B, istamycin A , istamycin B , istamycin B , istamycin A , istamycin C, istamycin A , istamycin C , istamycin C , istamycin X , istamycin A , istamycin Y , istamycin B , and istamycin FU-10 plus istamycin AP. In addition, a total of five sets of 1- or 3-epimeric pairs were chromatographically separated using a macrocyclic glycopeptide-bonded chiral column. The lower limit of quantification of istamycin-A present in S. tenjimariensis fermentation was estimated to be 2.2 ng/mL. The simultaneous identification of a wide range of 2-deoxy-aminocyclitol-type istamycin profiles from bacterial fermentation was determined for the first time by employing high-performance liquid chromatography with tandem mass spectrometry analysis and the separation of istamycin epimers.
[Mh] Termos MeSH primário: Aminoglicosídeos/biossíntese
Antibacterianos/biossíntese
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Espectrometria de Massas por Ionização por Electrospray
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 76774-97-5 (istamycins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/jssc.201600925


  2 / 9912 MEDLINE  
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[PMID]:29386433
[Au] Autor:Hatakeyama S
[Ad] Endereço:Graduate School of Biomedical Sciences, Nagasaki University.
[Ti] Título:[Stereocontrolled Total Synthesis of Biologically Active Natural Products].
[So] Source:Yakugaku Zasshi;138(2):191-209, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: This review article describes the total syntheses of englerin A, ophiodilactones A and B, marinomycin A, N-methylwelwitindolinone C isothiocyanate, tirandamycins A-D, and tirandalydigin, which possess intriguing biological activities and challenging structures with characteristic ring systems. The focus is on the synthetic methodologies that lead to the highly stereocontrolled assembly of these natural products.
[Mh] Termos MeSH primário: Produtos Biológicos/síntese química
[Mh] Termos MeSH secundário: Alcenos/síntese química
Alcenos/química
Aminoglicosídeos/síntese química
Aminoglicosídeos/química
Derivados de Benzeno/síntese química
Derivados de Benzeno/química
Produtos Biológicos/química
Alcaloides de Indol/síntese química
Alcaloides de Indol/química
Lactonas/síntese química
Lactonas/química
Macrolídeos/síntese química
Macrolídeos/química
Conformação Molecular
Sesquiterpenos de Guaiano/síntese química
Sesquiterpenos de Guaiano/química
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Alkenes); 0 (Aminoglycosides); 0 (Benzene Derivatives); 0 (Biological Products); 0 (Indole Alkaloids); 0 (Lactones); 0 (Macrolides); 0 (N-methylwelwitindolinone B isothiocyanate); 0 (Sesquiterpenes, Guaiane); 0 (englerin A); 0 (marinomycin A); 0 (ophiodilactone A); 0 (ophiodilactone B); 0 (tirandamycin C); 0 (tirandamycin D); 114118-91-1 (tirandalydigin); 34429-70-4 (tirandamycin A); 60587-14-6 (tirandamycin B)
[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.17-00187


  3 / 9912 MEDLINE  
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[PMID]:28456704
[Au] Autor:Schroeder CP; Van Anglen LJ; Dretler RH; Adams JS; Prokesch RC; Luu Q; Krinsky AH
[Ad] Endereço:Healix Infusion Therapy, Inc., 14140 Southwest Freeway, Suite 400, Sugar Land, TX 77478, USA.
[Ti] Título:Outpatient treatment of osteomyelitis with telavancin.
[So] Source:Int J Antimicrob Agents;50(1):93-96, 2017 Jul.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Telavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens including Staphylococcus aureus, the most frequent cause of osteomyelitis. Treatment is often challenging due to needs for surgical intervention along with prolonged administration of intravenous antimicrobials, frequently in an outpatient setting. This was a retrospective analysis of the efficacy and safety of telavancin for treatment of osteomyelitis provided as outpatient parenteral antimicrobial therapy (OPAT) in physician office infusion centres. Medical records of 60 patients receiving telavancin for osteomyelitis in 22 physician office infusion centres from 2010 to 2011 and 2013 to 2015 were reviewed. Of these, 60% were treated without hospitalisation, 37% had orthopaedic hardware and 56% had concurrent infections. Staphylococcus aureus was the most common pathogen (78%), primarily methicillin-resistant. The median duration of telavancin treatment in the outpatient setting was 21 days (range 3-105 days). Telavancin was used as first-line therapy in 32% of cases, following prior antibiotic failure in 47% and due to intolerance to previous agents in 22%, predominantly daptomycin or vancomycin. The telavancin dose was 10 mg/kg/day, adjusted for renal function in 25% of patients. The majority of patients self-administered telavancin at home via an elastomeric infusion pump. Overall clinical success was 73%. No significant differences in outcomes were observed with the presence of hardware, concurrent infection, concomitant therapies or type of osteomyelitis. Telavancin-associated adverse events occurred in 57%, with discontinuation in three patients (5%). These data demonstrate the effective and safe OPAT use of telavancin, providing an alternative for successful treatment of patients with osteomyelitis.
[Mh] Termos MeSH primário: Assistência Ambulatorial/métodos
Aminoglicosídeos/administração & dosagem
Antibacterianos/administração & dosagem
Infecções Bacterianas/tratamento farmacológico
Osteomielite/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Aminoglicosídeos/efeitos adversos
Antibacterianos/efeitos adversos
Bactérias/classificação
Bactérias/isolamento & purificação
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Pacientes Ambulatoriais
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); XK134822Z0 (telavancin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  4 / 9912 MEDLINE  
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[PMID]:29205135
[Au] Autor:Tada T; Uechi K; Nakasone I; Miyazato Z; Shinzato T; Shimada K; Tsuchiya M; Kirikae T; Fujita J
[Ad] Endereço:1​Department of Microbiology, Juntendo University School of Medicine, Tokyo, Japan.
[Ti] Título:A hemin auxotrophic Enterobacter cloacae clinical isolate with increased resistance to carbapenems and aminoglycosides.
[So] Source:J Med Microbiol;67(1):29-32, 2018 Jan.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Small-colony variants (SCVs) were obtained from an Enterobacter cloacae clinical isolate in Okinawa, Japan. One variant showed auxotrophy for hemin with a deletion of 20 365 nucleotides, dosC-ydiK-mmuP-mmuM-tauA-tauB-tauC-tauD-hemB-yaiT-yaiV-ampH-yddQ-sbmA-yaiW-yaiY-yaiZ, including hemB, and was more resistant to aminoglycosides and carbapenems, but more susceptible to aztreonam, than the parent strain.
[Mh] Termos MeSH primário: Aminoglicosídeos/farmacologia
Antibacterianos/farmacologia
Carbapenêmicos/farmacologia
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos
Enterobacter cloacae/efeitos dos fármacos
Enterobacter cloacae/isolamento & purificação
[Mh] Termos MeSH secundário: Aztreonam/farmacologia
Proteínas de Bactérias/genética
Enterobacter cloacae/genética
Hemina
Seres Humanos
Japão
Deleção de Sequência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Carbapenems); 743LRP9S7N (Hemin); G2B4VE5GH8 (Aztreonam)
[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:171206
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000655


  5 / 9912 MEDLINE  
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[PMID]:28873612
[Au] Autor:Feng J; She X; He X; Zhu J; Li Y; Deng C
[Ad] Endereço:Pharmaceutical Analysis Department, School of Pharmacy, Fudan University, Shanghai 201203, China.
[Ti] Título:Synthesis of magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls for selective and efficient residue analysis of aminoglycosides in milk.
[So] Source:Food Chem;239:612-621, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this study, magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls were synthesized for the first time by a two-step post-graft method. The obtained nano-composites were proven to hold many attractive features such as large specific surface area, uniform mesopores, high magnetic responsibility, and boronic acid-functionalized inner pore-walls. Aminoglycoside residues in milk were extracted using MG@mSiO -APB composites as restricted access matrix dispersive solid phase extraction adsorbents through the interaction between boronic acid groups and glucoside structures. Extraction conditions were optimized by studying the SPE parameters. Limits of detection of the method were as low as 5ngmL for streptomycin) and 2ngmL for dihydrostreptomycin. Finally, magnetic graphene/mesoporous silica composites with boronic acid-functionalized pore-walls were successfully applied to residue analysis in milk samples. Compared to the traditional extraction methods, using this nano-composites for aminoglycoside residues analysis in milk is more sensitive, effective and convenient.
[Mh] Termos MeSH primário: Leite
[Mh] Termos MeSH secundário: Aminoglicosídeos
Animais
Ácidos Borônicos
Grafite
Porosidade
Dióxido de Silício
Extração em Fase Sólida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Boronic Acids); 7631-86-9 (Silicon Dioxide); 7782-42-5 (Graphite)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE


  6 / 9912 MEDLINE  
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[PMID]:29049311
[Au] Autor:Ryals M; Pak K; Jalota R; Kurabi A; Ryan AF
[Ad] Endereço:Department of Surgery/Otolaryngology, University of California, San Diego, School of Medicine, La Jolla, California, United States of America.
[Ti] Título:A kinase inhibitor library screen identifies novel enzymes involved in ototoxic damage to the murine organ of Corti.
[So] Source:PLoS One;12(10):e0186001, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ototoxicity is a significant side effect of a number of drugs, including the aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are used to treat life-threatening illnesses. Although much progress has been made, the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs) remains incompletely understood. Given the critical role of protein phosphorylation in intracellular processes, including both damage and survival signaling, we screened a library of kinase inhibitors targeting members of all the major families in the kinome. Micro-explants from the organ of Corti of mice in which only the sensory cells express GFP were exposed to 200 µM of the ototoxic aminoglycoside gentamicin with or without three dosages of each kinase inhibitor. The loss of sensory cells was compared to that seen with gentamicin alone, or without treatment. Of the 160 inhibitors, 15 exhibited a statistically significant protective effect, while 3 significantly enhanced HC loss. The results confirm some previous studies of kinase involvement in HC damage and survival, and also highlight several novel potential kinase pathway contributions to ototoxicity.
[Mh] Termos MeSH primário: Aminoglicosídeos/toxicidade
Antibacterianos/toxicidade
Antineoplásicos/toxicidade
Inibidores Enzimáticos/farmacologia
Órgão Espiral/efeitos dos fármacos
Fosfotransferases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Transgênicos
Órgão Espiral/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); EC 2.7.- (Phosphotransferases)
[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:171020
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186001


  7 / 9912 MEDLINE  
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[PMID]:28913903
[Au] Autor:Krzysciak P; Chmielarczyk A; Pobiega M; Romaniszyn D; Wójkowska-Mach J
[Ad] Endereço:Department of Mycology, Jagiellonian University Medical College, Krakow, Poland.
[Ti] Título:Acinetobacter baumannii isolated from hospital-acquired infection: biofilm production and drug susceptibility.
[So] Source:APMIS;125(11):1017-1026, 2017 Nov.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Acinetobacter baumannii cause opportunistic nosocomial infections and is often multidrug resistant. It has ability to form biofilm. The possession of drug resistance mechanism and ability of biofilm formation seems to be the different way to enhancement of viability in stressful environment. In this study, we evaluate relation between these two factors. The biofilm formation was investigated in M63 medium with casein in microtiter plates, and the drug susceptibility was performed by disk diffusion methods. We found that 80-98% strains formed a biofilm. Strains showing sensitivity to amikacin and tobramycin from ICU produced more biofilm than strains showing resistance to these antibiotics. Ceftazidime-sensitive strains formed a smaller biofilm than resistant. The logistic regression shows association between drug resistance and strains originating from ICU. In case of ceftazidime, strong biofilm formation and descending from ICU reduced the likelihood of drug sensitivity. For other drugs such as aminoglycosides, fluoroquinolones, trimethoprim/sulfamethoxazole, and tetracycline, we found opposite relation (but it was not statistically significance). However, generally it seems that strong biofilm producers from ICUs are often more susceptible to antibiotics. This situation can be explained by the fact that bacteria protected in biofilm do not need mechanisms responsible for resistance of planktonic cells.
[Mh] Termos MeSH primário: Infecções por Acinetobacter/microbiologia
Acinetobacter baumannii/efeitos dos fármacos
Antibacterianos/farmacologia
Biofilmes/efeitos dos fármacos
Infecção Hospitalar/microbiologia
Plâncton/efeitos dos fármacos
[Mh] Termos MeSH secundário: Infecções por Acinetobacter/tratamento farmacológico
Acinetobacter baumannii/crescimento & desenvolvimento
Acinetobacter baumannii/isolamento & purificação
Idoso
Aminoglicosídeos/farmacologia
Biofilmes/crescimento & desenvolvimento
Cefalosporinas/farmacologia
Infecção Hospitalar/tratamento farmacológico
Meios de Cultura/química
Farmacorresistência Bacteriana Múltipla/fisiologia
Feminino
Fluoroquinolonas/farmacologia
Seres Humanos
Unidades de Terapia Intensiva
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Plâncton/crescimento & desenvolvimento
Plâncton/isolamento & purificação
Combinação Trimetoprima e Sulfametoxazol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Culture Media); 0 (Fluoroquinolones); 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12739


  8 / 9912 MEDLINE  
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[PMID]:28902596
[Au] Autor:Xie YL; Chakravorty S; Armstrong DT; Hall SL; Via LE; Song T; Yuan X; Mo X; Zhu H; Xu P; Gao Q; Lee M; Lee J; Smith LE; Chen RY; Joh JS; Cho Y; Liu X; Ruan X; Liang L; Dharan N; Cho SN; Barry CE; Ellner JJ; Dorman SE; Alland D
[Ad] Endereço:From the Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (Y.L.X., L.E.V., R.Y.C., C.E.B.), and Johns Hopkins University School of Medicine, Baltimore (D.T.A., S.E.D.) - both in M
[Ti] Título:Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.
[So] Source:N Engl J Med;377(11):1043-1054, 2017 09 14.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions. RESULTS: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 µg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 µg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 µg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater. CONCLUSIONS: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).
[Mh] Termos MeSH primário: Antituberculosos/farmacologia
DNA Bacteriano/análise
Farmacorresistência Bacteriana Múltipla/genética
Testes de Sensibilidade Microbiana/métodos
Mutação
Mycobacterium tuberculosis/efeitos dos fármacos
Sistemas Automatizados de Assistência Junto ao Leito
Análise de Sequência de DNA
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Aminoglicosídeos/farmacologia
Antituberculosos/uso terapêutico
China
Feminino
Fluoroquinolonas/farmacologia
Seres Humanos
Isoniazida/farmacologia
Masculino
Meia-Idade
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/isolamento & purificação
Estudos Prospectivos
República da Coreia
Sensibilidade e Especificidade
Escarro/microbiologia
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; EVALUATION STUDIES; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Antitubercular Agents); 0 (DNA, Bacterial); 0 (Fluoroquinolones); V83O1VOZ8L (Isoniazid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170914
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1614915


  9 / 9912 MEDLINE  
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[PMID]:28893366
[Au] Autor:Aldape MJ; Packham AE; Heeney DD; Rice SN; Bryant AE; Stevens DL
[Ad] Endereço:1​Department of Veterans Affairs Medical Center, 500 W. Fort St, Boise, ID 83712, USA.
[Ti] Título:Fidaxomicin reduces early toxin A and B production and sporulation in Clostridium difficilein vitro.
[So] Source:J Med Microbiol;66(10):1393-1399, 2017 Oct.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Fidaxomicin, a macrocyclic antibiotic, has been approved for the treatment of Clostridium difficile infection (CDI). Previous work by our group has demonstrated that some antibiotics at sub-inhibitory concentrations stimulate early toxin production and sporulation by C. difficile. Prior studies revealed that fidaxomicin, when added to late stationary-phase organisms, reduced exotoxin production and spore formation by C. difficile. However, the ability of fidaxomicin to trigger early virulence factor production and spore formation has never been investigated. METHODOLOGY: Sub-inhibitory concentrations of the RNA synthesis inhibitor fidaxomicin (1/4×, 1/8×, 1/16× MIC) were added immediately to lag-phase cultures of historical (strain 9689) and epidemic BI/NAP1/027 (strain 5325) strains of C. difficile, and their effects on sporulation and toxin A (TcdA) and toxin B (TcdB) production were compared.Results/Key findings. Even at sub-inhibitory concentrations, all doses of fidaxomicin reduced both TcdA and TcdB gene expression and protein production in the historical and epidemic C. difficile strains. Fidaxomicin also dose-dependently reduced viable spore production by the 9689 and 5325 strains. Reductions in spore formation were also observed in both strains treated with tigecycline and vancomycin. However, all concentrations of metronidazole stimulated a ~2 log increase in spore production by the 5325 isolate. CONCLUSION: The ability of fidaxomicin to suppress early exotoxin production and endospore formation by historical and epidemic strains of C. difficile may explain its clinical success in treating severe and recurrent cases of CDI disease.
[Mh] Termos MeSH primário: Aminoglicosídeos/farmacologia
Antibacterianos/farmacologia
Toxinas Botulínicas Tipo A/metabolismo
Clostridium difficile/efeitos dos fármacos
Clostridium difficile/metabolismo
[Mh] Termos MeSH secundário: Toxinas Botulínicas Tipo A/genética
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Esporos Bacterianos/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Anti-Bacterial Agents); 0Y70779M1F (rimabotulinumtoxinB); EC 3.4.24.69 (Botulinum Toxins, Type A); Z5N076G8YQ (lipiarmycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000580


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[PMID]:28734024
[Au] Autor:Bacot-Davis VR; Bassenden AV; Sprules T; Berghuis AM
[Ad] Endereço:McGill University, Biochemistry, 3649 Promenade Sir William Osler Room 470, Montreal, QC H3A 0G4, Canada.
[Ti] Título:Effect of solvent and protein dynamics in ligand recognition and inhibition of aminoglycoside adenyltransferase 2″-Ia.
[So] Source:Protein Sci;26(9):1852-1863, 2017 Sep.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aminoglycoside modifying enzyme (AME) ANT(2″)-Ia is a significant target for next generation antibiotic development. Structural studies of a related aminoglycoside-modifying enzyme, ANT(3″)(9), revealed this enzyme contains dynamic, disordered, and well-defined segments that modulate thermodynamically before and after antibiotic binding. Characterizing these structural dynamics is critical for in situ screening, design, and development of contemporary antibiotics that can be implemented in a clinical setting to treat potentially lethal, antibiotic resistant, human infections. Here, the first NMR structural ensembles of ANT(2″)-Ia are presented, and suggest that ATP-aminoglycoside binding repositions the nucleotidyltransferase (NT) and C-terminal domains for catalysis to efficiently occur. Residues involved in ligand recognition were assessed by site-directed mutagenesis. In vitro activity assays indicate a critical role for I129 toward aminoglycoside modification in addition to known catalytic D44, D46, and D48 residues. These observations support previous claims that ANT aminoglycoside sub-class promiscuity is not solely due to binding cleft size, or inherent partial disorder, but can be controlled by ligand modulation on distinct dynamic and thermodynamic properties of ANTs under cellular conditions. Hydrophobic interactions in the substrate binding cleft, as well as solution dynamics in the C-terminal tail of ANT(2″)-Ia, advocate toward design of kanamycin-derived cationic lipid aminoglycoside analogs, some of which have already shown antimicrobial activity in vivo against kanamycin and gentamicin-resistant P. aeruginosa. This data will drive additional in silico, next generation antibiotic development for future human use to combat increasingly prevalent antimicrobial resistance.
[Mh] Termos MeSH primário: Acetiltransferases/química
Acetiltransferases/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
[Mh] Termos MeSH secundário: Acetiltransferases/genética
Aminoglicosídeos/química
Aminoglicosídeos/metabolismo
Proteínas de Bactérias/genética
Farmacorresistência Bacteriana
Escherichia coli
Modelos Moleculares
Ressonância Magnética Nuclear Biomolecular
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Solventes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Bacterial Proteins); 0 (Recombinant Proteins); 0 (Solvents); EC 2.3.1.- (Acetyltransferases); EC 2.3.1.- (aminoglycoside acetyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170723
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3224



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