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[PMID]:28822261
[Au] Autor:Rasheed W; Shah MR; Perveen S; Ahmed S; Uzzaman S
[Ad] Endereço:H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
[Ti] Título:Revelation of susceptibility differences due to Hg(II) accumulation in Streptococcus pyogenes against CX-AgNPs and Cefixime by atomic force microscopy.
[So] Source:Ecotoxicol Environ Saf;147:9-16, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Solution based method for the formation of chemically modified silver nanoparticles (CX-AgNPs) using Cefixime as stabilizing and reducing agent was developed. The CX-AgNPs were characterized by AFM, UV-visible, FT-IR and MALDI-TOF MS. Bactericidal efficiency of CX-AgNPs and Cefixime against Streptococcus pyogenes was evaluated. Afterwards, susceptibility differences of Streptococcus pyogenes due to accumulation of Hg(II) against CX-AgNPs and Cefixime were estimated and validated through Atomic force microscopy. Selectivity and sensitivity of CX-AgNPs against Hg(II) was evaluated in a systematic manner. The CX-AgNPs was titrated against optically silent Hg(II) which induced enhancement in the SPR band of CX-AgNPs. The increase in intensity of SPR band of CX-AgNPs was determined to be proportionate to the concentration of Hg(II) in the range of 33.3-700µM obeying linear regression equation of y = 0.125x + 8.962 with the detection limit of 0.10µM and the coefficient of determination equals to 0.985 (n = 3). The association constant Ka of CX-AgNPs-Hg(II) was found to be 386.0095mol dm by using the Benesi Hildebrand plot.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Cefixima/farmacologia
Mercúrio/metabolismo
Nanopartículas Metálicas/química
Nanoconjugados/química
Prata/farmacologia
Streptococcus pyogenes/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antibacterianos/química
Cefixima/química
Limite de Detecção
Testes de Sensibilidade Microbiana
Microscopia de Força Atômica
Prata/química
Espectroscopia de Infravermelho com Transformada de Fourier
Streptococcus pyogenes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Nanoconjugates); 3M4G523W1G (Silver); 97I1C92E55 (Cefixime); FXS1BY2PGL (Mercury)
[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:170820
[St] Status:MEDLINE


  2 / 12112 MEDLINE  
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[PMID]:29211672
[Au] Autor:Stevens DL; Bryant AE
[Ad] Endereço:From the Veterans Affairs Medical Center, Boise, ID; and the University of Washington School of Medicine, Seattle.
[Ti] Título:Necrotizing Soft-Tissue Infections.
[So] Source:N Engl J Med;377(23):2253-2265, 2017 Dec 07.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Desbridamento
Fasciite Necrosante
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/efeitos adversos
Biomarcadores/sangue
Biópsia
Proteína C-Reativa/análise
Estado Terminal
Fasciite Necrosante/diagnóstico
Fasciite Necrosante/etiologia
Fasciite Necrosante/patologia
Fasciite Necrosante/terapia
Gangrena Gasosa
Seres Humanos
Oxigenação Hiperbárica
Imunoglobulinas Intravenosas/uso terapêutico
Infecções dos Tecidos Moles
Infecções Estreptocócicas/induzido quimicamente
Streptococcus pyogenes
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Biomarkers); 0 (Immunoglobulins, Intravenous); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMra1600673


  3 / 12112 MEDLINE  
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[PMID]:29260224
[Au] Autor:Gerber JS; Ross RK; Bryan M; Localio AR; Szymczak JE; Wasserman R; Barkman D; Odeniyi F; Conaboy K; Bell L; Zaoutis TE; Fiks AG
[Ad] Endereço:Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
[Ti] Título:Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.
[So] Source:JAMA;318(23):2325-2336, 2017 12 19.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics. Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]). Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Otite Média/tratamento farmacológico
Qualidade de Vida
Infecções Respiratórias/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença Aguda
Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico
Antibacterianos/uso terapêutico
Cefalosporinas/efeitos adversos
Cefalosporinas/uso terapêutico
Criança
Pré-Escolar
Feminino
Seres Humanos
Macrolídeos/efeitos adversos
Macrolídeos/uso terapêutico
Masculino
Faringite/tratamento farmacológico
Atenção Primária à Saúde
Estudos Retrospectivos
Sinusite/tratamento farmacológico
Infecções Estreptocócicas/tratamento farmacológico
Streptococcus pyogenes
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Macrolides); 74469-00-4 (Amoxicillin-Potassium Clavulanate Combination)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.18715


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[PMID]:29384948
[Au] Autor:Iitaka D; Ochi F; Nakashima S; Fujiyama J; Masuyama M
[Ti] Título:Treatment with antibodies against primary group A streptococcal peritonitis: A case report and a review of the literature.
[So] Source:Medicine (Baltimore);96(52):e9498, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Several reports describe severe group A streptococcal (GAS) infections causing septic shock, soft-tissue necrosis, and multiple organ failure known as streptococcal toxic shock syndrome (STSS). However, primary peritonitis with GAS is rare and most of them were undertaken surgical procedure. PATIENT CONCERNS: We herein reported the case of 26-year-old healthy woman with sudden severe abdominal pain and hypotension. Computed tomography (CT) showed that large amount of free fluid in the peritoneal cavity consist with peritonitis, and no free air. DIAGNOSES: Primary peritonitis with GAS. INTERVENTIONS: Proper antibiotic therapy according to blood culture results. OUTCOMES: After antibiotic therapy, the patient recovered well without complications. LESSONS: An appropriate diagnostic approach and prompt antibiotic therapy is essential in GAS primary peritonitis.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Peritonite/tratamento farmacológico
Infecções Estreptocócicas/tratamento farmacológico
Streptococcus pyogenes
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Peritonite/microbiologia
Infecções Estreptocócicas/microbiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009498


  5 / 12112 MEDLINE  
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[PMID]:29254479
[Au] Autor:Sekizuka T; Nai E; Yoshida T; Endo S; Hamajima E; Akiyama S; Ikuta Y; Obana N; Kawaguchi T; Hayashi K; Noda M; Sumita T; Kokaji M; Katori T; Hashino M; Oba K; Kuroda M
[Ad] Endereço:Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan.
[Ti] Título:Streptococcal toxic shock syndrome caused by the dissemination of an invasive emm3/ST15 strain of Streptococcus pyogenes.
[So] Source:BMC Infect Dis;17(1):774, 2017 12 18.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Streptococcus pyogenes (group A Streptococcus [GAS]) is a major human pathogen that causes a wide spectrum of clinical manifestations. Although invasive GAS (iGAS) infections are relatively uncommon, emm3/ST15 GAS is a highly virulent, invasive, and pathogenic strain. Global molecular epidemiology analysis has suggested that the frequency of emm3 GAS has been recently increasing. CASE PRESENTATION: A 14-year-old patient was diagnosed with streptococcal toxic shock syndrome and severe pneumonia, impaired renal function, and rhabdomyolysis. GAS was isolated from a culture of endotracheal aspirates and designated as KS030. Comparative genome analysis suggested that KS030 is classified as emm3 (emm-type) and ST15 (multilocus sequencing typing [MLST]), which is similar to iGAS isolates identified in the UK (2013) and Switzerland (2015). CONCLUSIONS: We conclude that the global dissemination of emm3/ST15 GAS strain has the potential to cause invasive disease.
[Mh] Termos MeSH primário: Choque Séptico/microbiologia
Infecções Estreptocócicas/microbiologia
Streptococcus pyogenes/isolamento & purificação
[Mh] Termos MeSH secundário: Antígenos de Bactérias/genética
Proteínas da Membrana Bacteriana Externa/genética
Seres Humanos
Epidemiologia Molecular
Tipagem de Sequências Multilocus
Choque Séptico/epidemiologia
Infecções Estreptocócicas/epidemiologia
Streptococcus pyogenes/classificação
Streptococcus pyogenes/genética
Suíça/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Outer Membrane Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2870-2


  6 / 12112 MEDLINE  
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[PMID]:28456061
[Au] Autor:Richter F; Fonfara I; Gelfert R; Nack J; Charpentier E; Möglich A
[Ad] Endereço:Bayer AG, Pharmaceuticals, Protein Engineering and Assays, 50829 Köln, Germany. Electronic address: florian.richter@bayer.com.
[Ti] Título:Switchable Cas9.
[So] Source:Curr Opin Biotechnol;48:119-126, 2017 Dec.
[Is] ISSN:1879-0429
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ever since its discovery, Cas9 from Streptococcus pyogenes has revolutionized biology by enabling analysis and engineering of genomes with unprecedented precision and ease. To fine-tune on-target effects and to mitigate adverse effects caused by untimely and off-target action of Cas9, strategies have been developed to control its activity at the post-translational stage via external trigger signals. Control is either achieved by modifying the Cas9 protein itself or its programmable RNA molecules. To date, switchable Cas9 variants responding to small ligands, light or temperature have been engineered. With these variants in hand, the regulation and modification of genomes can be accomplished in graded and ever more precise manner.
[Mh] Termos MeSH primário: Proteínas Associadas a CRISPR/metabolismo
Sistemas CRISPR-Cas
Regulação da Expressão Gênica
Engenharia Genética/métodos
Genoma Humano
[Mh] Termos MeSH secundário: Seres Humanos
Streptococcus pyogenes
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (CRISPR-Associated Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  7 / 12112 MEDLINE  
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ARANA-CHAVEZ, Victor Elias
Texto completo SciELO Brasil
[PMID]:29236898
[Au] Autor:Carnaval TG; Gonçalves F; Romano MM; Catalani LH; Mayer MAP; Arana-Chávez VE; Nishida AC; Lage TC; Francci CE; Adde CA
[Ad] Endereço:Universidade de São Paulo - USP, Dental School, Department of Stomatology, São Paulo, SP, Brazil.
[Ti] Título:In vitro analysis of a local polymeric device as an alternative for systemic antibiotics in Dentistry.
[So] Source:Braz Oral Res;31:e92, 2017 Dec 07.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The development of a biodegradable material with antimicrobial properties for local applications is required in the prevention and treatment of infectious diseases. The objective of this study was to produce blends of poly-L-lactide acid (PLLA) synthetic polymer associated with several antimicrobials, as an alternative in the prevention and treatment of infections, as well as to evaluate its cytotoxicity, release of antimicrobials and inhibit bacteria growth. Blends of PLLA added with 20% Amoxicillin, Metronidazole, Clindamycin or Azithromicyn were used to produce Films (F) or Meshs (M) by casting and electrospinning methods, respectively. Standardized discs of the films and meshs were stored in buffer solutions (pH 5 or 7.4) and aliquots were analyzed by high performance chromatography (HPLC) during 168 hours. Cytotoxicity on human gingival fibroblasts was tested after 24, 48 and 72h by MTT reaction. The antimicrobial capacity was determined against P. gingivalis and S. pyogenes. The specimens were weighed after 3 and 6 months of storage for degradation analysis. SEM was performed to control interfaces and degradation. Antimicrobials presented a continuous and exponential drug release. Analysis showed that both M and F were able to inhibit S. pyogenes and P. gingivalis growth, indicating the release of active antimicrobial agents. The products were not toxic to the fibroblasts. Amoxicillin-film showed more degradation than PLLA at both pHs (p < 0.05), whereas Azithromycin-meshes were more degraded than PLLA at pH 7.4 (p < 0.05). PLLA association with antimicrobials is biocompatible and may represent a potential tool for the local delivery of antimicrobials.
[Mh] Termos MeSH primário: Anti-Infecciosos/farmacologia
Materiais Biocompatíveis/farmacologia
Viabilidade Microbiana/efeitos dos fármacos
Poliésteres/farmacologia
Polímeros/farmacologia
Porphyromonas gingivalis/efeitos dos fármacos
Streptococcus pyogenes/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anti-Infecciosos/química
Materiais Biocompatíveis/química
Técnicas de Cultura de Células
Combinação de Medicamentos
Seres Humanos
Teste de Materiais
Polímeros/química
Telas Cirúrgicas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Biocompatible Materials); 0 (Drug Combinations); 0 (Polyesters); 0 (Polymers); 459TN2L5F5 (poly(lactide))
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


  8 / 12112 MEDLINE  
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[PMID]:27772680
[Au] Autor:Wawrzyniak M; Eilbert W
[Ad] Endereço:University of Illinois Affiliate Hospitals Residency Program, University of Illinois at Chicago College of Medicine, Chicago, IL.
[Ti] Título:Child With Sore Throat.
[So] Source:Ann Emerg Med;68(5):638-647, 2016 Nov.
[Is] ISSN:1097-6760
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Faringite/etiologia
Infecções Estreptocócicas/diagnóstico
Streptococcus pyogenes
[Mh] Termos MeSH secundário: Criança
Seres Humanos
Masculino
Faringite/patologia
Faringite/terapia
Infecções Estreptocócicas/complicações
Infecções Estreptocócicas/terapia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  9 / 12112 MEDLINE  
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[PMID]:28919415
[Au] Autor:Hoshino M; Nakakido M; Nagatoishi S; Aikawa C; Nakagawa I; Tsumoto K
[Ad] Endereço:Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
[Ti] Título:Biophysical characterization of the interaction between heme and proteins responsible for heme transfer in Streptococcus pyogenes.
[So] Source:Biochem Biophys Res Commun;493(2):1109-1114, 2017 Nov 18.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Streptococcus pyogenes, an important pathogen that causes a wide range of diseases, possesses the sia gene cluster, which encodes proteins involved in the heme acquisition system. Although this system was previously described, the molecular mechanism of effective heme transfer remains to be elucidated. Here, we have characterized the interactions between heme and each domain of Streptococcal hemoprotein receptor (Shr) and Streptococcal heme-binding protein (Shp). Our kinetic and thermodynamic analyses suggested that effective heme transfer within this system is achieved not only by affinity-based transfer but also by the difference of the binding driving force. The biophysical characterization of the above-mentioned interaction will lead to an indication for the selection of the target for a chemical screening of inhibitors as novel antibacterial agents based on biophysical approaches.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Proteínas de Transporte/metabolismo
Heme/metabolismo
Hemeproteínas/metabolismo
Hemoglobinas/metabolismo
Infecções Estreptocócicas/metabolismo
Streptococcus pyogenes/fisiologia
[Mh] Termos MeSH secundário: Seres Humanos
Modelos Moleculares
Ligação Proteica
Infecções Estreptocócicas/microbiologia
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Carrier Proteins); 0 (Hemeproteins); 0 (Hemoglobins); 0 (heme-binding protein); 42VZT0U6YR (Heme)
[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:170919
[St] Status:MEDLINE


  10 / 12112 MEDLINE  
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[PMID]:28904125
[Au] Autor:Nordström T; Pandey M; Calcutt A; Powell J; Phillips ZN; Yeung G; Giddam AK; Shi Y; Haselhorst T; von Itzstein M; Batzloff MR; Good MF
[Ad] Endereço:The QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia; and.
[Ti] Título:Enhancing Vaccine Efficacy by Engineering a Complex Synthetic Peptide To Become a Super Immunogen.
[So] Source:J Immunol;199(8):2794-2802, 2017 Oct 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peptides offer enormous promise as vaccines to prevent and protect against many infectious and noninfectious diseases. However, to date, limited vaccine efficacy has been reported and none have been licensed for human use. Innovative ways to enhance their immunogenicity are being tested, but rational sequence modification as a means to improve immune responsiveness has been neglected. Our objective was to establish a two-step generic protocol to modify defined amino acids of a helical peptide epitope to create a superior immunogen. Peptide variants of p145, a conserved helical peptide epitope from the M protein of , were designed by exchanging one amino acid at a time, without altering their α-helical structure, which is required for correct antigenicity. The immunogenicities of new peptides were assessed in outbred mice. Vaccine efficacy was assessed in a skin challenge and invasive disease model. Out of 86 variants of p145, seven amino acid substitutions were selected and made the basis of the design for 18 new peptides. Of these, 13 were more immunogenic than p145; 7 induced Abs with significantly higher affinity for p145 than Abs induced by p145 itself; and 1 peptide induced more than 10,000-fold greater protection following challenge than the parent peptide. This peptide also only required a single immunization (compared with three immunizations with the parent peptide) to induce complete protection against invasive streptococcal disease. This study defines a strategy to rationally improve the immunogenicity of peptides and will have broad applicability to the development of vaccines for infectious and noninfectious diseases.
[Mh] Termos MeSH primário: Antígenos de Bactérias/metabolismo
Proteínas da Membrana Bacteriana Externa/metabolismo
Proteínas de Transporte/metabolismo
Fragmentos de Peptídeos/metabolismo
Infecções Estreptocócicas/imunologia
Vacinas Estreptocócicas/imunologia
Streptococcus pyogenes/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos/sangue
Antígenos de Bactérias/genética
Antígenos de Bactérias/imunologia
Proteínas da Membrana Bacteriana Externa/genética
Proteínas da Membrana Bacteriana Externa/imunologia
Proteínas de Transporte/genética
Proteínas de Transporte/imunologia
Seres Humanos
Imunidade Humoral
Imunização
Camundongos
Camundongos Endogâmicos BALB C
Mutação/genética
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/imunologia
Engenharia de Proteínas
Infecções Estreptocócicas/prevenção & controle
Vacinas de Subunidades
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bacterial); 0 (Antigens, Bacterial); 0 (Bacterial Outer Membrane Proteins); 0 (Carrier Proteins); 0 (Peptide Fragments); 0 (Streptococcal Vaccines); 0 (Vaccines, Subunit); 0 (streptococcal M protein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700836



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