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  1 / 18344 MEDLINE  
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PMID:29377916
Autor:Tutykhina I; Esmagambetov I; Bagaev A; Pichugin A; Lysenko A; Shcherbinin D; Sedova E; Logunov D; Shmarov M; Ataullakhanov R; Naroditsky B; Gintsburg A
Dirección:Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health, Moscow, Russia.
Título:Vaccination potential of B and T epitope-enriched NP and M2 against Influenza A viruses from different clades and hosts.
Fuente:PLoS One; 13(1):e0191574, 2018.
ISSN:1932-6203
País de publicación:United States
Idioma:eng
Resumen:To avoid outbreaks of influenza virus epidemics and pandemics among human populations, modern medicine requires the development of new universal vaccines that are able to provide protection from a wide range of influenza A virus strains. In the course of development of a universal vaccine, it is necessary to consider that immunity must be generated even against viruses from different hosts because new human epidemic virus strains have their origins in viruses of birds and other animals. We have enriched conserved viral proteins-nucleoprotein (NP) and matrix protein 2 (M2)-by B and T-cell epitopes not only human origin but also swine and avian origin. For this purpose, we analyzed M2 and NP sequences with respect to changes in the sequences of known T and B-cell epitopes and chose conserved and evolutionarily significant epitopes. Eventually, we found consensus sequences of M2 and NP that have the maximum quantity of epitopes that are 100% coincident with them. Consensus epitope-enriched amino acid sequences of M2 and NP proteins were included in a recombinant adenoviral vector. Immunization with Ad5-tet-M2NP induced strong CD8 and CD4 T cells responses, specific to each of the encoded antigens, i.e. M2 and NP. Eight months after immunization with Ad5-tet-M2NP, high numbers of M2- and NP-responding "effector memory" CD44posCD62neg T cells were found in the mouse spleens, which revealed a long-term T cell immune memory conferred by the immunization. In all, the challenge experiments showed an extraordinarily wide-ranging efficacy of protection by the Ad5-tet-M2NP vaccine, covering 5 different heterosubtypes of influenza A virus (2 human, 2 avian and 1 swine).
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Antibodies, Viral); 0 (Epitopes); 0 (Nucleoproteins); 0 (Viral Matrix Proteins)


  2 / 18344 MEDLINE  
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PMID:28452706
Autor:Rowan NR; Wang EW; Kanaan A; Sahu N; Williams JV; Phillips CD; Lee SE
Dirección:Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Título:Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.
Fuente:Am J Rhinol Allergy; 31(2):105-108, 2017 Mar 01.
ISSN:1945-8932
País de publicación:United States
Idioma:eng
Resumen:BACKGROUND: Pulmonary colonization with antibiotic-resistant organisms in patients with cystic fibrosis (CF) is often preceded by upper-airway infections. Although there is a well-described relationship between pulmonary respiratory viral infections and overall disease progression of CF, the pathogenicity of respiratory viral infections in the paranasal sinuses of patients with CF remains unknown. With recent advances in respiratory virus detection techniques, this study sought to detect the presence of respiratory viruses in the paranasal sinuses of patients with CF in comparison with healthy controls and to correlate the viral presence with clinical measures of sinonasal disease. METHODS: This prospective individual cohort study compared 24 patients with CF with 14 healthy controls. Basic demographics, clinical measures of disease and respiratory viral screens (commercial multiplex) obtained directly from the paranasal sinuses were compared between the two groups. RESULTS: Respiratory viruses were detected in 33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p = 0.017). Respiratory viruses were only detected during the winter months, and the most commonly identified were influenza A and human rhinovirus strains. There was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients with CF with a positive viral test and those without a positive result. CONCLUSIONS: Respiratory viral detection is more commonly detected in the paranasal sinuses of patients with CF compared with healthy controls. Although respiratory viral presence did not correlate with a worse clinical severity of sinonasal disease, these findings may provide insight into the pathophysiology of CF and open new avenues for potential targeted therapy.
Tipo de publicación:JOURNAL ARTICLE


  3 / 18344 MEDLINE  
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PMID:29458688
Autor:Mitchell SL; Chang YC; Feemster K; Cárdenas AM
Dirección:1​Clinical Microbiology Laboratory, Children's Hospital of Pittsburgh of UPMC and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Título:Implementation of a rapid influenza A/B and RSV direct molecular assay improves emergency department oseltamivir use in paediatric patients.
Fuente:J Med Microbiol; 67(3):358-363, 2018 Mar.
ISSN:1473-5644
País de publicación:England
Idioma:eng
Resumen:PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness. RESULTS: Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours. Compared to the flu season prior to implementation of the Direct Flu/RSV, clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct Flu/RSV-positive patients in comparison to those with a negative test. CONCLUSIONS: Use of Direct Flu/RSV provides results rapidly, which leads to more appropriate use of oseltamivir. The ease of use of this assay and quick TAT allows for prompt decision-making, which is essential for patient care and effective disease control during the influenza season.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Antiviral Agents); 0 (Reagent Kits, Diagnostic); 20O93L6F9H (Oseltamivir)


  4 / 18344 MEDLINE  
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PMID:29324342
Autor:Wang PC; Chiu DC; Jan JT; Huang WI; Tseng YC; Li TT; Cheng TJ; Tsai KC; Fang JM
Dirección:Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
Título:Peramivir conjugates as orally available agents against influenza H275Y mutant.
Fuente:Eur J Med Chem; 145:224-234, 2018 Feb 10.
ISSN:1768-3254
País de publicación:France
Idioma:eng
Resumen:Peramivir is an efficacious neuraminidase (NA) inhibitor for treatment of influenza by intravenous administration. However, the efficacy of peramivir toward the H275Y mutant is appreciably reduced. To address this drawback, conjugation of peramivir with caffeic acid is devised in this study to enhance the binding affinity with neuraminidases. The C2-OH group of peramivir is elaborated to link with caffeate derivatives, giving the desired conjugates 8 and 9 that possess potent NA inhibitory activity against both wild-type and H275Y viruses with the IC values in nanomolar range. The molecular modeling reveals that the caffeate moiety of conjugate 9 prefers to reside in the 295-cavity of H275Y neuraminidase, thus providing additional hydrogen bonds and hydrophobic interactions to compensate the reduced binding affinity of the peramivir moiety due to Glu-276 dislocation in H275Y mutant. In comparison with peramivir, the lipophilicity of conjugates 8 and 9 also increases by incorporation of the caffeate moiety. Thus, conjugates 8 and 9 offer better effect to protect MDCK cells from infection of H275Y virus with low EC value (∼17 nM). Administration of conjugates 8 or 9 by oral gavage is effective in treatment of mice that are infected by lethal dose of wild-type or H275Y influenza viruses. Considering drug metabolism, since the ester linkage in conjugate 8 is susceptible to hydrolysis in plasma, conjugate 9 with robust amide linkage may be a better candidate for development into orally available anti-influenza drug that is also active to mutant viruses.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Antiviral Agents); 0 (Cyclopentanes); 0 (Guanidines); QW7Y7ZR15U (peramivir)


  5 / 18344 MEDLINE  
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PMID:29324866
Autor:More S; Yang X; Zhu Z; Bamunuarachchi G; Guo Y; Huang C; Bailey K; Metcalf JP; Liu L
Dirección:The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Título:Regulation of influenza virus replication by Wnt/ß-catenin signaling.
Fuente:PLoS One; 13(1):e0191010, 2018.
ISSN:1932-6203
País de publicación:United States
Idioma:eng
Resumen:Wnt/ß-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/ß-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/ß-catenin signaling during influenza virus infection. The activation of the Wnt/ß-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/ß-catenin signaling by iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of ß-catenin also reduced viral protein expression and virus production. iCRT14 acts at the early stage of virus replication. Treatment with iCRT14 inhibited the expression of the viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal administration of iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus infection.
Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
Nombre de substancia:0 (RNA, Viral); 0 (Wnt3A Protein)


  6 / 18344 MEDLINE  
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PMID:29173944
Autor:Zhurilo NI; Chudinov MV; Matveev AV; Smirnova OS; Konstantinova ID; Miroshnikov AI; Prutkov AN; Grebenkina LE; Pulkova NV; Shvets VI
Dirección:Lomonosov Institute of Fine Chemical Tehnologies, Moscow Technological University, Vernadskogo Pr. 78, 119454 Moscow, Russia.
Título:Isosteric ribavirin analogues: Synthesis and antiviral activities.
Fuente:Bioorg Med Chem Lett; 28(1):11-14, 2018 01 01.
ISSN:1464-3405
País de publicación:England
Idioma:eng
Resumen:The novel isosteric ribavirin analogues were synthesized by two different ways. Some of them showed significant antiviral action against hepatitis C virus (HCV), herpes simplex (HCV-1) and influenza A virus comparable to that of ribavirin itself. The data obtained confirm the proposed theory of the ribavirin possible antiviral activity mechanism related with bioisosterism.
Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nombre de substancia:0 (Antiviral Agents); 49717AWG6K (Ribavirin)


  7 / 18344 MEDLINE  
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PMID:29365305
Autor:Kwong JC; Schwartz KL; Campitelli MA; Chung H; Crowcroft NS; Karnauchow T; Katz K; Ko DT; McGeer AJ; McNally D; Richardson DC; Rosella LC; Simor A; Smieja M; Zahariadis G; Gubbay JB
Dirección:From the Institute for Clinical Evaluative Sciences (J.C.K., K.L.S., M.A.C., H.C., D.T.K., L.C.R.), Public Health Ontario (J.C.K., K.L.S., N.S.C., L.C.R., J.B.G.), Dalla Lana School of Public Health (J.C.K., K.L.S., N.S.C., A.J.M., L.C.R.), and the Departments of Family and Community Medicine (J.C.K
Título:Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
Fuente:N Engl J Med; 378(4):345-353, 2018 01 25.
ISSN:1533-4406
País de publicación:United States
Idioma:eng
Resumen:BACKGROUND: Acute myocardial infarction can be triggered by acute respiratory infections. Previous studies have suggested an association between influenza and acute myocardial infarction, but those studies used nonspecific measures of influenza infection or study designs that were susceptible to bias. We evaluated the association between laboratory-confirmed influenza infection and acute myocardial infarction. METHODS: We used the self-controlled case-series design to evaluate the association between laboratory-confirmed influenza infection and hospitalization for acute myocardial infarction. We used various high-specificity laboratory methods to confirm influenza infection in respiratory specimens, and we ascertained hospitalization for acute myocardial infarction from administrative data. We defined the "risk interval" as the first 7 days after respiratory specimen collection and the "control interval" as 1 year before and 1 year after the risk interval. RESULTS: We identified 364 hospitalizations for acute myocardial infarction that occurred within 1 year before and 1 year after a positive test result for influenza. Of these, 20 (20.0 admissions per week) occurred during the risk interval and 344 (3.3 admissions per week) occurred during the control interval. The incidence ratio of an admission for acute myocardial infarction during the risk interval as compared with the control interval was 6.05 (95% confidence interval [CI], 3.86 to 9.50). No increased incidence was observed after day 7. Incidence ratios for acute myocardial infarction within 7 days after detection of influenza B, influenza A, respiratory syncytial virus, and other viruses were 10.11 (95% CI, 4.37 to 23.38), 5.17 (95% CI, 3.02 to 8.84), 3.51 (95% CI, 1.11 to 11.12), and 2.77 (95% CI, 1.23 to 6.24), respectively. CONCLUSIONS: We found a significant association between respiratory infections, especially influenza, and acute myocardial infarction. (Funded by the Canadian Institutes of Health Research and others.).
Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T


  8 / 18344 MEDLINE  
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PMID:29323846
Autor:Nosik NN; Nosik DN; Chizhov AI
Título:A comparative analysis of virucidal efficiency of biocide agents.
Fuente:Vopr Virusol; 62(1):41-5, 2017.
ISSN:0507-4088
País de publicación:Russia (Federation)
Idioma:eng
Resumen:The main groups of biocide agents used for inactivation of bacteria and viruses were studied for their virucidal activity against enveloped (HIV, viral hepatitis C, influenza virus A) and non-enveloped viruses (poliovirus, adenovirus). Their efficiency was analyzed. Quarterly ammonium compounds (QAC) themselves are not able to properly inactivate non-enveloped viruses. However, they can be successfully applied in combination with other biocides (guanidines, aldehydes). Effective composition of QAC with amines and guanidines provided inactivation of viruses (4.0 lgTCID50) in concentrations of 0.166-0.280% for non-enveloped viruses and 0.080-00.185% for enveloped viruses. The combination of QAC with aldehydes is especially effective (0.04-0.64% for non-enveloped viruses). The virucidal efficiency does not directly depend on the QAC concentration in the chemical disinfectants.
Tipo de publicación:COMPARATIVE STUDY; JOURNAL ARTICLE
Nombre de substancia:0 (Aldehydes); 0 (Disinfectants); 0 (Guanidines); 0 (Quaternary Ammonium Compounds)


  9 / 18344 MEDLINE  
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PMID:29323841
Autor:Grebennikova TV; Syroeshkin AV; Chichaeva MA; Esper SA; Lvov DK
Título:Influenza A virus in the Western Arctic.
Fuente:Vopr Virusol; 62(1):11-7, 2017.
ISSN:0507-4088
País de publicación:Russia (Federation)
Idioma:eng
Resumen:Small bays of bird bazaars of the Arctic Kola Peninsula (Barents Sea) have been studied. RNA of influenza A virus was found in the surface microlayer (SM) and aerosol samples from the bays located beneath bird colonies. The nucleotide sequencing of the PCR fragments from the SM and the sea aerosol showed their identity for each bay. Virus transfer mechanism along the "surface microlayer - sea aerosol" path has been proposed. The kinetic scheme of the virus-host-environment interaction, which allows the dependence of the viral population size on the temperature to be simulated, has been developed.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Aerosols)


  10 / 18344 MEDLINE  
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PMID:29324781
Autor:Tewawong N; Marathe BM; Poovorawan Y; Vongpunsawad S; Webby RJ; Govorkova EA
Dirección:Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Título:Neuraminidase inhibitor susceptibility and neuraminidase enzyme kinetics of human influenza A and B viruses circulating in Thailand in 2010-2015.
Fuente:PLoS One; 13(1):e0190877, 2018.
ISSN:1932-6203
País de publicación:United States
Idioma:eng
Resumen:Amino acid substitutions within or near the active site of the viral neuraminidase (NA) may affect influenza virus fitness. In influenza A(H3N2) and B viruses circulating in Thailand between 2010 and 2015, we identified several NA substitutions that were previously reported to be associated with reduced inhibition by NA inhibitors (NAIs). To study the effect of these substitutions on the enzymatic properties of NA and on virus characteristics, we generated recombinant influenza viruses possessing either a wild type (WT) NA or an NA with a single I222V, S331G, or S331R substitution [in influenza A(H3N2) viruses] or a single D342S, A395T, A395V, or A395D NA substitution (in influenza B viruses). We generated recombinant (7:1) influenza A and B viruses on the genetic background of A/Puerto Rico/8/1934 (A/PR/8, H1N1) or B/Yamanashi/166/1998 (B/YAM) viruses, respectively. In contrast to the expected phenotypes, all the recombinant influenza A(H3N2) and B viruses carrying putative NA resistance substitutions were susceptible to NAIs. The Km and Vmax for the NAs of A/PR8-S331G and A/PR8-S331R viruses were higher than for the NA of WT virus, and the corresponding values for the B/YAM-D342S virus were lower than for the NA of WT virus. Although there was initial variation in the kinetics of influenza A and B viruses' replication in MDCK cells, their titers were comparable to each other and to WT viruses at later time points. All introduced substitutions were stable except for B/YAM-D342S and B/YAM-A395V which reverted to WT sequences after three passages. Our data suggest that inferring susceptibility to NAIs based on sequence information alone should be cautioned. The impact of NA substitution on NAI resistance, viral growth, and enzymatic properties is viral context dependent and should be empirically determined.
Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
Nombre de substancia:0 (Antiviral Agents); 0 (Enzyme Inhibitors); 0 (Viral Proteins); EC 3.2.1.18 (Neuraminidase)



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