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Pesquisa : B01.050.150.900.649.313.992.635.075.500 [Categoria DeCS]
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[PMID]:28794038
[Au] Autor:van Erp EA; van Kasteren PB; Guichelaar T; Ahout IML; de Haan CAM; Luytjes W; Ferwerda G; Wicht O
[Ad] Endereço:Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands liz.van.erp@rivm.nl.
[Ti] Título: Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated (FI)-RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs. It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960s vaccine trials, is still unclear. We hypothesized that antibodies present under either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Antivirais/imunologia
Receptores de IgG/metabolismo
Infecções por Vírus Respiratório Sincicial/imunologia
Vacinas contra Vírus Sincicial Respiratório/administração & dosagem
Vírus Sinciciais Respiratórios/imunologia
Índice de Gravidade de Doença
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Anticorpos Facilitadores
Estudos de Casos e Controles
Cercopithecus aethiops
Feminino
Seres Humanos
Lactente
Pulmão/imunologia
Pulmão/patologia
Pulmão/virologia
Monócitos/imunologia
Monócitos/patologia
Monócitos/virologia
Testes de Neutralização
Ratos
Receptores de IgG/imunologia
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Sigmodontinae
Vacinação
Células Vero
Proteínas do Envelope Viral/imunologia
Proteínas Virais de Fusão/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Receptors, IgG); 0 (Respiratory Syncytial Virus Vaccines); 0 (Viral Envelope Proteins); 0 (Viral Fusion Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE


  2 / 995 MEDLINE  
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[PMID]:28792853
[Au] Autor:Kosoy M; Reynolds P; Bai Y; Sheff K; Enscore RE; Montenieri J; Ettestad P; Gage K
[Ad] Endereço:1 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention , Fort Collins, Colorado.
[Ti] Título:Small-Scale Die-Offs in Woodrats Support Long-Term Maintenance of Plague in the U.S. Southwest.
[So] Source:Vector Borne Zoonotic Dis;17(9):635-644, 2017 Sep.
[Is] ISSN:1557-7759
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our longitudinal study of plague dynamics was conducted in north-central New Mexico to identify which species in the community were infected with plague, to determine the spatial and temporal patterns of the dynamics of plague epizootics, and to describe the dynamics of Yersinia pestis infection within individual hosts. A total of 3156 fleas collected from 535 small mammals of 8 species were tested for Y. pestis DNA. Nine fleas collected from six southern plains woodrats (Neotoma micropus) and from one rock squirrel (Otospermophilus variegatus) were positive for the pla gene of Y. pestis. None of 127 fleas collected from 17 woodrat nests was positive. Hemagglutinating antibodies to the Y. pestis-specific F1 antigen were detected in 11 rodents of 6 species. All parts of the investigated area were subjected to local disappearance of woodrats. Despite the active die-offs, some woodrats always were present within the relatively limited endemic territory and apparently were never exposed to plague. Our observations suggest that small-scale die-offs in woodrats can support maintenance of plague in the active U.S. Southwestern focus.
[Mh] Termos MeSH primário: Peste/veterinária
Sigmodontinae
Sifonápteros/microbiologia
Yersinia pestis/isolamento & purificação
[Mh] Termos MeSH secundário: Animais
Doenças Endêmicas
Peste/epidemiologia
Peste/microbiologia
Dinâmica Populacional
Sciuridae
Sudoeste dos Estados Unidos/epidemiologia
Zoonoses
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1089/vbz.2017.2142


  3 / 995 MEDLINE  
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[PMID]:28727788
[Au] Autor:Malcher SM; Pieczarka JC; Geise L; Rossi RV; Pereira AL; O'Brien PCM; Asfora PH; Fonsêca da Silva V; Sampaio MI; Ferguson-Smith MA; Nagamachi CY
[Ad] Endereço:Centro de Estudos Avançados da Biodiversidade, Laboratório de Citogenética, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brasil.
[Ti] Título:Oecomys catherinae (Sigmodontinae, Cricetidae): Evidence for chromosomal speciation?
[So] Source:PLoS One;12(7):e0181434, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Among the Oryzomyini (Sigmodontinae), Oecomys is the most speciose, with 17 species. This genus presents high karyotypic diversity (2n = 54 to 2n = 86) and many taxonomic issues at the species level because of the presence of cryptic species and the overlap of morphological characters. For these reasons the real number of species of Oecomys may be underestimated. With the aim of verifying if the taxon Oecomys catherinae is composed of more than one species, we made comparative studies on two populations from two regions of Brazil, one from the Amazon and another from the Atlantic Forest using both classical cytogenetics (G- and C-banding) and comparative genomic mapping with whole chromosome probes of Hylaeamys megacephalus (HME), molecular data (cytochrome b mitochondrial DNA) and morphology. Our results confirm that Oecomys catherinae occurs in the southeast Amazon, and reveal a new karyotype for the species (2n = 62, FNa = 62). The comparative genomic analysis with HME probes identified chromosomal homeologies between both populations and rearrangements that are responsible for the different karyotypes. We compared our results in Sigmodontinae genera with other studies that also used HME probes. These chromosomal differences together with the absence of consistent differentiation between the two populations on morphological and molecular analyses suggest that these populations may represent cryptic species.
[Mh] Termos MeSH primário: Arvicolinae/genética
Sigmodontinae/genética
[Mh] Termos MeSH secundário: Animais
Arvicolinae/anatomia & histologia
Brasil
Coloração Cromossômica
Cromossomos de Mamíferos
Feminino
Hibridização in Situ Fluorescente
Cariótipo
Cariotipagem
Masculino
Filogenia
Sigmodontinae/anatomia & histologia
Especificidade da Espécie
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[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:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181434


  4 / 995 MEDLINE  
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[PMID]:28714801
[Au] Autor:Milazzo ML; Cajimat MNB; Richter MH; Bradley RD; Fulhorst CF
[Ad] Endereço:1 Department of Pathology, University of Texas Medical Branch , Galveston, Texas.
[Ti] Título:Muleshoe Virus and Other Hantaviruses Associated with Neotomine or Sigmodontine Rodents in Texas.
[So] Source:Vector Borne Zoonotic Dis;17(10):720-729, 2017 Oct.
[Is] ISSN:1557-7759
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The broad objective of this study was to increase our knowledge of Muleshoe virus and other hantaviruses associated with cricetid rodents in Texas. Anti-hantavirus antibody was found in 38 (3.2%) of 1171 neotomine rodents and 6 (1.8%) of 332 sigmodontine rodents from 10 Texas counties; hantaviral RNA was detected in 23 (71.9%) of 32 antibody-positive rodents. Analyses of nucleocapsid protein gene sequences indicated Muleshoe virus infection in four hispid cotton rats (Sigmodon hispidus) from northern Texas; Bayou virus, three Texas marsh oryzomys (Oryzomys texensis) from the Gulf Coast; Limestone Canyon virus, five brush mice (Peromyscus boylii) from western Texas; and Sin Nombre virus-five Texas mice (P. attwateri), one Lacey's white-ankled deer mouse (P. laceianus), four white-footed mice (P. leucopus), and one fulvous harvest mouse (Reithrodontomys fulvescens) from northern, central, or southern Texas. The results of this study together with the results of a previous study revealed that Muleshoe virus, perhaps in association with S. hispidus, is distributed across northern Texas. Finally, the results of Bayesian analyses of glycoprotein precursor (GPC) gene sequences and pairwise comparisons of complete GPC (amino acid) sequences strengthened support for the notion that Muleshoe virus is distinct from Black Creek Canal virus, Bayou virus, and all other species included in the Bunyaviridae, genus Hantavirus.
[Mh] Termos MeSH primário: Infecções por Hantavirus/veterinária
Hantavirus/isolamento & purificação
Doenças dos Roedores/virologia
Sigmodontinae/virologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Regulação Viral da Expressão Gênica
Hantavirus/genética
Infecções por Hantavirus/epidemiologia
Infecções por Hantavirus/virologia
Proteínas do Nucleocapsídeo/genética
Proteínas do Nucleocapsídeo/metabolismo
Filogenia
RNA Viral/genética
Doenças dos Roedores/sangue
Doenças dos Roedores/epidemiologia
Texas/epidemiologia
Zoonoses
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Nucleocapsid Proteins); 0 (RNA, Viral)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1089/vbz.2017.2108


  5 / 995 MEDLINE  
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[PMID]:28605636
[Au] Autor:Russell CJ; Jones BG; Sealy RE; Surman SL; Mason JN; Hayden RT; Tripp RA; Takimoto T; Hurwitz JL
[Ad] Endereço:Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
[Ti] Título:A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge.
[So] Source:Virology;509:60-66, 2017 Sep.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human metapneumovirus (hMPV) infections pose a serious health risk to young children, particularly in cases of premature birth. No licensed vaccine exists and there is no standard treatment for hMPV infections apart from supportive hospital care. We describe the production of a Sendai virus (SeV) recombinant that carries a gene for a truncated hMPV fusion (F) protein (SeV-MPV-Ft). The vaccine induces binding and neutralizing antibody responses toward hMPV and protection against challenge with hMPV in a cotton rat system. Results encourage advanced development of SeV-MPV-Ft to prevent the morbidity and mortality caused by hMPV infections in young children.
[Mh] Termos MeSH primário: Antígenos Virais/imunologia
Portadores de Fármacos
Metapneumovirus/imunologia
Infecções por Paramyxoviridae/prevenção & controle
Vírus Sendai/genética
Proteínas Virais de Fusão/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Antígenos Virais/genética
Modelos Animais de Doenças
Metapneumovirus/genética
Infecções por Paramyxoviridae/imunologia
Sigmodontinae
Resultado do Tratamento
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Proteínas Virais de Fusão/genética
Vacinas Virais/administração & dosagem
Vacinas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Drug Carriers); 0 (Vaccines, Synthetic); 0 (Viral Fusion Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170812
[Lr] Data última revisão:
170812
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE


  6 / 995 MEDLINE  
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[PMID]:28443978
[Au] Autor:Vasconcelos DIB; Mota EM; Pelajo-Machado M
[Ad] Endereço:Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil.
[Ti] Título:Characterisation of the vascular pathology in Sigmodon hispidus (Rodentia: Cricetidae) following experimental infection with Angiostrongylus costaricensis (Nematoda: Metastrongylidae).
[So] Source:Mem Inst Oswaldo Cruz;112(5):328-338, 2017 May.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Angiostrongylus costaricensis is a nematode that causes human abdominal angiostrongyliasis, a disease found mainly in Latin American countries and particularly in Brazil and Costa Rica. Its life cycle involves exploitation of both invertebrate and vertebrate hosts. Its natural reservoir is a vertebrate host, the cotton rat Sigmodon hispidus. The adult worms live in the ileo-colic branches of the upper mesenteric artery of S. hispidus, causing periarteritis. However, there is a lack of data on the development of vasculitis in the course of infection. OBJECTIVE: To describe the histopathology of vascular lesions in S. hispidus following infection with A. costaricensis. METHODS: Twenty-one S. hispidus were euthanised at 30, 50, 90 and 114 days post-infection (dpi), and guts and mesentery (including the cecal artery) were collected. Tissues were fixed in Carson's Millonig formalin, histologically processed for paraffin embedding, sectioned with a rotary microtome, and stained with hematoxylin-eosin, resorcin-fuchsin, Perls, Sirius Red (pH = 10.2), Congo Red, and Azan trichrome for brightfield microscopy analysis. FINDINGS: At 30 and 50 dpi, live eggs and larvae were present inside the vasa vasorum of the cecal artery, leading to eosinophil infiltrates throughout the vessel adventitia and promoting centripetal vasculitis with disruption of the elastic layers. Disease severity increased at 90 and 114 dpi, when many worms had died and the intensity of the vascular lesions was greatest, with intimal alterations, thrombus formation, iron accumulation, and atherosclerosis. CONCLUSION: In addition to abdominal angiostrongyliasis, our data suggest that this model could be very useful for autoimune vasculitis and atherosclerosis studies.
[Mh] Termos MeSH primário: Angiostrongylus
Arterite/parasitologia
Aterosclerose/parasitologia
Infecções por Strongylida/complicações
[Mh] Termos MeSH secundário: Animais
Arterite/patologia
Aterosclerose/patologia
Modelos Animais de Doenças
Roedores
Sigmodontinae
Infecções por Strongylida/patologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


  7 / 995 MEDLINE  
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[PMID]:28419512
[Au] Autor:Suzuki Y
[Ad] Endereço:Graduate School of Natural Sciences, Nagoya City University, 1 Yamanohata, Mizuho-cho, Mizuho-ku, Nagoya-shi, Aichi-ken 467-8501, Japan.
[Ti] Título:Predicting receptor functionality of signaling lymphocyte activation molecule for measles virus hemagglutinin by docking simulation.
[So] Source:Microbiol Immunol;61(5):185-189, 2017 May.
[Is] ISSN:1348-0421
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Predicting susceptibility of various species to a virus assists assessment of risk of interspecies transmission. Evaluation of receptor functionality may be useful in screening for susceptibility. In this study, docking simulation was conducted for measles virus hemagglutinin (MV-H) and immunoglobulin-like variable domain of signaling lymphocyte activation molecule (SLAM-V). It was observed that the docking scores for MV-H and SLAM-V correlated with the activity of SLAM as an MV receptor. These results suggest that the receptor functionality may be predicted from the docking scores of virion surface proteins and cellular receptor molecules.
[Mh] Termos MeSH primário: Hemaglutininas Virais/imunologia
Ativação Linfocitária/imunologia
Vírus do Sarampo/imunologia
Sarampo/transmissão
Simulação de Acoplamento Molecular
Receptores Virais/metabolismo
Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo
[Mh] Termos MeSH secundário: Animais
Gatos
Bovinos
Cães
Seres Humanos
Sarampo/veterinária
Sarampo/virologia
Camundongos
Sigmodontinae/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hemagglutinins, Viral); 0 (Receptors, Virus); 0 (Signaling Lymphocytic Activation Molecule Family)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1111/1348-0421.12484


  8 / 995 MEDLINE  
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[PMID]:28375626
[Au] Autor:Huo L; Liu J; Dearing MD; Szklarz GD; Halpert JR; Wilderman PR
[Ad] Endereço:Department of Pharmaceutical Science, University of Connecticut School of Pharmacy , Storrs, Connecticut 06269-3092, United States.
[Ti] Título:Rational Re-Engineering of the O-Dealkylation of 7-Alkoxycoumarin Derivatives by Cytochromes P450 2B from the Desert Woodrat Neotoma lepida.
[So] Source:Biochemistry;56(16):2238-2246, 2017 Apr 25.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:On the basis of recent functional and structural characterization of cytochromes P450 2B from the desert woodrat (Neotoma lepida), the 7-alkoxycoumarin and 7-alkoxy-4-(trifluoromethyl)coumarin O-dealkylation profiles of CYP2B35 and CYP2B37 were re-engineered. Point mutants interchanging residues at seven positions in the enzyme active sites were created and purified from an Escherichia coli expression system. In screens for O-dealkylation activity, wild-type CYP2B35 metabolized long-chain 7-alkoxycoumarins but not 7-alkoxy-4-(trifluoromethyl)coumarins or short-chain 7-alkoxycoumarins. Wild-type CYP2B37 metabolized short-chain substrates from both series of compounds. CYP2B35 A367V showed maximal activity with 7-butoxycoumarin as opposed to 7-heptoxycoumarin in the parental enzyme, and CYP2B35 A363I/A367V produced an activity profile like that generated by CYP2B37. CYP2B35 A363I/A367V/I477F showed 7-ethoxycoumarin and 7-ethoxy-4-(trifluoromethyl)coumarin O-dealkylation rates similar to those of CYP2B37 and higher than those of the double mutant. A CYP2B35 septuple mutant retained a CYP2B37-like activity profile. In contrast, the CYP2B37 septuple mutant produced very low rates of O-dealkylation of all substrates. As mutating residue 108 in either enzyme was detrimental, this change was removed from both septuple mutants. Remarkably, the CYP2B35 sextuple mutant produced an activity profile that was a hybrid of that of CYP2B35 and CYP2B37, whereas the CYP2B37 sextuple mutant had almost no O-dealkylation activity. Docking of 7-substituted coumarin derivatives into a model of the CYP2B35 sextuple mutant based on a previous crystal structure of the 4-(4-chlorophenyl)imidazole wild-type complex revealed how the mutant can exhibit activities of both CYP2B35 and CYP2B37.
[Mh] Termos MeSH primário: Cumarínicos/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
[Mh] Termos MeSH secundário: Alquilação
Animais
Sistema Enzimático do Citocromo P-450/química
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/isolamento & purificação
Mutagênese Sítio-Dirigida
Sigmodontinae
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coumarins); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00097


  9 / 995 MEDLINE  
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[PMID]:28298602
[Au] Autor:Wang D; Phan S; DiStefano DJ; Citron MP; Callahan CL; Indrawati L; Dubey SA; Heidecker GJ; Govindarajan D; Liang X; He B; Espeseth AS
[Ad] Endereço:Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA dai_wang@merck.com.
[Ti] Título:A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.
[So] Source:J Virol;91(11), 2017 Jun 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 10 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 10 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.
[Mh] Termos MeSH primário: Vírus da Parainfluenza 5/genética
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sincicial Respiratório Humano/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Anticorpos Antivirais/imunologia
Cercopithecus aethiops
Modelos Animais de Doenças
Vetores Genéticos
Pulmão/virologia
Ratos
Infecções por Vírus Respiratório Sincicial/imunologia
Infecções por Vírus Respiratório Sincicial/virologia
Vacinas contra Vírus Sincicial Respiratório/administração & dosagem
Vacinas contra Vírus Sincicial Respiratório/genética
Vírus Sincicial Respiratório Humano/genética
Sigmodontinae
Vacinação
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/imunologia
Células Vero
Proteínas do Envelope Viral/genética
Proteínas Virais de Fusão/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (F protein, human respiratory syncytial virus); 0 (Respiratory Syncytial Virus Vaccines); 0 (Vaccines, Synthetic); 0 (Viral Envelope Proteins); 0 (Viral Fusion Proteins); 0 (attachment protein G)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171112
[Lr] Data última revisão:
171112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE


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[PMID]:28255942
[Au] Autor:Kohl KD; Dearing MD
[Ad] Endereço:Department of Biological Sciences, Vanderbilt University, 465 21st Ave South, Nashville, TN, 37235, USA. kevin.d.kohl@gmail.com.
[Ti] Título:Intestinal Lymphatic Transport: an Overlooked Pathway for Understanding Absorption of Plant Secondary Compounds in Vertebrate Herbivores.
[So] Source:J Chem Ecol;43(3):290-294, 2017 Mar.
[Is] ISSN:1573-1561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herbivores employ numerous strategies to reduce their exposure to toxic plant secondary chemicals (PSCs). However, the physiological mechanisms of PSC absorption have not been extensively explored. In particular, the absorption of PSCs via intestinal lymphatic absorption has been largely overlooked in herbivores, even though this pathway is well recognized for pharmaceutical uptake. Here, we investigated for the first time whether PSCs might be absorbed by lymphatic transport. We fed woodrats (Neotoma albigula) diets with increasing concentrations of terpene-rich juniper (Juniperus monosperma) either with or without a compound that blocks intestinal lymphatic absorption (Pluronic L-81). Woodrats consuming diets that contained the intestinal lymphatic absorption blocker exhibited increased food intakes and maintained higher body masses on juniper diets. Our study represents the first demonstration that PSCs may be absorbed by intestinal lymphatic absorption. This absorption pathway has numerous implications for the metabolism and distribution of PSCs in the systemic circulation, given that compounds absorbed via lymphatic transport bypass first-pass hepatic metabolism. The area of lymphatic transport of PSCs represents an understudied physiological pathway in plant-herbivore interactions.
[Mh] Termos MeSH primário: Herbivoria
Absorção Intestinal
Juniperus/metabolismo
Sistema Linfático/metabolismo
Sigmodontinae/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.1007/s10886-017-0828-x



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