Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio
Ano de defesa: | 2013 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Medicina/Pediatria e Sa?de da Crian?a
|
Departamento: |
Faculdade de Medicina
|
País: |
BR
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.pucrs.br/tede2/handle/tede/1411 |
Resumo: | Background : Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has shown to impair the growth of respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication and different aspects of RSV disease in an in vivo murine model. Methods : BALB/C mice were inoculated with 107 PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until day 4 post-RSV inoculation. Bronchoalveolar lavage, whole lung specimens and serum samples were harvested on day 5 post inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups. Results : On day 5 post-inoculation RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1 to 5 post-inoculation which was comparable to infected untreated mice (p>0.05), but higher than uninfected controls. Conclusions : Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk of RSV infection needs to be further explored. |
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Pitrez, Paulo M?rcio CondessaCPF:62579797068http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4763140Y0CPF:00872550060http://lattes.cnpq.br/3486514016305167Gualdi, Lucien Peroni2015-04-14T13:33:03Z2013-04-022013-03-12GUALDI, Lucien Peroni. Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio. 2013. 82 f. Tese (Doutorado em Pediatria e Sa?de da Crian?a) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2013.http://tede2.pucrs.br/tede2/handle/tede/1411Background : Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has shown to impair the growth of respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication and different aspects of RSV disease in an in vivo murine model. Methods : BALB/C mice were inoculated with 107 PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until day 4 post-RSV inoculation. Bronchoalveolar lavage, whole lung specimens and serum samples were harvested on day 5 post inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups. Results : On day 5 post-inoculation RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1 to 5 post-inoculation which was comparable to infected untreated mice (p>0.05), but higher than uninfected controls. Conclusions : Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk of RSV infection needs to be further explored.Introdu??o : Lactoferrina (LF) ? uma glicoprote?na presente no leite humano que possui efeitos antimicrobianos bem estabelecidos. Estudos in vitro, demonstram que a LF ? capaz de desestabilizar o crescimento do v?rus sincicial respirat?rio (VSR). Neste estudo procuramos avaliar o efeito da LF bovina (bLF) na replica??o do VSR, al?m de avaliar diferentes aspectos da doen?a causada por VSR in vivo em um modelo murino. M?todos : camundongos BALB/c foram inoculados com 107 UFP de VSR A2 ou EMEM 10%. bLF ou placebo foram administrados uma ou duas vezes ao dia por gavagem ou inje??o intraperitoneal (IP) em doses entre 2 e 10 mg/animal/dia, dois dias antes a 4 dias ap?s a inocula??o com VSR. Amostras de lavado broncoalveolar, pulm?es e sangue foram coletadas no dia 5 ap?s a inocula??o com o objetivo de avaliar a carga viral, inflama??o pulmonar e concentra??o de citocinas. Peso, obstru??o de via a?rea e gravidade da doen?a foram avaliados diariamente em todos os grupos do estudo. Resultados : No dia 5 ap?s a inocula??o do v?rus, a carga viral, inflama??o pulmonar e concentra??o de citocinas relacionadas a imunidade inata, respostas Th1, Th2 e Th17 no soro n?o demonstraram diferen?a, quando comparamos os animais infectados com RSV tratados com bLF e os animais infectados com RSV tratados com placebo, independente da dose ou via de administra??o (p>0.05). Al?m disso, a perda de peso, obstru??o de via a?rea e gravidade da doen?a foi similar entre os grupos tratados com bLF nos dias 1 a 5 ap?s a inocula??o do v?rus. Estes valores s?o compar?veis com os valores obtidos no grupo placebo, por?m significativamente aumentados quando comparados aos animais n?o-infectados. Conclus?o : a administra??o de bLF por via oral ou inje??o IP, em diferentes doses, n?o demonstrou atividade antiviral ou efeitos significativos na severidade da doen?a em um modelo murino de VSR. Se essas observa??es podem ser extrapoladas para crian?as em risco de desenvolver infec??es por VSR, essas quest?es necessitam ser melhor exploradas.Made available in DSpace on 2015-04-14T13:33:03Z (GMT). No. of bitstreams: 1 446716.pdf: 2485126 bytes, checksum: d0edbbefdafd57b69ebba83d7dfd395f (MD5) Previous issue date: 2013-03-12application/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/8732/446716.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Medicina/Pediatria e Sa?de da Crian?aPUCRSBRFaculdade de MedicinaMEDICINAPEDIATRIABRONQUIOLITELACTENTEIMUNOLOGIAPNEUMOLOGIACNPQ::CIENCIAS DA SAUDE::MEDICINAEfeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rioinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis3098206005268432148500600-8624664729441623247info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAIL446716.pdf.jpg446716.pdf.jpgimage/jpeg2898http://tede2.pucrs.br/tede2/bitstream/tede/1411/3/446716.pdf.jpg61331000e8f69772f8d35e36585d2459MD53TEXT446716.pdf.txt446716.pdf.txttext/plain110168http://tede2.pucrs.br/tede2/bitstream/tede/1411/2/446716.pdf.txt5c16d447f1df2ee31d4096a94fd1e63dMD52ORIGINAL446716.pdfapplication/pdf2485126http://tede2.pucrs.br/tede2/bitstream/tede/1411/1/446716.pdfd0edbbefdafd57b69ebba83d7dfd395fMD51tede/14112015-04-17 17:09:45.397oai:tede2.pucrs.br:tede/1411Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2015-04-17T20:09:45Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
title |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
spellingShingle |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio Gualdi, Lucien Peroni MEDICINA PEDIATRIA BRONQUIOLITE LACTENTE IMUNOLOGIA PNEUMOLOGIA CNPQ::CIENCIAS DA SAUDE::MEDICINA |
title_short |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
title_full |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
title_fullStr |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
title_full_unstemmed |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
title_sort |
Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio |
author |
Gualdi, Lucien Peroni |
author_facet |
Gualdi, Lucien Peroni |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Pitrez, Paulo M?rcio Condessa |
dc.contributor.advisor1ID.fl_str_mv |
CPF:62579797068 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4763140Y0 |
dc.contributor.authorID.fl_str_mv |
CPF:00872550060 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3486514016305167 |
dc.contributor.author.fl_str_mv |
Gualdi, Lucien Peroni |
contributor_str_mv |
Pitrez, Paulo M?rcio Condessa |
dc.subject.por.fl_str_mv |
MEDICINA PEDIATRIA BRONQUIOLITE LACTENTE IMUNOLOGIA PNEUMOLOGIA |
topic |
MEDICINA PEDIATRIA BRONQUIOLITE LACTENTE IMUNOLOGIA PNEUMOLOGIA CNPQ::CIENCIAS DA SAUDE::MEDICINA |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::MEDICINA |
description |
Background : Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has shown to impair the growth of respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication and different aspects of RSV disease in an in vivo murine model. Methods : BALB/C mice were inoculated with 107 PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until day 4 post-RSV inoculation. Bronchoalveolar lavage, whole lung specimens and serum samples were harvested on day 5 post inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups. Results : On day 5 post-inoculation RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1 to 5 post-inoculation which was comparable to infected untreated mice (p>0.05), but higher than uninfected controls. Conclusions : Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk of RSV infection needs to be further explored. |
publishDate |
2013 |
dc.date.available.fl_str_mv |
2013-04-02 |
dc.date.issued.fl_str_mv |
2013-03-12 |
dc.date.accessioned.fl_str_mv |
2015-04-14T13:33:03Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
GUALDI, Lucien Peroni. Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio. 2013. 82 f. Tese (Doutorado em Pediatria e Sa?de da Crian?a) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2013. |
dc.identifier.uri.fl_str_mv |
http://tede2.pucrs.br/tede2/handle/tede/1411 |
identifier_str_mv |
GUALDI, Lucien Peroni. Efeito de lactoferrina bovina na replica??o viral e doen?a cl?nica em modelo murino de v?rus sincicial respirat?rio. 2013. 82 f. Tese (Doutorado em Pediatria e Sa?de da Crian?a) - Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Porto Alegre, 2013. |
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http://tede2.pucrs.br/tede2/handle/tede/1411 |
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