Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
J Gen Virol ; 99(10): 1367-1380, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30102144

RESUMO

Thrombin has been demonstrated to be involved in several viral diseases including human metapneumovirus (hMPV) infections. We previously showed that immediate administration of thrombin inhibitor argatroban post-infection protected mice against hMPV disease. This current work aims at determining whether warfarin and heparin, two other anticoagulants inhibiting thrombin formation and activities, may also be used for treatment against hMPV in vivo. We found that immediate injections of argatroban, warfarin or heparin after virus challenge protected mice against hMPV infection, as evidenced by decreased or no mortality, less weight loss, reduced viral load and attenuated inflammation. However, delayed treatments starting 1 day post-infection with argatroban or warfarin almost did not impact the survival whereas delayed treatment with heparin induced an increased mortality during infection. Moreover, these treatments also did not reduce weight loss, viral replication and inflammation. In agreement with these results, thrombin generation was decreased upon immediate anticoagulant treatments but was unaltered upon delayed treatments. Thus, thrombin generation occurs at the onset of hMPV infection and thrombin inhibition may be only useful for the treatment of this disease when initiated in the early stage. In this case, heparin is not recommended because of its reduced efficacy on mortality in infected mice whereas argatroban and warfarin appear as safe and effective drugs for the treatment of hMPV disease. The antiviral and anti-inflammatory effects of argatroban occur via thrombin-dependent pathways whereas the mechanisms by which warfarin exerts its beneficial effects against hMPV infection were not elucidated and need to be further studied.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Infecções por Paramyxoviridae/tratamento farmacológico , Varfarina/administração & dosagem , Animais , Arginina/análogos & derivados , Modelos Animais de Doenças , Metapneumovirus/efeitos dos fármacos , Metapneumovirus/isolamento & purificação , Camundongos , Infecções por Paramyxoviridae/patologia , Infecções por Paramyxoviridae/virologia , Ácidos Pipecólicos/administração & dosagem , Sulfonamidas , Análise de Sobrevida , Resultado do Tratamento , Carga Viral , Replicação Viral/efeitos dos fármacos
2.
FEMS Immunol Med Microbiol ; 64(2): 255-64, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22066700

RESUMO

Iron constitutes a critical nutrient source for bacterial growth, so iron overload is a risk factor for bacterial infections. This study aimed at investigating the role of iron overload in modulating bacterial endotoxin-induced lung inflammation. Weaning male Wistar rats were intraperitoneally injected with saline or iron sucrose [15 mg kg(-1) body weight (bw), 3 times per week, 4 weeks]. They were then intratracheally injected with Pseudomonas aeruginosa lipopolysaccharide (LPS) (5 µg kg(-1) bw) or saline. Inflammatory indices were evaluated 4 or 18 h post-LPS/saline injection. At 4 h, LPS-treated groups revealed significant increases in the majority of inflammatory parameters (LPS-binding protein (LBP), immune cell recruitment, inflammatory cytokine synthesis, myeloperoxidase activity, and alteration of alveolar-capillary permeability), as compared with control groups. At 18 h, these parameters reduced strongly with the exception for LBP content and interleukin (IL)-10. In parallel, iron acted as a modulator of immune cell recruitment; LBP, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant 3, and IL-10 synthesis; and alveolar-capillary permeability. Therefore, P. aeruginosa LPS may only act as an acute lung inflammatory molecule, and iron overload may modulate lung inflammation by enhancing different inflammatory parameters. Thus, therapy for iron overload may be a novel and efficacious approach for the prevention and treatment of bacterial lung inflammations.


Assuntos
Sobrecarga de Ferro/metabolismo , Ferro/farmacologia , Lipopolissacarídeos/farmacologia , Pneumonia/metabolismo , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar/química , Permeabilidade Capilar/efeitos dos fármacos , Citocinas/análise , Citocinas/metabolismo , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado , Ácido Glucárico/administração & dosagem , Sobrecarga de Ferro/imunologia , Lipopolissacarídeos/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Peroxidase/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pseudomonas aeruginosa/imunologia , Ratos , Ratos Wistar , Desmame
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...