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2.
J Thromb Haemost ; 14(6): 1238-48, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26947929

RESUMO

UNLABELLED: Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. SUMMARY: Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection.


Assuntos
Células Epiteliais/virologia , Hemorragia/virologia , Infecções por Orthomyxoviridae/patologia , Alvéolos Pulmonares/metabolismo , Tromboplastina/deficiência , Animais , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Líquido da Lavagem Broncoalveolar , Deleção de Genes , Hemostasia , Inflamação , Vírus da Influenza A Subtipo H1N1 , Integrases/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tromboplastina/metabolismo
3.
Am J Transplant ; 14(12): 2893-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25376207

RESUMO

Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness 67 days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient's organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient's clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during prehospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location.


Assuntos
Rejeição de Enxerto/etiologia , Fibrose Pulmonar Idiopática/cirurgia , Transplante de Pulmão/efeitos adversos , Micoses/transmissão , Complicações Pós-Operatórias , Scopulariopsis/patogenicidade , Obtenção de Tecidos e Órgãos , Evolução Fatal , Humanos , Fibrose Pulmonar Idiopática/microbiologia , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/tratamento farmacológico , Scopulariopsis/isolamento & purificação , Doadores de Tecidos , Transplantados
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