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1.
Comput Biol Med ; 42(4): 446-57, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22245098

RESUMO

Atherosclerosis is the primary cause of CAD and cerebrovascular disease. Endothelin (ET)-1 is a vasoconstrictive peptide implicated in Atherosclerosis pathology. Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin. Reported inhibitors of ECE-1 and their IC(50) values were retrieved from literature and their structures were docked with the parent protein using the Molegro virtual docker. The obtained MolDock scores of each of the compounds are hereby reported and are subject to graphical analysis in conjunction with their respective IC(50) values to characterize potent inhibitors. A search was then run in the ZINC database for compounds with similar properties. Potent inhibitors with higher Dock scores and better Ranking were isolated and are reported.


Assuntos
Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/química , Ácido Aspártico Endopeptidases/metabolismo , Bases de Dados de Proteínas , Endotelina-1/metabolismo , Enzimas Conversoras de Endotelina , Glicopeptídeos/química , Glicopeptídeos/metabolismo , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Metaloendopeptidases/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade
2.
Ann Thorac Surg ; 59(1): 28-32, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7818354

RESUMO

Neonatal lung hypoplasia is frequently a fatal condition often associated with congenital diaphragmatic hernia. Unilateral lung transplantation rarely has been performed for this indication, although it is a potential solution. It is not known whether the transplant needs to function permanently or to act as a bridge until the native lung develops. It is also not known whether the native lung will grow in the face of an immunosuppressed state and chronic rejection of the transplanted lung. We therefore developed a porcine model of left lung rejection to study this. Infant swine underwent left lung transplantation. Chronic rejection occurred in all, resulting in nonfunction of the transplanted lung. The right lungs of these animals were compared with the right lungs of size-matched and age-matched control animals not given immunosuppressive treatment and not undergoing transplantation. There were no differences in terms of the functional residual capacity, airway compliance, and airway resistance among the groups. There was a significant increase in the pulmonary vascular resistance in the animals with transplanted lungs. There was also a significant increase in the lung weight in these animals. Unilateral pneumonectomies were done in 4 infant pigs to serve as controls. Three of the 4 did not survive the operation because of acute pulmonary failure. In conclusion, the study group exhibited evidence of compensatory growth that was not seen in the control animals, as shown by the increase in lung weight. This suggests that contralateral lung growth occurs in a growing animal, despite the effects of immunosuppression therapy and chronic rejection of the transplanted lung.


Assuntos
Rejeição de Enxerto , Transplante de Pulmão , Pulmão/crescimento & desenvolvimento , Mecânica Respiratória , Animais , Doença Crônica , Capacidade Residual Funcional , Pulmão/anormalidades , Complacência Pulmonar , Circulação Pulmonar , Troca Gasosa Pulmonar , Suínos , Porco Miniatura , Resistência Vascular
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