Your browser doesn't support javascript.
loading
Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis.
Sevransky, J E; Shaked, G; Novogrodsky, A; Levitzki, A; Gazit, A; Hoffman, A; Elin, R J; Quezado, Z M; Freeman, B D; Eichacker, P Q; Danner, R L; Banks, S M; Bacher, J; Thomas, M L; Natanson, C.
Afiliación
  • Sevransky JE; Department of Critical Care Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA. jsevransky@nih.gov
J Clin Invest ; 99(8): 1966-73, 1997 Apr 15.
Article en En | MEDLINE | ID: mdl-9109441
Tyrosine kinase-dependent cell signaling is postulated to be a pivotal control point in inflammatory responses initiated by bacterial products and TNF. Using a canine model of gram-negative septic shock, we investigated the effect of tyrosine kinase inhibitors (tyrphostins) on survival. Animals were infected intraperitoneally with Escherichia coli 0111: B4, and then, in a randomized, blinded fashion, were treated immediately with one of two tyrphostins, AG 556 (n = 40) or AG 126 (n = 10), or with control (n = 50), and followed for 28 d or until death. All animals received supplemental oxygen, fluids, and antibiotics. Tyrphostin AG 556 improved survival times when compared to controls (P = 0.05). During the first 48 h after infection, AG 556 also improved mean arterial pressure, left ventricular ejection fraction, cardiac output, oxygen delivery, and alveolar-arterial oxygen gradient compared to controls (all P < or = 0.05). These improvements in organ injury were significantly predictive of survival. Treatment with AG 556 had no effect on clearance of endotoxin or bacteria from the blood (both P = NS); however, AG 556 did significantly lower serum TNF levels (P = 0.03). These data are consistent with the conclusion that AG 556 prevented cytokine-induced multiorgan failure and death during septic shock by inhibiting cell-signaling pathways without impairing host defenses as determined by clearance of bacteria and endotoxin.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 3_ND / 6_ODS3_enfermedades_notrasmisibles Problema de salud: 2_enfermedades_transmissibles / 3_neglected_diseases / 3_zoonosis / 6_digestive_diseases / 6_other_malignant_neoplasms Asunto principal: Peritonitis / Fenoles / Proteínas Tirosina Quinasas / Tirfostinos / Inhibidores Enzimáticos / Infecciones por Escherichia coli / Insuficiencia Multiorgánica / Nitrilos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: J Clin Invest Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 2_ODS3 / 3_ND / 6_ODS3_enfermedades_notrasmisibles Problema de salud: 2_enfermedades_transmissibles / 3_neglected_diseases / 3_zoonosis / 6_digestive_diseases / 6_other_malignant_neoplasms Asunto principal: Peritonitis / Fenoles / Proteínas Tirosina Quinasas / Tirfostinos / Inhibidores Enzimáticos / Infecciones por Escherichia coli / Insuficiencia Multiorgánica / Nitrilos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: J Clin Invest Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos
...