RESUMO
Plasma fibronectin deficiency has been documented in critically ill surgical, trauma, and burn patients. Human plasma fibronectin was isolated by gelatin-Sepharose affinity chromatography and evaluated with respect to its opsonic activity following pasteurization, its in vivo clearance kinetics, and its short-term influence on cardiovascular hemodynamics in postoperative septic sheep. Six patients with low plasma fibronectin levels were also evaluated with respect to temporal changes of immunoreactive fibronectin and opsonic activity following infusion of fibronectin at a dose calculated to elevate the plasma fibronectin level to 400 micrograms/ml. With utilization of three different in vitro radioisotopic phagocytic assays, i.e., liver slice assay, peritoneal macrophage monolayer assay, and Kupffer cell monolayer assay, retention of opsonic activity by fibronectin following pasteurization was documented. The normal biphasic kinetics associated with plasma clearance of fibronectin were also not altered by pasteurization. In postoperative septic sheep with hemodynamic instability, intravenous infusion of 500 mg of purified human fibronectin initiated no abnormal hemodynamic response. Indeed, as compared with placebo, the infusion of fibronectin into the postoperative septic sheep resulted in a more stable systemic vascular resistance and pulmonary vascular resistance with a higher arterial pressure. It also elevated immunoreactive fibronectin levels (p less than 0.05) and increased opsonic activity (p less than 0.05). Surgical, trauma, and burn patients (ages 18 to 80 years) with low plasma fibronectin levels (160 to 236 micrograms/ml) manifested no disturbance in cardiovascular, respiratory, or hematologic parameters following fibronectin infusion (590 to 988 mg per patient), but did display an early increase of opsonic activity. This standardized, pasteurized, and opsonically active preparation of purified human plasma fibronectin (5.0 mg/ml after reconstitution) has utility for future randomized clinical trials in injured patients with sepsis.
Assuntos
Queimaduras/sangue , Fibronectinas/sangue , Proteínas Opsonizantes , Fagocitose , Procedimentos Cirúrgicos Operatórios , Ferimentos e Lesões/sangue , Adolescente , Adulto , Idoso , Animais , Fibronectinas/administração & dosagem , Fibronectinas/farmacologia , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Infecções por Pseudomonas/fisiopatologia , Ratos , Ratos Endogâmicos , Sepse/fisiopatologia , Ovinos , Resistência Vascular/efeitos dos fármacosAssuntos
Fígado/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Hormônios Adeno-Hipofisários/farmacologia , Animais , Fatores de Coagulação Sanguínea/biossíntese , Epinefrina/farmacologia , Hidrocortisona/farmacologia , Hipotálamo/fisiologia , Fígado/efeitos dos fármacos , Masculino , RatosRESUMO
The capacity of a peptide isolated from hypophysis (HTH) to affect liver function is further supported by the results of pilot experiments on lipid and protein metabolism. Administration of purified peptide to rats induces reduction in plasma proteins and increase in plasma cholesterol with an abnormal free/esterifield cholesterol ratio in liver. Cholesterol in bile and bile volume excretion increase above normal and the concentration of other substances known to be modified by liver activity shows values different to normals.
Assuntos
Metabolismo dos Lipídeos , Fígado/fisiologia , Peptídeos/farmacologia , Hormônios Hipofisários/farmacologia , Proteínas/metabolismo , Glândulas Suprarrenais/fisiologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Tamanho do Órgão , Hipófise/fisiologia , Coelhos , Ratos , Estimulação Química , Fatores de TempoRESUMO
The capacity of a peptide isolated from hypophysis (HTH) to affect liver function is further supported by the results of pilot experiments on lipid and protein metabolism. Administration of purified peptide to rats induces reduction in plasma proteins and increase in plasma cholesterol with an abnormal free/esterifield cholesterol ratio in liver. Cholesterol in bile and bile volume excretion increase above normal and the concentration of other substances known to be modified by liver activity shows values different to normals.
RESUMO
The capacity of a peptide isolated from hypophysis (HTH) to affect liver function is further supported by the results of pilot experiments on lipid and protein metabolism. Administration of purified peptide to rats induces reduction in plasma proteins and increase in plasma cholesterol with an abnormal free/esterifield cholesterol ratio in liver. Cholesterol in bile and bile volume excretion increase above normal and the concentration of other substances known to be modified by liver activity shows values different to normals.
