RESUMEN
Bacterial lipopolysaccharide given intravenously at 30 mg/kg to anesthetized rats results in rapid systemic hypotension and hypovolemia, elaboration of cytokines, increased proteolysis and vascular endothelial dysfunction. When a monoclonal antibody SdJ5-1.17.15 (SdJ5) directed against the lipid A moiety of lipopolysaccharide was administered at (1.25 or 5.0 mg/kg) 5 min prior to the endotoxin, significant protection was afforded to rats. This protection was manifested by a significant reduction in the early hypotension, as well as attenuation of hypovolemia and proteolysis. To evaluate endothelial function, superior mesenteric artery rings were isolated from endotoxemic rats 4 h after endotoxic challenge. Lipopolysaccharide (LPS) significantly reduced superior mesenteric artery vasorelaxation to acetylcholine and A23187, two endothelium-dependent vasodilators, but not to NaNO2, an endothelium-independent vasodilator. SdJ5 significantly preserved vasorelaxation responses to both acetylcholine and A23187, indicating a marked degree of endothelial preservation by this anti-lipid A monoclonal antibody. The protection was dose-dependent since 0.3 mg/kg of SdJ5 did not provide significant protection in any variable measured. Moreover, there was no significant difference between the 1.25 mg/kg and 5.0 mg/kg dose of SdJ5. Furthermore, plasma concentrations of TNF-alpha, a cytokine involved in mediating many of the effects associated with endotoxemia, was significantly reduced in SdJ5-treated animals. Thus, SdJ5 appears to be capable of counteracting many of the in vivo sequelae of endotoxemia in rats.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Lípido A/toxicidad , Músculo Liso Vascular/efectos de los fármacos , Choque Séptico/prevención & control , Acetilcolina/farmacología , Análisis de Varianza , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacología , Proteínas Sanguíneas/metabolismo , Calcimicina/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Humanos , Hipotensión/tratamiento farmacológico , Inmunoglobulina M/inmunología , Lípido A/administración & dosificación , Lípido A/inmunología , Masculino , Arterias Mesentéricas/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Choque Séptico/tratamiento farmacológico , Choque Séptico/metabolismo , Nitrito de Sodio/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To assess the association between women with preterm premature rupture of membranes and 41 potential risk factors, we conducted a case-control study in six United States tertiary perinatal centers. The study involved completion of a comprehensive questionnaire for 341 women with preterm premature rupture of membranes in singleton pregnancies from 20 to 36 weeks' gestation and 253 control women matched for maternal age, gestational age, parity, clinic or private patient status, and previous vaginal or cesarean delivery. Univariate analysis revealed 11 variables associated with a significantly (p less than 0.05) increased risk of preterm premature rupture of membranes. After multiple logistic regression analysis, three variables remained in the model as independent risk factors: antepartum vaginal bleeding in more than one trimester (odds ratio 7.4; 95% confidence interval, 2.2, 25.6), current cigarette smoking (odds ratio, 2.1; 95% confidence interval, 1.4, 3.1), and previous preterm delivery (odds ratio, 2.5; 95% confidence interval, 1.4, 2.5). Cessation of cigarette smoking by pregnant women may reduce the risk of preterm premature rupture of membranes. Further study is necessary to determine the nature of the relationship between antepartum vaginal bleeding and preterm premature rupture of membranes.