Digibind attenuates cytokine TNFalpha-induced endothelial inflammatory response: potential benefit role of digibind in preeclampsia.

OBJECTIVE: Exaggerated inflammatory response occurs in preeclampsia. Preeclampsia is also associated with elevated endogenous digoxin-like factors (EDLFs). Clinical data suggest that Digibind (a polyclonal sheep digoxin binding Fab fragment) binds to EDLF and may have the potential to attenuate vasoconstriction and other clinical symptoms of preeclampsia. This study was undertaken to determine if Digibind could attenuate increased endothelial inflammatory response induced by tumor necrosis factor-alpha (TNFalpha). STUDY DESIGN: Confluent endothelial cells were treated with TNFalpha at different concentrations with or without Digibind in culture. Endothelial adhesion molecule ICAM, VCAM and E-selectin expressions were determined by an immunoassay directly detected on the endothelial surface. Effects of Digibind on TNFalpha-induced extracellular signal-regulated kinase and Na(+)/K(+)-ATPase expressions were also examined. RESULT: (1) TNFalpha induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFalpha-induced upregulation of endothelial E-selectin, ICAM and VCAM expressions. The blocking effect was in a concentration dependent manner; (3) Digibind had no effects on TNFalpha-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFalpha-induced downregulation of Na(+)/K(+)-ATPase beta1 expression. CONCLUSION: Digibind may exert beneficial effects by preserving cell membrane Na(+)/K(+)-ATPase function and consequently to offset increased inflammatory response in endothelial cells.

Use of misoprostol on an outpatient basis for postdate pregnancy.

OBJECTIVE: Within the obstetric community, several studies suggest that cervical ripening and labor induction after 40 weeks' gestation leads to improved maternal and neonatal outcomes. The most effective drug regimen to safely promote labor has not been determined. METHOD: Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks' gestation, and an unfavorable Bishop score were assigned randomly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses. RESULTS: Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg. The mean interval (+/-standard deviation) from start of cervical ripening to delivery was 2.4 days +/-0.3 vs. 3.9 days +/-0.7 for the 50 and 25 microg groups (P<0.05). No adverse events were noted. However, due to small sample size, less frequent adverse events may be missed. Type II errors cannot be excluded. CONCLUSION: In the prevention of postdate pregnancy, outpatients use of oral misoprostol 50 microg appears to result in earlier delivery, as compared to 25 microg.