Preeclampsia (PE), new onset hypertension, is characterized by decreased fetal weight, elevated cytolytic natural killer (NK) cells and placental ischemia during pregnancy. Cytolytic NK are thought to play a role in fetal demise as they have also been shown to be increased in patients suffering from miscarriage.Currently, there is no effective treatment for PE except for early delivery, making PE the leading cause for premature births worldwide. Multiple injections of 17-hydroxyprogesterone caproate (17-OHPC) is used for prevention of preterm labor, but not for management of PE. We have shown that injections of 17-OHPC to the RUPP rat model of PE improves some but not all facets of PE observed in this model. Therefore this study was designed to test the hypothesis that injections of 17-OHPC on both day 15 (GD15) and GD (18) improve outcomes of hypertension in response to placental ischemia. To do so, 17-OHPC (3.32mg/kg) was administered intraperitoneally on GD 15 and 18 to reduced uterine perfusion pressure (RUPP) rats, carotid catheters were inserted on GD 18 and blood pressure (MAP) andplacental cytolytic NK cells were measured on GD 19. MAP in normal pregnant (NP) rats (n=8) was 104±4,119±
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in RUPP rats (n=5) and 102±5 mmHgin RUPP+17-OHPC GD15 &18 (n=4), p <0.05.Total number of placental NK cells was 8.5± 3 in NP, 20±2 in RUPP rats, which decreased to 4.7± 3 % in RUPP+17-OHPC GD15 &18, p<0.05. Activated placental NK cells was 3.4± 1.6 in NP, 10.5±2.3 in RUPP, which improved to 2.7± 2.7 % in RUPP+17-OHPCGD15 & 18, p <0.05.In conclusion, administration of 17-OHPC on days 15 and 18 decreased hypertension and NK cells that are associated with PE in the RUPP ratand should be considered for addition to the management of PE.
Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study