Autophagy in the placenta of women with hypertensive disorders in pregnancy.

INTRODUCTION: Autophagy has not been studied extensively in the human placenta. This study was performed to determine whether autophagy is increased in the placentas of women with hypertensive disorders in pregnancy compared to normotensive pregnancies. METHODS: LC3-II and p62 protein expression were examined by quantitative Western blotting analysis in 40 placentas from women not experiencing labor pains. The 40 placentas were from 13, 8, and 19 women with preeclampsia, gestational hypertension, and normal pregnancy, respectively. Hypertensive disorders in pregnancy included preeclampsia and gestational hypertension. RESULTS: LC3-II expression was significantly increased, while that of p62 was significantly reduced in 21 placentas of women with hypertensive disorders compared to those with normal blood pressure irrespective of the presence or absence of fetal growth restriction (FGR). LC3-II expression was also significantly increased in 13 placentas of women with preeclampsia irrespective of the presence or absence of FGR. DISCUSSION: The results of this study suggested that autophagy is active in the placenta of hypertensive disorders even in the absence of FGR.

Antenatal fibrinogen concentrations and postpartum haemorrhage.

BACKGROUND: It is unclear whether antenatal fibrinogen concentrations are associated with postpartum haemorrhage. METHODS: This retrospective study included 871 women with a singleton pregnancy but no known risk factors for postpartum haemorrhage, in whom fibrinogen concentration was measured within the 21 days before delivery. Correlation between antenatal fibrinogen concentrations and estimated blood loss was analysed. We tested the hypothesis that the risk of postpartum haemorrhage was higher in women with antenatal fibrinogen concentrations of <3.3 g/L. Postpartum haemorrhage was defined as an estimated blood loss ⩾700 mL following vaginal delivery and ⩾1000 mL following caesarean delivery. RESULTS: In women delivering vaginally (n=337), estimated blood loss tended to increase with decreasing antenatal fibrinogen concentration (R=-0.107, P=0.05), median fibrinogen concentration was significantly lower in 69 women with postpartum haemorrhage than in 268 women without postpartum haemorrhage (3.93 vs. 4.18 g/L, P=0.025), and postpartum haemorrhage occurred significantly more often in women with fibrinogen concentrations <3.3 g/L than in those with concentrations ⩾3.3 g/L (38% [11/29] vs. 19% [58/308], P=0.018). In women undergoing caesarean delivery (n=534), median fibrinogen concentration did not differ between those who experienced postpartum haemorrhage (n=128) and those who did not (n=406) (4.18 g/L vs. 4.07 g/L, P=0.43). Antenatal fibrinogen concentrations of <3.3g/L were not associated with higher rates of postpartum haemorrhage (26% [11/43] vs. 24% [117/491], P=0.80). CONCLUSIONS: Antenatal fibrinogen concentration <3.3g/L may be a risk factor for postpartum haemorrhage among women following vaginal delivery.

Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.

The desire to replace the amide backbone of renin inhibitors with a new scaffold led us to explore vinylogous amides (enaminones). An initial attempt proved unsuccessful, a result explained after the fact via docking experiments. Based on this lesson, we designed a different vinylogous amide scaffold which incorporated one or more pyrrolinone rings into the backbone. Three of the four compounds gave IC50S in the 0.6 to 18 microM range. These compounds did not inhibit HIV-1 protease. Taken together, the results reported herein provide insights into the role of hydrogen bonding and steric interactions for binding to renin.