Prediction of preeclampsia by placental protein 13 and background risk factors and its prevention by aspirin.

AIM: Evaluation of placental protein 13 (PP13) and risk factors (RFs) as markers for predicting preeclampsia (PE) and use of aspirin for PE prevention. MATERIALS AND METHODS: First-trimester pregnancy screening was based on having PP13 level ≤0.4 multiple of the median (MoM) and/or at least one major risk factor (RF) for PE. Management was by routine care or combined with daily treatment with 75 mg aspirin between 14 and 35 weeks of gestation. RESULTS: Of 820 deliveries, 63 women developed PE (7.7%). Median PP13 levels was 0.2MoM in the PE group compared with 0.83MoM among unaffected and 1.0MoM in unaffected not treated with aspirin (P<0.0001). Low PP13 was a better predictor for PE versus major RFs, particularly for young nuliparous. Combining low PP13 with RFs increased prediction accuracy. Mean arterial pressure (not included in the initial prediction), could add to prediction accuracy when combined with low PP13 and RFs. PE prevention by aspirin was most effective when the risk was determined by low PP13 alone, less effective for combining low PP13 with RFs, and ineffective when determined by RFs alone. CONCLUSION: When PE risk is determined by low first trimester PP13 or by combined low PP13 and RFs, prevention with aspirin is warranted.

First trimester maternal serum placental protein 13 levels in singleton vs. twin pregnancies with and without severe pre-eclampsia.

AIMS: To determine first trimester maternal serum placental protein 13 (PP13) in singletons vs. twins with and without severe preeclampsia (PE). METHODS: Serum samples were prospectively collected at 8-14 weeks of gestation. PP13 was determined by solid-phase immunoassay. Patients were recruited in community clinics throughout the country, and from the twin antenatal assessment clinic in Assaf Harofeh Medical Center, Zerifin, Israel. Demographics, medical, and pregnancy history were obtained at enrollment. Pregnancy outcome was collected after delivery. PP13 was compared by the Wilcoxon rank sum test. RESULTS: In singletons, PP13 declined with maternal weight and was lower in in vitro fertilization. Levels were converted into multiples of the median (MoMs) accordingly. In twins, the median was 1.74 MoM (n=76) vs. 1.00 in singletons (n=676, P<0.0001). Among twins with severe PE (n=10), the median was 1.53 MoM vs. 1.74 in unaffected twins (P=0.10), and 2.26 (n=6) for mild PE (P=0.30). Among singletons with severe PE, the median was 0.44 MoM (n=26, P<0.0001), and for mild PE 0.62 (n=17, P<0.001). CONCLUSION: PP13 is higher in twins than singletons, corresponding to the larger placental mass. Among singletons with severe PE, levels were significantly reduced, however, among twins, only a non-significant tendency for a reduction was recorded, and warrants further investigation in a larger series.

Hsp90 and angiogenesis in bone disorders--lessons from the avian growth plate.

Thiram-induced tibial dyschondroplasia (TD) and vitamin-D deficiency rickets are avian bone disorders of different etiologies characterized by abnormal chondrocyte differentiation, enlarged and unvascularized growth plates, and lameness. Heat-shock protein 90 (Hsp90) is a proangiogenic factor in mammalian tissues and in tumors; therefore, Hsp90 inhibitors were developed as antiangiogenic factors. In this study, we evaluated the association between Hsp90, hypoxia, and angiogenesis in the chick growth plate. Administration of the Hsp90 inhibitor to TD- and rickets-afflicted chicks at the time of induction resulted in reduction in growth-plate size and, contrary to its antiangiogenic effect in tumors, a major invasion of blood vessels occurred in the growth plates. This was the result of upregulation of the VEGF receptor Flk-1, the major rate-limiting factor of vascularization in TD and rickets. In addition, the abnormal chondrocyte differentiation, as characterized by collagen type II expression and alkaline phosphatase activity, and the changes in hypoxia-inducible factor-1α (HIF-1α) in both disorders were restored. All these changes resulted in prevention of lameness. Inhibition of Hsp90 activity reduced growth-plate size, increased vascularization, and mitigated lameness also in TD chicks with established lesions. In summary, this is the first reported demonstration of involvement of Hsp90 in chondrocyte differentiation and growth-plate vascularization. In contrast to the antiangiogenic effect of Hsp90 inhibitors observed in mammals, inhibition of Hsp90 activity in the unvascularized TD- and rickets-afflicted chicks resulted in activation of the angiogenic switch and reinstated normal growth-plate morphology.