Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells.

Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34, CHOP, and SDF2. At the protein level, GRP78, SDF2, p-eIF2α, and p-eIF2α/eIF2α ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 α/elF2α increased after 12 h of treatment, while the gene expression of GADD34, ATF4, and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder.

Preeclampsia and superimposed preeclampsia: The same disease? The role of angiogenic biomarkers.

OBJECTIVE: We aimed to compare sFlt-1 and placental growth factor (PlGF) levels and the sFlt-1/PlGF ratio between women with preeclampsia and superimposed preeclampsia to, respectively, normotensive and chronic hypertensive ones. STUDY DESIGN: We performed a prospective two-armed cohort in a tertiary teaching hospital in Sao Paulo, Brazil, including 37 normotensive and 60 chronic hypertensive pregnant women. We assessed the serum levels of sFlt-1 and PlGF at 20, 26, 32, and 36 gestational weeks by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Having preeclampsia and superimposed preeclampsia. RESULTS: Among normotensive and chronic hypertensive pregnancies, 4 (10.8%) and 14 (23.3%) women developed preeclampsia and superimposed preeclampsia, respectively. Compared with those who remained normotensive, the preeclampsia women presented higher sFlt-1 levels at 32 gestational weeks (4323.45 pg/mL vs. 2242.04 pg/mL, p = 0.019), lower PlGF levels at 20 (183.54 pg/mL vs. 337.38 pg/mL, p = 0.034), 32 (169.69 pg/mL vs. 792.53 pg/mL, p = 0.001), and 36 gestational weeks (252.99 pg/mL vs. 561.81 pg/mL, p = 0.029), and higher sFlt-1/PlGF ratios at 26 (9.02 vs. 1.84, p = 0.004), 32 (23.61 vs. 2.55, p = 0.001), and 36 gestational weeks (49.02 vs. 7.34, p = 0.029). On the other hand, compared with those who remained chronic hypertensive, the superimposed preeclampsia women only presented a higher sFlt-1/PlGF ratio at 32 gestational weeks (9.98 vs. 2.51, p = 0.039). CONCLUSION: Although angiogenic imbalance is clearly related to preeclampsia, it seems to play a more modest role in superimposed preeclampsia, in which other mechanisms should also be investigated.

Diffusion imaging may predict reversible brain lesions in eclampsia and severe preeclampsia: initial experience.

OBJECTIVE: The purpose of this study was to validate diffusion-weighted magnetic resonance imaging in the prediction of the evolutive course of brain edema and to establish its pathophysiologic presence in patients with eclampsia/severe preeclampsia. STUDY DESIGN: Seventeen patients with a clinical diagnosis of severe eclampsia/preeclampsia and T2 hyperintense brain lesions on routine magnetic resonance imaging were evaluated at hospital admission and 8 weeks later. RESULTS: Brain edema was reversible in 13 patients and irreversible in 4 patients, as indicated on follow-up magnetic resonance imaging. Sixteen of 17 patients were differentiated accurately into reversible and irreversible groups on the basis of diffusion imaging on hospital admission. Diffusion-weighted magnetic resonance imaging demonstrated a significant increase in water mobility in abnormal regions compared with normal-appearing brains in patients in the reversible group (1.34+/-0.10 mm(2) vs 0.79+/-0.08 mm(2)/s x 10(-3), P<.001). In the irreversible group, restricted water diffusion was present, which was consistent with cytotoxic edema and early brain infarction in 3 of 4 patients. CONCLUSION: Diffusion-weighted magnetic resonance imaging can predict successfully the evolutive course of brain edema in an acute setting in these patients. Our findings indicate that brain edema is vasogenic, although ischemic/cytotoxic edema was observed less commonly.

Cardiotocografia basal: estudo da validade e alicalçao do teste em hospital de nível secundário / Basal cardiotocography: value and use of the best in a secondary level hospital

Foi feito um estudo no Hospital da Universidade de Brasília, em um grupo de 94 pacientes obstétricas de alto risco, submetidas a um teste de validade nao-estresse de Coraçao Fetal. As análises mostraram uma sensibilidade de 75 por cento, um valor Cohen's Kappa apresentou um índice equivalente a 0,64 (p , 0,01). As consideraçoes sobre o estudo visaram principalmente o curso dos casos, assim como os resultados perinatais dos mesmos