Unzila Ali

IL-6 Trans-Signaling System in Intra-Amniotic Inflammation, Preterm Birth, and Preterm Premature Rupture of the Membranes

Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15+ (polymorphonuclear), and CD3+ (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.

Amniotic Fluid Angiopoietin-1, Angiopoietin-2, and Soluble Receptor Tunica Interna Endothelial Cell Kinase-2 Levels and Regulation in Normal Pregnancy and Intraamniotic Inflammation-Induced Preterm Birth

BACKGROUND Angiopoietin-1 (Ang-1) and Ang-2 act selectively on endothelial cells by engaging the Tunica interna endothelial cell kinase-2 (Tie2) receptor. A soluble form of Tie2 (sTie2) blocks angiopoietin bioactivity. OBJECTIVE The aim of the study was to characterize changes and expression patterns of Ang-1, Ang-2, and sTie2 in amniotic fluid (AF) and placenta during human pregnancy and intraamniotic inflammation (IAI)-induced preterm birth. DESIGN AND SETTING We conducted a cross-sectional study at a tertiary university hospital. PATIENTS AF levels of Ang-1, Ang-2, and sTie2 were evaluated in 176 women during second trimester (n = 40), third trimester (n = 37), and preterm labor (positive IAI, n = 50; negative IAI, n = 49). Placenta and cord blood of select women were analyzed. MAIN OUTCOME MEASURES Ang-1, Ang-2, sTie2, and IL-6 were evaluated by ELISA. Real-time PCR measured Ang-1, Ang-2, and Tie2 placental mRNA levels. Placenta was immunostained for Ang-1 and Ang-2. Placental explant cultures were stimulated with lipopolysaccharide, Pam3Cys, and modulators of protein synthesis/secretion (cycloheximide, monensin, and brefeldin A). RESULTS In normal pregnancy, the levels and ratios of AF Ang-1, Ang-2, and sTie2 varied with gestational age (GA) (P < 0.001). PCR revealed corresponding changes in placental Ang-1 and Ang-2, but not Tie2, mRNA. IAI raised AF Ang-1, Ang-2, and sTie2 above the expected level for GA without affecting their placental mRNA. Ang-2 immunoreactivity appeared enhanced in areas of villous edema. AF Ang-2/Ang-1 ratio was an important determinant of cord blood IL-6 (P < 0.001). Ex-vivo, sTie2 release was increased by Golgi disrupting but not bacterial mimic agents. CONCLUSIONS Ang-1, Ang-2, and sTie2 are physiological constituents of AF that are GA and IAI regulated. Ang-2/Ang-1 ratio may play a role in modulating the fetal inflammatory response to IAI. Placental sTie2 shedding likely involves a Golgi-mediated mechanism.

The role of urinary soluble endoglin in the diagnosis of pre‐eclampsia: comparison with soluble fms‐like tyrosine kinase 1 to placental growth factor ratio

Please cite this paper as: Buhimschi C, Baumbusch M, Dulay A, Lee S, Wehrum M, Zhao G, Bahtiyar M, Pettker C, Ali U, Funai E, Buhimschi I. The role of urinary soluble endoglin in the diagnosis of pre‐eclampsia: comparison with soluble fms‐like tyrosine kinase 1 to placental growth factor ratio. BJOG 2010;117:321–330.

Outcomes of small bowel obstruction in patients with previous gynecologic malignancies

BACKGROUND Features predictive of malignant small bowel obstructions among patients with previous gynecologic malignancies remain undetermined. METHODS Predictors of malignancy and mortality among patients with gynecologic malignancies and bowel obstructions were identified through a retrospective review of records. RESULTS Malignancy was noted among 69.8% of 189 patients included in the analysis. Advanced-stage cancer (P = .006, odds ratio [OR] = 6.62), ovarian malignancy (P = .001, OR = 25.64), and early-onset obstruction (P = .014) predicted malignant etiology, whereas chemotherapy (P < .001, OR = .02) or radiation therapy (P = .027, OR = .09) predicted benign obstruction. The average survival was 9 months versus 49 months for malignant and benign obstructions, respectively. Ovarian cancer (P = .009, hazard ratio [HR] = 4.45), anemia (P = .001, HR = 1.11), and renal dysfunction (P < .001, HR 1.81) impaired survival. CONCLUSIONS Palliative care should be considered for patients with advanced-stage cancer, ovarian malignancy, and a shorter time interval between cancer diagnosis and bowel obstruction, especially in the setting of anemia and renal dysfunction.

A Successful Pregnancy Outcome following the Ross Procedure: A Case Report

For women requiring valve replacement surgery, it is unclear which type of valve offers the greatest chance of a healthy pregnancy. This case describes a successful pregnancy outcome following the Ross procedure, which involves replacing the aortic valve with an autologous pulmonary valve. Due to left ventricular outflow tract obstruction, this patient required an aortic valve replacement surgery. She underwent the Ross procedure at age 16 and became pregnant 11 years later. During pregnancy, she was able to avoid the risks of anticoagulation. She underwent an assisted second stage of labor and went on to deliver a healthy infant. This case illustrates that the Ross procedure may be an alternative treatment for aortic valve replacements in women of child-bearing age.