Publications by Year: 2011

2011

Georgiou H, Thio Y, Russell C, Permezel M, Heng Y, Lee S, Tong S. Association between maternal serum cytokine profiles at 7-10 weeks' gestation and birthweight in small for gestational age infants. Am J Obstet Gynecol. 2011;204(5):415.e1–415.e12. doi:10.1016/j.ajog.2010.12.005
OBJECTIVE: The purpose of this study was to investigate whether birth of a small-for-gestational-age (SGA) baby (birthweight, 10th percentile) is preceded by altered maternal serum cytokine profiles at early pregnancy, compared with control babies (birthweight, 30-80th percentile). STUDY DESIGN: A retrospective case-control study of maternal serum collected prospectively across 7-10 weeks of gestation from women attending their first prenatal visit (SGA, 57 cases; control subjects, 71 cases selected retrospectively). Serum concentrations of 27 cytokines were measured in each sample and analyzed by 2-way analysis of variance and nonparametric tests. Logistic regression was used for predictive modeling. RESULTS: Of 21 detectable cytokines/chemokines, 14 analytes varied significantly (P ≤ .030) among those women who were destined to deliver an SGA baby, when compared with control subjects. Of the cytokines that varied in association with SGA, interferon-γ concentrations increased, and major proinflammatory (interleukin [IL]-2, -7, -12) and antiinflammatory (IL-1 receptor antagonist, -4, -10, -13) cytokine concentrations decreased. Eotaxin and macrophage inflammatory protein-1α were higher; monocyte chemoattractant protein-1 and IL-8 were lower. CONCLUSION: SGA births may be preceded by altered immune cytokine profiles at 7-10 weeks of gestation.
Transient receptor potential vanilloid 1 (TRPV1), neurokinin 1 (NK1) receptor and substance P (SP) immunoreactivity (-ir) and mRNA in the rat lumbosacral spinal cord and urinary bladder were measured 24h after s.c. injection of the vanilloids, capsaicin (50mg/kg) and resiniferatoxin (RTX, 100μg/kg), or vehicle (10% ethanol/10% Tween 80/saline). In the spinal cord, capsaicin significantly reduced TRPV1 and SP-ir (40-45%) in laminae I/II compared to controls, while RTX produced decreases of ~35%. NK1-ir in the spinal cord was unaffected by both vanilloid treatments. In the bladder, SP-ir was reduced in urothelial cells of some capsaicin- and RTX-treated rats, while SP-ir in the suburothelium and muscularis was significantly reduced by RTX. A significant increase in NK1-ir was observed in the urothelium and muscularis after capsaicin administration. Capsaicin significantly increased SP mRNA in the spinal cord, and TRPV1 and SP mRNA in the bladder, whereas RTX increased TRPV1, SP and NK1 mRNA in the spinal cord, and TRPV1 and SP mRNA in the bladder. These data suggest that stimulation of TRPV1 by low dose vanilloid administration can rapidly (within 24h) alter both transcription and translation of TRPV1 channels, SP and NK1 receptors in the rat urinary bladder and spinal cord.
Heng Y, Di Quinzio M, Permezel M, Rice G, Georgiou H. Cystatin A protease inhibitor and cysteine proteases in human cervicovaginal fluid in term pregnancy and labor. Am J Obstet Gynecol. 2011;204(3):254.e1–7. doi:10.1016/j.ajog.2010.10.912
OBJECTIVE: The purpose of this study was to investigate the temporal changes in immunoreactive cystatin A and the enzymatic activity of cathepsins B, H, L, and S in human cervicovaginal fluid (CVF) in late pregnancy and spontaneous labor. STUDY DESIGN: CVF was collected weekly (n = 95 women) from 36 weeks gestation until spontaneous term labor. Cystatin A was quantified using enzyme-linked immunosorbent assay. The enzyme activity of cathepsins B, H, L, and S was measured with fluorometric enzyme assay kits. RESULTS: Cystatin A significantly decreased towards (P = .016, 2-way analysis of variance) and during labor (P .001, 2-way analysis of variance). Enzymatic activity of cathepsins B, H, and S did not change with labor onset (P = .452, P = .703, P = .411, respectively, 2-way analysis of variance). CONCLUSION: In late gestation, CVF-decreased expression of the cysteine protease inhibitor, cystatin A, is associated with labor. Although the role and contribution of cystatin A to increased extracellular matrix remodeling has yet to be elucidated, the data that were obtained are consistent with this hypothesis.