H. Ko

COX-2 expression and inflammatory effects by diesel exhaust particles in vitro and in vivo.

Recent studies have shown that diesel exhaust particles (DEP) have adverse effects on the respiratory tract in vitro and in vivo, related to various pro-inflammatory cytokines and inflammatory mediators. The inflammation induced by the production of cyclooxygenase (COX)-2, an important mediator of inflammation and tumor promotion, and excess eicosanoids may be central to the pathogenesis of DEP-induced airway inflammation. However, the role of COX-2 in the pathogenesis of DEP-induced lung inflammation remains unclear, especially in vivo. In this study, we demonstrated that treatment with 50 microg/ml of DEP for 24h induced the expression of the COX-2 gene at both the transcriptional and protein levels, which led to an increase in the release of prostaglandin E(2) (PGE(2)) in A549 cells. In addition, the increased levels of COX-2 and PGE(2) by DEP exposure were significantly suppressed by treatment with 50 pg/ml of dexamethasone (Dex). We also showed that exposure to 25 mg/kg of DEP induced the expression of the COX-2 protein in mouse lung tissues, and this increased COX-2 expression was attenuated by pretreatment with 5 mg/kg of Dex. These findings suggest that COX-2 may play an important role in the pathogenesis of DEP-induced pulmonary inflammation, which is effectively inhibited by glucocorticoid treatment.

Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K‑dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation

Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins. Moreover, BK treatment suppressed cell migration and tubular formation in response to VEGF-A. These anti-angiogenic activities of BK were associated with the inactivation of mitogenic signaling pathways including extracellular signal-regulated kinase, Akt and p70S6K, and the subsequent downregulation of VEGFR-2 and matrix metalloproteinase-2. Taken together, these findings suggest further evaluation and development of BK as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis

In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo. These anti-angiogenic activities of marmesin were mediated through inactivation of VEGF-A-stimulated signaling pathways, and down-regulation of cell surface signaling molecules including VEGF receptor-2, human epidermal growth factor receptor-2, integrin β1 and integrin-liked kinase. Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression

Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. We also show that LF treatment inhibited cell invasion and tube formation in HUVECs. These anti-angiogenic activities of LF were associated with the inactivation of mitogenic signaling pathways, induction of vascular endothelial (VE)-cadherin distribution at cell-cell contacts and inhibition of matrix metalloproteinase (MMP) expression. Collectively, our findings demonstrate the pharmacological functions and molecular mechanisms of LF in regulating endothelial cell fates, and support further development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related disorders including cancer.

OC10.08: *The risk of preterm birth in vanishing twin: a multicentre prospective cohort study

S. Jisu1, S. Lee1, Y. Han2, M. Kim2, J. Shim3, M. Lee3, S. Oh4, J. Lee5, S. Kim6, D. Cha6, G. Cho7, H. Kwon8, B. Kim9, M. Park10, H. Cho11, H. Ko12, C. Park1, J. Park1, J. Jun1, H. Ryu2, S. Lee1 1Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Centre, Dankook University College of Medicine, Seoul, Republic of Korea; 3Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea; 4Obstetrics and Gynecology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 5Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea; 6Obstetrics and Gynecology, CHA Gangnam Medical Centre, CHA University, Seoul, Republic of Korea; 7Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Republic of Korea; 8Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Republic of Korea; 9Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Centre, Seoul, Republic of Korea; 10Obstetrics and Gynecology, Ewha Woman’s University, Seoul, Republic of Korea; 11Obstetrics and Gynecology, CHA Bundang Medical Centre, CHA University, Sung Nam, Republic of Korea; 12Obstetrics and Gynecology, Catholic University of Korea College of Medicine, Seoul, Republic of Korea

OP09.03: Serial cervical length as a predictor of histologic chorioamnionitis in late preterm birth: Short oral presentation abstracts

4. Multivariate analysis revealed change of the cervical length between mid-trimester and early third trimester were independently associated with an increased risk for histologic chorioamnionitis in late preterm birth. (adjusted odds ratio(OR) 2.799(95% confidence interval(CI) 1.352-5.796), p=0.006) Conclusion In late preterm birth, greater change of cervical length between mid-trimester and early third trimester is independently associated with an increased risk of histologic chorioamnionitis.

P01.03: Ultrasound assessment of cervical length and volume: comparison of transabdominal and transvaginal approach

A. Shrim5, R. Beloosesky6, M. Steinberg6,5, K. Nizar3, Y. Ginsberg1, Z. Weiner2, D.M. Schwake4 1Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel; 2Rambam Medical Centre, Haifa, Israel; 3Obstetrics and Gynecology, Rambam Medical Centre, Acre, Israel; 4Obstetrics and Gynecology Ultrasound Unit, Rambam Medical Centre, Haifa, Israel; 5Technion Israel, Neve Yarak, Israel; 6Obstetrics and Gynecology, Rambam Medical Centre, Haifa, Israel

P19.02: Epignathus combined with cleft palate and bifid tongue: a case report

Background: Preterm asymptomatic cervical dilatation or ‘‘cervical incompetency’’ has been associated with microbial invasion of the amniotic cavity (MIAC). It remains unclear if MIAC is a cause or a consequence in this situation. We are reporting a case of a 34 y.o.woman who had 3 pregnancies complicated with asymptomatic cervical dilatation and MIAC. Case: The first pregnancy, she presented with few abdominal cramps at 20 weeks’ gestation. A dilated cervix with bulging amniotic membranes was found and MIAC with Mycoplasma hominis was diagnosed. She was treated with antibiotics and cerclage and delivered at 35 weeks’. The second pregnancy, she underwent a prophylactic cervical cerclage at 14 weeks’, without antibiotics and ended up with a PROM at 24 weeks’ followed by clinical chorioamnionitis and delivery at 26 weeks’. For the third pregnancy, transvaginal ultrasound performed at 15 weeks’ showed normal cervical length but the presence of intra-amniotic sludge. An amniocentesis revealed MIAC with Mycoplasma hominis and she was treated with IV antibiotics. At 19 weeks, she presented with asymptomatic cervical dilatation and transvaginal ultrasound showed an important accumulation of amniotic sludge. She was admitted for IV antibiotics and cervical cerclage on the next day. Unfortunately, she reached complete cervical dilatation without evidence of regular uterine contractions. Vaginal misoprostol was given and she delivered at 19 weeks. For the fourth pregnancy, she had a cervical cerclage placed at 12 weeks’ gestation and she received daily prophylactic erythromycin from 12 to 34 weeks’ gestation. She delivered at 38 weeks’ of a healthy boy. Discussion: In this case, we found MIAC that was present several days before the first signs of cervical changes in a woman with a diagnosis of incompetent cervix. This case also confirms that mid-trimester intra-amniotic sludge is predictive of MIAC in asymptomatic woman. Prophylactic antibiotics should be considered in women at high-risk of MIAC in combination with cervical cerclage.

P09.31: Intrauterine vesicoamniotic shunt of posterior urethral valve at early second trimester

Neonatal morbidities including acute respiratory distress, chronic lung disease, requirement for ventilatory assistance, patent ductus arteriosus, hypotension, and oliguric renal failure had a lower incidence in the laser group. On brain imaging, ischaemic brain injury was seen in 12% of the pre-laser group and none in the laser group of infants (p = 0.01). Conclusions: These findings indicate that perinatal outcomes are improved with less neonatal morbidity for pregnancies with severe TTTS following introduction of a laser program. It is suggested that laser ablation of communicating placental vessels may be the preferred treatment, consistent with the recent results from a randomised controlled trial.

P09.01: The applications of prenatal MRI: the value and limitations

This study was to develop fetal growth curves and percentile growth charts for a Jamaican population. 499 jamaican women of African descent were enrolled in a prospective study from the maternity clinic of the University Hospital of the West Indies., Kingston, Jamaica. The women had serial scans between 14–37 weeks’ gestation to measure fetal growth. The measurements performed were BPD, HC, AC and FL. A total of 2574 scans were performed (mean 5.2 per woman). The data was used to plot centile growth charts for the Jamaican fetus. Birthweights vary between ethnic groups so must fetal growth. At present fetal growth in Jamaica is assessed using charts based on Caucasian populations. Fetal growth charts derived from this data would more accurately predict the at-risk fetus and hence improve obstetric care.