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Exaggerated hypoxia-related endothelin-1 (ET-1) production in preeclamptic placentae comparing to normal placentae
SMFM Abstracts S125 389 INSULIN PUMP COMPARED TO INJECTED INSULIN IN PREGNANT WOMEN WITH TYPE 1 DIABETES YVONNE CHENG1, INGRID BLOCK-KURBISCH2, MARIBETH INTURRISI3, ALLA USTINOV2, AARON CAUGHEY2, 1University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California, 2University of California, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California, 3University of California, San Francisco, School of Nursing, San Francisco, California OBJECTIVE: To examine perinatal outcomes and factors associated with insulin pump versus conventional injection therapy in women with type 1 diabetes mellitus. STUDY DESIGN: This is a retrospective cohort study of women with type 1 diabetes mellitus (DM) enrolled in the California Diabetes and Pregnancy Program (CDAPP) between 2001 and 2004. Women managed with insulin pump infusion were compared to those treated with conventional insulin injections. Measures of glycemic control and perinatal outcomes were examined using Student´s t and chi-square tests. Potential confounders, including maternal age, parity, ethnicity, gestational age entering CDAPP, and weight gain during pregnancy, were controlled for using multivariate logistic regression analyses. A p-value !0.05 and 95% confidence intervals (CI) were used to indicate statistical significance. RESULTS: Among the 688 women with type 1 DM, 60 (8.7%) were treated with insulin pumps and 628 (91.3%) with insulin injections. Women managed on insulin pumps had lower mean of hemoglobin (Hgb) A1c values compared to those with insulin injections (6.7% vs. 7.7%, p!0.001). They were also less likely to undergo cesarean delivery (see Table). CONCLUSION: Women with type 1 DM managed with insulin pump are more likely to have a lower HgbA1c !6.0% and lower rates of cesarean delivery, but no differences in rates of preterm delivery, birthweight, or intensive care nursery admission. Insulin pump compared to insulin injections
Hgb A1c!6.0% Cesarean delivery Preterm delivery Birthweight O4000gm Intensive care nursery admission
Insulin Pump (n = 60)
Insulin Injection (n = 628)
Adjusted OR (95% CI)
25.0% 44.6% 30.3% 15.0% 38.7%
12.6% 58.8% 28.5% 14.0% 34.9%
3.37 0.51 0.97 0.72 1.06
(1.08-10.5) (0.21-0.96) (0.48-1.95) (0.30-1.73) (0.42-2.68)
391 TOWARDS BETTER UNDERSTANDING OF PRE-ECLAMPSIA: COMPARATIVE PROTEOMIC ANALYSIS USING PREECLAMPTIC PLACENTA YOUNG NAM KIM1, DAE HOON JEONG1, SU JEON JEONG1, DAE SHIM LEE2, HYUNG KYU KIM3, NARI KIM3, MOHAMAD WARDA3, JIN HAN3, KI TAE KIM1, 1InJe University, Obstetrics & Gynecology, Busan, South Korea, 2InJe University, Paik Institute for Clinical reserch, Busan, South Korea, 3InJe University, Department of Physiology, Busan, South Korea OBJECTIVE: Preeclampsia, a pregnancy-specific syndrome of hypertension, proteinuria, and other systemic disturbance, is a state of widespread endothelial dysfunction secondary to defective placentation. Our research was trying to reveal possible placental factors to explain pathogenesis of preclampsia. STUDY DESIGN: We performed comparative analysis of differentially expressed placental proteins with placenta from eight normal pregnancies and eight pregnancies complicated by preeclampsia. Proteome analysis was performed using 2D gel electrophoresis and MALDI-TOF MS analysis. The MALDI-TOF MS identified proteins were confirmed by western blotting analysis. RESULTS: The results revealed 20 highly expressed proteins in preeclamptic placenta. The double fold increase in smooth muscle myosin light chain, as shown in preeclampsia over normal group, provides an evidence of disrupted placental development with inefficient transformation of placental vessels into low-resistance channels. The resultant intermittent ischemic stress with possible oxidative damage evoked expression of both anti-stress chaperonin and anti-oxidative damage isocitrate dehydrogenase. The observed over expression of wide range of multi-conductance channels e.g. voltage-dependant anion channel and nuclear chloride channel, are more likely to initiate tipping the delicate balance towards placental apoptosis with consequent up-regulation of degenerative cellular protease activity e.g. cathepsin D. Moreover, additional ultimate anti-stress defensive mechanisms have to be activated. Therefore, glutathione S-transferases and aldehyde reductase were up regulated to compete with the electrophilic endobiotics and toxic lipid-derived aldehydes, respectively. Interestingly, ER-60 protease (also named ERp57) over expression evidently proves immune defense strategy remodeling in preeclampsia group. CONCLUSION: Although the precise mechanism by which preeclampsia disrupts placental function is still in debate, the current finding affords many contact points explanation about its possible related stress alterations. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.427
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.425
390 MATERNAL SERUM IL-16 LEVELS WERE ELEVATED IN WOMEN WITH PREECLAMPSIA COMPARED TO THAT IN WOMEN WITH NORMAL PREGNANCIES YUPING WANG1, YANPING ZHANG1, YANG GU1, LISA PHILIBERT1, DAVID LEWIS1, 1 Louisiana State University Medical Center at Shreveport, OB/GYN, Shreveport, Louisiana OBJECTIVE: IL-16 plays an important role in innate immune responses and exerts chemo-attractant activity for T cells. The functional bioactivity of IL-16 is related to T cell migration, cell cycle progression, and inhibition of HIV replication. IL-16 also plays a role during inflammatory response and it is spontaneously released during apoptosis by peripheral blood monocytes. This study was undergone to evaluate if altered IL-16 levels occur in women with preeclampsia (PE). STUDY DESIGN: Maternal serum samples were extracted from venous blood obtained from 71 pregnant women at the time of admission to Labor and Delivery Unit at LSUHSC-Shreveport with 34 normal and 37 PE pregnancies. Serum concentrations for IL-16 were measured by enzyme-linked immunosobent assay (ELISA). All samples were measured in duplicate. Data were analyzed by nonparametric Mann Whitney test. A p level less than 0.05 was considered statistically different. We also examined: 1) IL-16 expression in maternal vessel endothelium by immunohistochemical staining of subcutaneous (sc) fat tissues obtained during the time of cesarean section; and 2) IL-16 mRNA expression in isolated maternal leukocytes by RT-PCR. RESULTS: Maternal serum IL-16 concentrations were significantly higher in PE than in normal pregnancies, 442.41 G 53.19 vs. 217.26 G 29.57 pg/ml (mean G S.E.), p ! 0.001, with Power = 0.946, Alpha = 0.05, Tail = 2, respectively. IL-16 was positively expressed in maternal vascular endothelium from both normal and PE pregnancies. IL-16 c-terminal mRNA expression was reduced in leukocytes from PE. CONCLUSION: The positive expression of IL-16 in vascular endothelium and leukocytes implicate that this cytokine may be involved in immune, inflammatory, and apoptotic processes in the maternal vascular system during normal pregnancy. A higher serum level of IL-16 in women with PE may constitute the exaggerated inflammatory response and altered immune system in the PE syndrome. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.426
392 EXAGGERATED HYPOXIA-RELATED ENDOTHELIN-1 (ET-1) PRODUCTION IN PREECLAMPTIC PLACENTAE COMPARING TO NORMAL PLACENTAE YONGWON PARK1, JA-YOUNG KWON1, YOUNG-HAN KIM1, YURI KIM1, JAE-HAK LIM1, MOUNG-HWA KANG1, 1Yonsei University College of Medicine, Department of Obstetrics and Gynecology, Seoul, South Korea OBJECTIVE: To evaluate endothelin-1 (ET-1) expression in the villous explants from normal and preeclamptic (PE) placentae under hypoxic condition. STUDY DESIGN: Villous explants from normal (n = 5) and PE (n = 4) placentae were obtained. To obtain hypoxic culture condition, villous explants were cultured in hypoxic chamber or treated with deferoxamine (DFO). ET-1 mRNA expressions in villous explants were evaluated by RT-PCR following 0, 24, and 48 h of culture in hypoxic chamber, and 0, 2, 4, 6 h following DFO treatment. ET-1 protein levels in media were measured by enzyme immunoassay. RESULTS: After 24 and 48hours of incubation of villous explants from normal and PE placentaein hypoxic chamber, ET-1 mRNA and protein level increased in both group, however, ET-1 production seemed to be more exaggerated in the villous from PE placenta. During 6 h of DFO exposure, ET1 mRNA level was increased in the villous explants from PE placenta comparing to those from normal placenta (p!0.05). Interestingly, the increase in the villous explants from PE placenta was enhanced than those from normal placenta. Concordantly, increments of protein level between 0 to 2h and 2 to 4 h were significantly higher in villous explants from PE placenta(p!0.05). CONCLUSION: ET-1 mRNA and protein were increased in villous explants from PE placenta compared to those from normal placenta. Furthermore, villous explants from PE placenta showed upregulated ET-1 expression upon hypoxic stimulation. This enhanced sensitivity to hypoxia may contribute to ET-1 overexpression in PE placenta in vivo and it needs further investigation for clarification. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.428
Hgb A1c!6.0% Cesarean delivery Preterm delivery Birthweight O4000gm Intensive care nursery admission
Insulin Pump (n = 60)
Insulin Injection (n = 628)
Adjusted OR (95% CI)
25.0% 44.6% 30.3% 15.0% 38.7%
12.6% 58.8% 28.5% 14.0% 34.9%
3.37 0.51 0.97 0.72 1.06
(1.08-10.5) (0.21-0.96) (0.48-1.95) (0.30-1.73) (0.42-2.68)
391 TOWARDS BETTER UNDERSTANDING OF PRE-ECLAMPSIA: COMPARATIVE PROTEOMIC ANALYSIS USING PREECLAMPTIC PLACENTA YOUNG NAM KIM1, DAE HOON JEONG1, SU JEON JEONG1, DAE SHIM LEE2, HYUNG KYU KIM3, NARI KIM3, MOHAMAD WARDA3, JIN HAN3, KI TAE KIM1, 1InJe University, Obstetrics & Gynecology, Busan, South Korea, 2InJe University, Paik Institute for Clinical reserch, Busan, South Korea, 3InJe University, Department of Physiology, Busan, South Korea OBJECTIVE: Preeclampsia, a pregnancy-specific syndrome of hypertension, proteinuria, and other systemic disturbance, is a state of widespread endothelial dysfunction secondary to defective placentation. Our research was trying to reveal possible placental factors to explain pathogenesis of preclampsia. STUDY DESIGN: We performed comparative analysis of differentially expressed placental proteins with placenta from eight normal pregnancies and eight pregnancies complicated by preeclampsia. Proteome analysis was performed using 2D gel electrophoresis and MALDI-TOF MS analysis. The MALDI-TOF MS identified proteins were confirmed by western blotting analysis. RESULTS: The results revealed 20 highly expressed proteins in preeclamptic placenta. The double fold increase in smooth muscle myosin light chain, as shown in preeclampsia over normal group, provides an evidence of disrupted placental development with inefficient transformation of placental vessels into low-resistance channels. The resultant intermittent ischemic stress with possible oxidative damage evoked expression of both anti-stress chaperonin and anti-oxidative damage isocitrate dehydrogenase. The observed over expression of wide range of multi-conductance channels e.g. voltage-dependant anion channel and nuclear chloride channel, are more likely to initiate tipping the delicate balance towards placental apoptosis with consequent up-regulation of degenerative cellular protease activity e.g. cathepsin D. Moreover, additional ultimate anti-stress defensive mechanisms have to be activated. Therefore, glutathione S-transferases and aldehyde reductase were up regulated to compete with the electrophilic endobiotics and toxic lipid-derived aldehydes, respectively. Interestingly, ER-60 protease (also named ERp57) over expression evidently proves immune defense strategy remodeling in preeclampsia group. CONCLUSION: Although the precise mechanism by which preeclampsia disrupts placental function is still in debate, the current finding affords many contact points explanation about its possible related stress alterations. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.427
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.425
390 MATERNAL SERUM IL-16 LEVELS WERE ELEVATED IN WOMEN WITH PREECLAMPSIA COMPARED TO THAT IN WOMEN WITH NORMAL PREGNANCIES YUPING WANG1, YANPING ZHANG1, YANG GU1, LISA PHILIBERT1, DAVID LEWIS1, 1 Louisiana State University Medical Center at Shreveport, OB/GYN, Shreveport, Louisiana OBJECTIVE: IL-16 plays an important role in innate immune responses and exerts chemo-attractant activity for T cells. The functional bioactivity of IL-16 is related to T cell migration, cell cycle progression, and inhibition of HIV replication. IL-16 also plays a role during inflammatory response and it is spontaneously released during apoptosis by peripheral blood monocytes. This study was undergone to evaluate if altered IL-16 levels occur in women with preeclampsia (PE). STUDY DESIGN: Maternal serum samples were extracted from venous blood obtained from 71 pregnant women at the time of admission to Labor and Delivery Unit at LSUHSC-Shreveport with 34 normal and 37 PE pregnancies. Serum concentrations for IL-16 were measured by enzyme-linked immunosobent assay (ELISA). All samples were measured in duplicate. Data were analyzed by nonparametric Mann Whitney test. A p level less than 0.05 was considered statistically different. We also examined: 1) IL-16 expression in maternal vessel endothelium by immunohistochemical staining of subcutaneous (sc) fat tissues obtained during the time of cesarean section; and 2) IL-16 mRNA expression in isolated maternal leukocytes by RT-PCR. RESULTS: Maternal serum IL-16 concentrations were significantly higher in PE than in normal pregnancies, 442.41 G 53.19 vs. 217.26 G 29.57 pg/ml (mean G S.E.), p ! 0.001, with Power = 0.946, Alpha = 0.05, Tail = 2, respectively. IL-16 was positively expressed in maternal vascular endothelium from both normal and PE pregnancies. IL-16 c-terminal mRNA expression was reduced in leukocytes from PE. CONCLUSION: The positive expression of IL-16 in vascular endothelium and leukocytes implicate that this cytokine may be involved in immune, inflammatory, and apoptotic processes in the maternal vascular system during normal pregnancy. A higher serum level of IL-16 in women with PE may constitute the exaggerated inflammatory response and altered immune system in the PE syndrome. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.426
392 EXAGGERATED HYPOXIA-RELATED ENDOTHELIN-1 (ET-1) PRODUCTION IN PREECLAMPTIC PLACENTAE COMPARING TO NORMAL PLACENTAE YONGWON PARK1, JA-YOUNG KWON1, YOUNG-HAN KIM1, YURI KIM1, JAE-HAK LIM1, MOUNG-HWA KANG1, 1Yonsei University College of Medicine, Department of Obstetrics and Gynecology, Seoul, South Korea OBJECTIVE: To evaluate endothelin-1 (ET-1) expression in the villous explants from normal and preeclamptic (PE) placentae under hypoxic condition. STUDY DESIGN: Villous explants from normal (n = 5) and PE (n = 4) placentae were obtained. To obtain hypoxic culture condition, villous explants were cultured in hypoxic chamber or treated with deferoxamine (DFO). ET-1 mRNA expressions in villous explants were evaluated by RT-PCR following 0, 24, and 48 h of culture in hypoxic chamber, and 0, 2, 4, 6 h following DFO treatment. ET-1 protein levels in media were measured by enzyme immunoassay. RESULTS: After 24 and 48hours of incubation of villous explants from normal and PE placentaein hypoxic chamber, ET-1 mRNA and protein level increased in both group, however, ET-1 production seemed to be more exaggerated in the villous from PE placenta. During 6 h of DFO exposure, ET1 mRNA level was increased in the villous explants from PE placenta comparing to those from normal placenta (p!0.05). Interestingly, the increase in the villous explants from PE placenta was enhanced than those from normal placenta. Concordantly, increments of protein level between 0 to 2h and 2 to 4 h were significantly higher in villous explants from PE placenta(p!0.05). CONCLUSION: ET-1 mRNA and protein were increased in villous explants from PE placenta compared to those from normal placenta. Furthermore, villous explants from PE placenta showed upregulated ET-1 expression upon hypoxic stimulation. This enhanced sensitivity to hypoxia may contribute to ET-1 overexpression in PE placenta in vivo and it needs further investigation for clarification. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.428