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  • Gustafsson, JA (författare)
  • Novel aspects of estrogen action
  • 2000
  • Ingår i: Journal of the Society for Gynecologic Investigation. - 1071-5576. ; 7:11 Suppl, s. S8-S9
  • Tidskriftsartikel (refereegranskat)
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  • Nash, Peppi, et al. (författare)
  • Placental dysfunction in Suramin-treated rats : impact of maternal diabetes and effects of antioxidative treatment
  • 2005
  • Ingår i: Journal of the Society for Gynecologic Investigation. - : Springer Science and Business Media LLC. - 1071-5576 .- 1556-7117. ; 12:3, s. 174-184
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model. METHODS: Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20. RESULTS: In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E. CONCLUSION: Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.
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  • Pierzynski, P, et al. (författare)
  • Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregnant women
  • 2004
  • Ingår i: Journal of the Society for Gynecologic Investigation. - : Springer Science and Business Media LLC. - 1071-5576. ; 11:6, s. 384-387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound. OBJECTIVE: To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term. METHODS: Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin, administration to isolated myometrial strips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA(2) values were calculated. RESULTS: Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA(2) value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA(2), results were 9.89 and 7.8 1, respectively. None of these pA(2) values differed to any statistically significant degree. CONCLUSION: The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor. Copyright (C) 2004 by the Society for Gynecologic Investigation.
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