Gurkan Yazici

Effects of HA-1077 and Y-27632, two rho-kinase inhibitors, in the human umbilical artery

A role for the small G protein rho and rho-kinase has been shown in smooth muscle contraction regarding Ca++ sensitivity. However, there are no data in the literature assessing how this system operates in human umbilical arteries (HUA). Therefore, we evaluated the effects of HA-1077 and Y-27632, two rho-kinase inhibitors, on agonist-(5-hydroxytryptamine [5-HT]) and depolarization-induced (KCl) contractions of HUA. HA-1077 and Y-27632 inhibited 5-HT-induced contractile responses at 10−4M concentration but not at 10−5M. HA-1077 at 10−4M also significantly attenuated contractions induced by 20 mM KCl. In addition, HUA precontracted with 5-HT relaxed concentration dependently in response to HA-1077 and Y-27632. When precontracted with KCl, HUA also relaxed dose-dependently in response to HA-1077, but the maximal relaxation was significantly smaller than the response obtained when precontracted with 5-HT. To determine possible involvement of rho-kinase on agonist-induced intracellular calcium-mediated contractions, tissues were precontracted with 5-HT in Ca++-free Krebs solution before cumulative addition of HA-1077 or Y-27632 (10−7 to 10−4M). Both rho-kinase inhibitors relaxed HUA completely. Maximum relaxations of HUA to HA-1077 and Y-27632 were significantly larger than the responses seen in normal Krebs solution and were obtained with lower concentrations of the drugs considered to be more specific for rho-kinase inhibition. However, preincubation of HUA with HA-1077 or Y-27632 (10−5M for both) did not affect the 5-HT-induced contractions in this medium. Finally, immunoblot experiments revealed the expression of rho-kinase isoform rockII protein in HUA. These results indicate that rhoA/rho-kinase pathway can contribute to agonist-induced contractions of HUA. However, this effect appears to be limited to intracellular calcium-induced contractions and may be more important in sustaining contractions rather than the initial phase of force development.

Progressive Cervical Length Changes versus Single Cervical Length Measurement by Transvaginal Ultrasound for Prediction of Preterm Delivery

Background: To evaluate cervical length changes as predictors of preterm delivery. Methods: Two hundred and fifty-seven pregnant women underwent transvaginal ultrasound examination at 16 and 24 weeks of gestation. Cervical length was measured and the difference between the 2 measurements was calculated. The sensitivity, specificity, positive predictive value and negative predictive value of cervical length and cervical length changes were calculated and these methods were compared by receiver-operating characteristic (ROC) curve analysis. Results: Preterm delivery (before 37 weeks of gestation) occurred in 19 patients (7.4%). The mean cervical length was shorter in the preterm group, the area under the ROC curve for prediction of preterm delivery was 0.914, ultrasound had a sensitivity of 84.2% to predict preterm delivery with a false-positive rate of 18.5%, and the relative risk was 4.56 at the 34.3-mm cutoff value at 24 weeks of gestation. In contrast, a cervical length change on transvaginal ultrasound had a sensitivity of 73.3% to predict preterm delivery with a false-positive rate of 18.1%, and the relative risk was 4.08 at the 6.6-mm cutoff value. Conclusion: A single cervical length measurement obtained at 24 weeks of gestation can predict preterm delivery as accurately as cervical length change.