Piotr Pierzynski

Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregnant women

Background: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocininduced 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 stips 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 pA2 values were calculated. Results: Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 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.

The effect of combined tocolysis on in vitro uterine contractility in preterm labour

PURPOSE Animal models have confirmed high efficiency of combined tocolytic treatment in preterm labour. In humans, the recommended doses of tocolytic drugs prolong pregnancy in threatened preterm labour. The aim of the study was to evaluate the inhibitory effect of dual combinations of atosiban, nifedipine and celecoxib on human myometrial strips contractility on the in vitro model of preterm labour. MATERIAL/METHODS Two groups of patients who delivered by cesarean section were involved in the study: 36 patients who delivered preterm between the 24(th) and 34(th) week of pregnancy and 40 patients who delivered at term. Myometrial samples were obtained from the lower uterine segment during cesarean sections. Contractile activity was recorded with digital software for each drug combination: atosiban/nifedipine; atosiban/celecoxib, nifedipine/celecoxib. Tocolytic efficiency of the drug combinations was assessed using IC(50) parameter - a molar drug concentration inhibiting 50% of contractility. RESULTS The atosiban/nifedipine combination has shown additive tocolytic effect on myometrial strips contractility in preterm and term patients. The other combinations: atosiban/celecoxib and nifedipine/celecoxib presented only antagonistic effects in both studied groups. CONCLUSIONS The effect of the combined therapy on human myometrial contractility presented in the study could be a base for further in vivo clinical trials.

Potential first trimester metabolomic biomarkers of abnormal birth weight in healthy pregnancies

Macrosomia and low birth weight (LBW) can be associated with pregnancy complications and may affect the long‐term health of the child. The aim of this study was to evaluate the metabolomic serum profiles of healthy pregnant women to identify early biomarkers of macrosomia and LBW and to understand mechanisms leading to abnormal fetal growth not related to mothers body mass index or presence of gestational diabetes.

Effect of short-term, low-dose treatment with tamoxifen in patients with primary dysmenorrhea

Current treatment of painful periods and other symptoms related to primary dysmenorrhea (PD) is usually commenced with non-steroidal anti-inflammatory drugs or oral contraceptives, which fails in about 10% of affected patients. Tamoxifen, a selective estrogen-receptor modulator (SERM), has been demonstrated to directly inhibit uterine contractions, causing improvement in uterine blood flow. It could be considered for application in selected groups of dysmenorrheic patients, for instance carriers of breast cancer-associated antigen (BRCA) genes, breast cancer survivors or women with advanced endometriosis. Thus the aim of the present study was to investigate the effect of short-term treatment with tamoxifen on PD and PD-related symptoms, as well as its direct effect on parameters of intrauterine pressure during the painful menstruation, in a group of dysmenorrheic patients. After two cycles of administration of tamoxifen we noted a significant decrease in bleeding together with reductions in the severity of menstrual cramps, diarrhea, headache, fatigue and anxiety. In intrauterine pressure assessments, tamoxifen significantly decreased propagation of uterine contractions. In conclusion, SERMs such as tamoxifen may constitute a therapeutic option in selected groups of patients, improving dysmenorrheic symptoms. Additionally to its receptor-mediated effects, tamoxifen was shown to exert a direct influence on uterine contractile activity that may explain the decrease of menstrual pain and cramps noted in the studied group.

New research models and novel signal analysis in studies on preterm labor: a key to progress?

Preterm labor affects up to 20% of pregnancies, is considered a main cause of associated neonatal morbidity and mortality and is responsible for neonatal care costs of multimillion euros. In spite of that, the commercial market for this clinical indication is rather limited, which may be also related to high liability. Consequently, with only a few exceptions, preterm labor is not in the orbit of great interest of the pharmaceutical industry. Coordinated effort of research community may bring the change and help required to reduce the influence of this multifactorial syndrome on society. Between the novel techniques that are being explored in a SAFE (The Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network) group, there are new research models of preterm labor as well as novel methodology of analysis of biological signals. In this article, we briefly describe new clinical and nonclinical human models of preterm labor as well as summarize some novel methods of data processing and analysis that may be used in the context of preterm labor.

Oxytocin and fetal membranes in preterm labor: current concepts and clinical implication

Preterm birth is associated with up to 90% of perinatal deaths. In spite of numerous clinical and preclinical research programs ,its incidence has not changed throughout the past decade. An observation that the oxytocin antagonist atosiban delays preterm labor and is significantly more potent than vasopressin1a receptors gave rise to research on the role of vasopressin blockade in tocolysis and vasopressin itself in preterm labor. Successful tocolysis allows the introduction of intrauterine steroid treatment of the fetus ,which reduces the chance of developing infant respiratory distress syndrome and intracranial hemorrhage. Fetal membranes ,decidua and placenta are considered a possible site of initiation of parturition ,both term and preterm. Research on the biology of these tissues may shed new light on current concepts of the pathophysiology of preterm labor. We here present a short review on the role of oxytocin ,oxytocin receptor blockade and fetal membranes in preterm labor.