Karol Dokus

Anti-apoptotic and pro-apoptotic gene expression evaluated from eutopic endometrium in the proliferative phase of the menstrual cycle among women with endometriosis and healthy controls

OBJECTIVE Endometriosis affects 5-15% of women in the general population and 40% of women seeking infertility evaluation. Its etiology and pathogenesis is controversial. Abnormalities of genes involved in the regulation of apoptosis have been thought to play a role in origin. Hence, we investigated the expression of pro-apoptotic and anti-apoptotic genes in eutopic endometrium from women with endometriosis and healthy controls in relation to disease occurrence and severity. STUDY DESIGN A prospective study in women undergoing laparoscopic surgery for pelvic pain was conducted. In total, 45 women (30 healthy controls and 15 patients) matched inclusion criteria. The mRNA expression of apoptotic genes (p53, Bcl-x(L,S) and Bax) from eutopic endometrium was detected by RT-PCR. RESULTS A significant increase in expression of mRNA p53 (1.42 versus 1.02; p<0.05), and Bcl-x(S) (0.41 versus 0.19; p=0.0006) was found in women with endometriosis compared to healthy controls. Insignificantly increased expression was found for Bax (1.22 versus 1.15). The expression of anti-apoptotic Bcl-x(L) was unchanged (1.08 versus 1.07). The Bcl-x(L)/Bcl-x(S) ratio was twofold higher (5.63 versus 2.63) in controls. By stratifying patients by disease stage we have revealed an increased mRNA expression of apoptotic genes in patients with grades III-IV endometriosis compared to those with grades I-II. However, the difference was significant only for Bcl-x(S) expression (p<0.05). CONCLUSIONS Results suggest that an increased transcription of pro-apoptotic genes (p53 and Bcl-x(S)) in eutopic endometrium is significantly associated with endometriosis, which indicates dysregulation of apoptotic gene transcription associated with disease.

Fibronectin, plasminogen activator inhibitor type 1 (PAI-1) and uterine artery Doppler velocimetry as markers of preeclampsia

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups. Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p < 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia. Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.

Participation of BKCa2+ and KATP potassium ion channels in the contractility of human term pregnant myometrium in in vitro conditions

Aim:  The aim of this study was to assess the participation of ligand‐sensitive potassium large conductance calcium‐activated ion channels (BKCa2+) and adenosine triphosphate (ATP)‐sensitive potassium ion channels (KATP) using its openers (NS1619 and pinacidil) in the contractility of human term pregnant myometrium in in vitro conditions.

Utero‐relaxant effect of PDE4‐selective inhibitor alone and in simultaneous administration with β2‐mimetic on oxytocin‐induced contractions in pregnant myometrium

Background:  The objective of the study was to observe the effect of rolipram, the prototype phosphodiesterase 4 selective inhibitor, on oxytocin‐induced contractions of human term myometrial strips, and compare the effect with salbutamol, β2‐adrenergic agonist, in single and the simultaneous application.

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Background/Aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. Methods: Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Students t test and, for categorical variables, the Pearson χ2 or Fishers exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. Results: The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.

Uterine activity and ductus venosus flow velocity patterns during the first stage of labor

Objective: To analyze the effects of uterine contractions on ductus venosus (DV) pulsatility during the first stage of labor. Methods: Twenty healthy women were examined. Measurements were taken at three stages of cervical dilatation (< 4 cm, 4–7 cm and ≥ 8 cm) during and between contractions. Peak velocity during ventricular systole (S) and atrial contraction (A), pulsatility index for veins (DV PIV), ductus venosus index (DVI) and the S/A ratio were measured. Results: The DV was observed successfully in 16 cases. The mean S velocity did not change significantly (64 cm/s during and 65 cm/s between contractions). The mean A velocity decreased significantly from 35 cm/s measured between contractions to 29 cm/s during contractions (P < 0.0001). The mean DV PIV and DVI were significantly higher during contractions (0.72 and 0.55) than between contractions (0.57 and 0.45) (P < 0.0001). There were no significant differences in means between stages of cervical dilatation. Conclusion: Significant differences during and between uterine contractions can be observed in DV pulsatility during normal labor.

Recurrent secondary postpartum hemorrhages due to placental site vessel subinvolution and local uterine tissue coagulopathy

BackgroundPostpartum hemorrhage (PPH) represents a serious problem for women and obstetricians. Because of its association with hemorrhagic shock and predisposition to disseminated coagulopathy, it is a leading cause of maternal deaths worldwide. Furthermore, the jeopardy of PPH is rising with the secondary form of PPH occurring between 24 hours and 6 weeks postpartum, when women are already discharged home. The causes of this pathology are severe inflammation (endometritis), inherited coagulation disorders, consumptive coagulopathy, and retained products of conceptions. Others are of rare occurrence, such as vessel subinvolution (VSI) of the placental implantation site, uterine artery pseudoaneurysm, or trauma.Case presentationWe present a rare form of recurrent secondary postpartum hemorrhage in a woman after uncomplicated cesarean delivery, with review of the literature linked to the management of this situation originating in the rare local VSI in the placental implantation site, defective decidual homeostasis, and coagulopathy confined to the uterus.ConclusionThe placental site VSI is one of the rare causes of secondary PPH, and this situation is frequently underdiagnosed by clinicians. The histological confirmation of dilated “clustered”-shaped myometrial arteries partially occluded by thrombi of variable “age” together with the presence of endovascular extravillous trophoblasts confirms the diagnosis.

Impact of fetal pulse oximetry and ST analysis surveillance withdrawal on rates of obstetric surgery and frequency of low birth umbilical artery pH: a cause of rising caesarean rates?

A retrospective observational study on a sample of 13,413 deliveries analysed the effect of a withdrawal of the CTG additional diagnostic methods of fetal hypoxia (fetal pulse oximetry and ST analysis of the fetal ECG) on operative delivery rates and frequency of the umbilical arterial pH < 7.15. Following the withdrawal, obstetricians are more likely to perform caesarean sections for fetal hypoxia (OR 2.23, 95% CI 1.94–2.55, p < 0.0001) and labour dystocia (OR 1.45, 95% CI 1.18–1.77, p = 0.0003), which increases the overall caesarean rate (OR 1.49, 95% CI 1.38–1.61, p < 0.0001), although decreases the incidence of birth umbilical arterial pH < 7.15 (OR 0.43, 95% CI 0.22–0.85, p = 0.015). This also leads to the significant decline in overall frequency of instrumental vaginal deliveries (OR 0.58, 95% CI 0.48–0.71). In order to decrease the overall caesarean rate, obstetricians need to be supported by more accurate and possibly automated diagnostic tools for intrapartum fetal hypoxia.

Physiological changes in blood flow velocities in the superior mesenteric and coeliac artery in healthy term fetuses and newborns during perinatal period.

Objective. The aim was to describe the course of physiological changes in coeliac artery (CA) and superior mesenteric artery (SMA) blood flow velocities (BFVs) during the perinatal period in healthy term fetuses and infants as it has not been studied in detail so far. Methods. This prospective Doppler ultrasound study included 50 infants. The examinations were performed in a fetus after the completion of 36.0 gestation weeks before the onset of labor and in infants postnatally at the ages of 2, 24, and 72 h. Results. The end-diastolic velocity (EDV) in the CA was generally higher than in the SMA (p < 0.001). The EDV in the SMA decreased postnatally (8.4 vs. −7.2, p < 0.001) and showed negative values in 92% of infants. By 24 h of postnatal age, EDV in the SMA had become positive in all of the infants (mean 13.8 cm/s, p < 0.001). The EDV in CA had only positive values. The changes in EDV in both vessels were reflected by changes in the resistance index in inverse manner. Conclusions. BFV in the CA and SMA changed dramatically in the perinatal period; the most remarkable changes occurred within the first 24 h of life.

Comment on: Goldberg et al. Circadian Variation in the Response to the Glucose Challenge Test in Pregnancy: Implications for Screening for Gestational Diabetes Mellitus. Diabetes Care 2012;35:1578–1584

We read with great interest the article by Goldberg et al. (1), in which the authors sought to further characterize the metabolic phenotype of the population of pregnant women with the positive glucose challenge test (GCT) test in relation to the time of day when the test was done. They found that women who had GCT done in the afternoon have a better metabolic function and a lower risk of subsequent gestational diabetes mellitus (GDM) on the consecutive oral glucose tolerance test (OGTT). In other …