Cadmium and Lead in Women Who Miscarried.

BACKGROUND: Cadmium (Cd) and lead (Pb) are toxic elements which, when ingested excessively in food and drinking water, accumulate in selected organs and pass through the placenta barrier to the foetus, showing teratogenic effects. The aim of the study was to determine the concentration of Cd and Pb in blood and placental tissue in women who miscarried. METHODS: The study group consisted of 83 women who miscarried. The control group included 35 women in the first trimester of pregnancy and after childbirth. The experimental materials consisted of whole blood and fragments of placental tissue. The concentrations of Cd and Pb were determined using atomic absorption spectrometry (AAS) with electrothermal atomization in a graphite furnace and by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in standard mode. RESULTS: The average concentration of Cd (2.730 ± 2.07 µg/L) and Pb (35.54 ± 11.0 µg/L) in the blood of women with miscarriage was higher in comparison to the level of these toxic metals in the blood of women from the control group (Cd 1.035 ± 0.59 µg/L; Pb 27.11 ± 4.6 µg/L). The average Cd (214.4 ± 514 µg/L) and Pb (199.6 ± 348 µg/L) content in the placenta of women with miscarriage was higher in comparison to the amount of these elements in the placenta of women from the control group (Cd 127.4 ± 85 ng/L; Pb 26.35 ± 7.9 ng/L). Tobacco smoking significantly affected cadmium blood levels and the placental tissue content in women who miscarried. CONCLUSIONS: Elevated Cd and Pb concentrations in the blood and placenta of pregnant women may be connected with the occurrence of miscarriage; therefore, the levels of these heavy metals should be monitored in women who plan pregnancy. It seems that determining the level of molar ratio between toxic metal and antioxidant elements can be analyzed as a marker for selection for control examinations as a valuable complement to existing diagnostic procedures in prevention, especially in early pregnancy. Additional diagnostic methods should be established as new tools in perinatal care in order to enable early diagnosis of pregnancy pathology and, especially, to prevent miscarriage.

Differences in permeability of preterm and term fetal membranes to calcium ions - Preliminary report.

The metabolic activity of amniochorion contributes to the control of activation of labor-type uterine contractions. The study presents an experimental model of transport of calcium ions across the human amniochorion sampled directly after cesarean section in patients delivering both at term and prematurely. Transmembrane transport of calcium ions was lower in preterm vs. term tissue samples. The differences in permeability were most pronounced in the first 60 min of experiments. The results of the study provide evidence for the existence of an active mechanism of calcium transport which can contribute to regulating the contractility of the uterus.

Antioxidant status in women who have had a miscarriage.

PURPOSE: During normal pregnancy there is an oxido-reductive balance between action of pro-oxidative factors. The aim of this study was to evaluate the total antioxidant status (TAS) and glutathione peroxidase (GSH-Px) activity, and the content of selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) in women who have had a miscarriage. PATIENTS AND METHODS: The study group consisted of 83 women who had had miscarriages. The control group included 35 women in the first trimester of pregnancy, and 35 pregnant women after childbirth. RESULTS: TAS activity and Cu concentration in serum in women who experienced a miscarriage were significantly lower, but Mn level - higher, than in women in the first trimester of pregnancy. The content of Se, Cu and Mn in placental tissue in patients who have had a miscarriage was significantly higher, while Zn content was lower than in pregnant women at full-term delivery. CONCLUSIONS: Our findings, provided in the research, enable us to claim that the total antioxidative status is significantly lower in women who have had a miscarriage. Low level of Zn but high of Mn in the examined biological material may be indicative to the incidence of miscarriage.

Chemokines profiling of patients with preterm birth.

INTRODUCTION: Nowadays it is thought that the main cause of premature birth is subclinical infection. However, none of the currently used methods provide effective prevention to preterm labor. The aim of the study was to determine the concentration of selected chemokines in sera of patients with premature birth without clinical signs of infection (n = 62), threatened preterm labor (n = 47), and term births (n = 28). METHOD: To assess the concentration of chemokines in the blood serum, we used a multiplex method, which allows the simultaneous determination of 40 chemokines per sample. The sets consist of the following chemokines: 6Ckine/CCL21, Axl, BTC, CCL28, CTACK/CCL27, CXCL16, ENA-78/CXCL5, Eotaxin-3/CCL26, GCP-2/CXC, GRO (GRO α /CXCL1, GRO ß /CXCL2 and GRO γ /CXCL3), HCC-1/CCL14, HCC-4/CCL16, IL-9, IL-17F, IL18-BPa, IL-28A, IL-29, IL-31, IP-10/CXCL10, I-TAC/CXCL11, LIF, LIGHT/TNFSF14, Lymphotactin/XCL1, MCP-2/CCL8, MCP-3/CCL7, MCP-4/CCL13, MDC/CCL22, MIF, MIP-3 α /CCL20, MIP-3- ß /CCL19, MPIF-1/CCL23, NAP-2/CXCL7, MSP α , OPN, PARC/CCL18, PF4, SDF-1/CXCL12, TARC/CCL17, TECK/CCL25, and TSLP. RESULTS: We showed possible implication of 4 chemokines, that is, HCC-4, I-TAC, MIP-3 α , and TARC in women with symptoms of preterm delivery. CONCLUSION: On the basis of our findings, it seems that the chemokines may play role in the pathogenesis of preterm labor. Defining their potential as biochemical markers of preterm birth requires further investigation on larger group of patients.

Assessment of the selected biochemical markers in predicting preterm labour.

OBJECTIVE: The differential diagnosis between preterm and false labour remains one of the most challenging issues in perinatal medicine. AIM: To assess the prognostic importance of the selected biochemical markers in predicting preterm labour. MATERIAL AND METHODS: 74 patients hospitalized due to threatening preterm labour. 51 women gave birth prematurely; the remaining 23 were diagnosed with false labour. We used ELISA arrays to study 13 proteins: IGFBP-1, IGFBP-2, BDNF, L-Selectin, E-Selectin, ICAM-1, PECAM, VCAM-1, MIP-1 delta (MIP-1d) MIP-3ß (MIP-3b), Eotaxin-1, Eotaxin-2, BLC. RESULTS: An increased risk of preterm labour should be expected when the serum concentration for: IGFBP-1 > 158.83 pg/ml (sens. 0.608, sp. 0.609, p < 0.0001); MIP-1d < 27.66 pg/ml (sens. 0.627, sp. 0.627, p = 0.021); BDNF >36.54 pg/ml (sens. 0.630, sp. 0.647, p = 0.002); BLC >25.46 pg/ml (sens. 0.588, sp. 0.609, p < 0.001); Eotaxin-1 >1.16 pg/ml (sens. 0.633, sp. 0.652). CONCLUSION: There have been reported statistically significant differences in serum concentrations of selected proteins in women with preterm labour and false labour.

Expression of selected genes in preterm premature rupture of fetal membranes.

OBJECTIVE: To analyse the expression of 15 genes encoding receptors and enzymes associated with the molecular mechanism of the tocolytic drugs atosiban (oxytocin receptor antagonist), nifedipine (calcium channel blocker) and celecoxib (selective cyclo-oxygenase-2 inhibitor) in preterm labor patients with premature rupture of fetal membranes in relation to symptoms of intrauterine infection and preterm labor risk factors. DESIGN: Experimental molecular study. SETTING: Tertiary obstetric care center. SAMPLE: Myometrial samples were obtained during cesarean sections from 35 patients who delivered preterm with unverified symptoms of intrauterine infection, 35 patients who delivered preterm without symptoms of intrauterine infection and 90 women who delivered at term. METHODS: The Micro Fluidic Profiling Card analytic system was used to evaluate mRNA expression of the genes of interest. MAIN OUTCOME MEASURES: The relative quantification values for mRNA expression. RESULTS: The median oxytocin receptor and cyclo-oxygenase-2 mRNA expression in preterm patients with clinical symptoms of intrauterine infection was significantly higher than in preterm patients without symptoms. The median mRNA expression of ß(1) , ß(3) and ß(4) subunits of the L-type calcium channel and prostaglandin E(2) receptor was significantly higher in preterm patients compared with term patients. CONCLUSIONS: The mRNA expression of hormones, enzymes and their receptors associated with tocolytic actions can differ in various clinical conditions. The expression of these genes is regulated at different levels and can be modified by inflammatory factors, which affect their functions.

Spontaneous rupture of unscarred uterus in the early second trimester: a case report of placenta percreta.

BACKGROUND: Prevalence of uterine rupture at delivery has been recently estimated at less than 1 in 2500 deliveries. Spontaneous uterine rupture in the early mid-trimester (16 weeks gestation or less), is far less frequent. We report a case of uterine rupture due to placenta percreta in otherwise uncomplicated pregnancy CASE: A 35-year-old, gravida 5, para 5, at 15wk 2d gestation (menstrual age) with negative history of uterine scarring suddenly developed symptoms of incipient hypovolemic shock while being hospitalized for imminent miscarriage. On exploratory laparotomy we found a midline uterine rupture infiltrated by the placenta. Supracervical hysterectomy was performed. Postoperative lab analysis confirmed the elevated serum AFP levels. CONCLUSION: Abnormal placentation and subsequent uterine rupture should be taken into consideration also in women in the second trimester who have no history of uterine instrumentation.

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery.

Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I - pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II - threatened preterm labour patients between 24-34 weeks of gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery.

Synchronization in the bivariate intrauterine pressure signals' nonlinear dynamics methods.

It was shown earlier that nonlinear processes probably generate uterine contractions. In this study, the nonlinear synchronization measures (the mutual correlation dimension, the cross-approximate entropy, the mutual information and the nonlinear interdependencies) were employed to analyze the association between two time series representing the uterine contraction activity. Here the notion of synchronization is used in a loose sense as the synonym of correlation, the similarity of the signals or the similarity of their dynamics. The signals were recorded from the different topographic regions of the uterus: the cervix and the fundus. The results obtained by means of different algorithms are different but qualitatively similar for the checked methods.

[Evaluation of carbetocin (pabal) efficacy in the prevention of the postpartum hemorrhage in women after cesarean section--preliminary report]. / Ocena skutecznosci stosowania karbetocyny w profilaktyce krwawien poporodowych u kobiet po cieciu cesarskim--doniesienie wstepne.

OBJECTIVES: The aim of this study was to evaluate the efficacy of carbetocin in prevention of PPH in women after cesarean section. MATERIAL AND METHODS: We enrolled 60 patients who had undergone cesarean section in tertiary referential center, Department of Perinatology, Medical University of Lodz, Poland, between January and June 2008. Each patient obtained a single 100 microg dose of carbetocin intravenously during cesarean section, immediately after the delivery of the baby and prior to the delivery of the placenta. We evaluated postoperative blood parameters in 2 and 12 hours after the operation, the proportion of patients requiring additional uterotonic agents and adverse events in the whole population and in the group of women with high risk of PPH. RESULTS: 58.1% of patients underwent emergency and 41.3% elective cesarean section delivery. The risk factor of PPH was identified in 38 women (63.3%). The results of this study indicate that carbetocin produces rapid and long-lasting uterine tone. A small drop in mean hemoglobin and hematocrit levels 2 and 12 hours after the operation was observed. 15% of patients required the use of additional uterotonic agents. In the group of women with high risk of PPH, carbetocin appeared to be effective in 79% of the patients. Only 11.4% of patients had minor adverse events. CONCLUSIONS: Carbetocin appears to be an effective new drug in the prevention of postpartum hemorrhage, not only among women undergoing cesarean section but also in the group of women with PPH risk factors.

Uterine contraction signals--application of the linear synchronization measures.

OBJECTIVE: In physiological research, there are not too many studies on multivariate data sets, containing two or more simultaneously recorded time series. It is important to examine synchronization in these kinds of signals. The aim of this study is to present the linear measures: the cross-correlation function, the coherence function, the wavelet cross-correlation and the wavelet coherence to assess synchronization between contractions in different topographic regions of the uterus. STUDY DESIGN: Spontaneous uterine activity was recorded directly by a dual micro-tip catheter (Millar Instruments, Inc., USA). The device consisted of two ultra-miniature pressure sensors. One sensor was placed in the fundus, the other one in the cervix. For this analysis, a healthy patient with normal contractions, a patient with dysmenorrhea, a patient with fibromyomas in the follicular phase, and the patient with endometriosis were selected. RESULTS: For each method the values of synchronization parameters for normal contractions were higher than the values of these parameters for other pairs of signals. The differences between these four groups of the uterine contraction signals were clear. The lowest values of the synchronization measures were in the case of dysmenorrheic patient. CONCLUSION: The analysis of synchronization of the uterine contractions signals may have a diagnostic value. For intrauterine pressure signals results obtained by means of different synchronization methods are different, but consistent.

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.

Reductionist and system approaches to study the role of infection in preterm labor and delivery.

A substantial number of patients with preterm labor and delivery do not show clinical signs of infection, however, it is the subclinical form which is the main causative factor and often results in premature delivery. The hitherto commonly applied methods of inflammation detection are based either on potentially hazardous amniocentesis or still insufficient inflammation-related protein measurement in the serum or other biological fluids. The advent of new "omics" technologies has led to a paradigm-shift in experimental approach which tends to primarily generate rather than form hypotheses. This has resulted in a surge of wealth of data composed of sets of individual or clusters of new genes and proteins that can be of potential importance as new markers of inflammation leading to preterm labor. It is hoped that as a result of those new methodologies the overall perception of medical research and practice would gradually change from reductionist to systems approach. Despite several successes of reductionism in the diagnosis and treatment of preterm labor it seems that system-based methodology would contribute to a more favorable personalized rather than one-for-all patient assistance. In this review we present the current knowledge on this new attractive field of medical studies with emphasis on early detection of infection related with preterm labor.

Uterine contractility: visualization of synchronization measures in two simultaneously recorded signals.

The analysis of the uterine contraction signals in nonpregnant states gives information about physiological changes during the menstrual cycle. Spontaneous uterine activity was recorded directly by a dual microtip catheter. The device consisted of two ultra-miniature pressure sensors. One sensor was placed in the fundus, the other in the cervix. It was important to identify time delays between contractions in two topographic locations, which may be of potential diagnostic significance in various pathologies: dysmenorrhea, endometriosis, and fecundity disorders. In this study the following synchronization measures-the cross-correlation, the semblance, the mutual information-were used to visualize the time delay changes over time. These measures were computed in a moving window with a width corresponding to approximately two or three contractions. As a result, the running synchronization functions were obtained. The running synchronization functions visualize changes in the propagation of the two simultaneously recorded signals. The propagation% parameter assessed from these functions allows for quantitative description of synchronization. Finally, we illustrate the use of running synchronization functions to investigate the effect of treatment with tamoxifen on primary dysmenorrhea.

[Serum cotinine level as a biomarker of tobacco smoke exposure during pregnancy]. / Stezenie kotyniny w osoczu jako biomarker czynnej i biernej ekspozycji kobiet ciezarnych na dym tytoniowy.

AIM: The aim of the study was to evaluate the reliability of self-reported smoking status and environmental tobacco smoke exposure (ETS) during pregnancy, assessing serum cotinine level. METHODS: The prospective cohort study was conducted in 2 antenatal care units in Lodz, Poland. Study population consisted of 183 pregnant women between 20-24 weeks of pregnancy. All of the women who agreed to participate in the study were interviewed to investigate certain socio-demographic, lifestyles, behavioural characteristics and obstetric background. Self-reported smoking status and ETS exposure were verified with the help of serum cotinine level. Cotinine level was analyzed by means of gas chromatography with mass spectroscopy (GC-MS). We choose more than 15 ng/ml as serum cotinine level for smokers, 2-15 ng/ml for ETS exposure and less than 2 ng/ml for non-smokers not exposed to ETS. RESULTS: Among non-smoking and not ETS-exposed women, 17% had cotinine level indicating active smoking and 74% ETS exposure. About 4% of the women who indicated ETS exposure during pregnancy had serum cotinine level higher than 15 ng/ml indicating active smoking. CONCLUSIONS: The information about active and passive smoking during pregnancy obtained from mothers and based on the questionnaire does not indicate objective maternal exposure to tobacco smoke.

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.

[B lynch suture for post partum heamorrhage due to uterine atony]. / Zastosowanie szwu lyncha typu b w leczeniu krwotoku poporodowego w przebiegu atonii macicy.

Uterine atony and concomittant massive haemorrhage is one of the most dangerous complications of labour. Conventional, conservative treatment approach comprising of oxytocics such as oxytocin, methergin or prostaglandins may fail in some cases, mandating surgical techniques, including hysterectomy. B Lynch compression uterine suture may be a safe and effective method of treatment in post partum heamorrhage and in most of cases may replace more complicated techniques. In this article, together with referring the technical aspects of this procedure, we present a case of successful treatment.

Visualization of synchronization of the uterine contraction signals: running cross-correlation and wavelet running cross-correlation methods.

In physiological research, we often study multivariate data sets, containing two or more simultaneously recorded time series. The aim of this paper is to present the cross-correlation and the wavelet cross-correlation methods to assess synchronization between contractions in different topographic regions of the uterus. From a medical point of view, it is important to identify time delays between contractions, which may be of potential diagnostic significance in various pathologies. The cross-correlation was computed in a moving window with a width corresponding to approximately two or three contractions. As a result, the running cross-correlation function was obtained. The propagation% parameter assessed from this function allows quantitative description of synchronization in bivariate time series. In general, the uterine contraction signals are very complicated. Wavelet transforms provide insight into the structure of the time series at various frequencies (scales). To show the changes of the propagation% parameter along scales, a wavelet running cross-correlation was used. At first, the continuous wavelet transforms as the uterine contraction signals were received and afterwards, a running cross-correlation analysis was conducted for each pair of transformed time series. The findings show that running functions are very useful in the analysis of uterine contractions.

Decreased serum level of macrophage inflammatory chemokine-3beta/CCL19 in preterm labor and delivery.

OBJECTIVE: Chemokines are small soluble molecules which mediate leukocyte migration and may be involved in the pathophysiology of preterm labor. We aimed to determine if serum concentrations of selected chemokines are changed in preterm labor and delivery. STUDY DESIGN: A novel array-based enzyme-linked immunosorbent assay was used to quantitate serum levels of nine chemokines from a single sample: MDC/CCL22, TARC/CCL17, ITAC/CXCL11, I-309/CCL1, IP-10/CXCL10, MIP-1alpha/CCL3, -1beta/CCL4, -3alpha/CCL20 and -3beta/CCL19. Women in preterm labor who delivered (n = 17), women at preterm pregnancy not in labor (n = 13) and women in labor at term (n = 8) participated. RESULTS: In the preterm delivery group of patients, the MIP-3beta/CCL19 concentration was in mean (+/-S.D.) 70.4+/-31.7 pg/mL, which was significantly lower than that in preterm gravidas not in labor of 123+/-34 pg/mL (p < 0.001) and those in labor at term of 118+/-25.6 pg/mL (p < 0.01). The other measured chemokines did not differ significantly. CONCLUSIONS: Of a small number of examined chemokines, we were able to show that one of them, MIP-3beta/CCL19 was significantly lower in women with preterm labor and delivery. Whether or not this chemokine has a potential as biochemical marker of preterm delivery remains to be determined.