Value of cervicovaginal fluid cytokines in prediction of fetal inflammatory response syndrome in pregnancies complicated with preterm premature rupture of membranes (pPROM).

Background Preterm premature rupture of membranes (pPROM) is associated with a high risk of prematurity and complications of fetal inflammatory response syndrome (FIRS). The aim of the study is to determine any correlations between the concentration of selected cytokines contained in the cervicovaginal secretion eluates and in the umbilical cord plasma in patients with pPROM and to find the noninvasive markers of FIRS in order to pinpoint the optimal time of the delivery. Methods The study included 80 patients with pPROM between the 24th and 34th week of gestation. The cervicovaginal fluid and umbilical cord blood were collected. Interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 19 (IL-19) and tumor necrosis factor-α (TNF-α) concentrations were measured in both materials. For the statistical analysis, SigmaStat3.5 software was used. Results There was no direct association in levels of IL-6, TNF-α, IL-10 and IL-19 between the cord blood and cervicovaginal secretions within the studied group. The cut-off point of IL-6 of 26.8 pg/mL in the vaginal fluid had high sensitivity and specificity in order to discriminate between newborns with and without FIRS (81.08%; 76.74%). Conclusion Further studies are needed on a larger group of participants to demonstrate that an elevated concentration of IL-6 above 26.8 pg/mL in the cervicovaginal secretion eluate is an indirect noninvasive marker of FIRS.

Alternation of ten-eleven translocation 1, 2, and 3 expression in eutopic endometrium of women with endometriosis-associated infertility.

Little is known about the differences in ten-eleven translocation 1, 2, and 3 (TET1-3) expression in the endometrial phases in eutopic endometrium from infertile women with endometriosis (IWE) and fertile women without endometriosis (FW). Using RT-qPCR and western blot analysis, we assessed the TET expression in the mid-follicular and mid-luteal phases in eutopic endometrium from IWE (n = 38) and FW (n = 18). Both IWE and FW underwent laparoscopic and histological examinations for endometriosis. In the mid-luteal eutopic endometrium in IWE, compared to that of FW, we found significantly reduced levels of TET1 transcripts and proteins (p = .001 and p = .003, respectively) at the severity stage of I/II (p = .029 and p = .003, respectively) and transcripts only at the severity stage of III/IV (p = .003). In the mid-follicular eutopic endometrium of IWE, compared to that of FW, there was a statistically significant reduction in TET2 transcript levels at the severity stage of III/IV (p = .037). Compared to the mid-follicular endometrium, we found a statistically significant increase in TET3 transcript levels during the mid-luteal phase in the eutopic endometrium of all IWE (p = .034) and in the severity stage of III/IV (p = .025). We observed a change in the expression levels of TET1-3 in the eutopic endometrium of IWE.

The assessment of GWAS - identified polymorphisms associated with infertility risk in Polish women with endometriosis.

OBJECTIVES: Genome-wide association studies in patients with endometriosis revealed ten significant single nucleo-tide polymorphisms (SNPs) in the Caucasian population, which include rs12700667 near NFE2L3, rs12037376 in WNT4, rs7521902 near WNT4, rs13394619 in GREB1, rs10859871 near VEZT, rs1537377 near CDKN2B-AS1, rs4141819 near ETAA1, rs7739264 near ID4, rs1519761 near RND3 and rs6542095 near IL1A. MATERIAL AND METHODS: We replicated ten polymorphisms among infertile women with endometriosis (n = 315) and healthy fertile women (n = 406) in the Polish Caucasian population. Genotyping was conducted either by high-resolution melting curve analysis or by a pre-designed TaqMan probe. RESULTS: For all infertile women with endometriosis, the p values of the Cochran-Armitage trend test for the rs12700667 SNP was ptrend = 0.038 and the odds ratio (OR) for the risk allele frequency (RAF) of rs12700667 was 1.304 (95% CI = 1.009-1.685; p = 0.042). In patients with endometriosis with severity stages III/IV, ptrend for rs12700667 SNP was 0.036 and OR for the RAF was 1.394 (95% CI = 1.010-1.923; p = 0.043). In infertile women with endometriosis with severity stages III/IV for rs4141819 SNP, we observed ptrend = 0.026 and for RAF the OR = 1.350 (95% CI = 1.032-1.766; p = 0.029). CONCLUSIONS: Our results demonstrate association of RAF of rs12700667 and rs4141819 SNPs with infertility in Polish women with advanced endometriosis.

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

OBJECTIVES: The development of endometriosis is associated with changes in the expression of genes encoding the 3ß-hydroxysteroid dehydrogenase type II (HSD3B2) and 17ß-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. MATERIAL AND METHODS: Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. RESULTS: In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. CONCLUSIONS: Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

Involvement of 17ß-hydroxysteroid dehydrogenase type gene 1 937 A>G polymorphism in infertility in Polish Caucasian women with endometriosis.

PURPOSE: Endometriosis is considered to be an estrogen-related chronic inflammatory disease. The 17ß-hydroxysteroid dehydrogenase 1 (HSD17B1) converts estrone to 17ß estradiol. The role of HSD17B1 937 A>G (rs605059) single nucleotide polymorphism (SNP) in development of endometriosis is still disputable. This study evaluated the association of the HSD17B1 937 A>G (rs605059) SNP with infertile women affected by endometriosis from Polish Caucasian population. METHODS: The genotyping of cases (n = 290) and fertile women (n = 410) was conducted by high-resolution melting curve analysis. RESULTS: Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with endometriosis in stages I and II. The p trend and p allelic values calculated for the HSD17B1 937 A>G polymorphism were statistically significant and were equal to 0.001 and 0.0009, respectively. There was a significant association for the dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178-3.304), p = 0.009, and for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178-2.770), p = 0.006. However, we did not find statistical association of HSD17B1 937 A>G polymorphism with all infertile women with endometriosis or infertile women with endometriosis in stages III and IV. CONCLUSION: Our genetic study demonstrated HSD17B1 937 G variant as a risk factor for infertility in women with stage I and II endometriosis in Polish Caucasian patients.

Polyhydramnios - frequency of congenital anomalies in relation to the value of the amniotic fluid index.

OBJECTIVES: The aims of our study were to assess the correlation between the amniotic fluid index (AFI) value and the frequency and type of fetal anomalies. MATERIAL AND METHODS: The material included 94 patients at the third trimester of pregnancy, 60 with mild polyhydramnios, 19 with moderate one, and 15 with severe one. Polyhydramnios was diagnosed if AFI was > 24 cm. All patients were divided into three groups based on the value of AFI: 1) mild polyhydramnios with AFI between 24.1 and 29.9 cm, 2) moderate polyhydramnios with AFI between 30-34.9 cm, and 3) severe polyhydramnios with AFI ≥ 35 cm. RESULTS: The incidence of fetal malformations correlated significantly with the degree of polyhydramnios and was the highest in patients with severe polyhydramnios (53.3%, p = 0.002). Congenital malformations of the gastrointestinal tract were the most frequent fetal anomalies in the whole group of patients (5.3%). Trisomy 18 was the most frequent aneuploidy found in women with polyhydramnios (2.1%). CONCLUSIONS: The incidence of fetal congenital anomalies significantly increases with the degree of polyhydramnios, being most frequent in severe one and rather rare in a mild one. Congenital malformations of the gastrointestinal tract were the most frequent anomalies in patients with polyhy-dramnios, especially in women with severe polyhydramnios.

[Concentration of pro-inflammatory interleukins in cervical secretions of women with PROM and in the umbilical cord blood of their newborns]. / Analiza stezenia prozapalnych interleukin w wydzielinie szyjkowej kobiet z PROM i we krwi pepowinowej ich noworodków.

OBJECTIVES: The aim of the study was to analyze the levels of pro-inflammatory interleukins in cervical secretions of women with PROM, depending on Ureaplasma spp. infection and the time elapsed since the rupture of the membranes, and to correlate their concentration in cervical secretions and in cord blood of the newborns. MATERIAL AND METHODS: The study included 30 women with PROM between 24 and 33+6 weeks of gestation. Cervical swabs from women with confirmed rupture of membranes taken at certain intervals and umbilical cord blood of their newborns constituted the study material. Cervical secretions were evaluated microbiologically and by the PCR method. Concentrations of IL-6, IL-19, IL-10 and TNF-α were analyzed by ELISA. RESULTS: Ureaplasma spp. were the most frequently isolated microorganisms in cervical secretions of women with PROM. Secretion of interleukins in the cervix was not influenced by time elapsed since the PROM. Comparison of interleukin levels in cord blood of newborns born to mothers with and without Ureaplasma spp infection revealed significantly higher levels of IL-6 in the case of Ureaplasma spp. A positive correlation between IL-6 and TNF-α levels in cervical secretions and in cord blood of mothers with PROM and Ureaplasma spp. was detected. CONCLUSIONS: 1. Cervical culture method appears to be sufficient for detecting Ureaplasma spp. 2. Pro-inflammatory interleukins, especially IL-6, obtained by non-invasive methods can be used to predict fetal inflammatory response.

Prediction of short-term newborn infectious morbidity based on maternal characteristics in patients with PPROM and Ureaplasma species infection.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) complicates about 5% of pregnancies. Ureaplasma species is the most common pathogen found in the amniotic fluid in pregnancieneonatal outcome. The aim of the following study was to evaluate the impact of colonization with the Ureaplasma spp. on pregnant women with PPROM, coin fection with different microorganisms, and antimicrobial treatment on neonatal outcome. MATERIAL AND METHODS: The study included 30 women with PPROM hospitalized in Division of Reproduction in s complicated by PPROM. It is speculated that it requires a coin fection to produce unfavorable Poznan's K. Marcinkowski University of Medical Sciences. Swabs from cenvical canal were obtained for the identifidation of bacterial and ureaplasma tic infections by culture and POR. RESULTS: The presence of any infection during the pregnancy a fter PP ROM was con firmed in 22 patients (Ureaplasma spp. in 12 patients, coin fection in 10 women). The cure rate for Ureaplasma species and other infections was 17% (2/12 patients) and 23% (5/22 patients), respectively There was no correlation between Ureaplasma species infection, coin fection, and cure status with the infection in the newborn. The PPROM to delivery duration also did not affect the newborn infection status. A negative relationship with leukocyte level was detected in patient with newborn infection. CONCLUSIONS: The presence of colonization with Ureaplasma species is not attributable to neonatal short-term morbidity The evaluation of maternal biochemical and microbiological data, regardless of the duration of the pregnancy after PPROM or the cure status, does not add any insight into the newborn infection status.

[Assessment of in vitro impact of low molecular weight heparin on expression of heparanase and heparin binding growth factors in the endometrium of women with impaired reproduction]. / Ocena wplywu in vitro niskoczasteczkówej heparyny na ekspresje heparanazy i czynników wzrostu wiazacych heparyne w endometriumn kobiet z zaburzonym rozrodem.

UNLABELLED: Heparin has a beneficial effect in the treatment of recurrent miscarriages and positively affects implantation rates in the IVF procedure in women with reproductive disorders not associated with thrombophilia. Several studies have indicated that heparin, by blocking the enzymatic activity of heparanase, may affect the structure and function of the extracellular matrix (ECM) and related growth factors. Disturbances in the remodeling (ECM) are believed to be the potential cause of implantation disorders and recurrent miscarriages. OBJECTIVES: The aim of the study was the evaluation, on an in vitro model, of the effect of low molecular weight heparin (LMWH) on the expression of heparanase (HPSE) and, important for successful implantation and invasion of trophoblast, heparan sulfate (HS)--binding growth factors, i.e., heparin-binding epidermal growth factor-like (HB-EGF), vascular endothelial growth factor (VEGF-A), fibroblast growth factor (FGF2) in the endometrium, during the implantation window in women with recurrent miscarriage. METHOD: Biopsy samples, obtained from 10 patients with two or more unexplained miscarriages, were used to construct a co-culture of glandular epithelial cells and stroma. Endometrium in vitro model was supplemented with steroid hormones and enoxaparin 5 ug/ml. Using the qPCR, we assessed, relative levels of the HPSE, HB-EGF, VEGF-A and FGF2 transcripts in glandular epithelium and stroma in cell culture. Using ELISA, we measured con- centrations of the mentioned above factors in culture medium. RESULTS: A statistically significant increase in the relative level of HPSE, HB-EGF VEGF-A, FGF2 transcripts in the cells of the glandular epithelium and stroma (p<0.001), as well as their increased concentration in the medium of cultures treated with steroid hormones (p<0.001) were observed. However we found no effect of LMWH supple- mentation on the level of the investigated factors. CONCLUSIONS: Our results show that the importance of the HPSE hydrolytic activity in the endometrium, during the implantation window, may have a secondary function, and/or that beneficial effects of LMWH in women with impaired reproduction have no significant, direct connection with the, catalyzed by HPSE, reconstruction of the ECM and with release of heparin-binding growth factors.

Effects of Spherical and Rod-like Gold Nanoparticles on the Reactivity of Human Peripheral Blood Leukocytes.

Gold nanoparticles (GNPs) are widely used in the technological and biomedical industries, which is a major driver of research on these nanoparticles. The main goal of this study was to determine the influence of GNPs (at 20, 100, and 200 µg/mL concentrations) on the reactivity of human peripheral blood leukocytes. Flow cytometry was used to evaluate the respiratory burst activity and pyroptosis in monocytes and granulocytes following incubation with GNPs for 30 and 60 min. Furthermore, the concentration of interleukin-1ß (IL-1ß) in human blood samples was assessed using enzyme-linked immunosorbent assay (ELISA) after their incubation with GNPs for 24 h. Under the conditions tested in the study, the GNPs did not significantly affect the production of reactive oxygen species in the granulocytes and monocytes that were not stimulated using phorbol 12-myristate 13-acetate (PMA) in comparison to the samples exposed to PMA (p < 0.05). Compared to the control sample, the greatest significant increase in the mean fluorescence intensity of the granulocytes occurred in the samples incubated with CGNPs = 100 and 200 µg/mL for tinc = 30 and 60 min (p < 0.05). From our results, we conclude that the physicochemical properties of the nanoparticles, chemical composition, and the type of nanoparticles used in the unit, along with the unit and incubation time, influence the induced toxicity.

Polymorphic variants of CYP17 and CYP19A and risk of infertility in endometriosis.

OBJECTIVE: Endometriosis is recognized as an estrogen-dependent disease. There are conflicting data demonstrating single nuclear polymorphisms (SNPs) of CYP17 and CYP19 steroidogenic genes as related to endometriosis risk. We assessed the CYP17 5'-untranslated region -34 A/G (rs743572) and CYP19 Ex10 + C1558T (rs10046) SNPs in stage I-II endometriosis. DESIGN: Case-control study. SETTING: Division of reproduction at a university department in Poland. POPULATION: A total of 115 women with diagnosed stage I-II endometriosis according to the revised American Society for Reproductive Medicine (rASRM) classification and 197 fertile women as controls. METHODS: The SNPs CYP17 -34 A/G and CYP19 Ex10 + C1558T were identified by high-resolution melting curve analysis. MAIN OUTCOME MEASURES: Genotype prevalence and odds ratio for recessive and dominant genetic model for CYP17 and CYP19 SNPs. RESULTS: We observed a significantly increased CYP17 GG and GA genotype frequency in women diagnosed with rASRM stage I-II endometriosis compared with fertile women (OR = 2.4; 95% CI 1.4-4.2, p = 0.002). We also found a significantly increased CYP17 G allele frequency in cases compared with controls (OR = 1.6; 95% CI 1.2-2.2, p = 0.004). There were no significant differences in the distribution of the CYP17 GG genotype and CYP19 Ex10 + C1558T polymorphism between women diagnosed with rASRM stage I-II endometriosis and controls. CONCLUSION: The CYP17 -34 G variant, previously associated with increased 17ß-estradiol production, displayed a contribution to stage I-II endometriosis in women from a Polish population. Increased 17ß-estradiol concentration in carriers of the CYP17 -34 G variant might contribute to endometriosis and associated pathological processes.

The FCRL3 -169T>C polymorphism and the risk of endometriosis-related infertility in a Polish population.

OBJECTIVE: Recently, the FCRL3 -169T>C (rs7528684) single-nucleotide polymorphism (SNP) has been demonstrated to be a risk factor of endometriosis related infertility. We studied whether the FCRL -169T>C SNP can be associated with endometriosis-related infertility in a sample of the Polish population METHODS: Using PCR-RFLP analysis we genotyped 141 infertile women with endometriosis and 519 fertile women. FCRL3 transcript levels were determined by reverse transcription and real-time quantitative PCR analysis in CD19(+) B cells from women with endometriosis-associated infertility and fertile women RESULTS: We found a significantly increased frequency of the FCRL3 C/C genotype in women with endometriosis-associated infertility than controls [OR = 1.681 (95 % CI = 1.120-2.522, p = 0.0116, p corr = 0.0348)]. There was also a statistically increased frequency of the C/C and C/T genotypes in patients compared with controls [OR = 2.009 (95 % CI = 1.214-3.324, p = 0.0059, p corr = 0.0177)]. The p value of the χ (2) test for the trend observed for the FCRL3 -169T>C polymorphism was also statistically significant (p trend = 0.0012, p corr = 0.0036). We also found significantly increased FCRL3 transcript levels in carriers of the FCRL3 -169 CC vs TT and CT vs TT genotype both in women with endometriosis-related infertility (p = 0.012; p = 0.015) and fertile women (p = 0.017; p = 0.032) CONCLUSIONS: FCRL3 -169T>C polymorphism alters the expression of FCRL3 and can be a risk factor of endometriosis-related infertility.

[Concentrations of antiangiogenic factors, triglycerides, glucose and insulin in women with two types of preeclampsia]. / Ocena stezenia czynników antyangiogennych, triglicerydów, glukozy, insuliny oraz SHBG u kobiet z dwoma postaciami stanu przedrzucawkowego.

OBJECTIVES: Assessment of serum concentrations of antiangiogenic factors, triglycerides, glucose, insulin and SHBG in women with two forms of preeclampsia (placental and maternal). MATERIAL AND METHODS: The study was conducted among 30 patients with placental preeclampsia and 20 women with maternal form of the disease. All patients were hospitalized at the Division of Reproduction, Poznan University of Medical Sciences, between 2010-2012. The placental form of preeclampsia was diagnosed in cases when Doppler signs of placental insufficiency were present. The maternal type of the disease was diagnosed in the absence of coexisting markers of placental insufficiency in the Doppler study ELISA was used to determine the concentrations of antiangiogenic factors (sFlt-1 and sEng). RESULTS: The placental form of preeclampsia was diagnosed significantly earlier than maternal type of the disease. In women with placental preeclampsia the gestational age at delivery and newborn birth weight were significantly lower than in patients with maternal preeclampsia. IUGR incidence (expressed as a percentage) was significantly higher in patients with placental preeclampsia as compared to the women with maternal form of the disease. Serum concentrations of sFlt-1 and sEng were significantly higher in women with placental preeclampsia. No differences in concentrations of glucose, insulin, triglycerides and SHBG were found between groups. CONCLUSIONS: 1. The Two Stage Model of preeclampsia, characterized by increased concentrations of antiangiogenic factors in maternal blood secondary to decreased placental blood flow seems to better explain the pathophysiology of the placental form of preeclampsia than the maternal one. 2. Late onset of clinical symptoms in maternal preeclampsia, lower incidence of IUGR, as well as lower concentrations of antiangiogenic factors in maternal blood, do not indicate the primary role of placental pathology in the pathogenesis of the disease. 3. In spite of no difference in metabolic abnormalities in third trimester of pregnancy between two types of preeclampsia, the patophysiology of the two forms of the disease seems to be different. 4. The obtained results of metabolic markers in women with two types of preeclampsia justify the need of further studies in this field in first trimester of pregnancy.

Aberrant claudin-4 transcript levels in eutopic endometrium of women with idiopathic infertility and minimal endometriosis.

INTRODUCTION: Claudin-4 (CLDN4) is a transmembrane protein, responsible for cellular contact and organization. A different expression of claudin 4 in the endometrium, depending on the menstrual cycle and with peak at the aim of the 'implantation window', has been observed. CLDN4 is believed to play an important role in embryo implantation. THE AIM: The aim of the study was to compare the mRNA CLDN4 expression levels in two subgroups of infertile women (idiopathic infertility or minimal endometriosis) and compare them to fertile controls. METHOD: The study included 36 women with idiopathic infertility and 24 with minimal endometriosis. The control group comprised 26 women. Eutopic endometrium samples were collected with a Pipelle device during the implantation window. Firstly mRNA was extracted from the endometrium and reverse transcribed into cDNA. Real time PCR was used for the assessment of relative expression levels. RESULTS: The observed transcription level of CLDN4 did not differ statistically between the studied groups, but was significantly higher when compared to controls. CONCLUSIONS: Exceedingly high levels of CLDN4 might negatively influence fertility rates.

Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility.

BACKGROUND: A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. METHODS: Using Real-time quantitative PCR (RQ-PCR) and western blotting analysis we studied the HOXA11 transcript and protein levels in mid-luteal eutopic endometrium from eighteen infertile women with minimal endometriosis, sixteen healthy fertile women and sixteen infertile women with fallopian tubal occlusion from the Polish population. We also evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in these groups of women. RESULTS: There were significantly lower levels of HOXA11 transcripts (p = 0.003, p = 0.041) and protein (p = 0.004, p = 0.001) in women with endometriosis as compared to fertile women and infertile women with tubal occlusion. Moreover, we found significantly higher methylation levels of the CpG region in the first exon of HOXA11 in infertile women with endometriosis compared with fertile women (p < 0.001) and infertile women with tubal occlusion (p < 0.001). We also observed significantly increased levels of DNMT3A transcript in women with endometriosis than fertile women (p = 0.044) and infertile women with tubal occlusion (p = 0.047). However, we did not observe significant differences in DNMT1 and DNMT3B transcript levels between these investigated groups of women. CONCLUSIONS: We confirmed that reduced HOXA11 expression may contribute to endometriosis-associated infertility. Moreover, we found that DNA hypermethylation can be one of the possible molecular mechanisms causing a decrease in HOXA11 expression in the eutopic mid-secretory endometrium in infertile women with endometriosis.

[Assessment of uterine arteries Doppler in the first half of pregnancy in women with thrombophilia]. / Ocena przeplywów krwi w tetnicach macicznych w pierwszej polowie ciazy u pacjentek z trombofilia.

OBJECTIVES: Assessment of uterine artery blood flow in women with congenital thrombophilia and antiphospholipid syndrome (APS) in the first half of pregnancy MATERIAL AND METHODS: Uterine arteries blood flow was assessed in a Doppler examination in 20 women with thrombophilia (15 with congenital thrombophilia, 5 with APS) at 12 and 20 weeks gestation at the Division of Reproduction, Poznan University of Medical Sciences, between 2000 and 2012 The control group consisted of 20 multiparous pregnant women with no history of pregnancy complications. All patients with thrombophilia received enoxaparin or enoxaparin and aspirin before enrollment into the study Patients from the control group did not receive any antithrombotic prophylaxis. The mean Pulsatility Index (PI) of both uterine arteries and the presence or the absence of the "notch" was assessed, both at 12 and 20 weeks gestation in each patient from the study and from the control groups. RESULTS: Mean PI values in the uterine arteries at 12 weeks in patients with thrombophilia and in controls were 1.82 (1.00-3.13) and 1.52 (1.30-1.88), respectively (p = 0.08). Mean PI value in the uterine arteries was 7.27 (0.61-2.48) in women with thrombophilia at 20 weeks, which turned out to be significantly higher (p = 0.026) than in the control group 1.07 (0.8-1.24). The bilateral "notch" was found at 12 weeks gestation in 40% of patients with thrombophilia vs. 0% in the control group (p = 0.03). There was no significant difference between the groups in this parameter at 20 weeks. CONCLUSIONS: 1. An increased impedance of flow was found in the uterine arteries in patients with thrombophilia at 12 and 20 weeks gestation in spite of antithrombotic prophylaxis. 2. Thrombotic episodes in patients with thrombophilia cannot be explained solely by the presence of placental thrombosis.

[Incidence of hereditary thrombophilia in women with pregnancy loss in multi-center studies in Poland]. / Czestosc wystepowania trombofilii wrodzonej u kobiet z utrata ciaz w wieloosrodkowych badaniach w Polsce.

AIM: The aim of this study was to estimate the prevalence of factor V Leiden and prothrombin gene G20210A mutation among women with pregnancy loss in Poland. MATERIAL AND METHODS: we analyzed a group of 396 women (mean age of 30.4 (+/- 4.6) years), who experienced at least one pregnancy loss. Patients were recruited from 6 academic centers (Poznan, Bialystok, Lublin, Wroclaw Bydgoszcz, Gdansk), and were divided into the following groups: 122 patients with 3 episodes of early recurrent pregnancy loss (group 1), 87 patients with late pregnancy loss (group 2) and 46 patients with intrauterine pregnancy loss (group 3). Patients who did not fulfill the above inclusion criteria were divided into additional groups. 50 healthy women (mean age of 29.2 (+/- 4.5) years), having at least one child, constituted the control group. Factor V Leiden mutation and prothrombin G20210A gene mutation were examined in all 396 women with pregnancy loss and 50 controls. For molecular analysis peripheral blood was tested. Genome DNA isolation from lymphocyte was performed with commercial assay QIAampDNA Blood Mini Kit. RESULTS: Among 396 women with unexplained loss of at least one pregnancy 36 (9.1%) were carriers of inherited thrombophilia. Factor V Leiden mutation was present in 29 women (73%), prothrombin gene mutation G20210A in 6 (1.5%) and in 1 (0.3%) patient both mutations were detected. No coagulation defects were found in the control group. Factor V Leiden mutations was the most common disorder (21.7%) in patients with intrauterine demise and was significantly higher than in the group of women with early recurrent and late losses, p<0.011 and p<0,006 respectively The frequency of G20210 A prothrombin gene mutation did not differ substantially between the examined groups; the highest number (2.6%) was found in women with early and late pregnancy losses, and the lowest number (0.8%) was seen in women with early recurrent miscarriages. CONCLUSION: Factor V Leiden screening should be performed, regardless of negative history of thrombosis, in patients who experienced intrauterine fetal demise or recurrent early miscarriages.

Serum levels of soluble FMS-like tyrosine kinase 1 and endothelial glycocalyx components in early- and late-onset preeclampsia.

INTRODUCTION: The most popular model of preeclampsia (PE) is a two-stage one in which the first stage involves a decreased perfusion of the placenta and the second stage is characterized by maternal endothelial injury and dysfunction. This model seems to be more appropriate for early-onset PE, than for the late-onset disease, as in the case of the latter the event of reduced placental perfusion seems is less obvious.The aim of the study was to assess the possible correlations between the serum levels of soluble FMS-like tyrosine kinase 1 (sFlt-1) and the components of endothelial glycocalyx (EG), namely syndecan -1 (SDC-1) and hyaluronan (HA), as the markers of endothelial damage, in patients with early- and late-onset PE. MATERIALS AND METHODS: The study was conducted among 60 women in their late second and third trimester of the singleton pregnancy, including 20 patients with early-onset PE, 20 with late-onset PE, and 20 women with normal pregnancy, who served as the control group. All patients were hospitalized between 2015 and 2018 at the Division of Reproduction of Poznan University of Medical Sciences. The women in the control group were matched by gestational age with the patients in the study groups. RESULTS: The median serum level of sFlt-1 was the highest in the patients with early-onset PE (3.53 (2.73-4.5) pg/ml) but it was not statistically different from the level in the patients with late-onset PE (3.14 (2.2-3.4) pg/ml). The mean serum level of SDC-1 also did not differ significantly between the two groups of patients with PE (6.17 ± 2.2 ng/ml in early-onset PE; 6.42 ± 2.2 ng/ml in late-onset PE). Both values of SDC-1 were significantly lower than that in the healthy pregnant women (11 ± 2.62 ng/ml, p < .001). The median concentrations of HA did not differ between patients with early- (236.6 (101.1-351.9) ng/ml) and late-onset PE (234.7 (46.8-324.2) ng/ml). However, the levels in these study groups were significantly higher than in the control group (113.9 (30.9-379.8) ng/ml, p < .001). There was no significant correlation found between the serum concentrations of sFlt-1 and both HA and SDC-1; however, such trend was noticed between the serum concentrations of sFlt-1 and HA in patients with early-onset PE, but not in those with the late-onset disease. CONCLUSIONS: Evaluation of serum concentrations of HA in patients with PE was found to be more useful in the assessment of endothelial injury, compared to the assessment of SDC-1.The degree of EG damage was comparable in patients with early- and late-onset PE. The pathomechanism of the damage seems to be more sFlt-1 dependent in patients withearly- onset PE than in the case of late-onset disease. The two-stage model of PE is more appropriate for early - onset PE, whereas the pathophysiology of the late-onset disease is rather more complex and heterogenous.

Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus.

Preeclampsia (PE) is one of the leading causes of mortality and morbidity in pregnant women. Pregestational diabetes (PGDM) patients are prone to vascular complications and preeclampsia, whereas vascular exposure to hyperglycemia induces inflammation, vascular remodeling, and arterial stiffness. Corin is a serine protease, converting inactive pro-atrial natriuretic peptide (pro-ANP) into an active form. It also promotes salt and water excretion by activating atrial natriuretic peptide (ANP), and significantly increases trophoblast invasion. The study aimed to determine whether corin may be a predictor of PE in a high-risk group-women with long-term PGDM. The nested case-control prospective study involved 63 patients with long-term pregestational type 1 diabetes (PGDM). In total, 17 patients developed preeclampsia (the study group), whereas 43 patients without PE constituted the control group. To assess corin concentration, blood samples were collected at two time points: between 18th-22nd week of gestation and 28th-32nd week of gestation. PE patients presented significantly higher mid-gestation corin levels, urine protein loss in each trimester, serum creatinine in the third trimester, and lower creatinine clearance in the third trimester. The results of our study indicate that serum corin assessment may play a role in predicting preeclampsia. Thus, it may be included in the PE risk calculator, initially in high-risk groups, such as patients with PGDM.

Biomedical Ti-Nb-Zr Foams Prepared by Means of Thermal Dealloying Process and Electrochemical Modification.

The paper presents results of preparation and modification of Ti20Nb5Zr foams by a thermal dealloying method followed by electrochemical modification. The first step of this study was the preparation of Ti20Nb5Zr30Mg nanopowder using mechanical alloying (MA). The second was forming green compacts by cold pressing and then sintering with magnesium dealloyed from the structure, which resulted in pores formation. The next step was surface modification by electrochemical etching and silver nanoparticle deposition. Porosity, morphology, mechanical properties as well as biocompatibility and antibacterial behavior were investigated. Titanium foam porosity up to approximately 60% and wide pore size distribution were successfully prepared. The new materials have shown positive behavior in the MTT assay as well as antibacterial properties. These results confirmed great potential for thermal dealloying in preparation of porous structures.