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Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants., Patients and Methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure> 160/110 mmHg with proteinuria> 5 g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays., Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed., Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.

Background: The aim of this study was to determine the maternal serum concentrations of eNOS, ADMA, and homocysteine in preeclamptic pregnancies., Material and Methods: The study was carried out on 62 patients with pregnancy complicated by early onset and 53 patients with late onset preeclampsia. The control group consisted of 65 healthy normotensive pregnant patients. The serum eNOS, ADMA and homocysteine concentrations were determined using ELISA assays., Results: Our study revealed elevated levels of homocysteine and ADMA in the serum of women with preeclampsia. The highest levels were observed in patients with early onset preeclampsia, but the differences between both groups of preeclamptic patients with early and late onset of preeclampsia were not statistically significant. Both groups of preeclamptic women had slightly lower levels of maternal serum endothelial nitric oxide synthase than in normotensive pregnant women, but these differences were not statistically significant., Conclusions: The higher levels of homocysteine and ADMA observed in patients with early onset preeclampsia may suggest that higher levels of maternal serum homocysteine and ADMA correlate with the severity, and may determine the earlier clinical onset of the disease. The elevated levels of ADMA and the unchanged levels of eNOS in preeclamptic pregnancies suggest that NO deficiency in this pregnancy disorder results not from a reduced level or activity of eNOS, but from elevated levels of ADMA, an endogenous eNOS inhibitor. The lowering of increased levels of homocysteine and ADMA may be helpful in therapy of vascular disturbances occurring in preeclampsia.

Background: The aim of this study was to show differences of maternal serum sP-selectin levels in pregnancies complicated by intrauterine fetal growth restriction (IUGR) in the course of preeclampsia and to compare the results with normotensive pregnant women with isolated IUGR. These studies were also conducted on preeclamptic pregnancies with appropriate-for-gestational-age weight infants and on the control normotensive pregnant women., Material and Methods: The study was carried out on 55 patients with pregnancy complicated by fetal growth restriction in the course of preeclampsia, 70 normotensive patients with pregnancies complicated by isolated IUGR, 39 preeclamptic patients with appropriate-for-gestational-age weight fetuses and 54 healthy normotensive pregnant patients with normal fetal growth. Maternal serum levels of sP-selectin were determined using the enzyme-linked immunosorbent assay., Results: Levels of sP-selectin were higher in women with pregnancy complicated by preeclampsia with and without IUGR; whereas, in the group of normotensive pregnant women with isolated fetal growth restriction, serum sP-selectin levels tended to be lower than in the control subjects, but this difference was not statistically significant. The mean values were 192.05±70.96 ng/mL in the IUGR group, 293.18±222.92 ng/mL in the PI group, 379.78±353.13 ng/mL in the P group and 227.96±134.04 ng/mL in the healthy controls (p<0.001*)., Conclusions: Our findings may suggest that the elevated level of the soluble P-selectin is associated with preeclampsia, and that it may confirm the presence of platelet and endothelial activation, the presence of the hypercoagulant state and may be due to the systemic inflammatory response in this serious pregnancy disorder.

Objective: The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction., Methods: The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays., Results: A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia., Conclusion: These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

Objective: The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls., Patients and Methods: The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay., Results: Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight., Conclusions: Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.

Objective: The aim of this study was to evaluate maternal asymmetric dimethylarginine (ADMA) levels in pregnancies complicated by isolated fetal intrauterine growth restriction (IUGR), in preeclamptic pregnancies with and without IUGR, and in healthy normotensive pregnant women with proper weight fetuses., Patients and Methods: The study was carried out on 54 normotensive pregnant patients with pregnancy complicated by IUGR, 35 patients with IUGR in the course of preeclampsia, 29 preeclamptic patients with appropriate-for-gestational-age weight infants and 54 healthy normotensive pregnant patients. The ADMA concentrations were evaluated using an ELISA assay., Results: The preeclamptic women and normotensive patients with pregnancy complicated by isolated IUGR revealed higher levels of maternal serum ADMA. The mean values of maternal serum ADMA were 0.5730 ± 0.1769 μmol/l in the P group, 0.5727 ± 0.1756 μmol/l in the PI group, 0.6129 ± 0.1517 μmol/l in the IUGR group, and 0.5017 ± 0.1116 μmol/l in the control group. The levels of ADMA were additionally higher in the patients with HELLP syndrome and in patients with pregnancy complicated by eclampsia., Conclusions: It seems that ADMA is an active agent not only in preeclamptic patients, but also in normotensive pregnant women with isolated fetal IUGR and could be a marker of severity of preeclampsia.

Objective: The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies., Patients and Methods: The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria)., Results: Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008 ± 625.703 ng/ml in group P, 275.873 ± 174.339 ng/ml in group PI, and 288.719 ± 199.039 ng/ml in the control group, respectively., Conclusions: Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.

Background: Our study was a continuation of the research on the immunological pathology and changes associated with pregnancy complicated by preeclampsia. The aim of this study was to compare the levels of soluble CD30 in maternal serum in the group of women with preeclamptic pregnancy and in the control group of normotensive healthy pregnant women., Material and Methods: The study was carried out in 50 patients with pregnancies complicated bysevere preeclampsia (Pre group). The control group consisted of 34 healthy normotensive pregnant patients with singleton uncomplicated pregnancies (group K). Maternal serum soluble CD30 concentrations were estimated using a sandwich ELISA assay. There were no statistically significant differences in gravidity, parity, maternal age, body height and BMI in patient profiles between groups. Maternal weight was lower in the control group of patients than in the group of preeclamptic patients. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study group ofpreeclamptic pregnant women than in the control group., Results: The levels of maternal serum soluble CD30 in preeclamptic women did not differ in comparison with healthy controls. The mean values were 21.257+/-10.304 ng/mL in the Pre group compared with 21.806+/-11.076 ng/mL in the control group., Conclusions: Since preeclampsia is not associated with a fall of the maternal soluble CD30 level it can not constitute a measure of improving diagnostic and therapeutic management.

This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: The aim of this study was the comparative analysis of the sP-selectin in pregnancies complicated by severe preeclampsia with intrauterine normal growth and small-for-gestational-age foetus., Patients and Methods: The study was carried out on 14 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 13 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 13 healthy normotensive pregnant patients with singleton uncomplicated pregnancies (group C). Maternal serum soluble P-selectin concentrations were estimated using sandwich ELISA assay according to the manufacturer's instructions., Results: Pregnant women with severe preeclampsia had higher maternal serum sP-selectin levels than the normotensive controls. The sP-selectin levels were highest and statistically significant in preeclamptic patients with appropriate-for-gestational-age weight infants., Conclusions: Our findings indicate an association between the increased levels of sP-selectin and severe preeclampsia. However, further studies are required to validate this association and explore the possibility of clinical importance and causative role of sP-selectin in the pathogenesis of preeclampsia.

Objective: the aim of this study was a comparative analysis of the maternal and umbilical cord Vascular Endothelial Growth Factor A (VEGF-A) and its soluble Receptor type 1 (sVEGF-R1) serum concentrations in pregnancies complicated by preeclampsia with and without intrauterine growth retardation (IUGR) and in normotensive pregnancies., Patients and Methods: the study was carried out on 9 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 9 pregnant patients with severe preeclampsia complicated by intrauterine growth retardation (IUGR) (group PI). The control group were 8 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum human VEGF-A and sVEGF-R1 concentrations were assessed using ELISA assay., Results: in our study in both groups of preeclamptic women (P and PI) the concentrations of maternal serum VEGF were lower and the concentrations of soluble VEGF receptor type 1 were higher than in the healthy pregnant women. The umbilical cord concentrations of sVEGF-R1 were increased in the group with preeclampsia complicated by IUGR and decreased in the preeclamptic women with the normal for gestational age foetal growth. On the other hand VEGF concentrations were lower in preeclampsia with IUGR and higher in the preeclamptic women without IUGR., Conclusion: it seems that VEGF may be responsible for the adequate perfusion of fetoplacental unit, normal foetal oxygenation, nutrition and appropriate intrauterine foetal growth. However, it is necessary to conduct further studies on a larger group of patients.

Objectives: The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies., Patients and Methods: The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method., Results: There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood., Conclusions: It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR)., Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA)., Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.

Objective: The aim of this study was determination and comparative analysis of the maternal and umbilical cord sCD40L serum levels in pregnancies complicated by pre-eclampsia with and without intrauterine growth retardation (IUGR) and in normotensive pregnancies., Patients and Methods: The study was carried out on 16 patients with singleton pregnancies complicated by severe pre-eclampsia with appropriate-for-gestational-age weight infants and 14 pregnant patients with severe pre-eclampsia complicated by IUGR. The control group consisted of 13 healthy normotensive delivering patients. Five milliliters of blood were taken by venipuncture from each pre-eclamptic patient and from each woman from the control group before active phase of labor and 5 ml of umbilical vein blood were taken immediately after delivery and collected in sterile tubes. Maternal and umbilical serum sCD40L concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Our results reveal the higher levels of maternal and umbilical sCD40L serum levels in pregnancy complicated by pre-eclampsia with and without IUGR. The mean maternal values were 4.022 +/- 2.399 ng/ml in group P, 3.914 +/- 2.824 ng/ml in group PI and 0.885 +/- 0.064 ng/ml in healthy controls. The mean umbilical values were 2.633 +/- 1.984 ng/ml in group P, 2.703 +/- 1.996 ng/ml in group PI and 1.112 +/- 0.436 ng/ml in the control group. It seems that these higher concentrations of sCD40L protect maternal immune cells bearing CD40 receptor from Fas-mediated apoptosis. Our findings may suggest also enhanced platelet activation in pre-eclamptic patients. It may be one of the factors responsible for the enhanced procoagulatory and proinflammatory properties, and increased cytokine production, and endothelial cell dysfunction in pregnancies complicated by pre-eclampsia., (Copyright 2007 S. Karger AG, Basel.)

Objective: The aim of this study was to determine the maternal and umbilical vein soluble Fas and its ligand (sFasL) serum levels in pregnancies complicated by preeclampsia with intrauterine growth retardation (IUGR)., Patients and Methods: The study was carried out on 11 preeclamptic delivering patients in the third trimester of pregnancy with severe preeclampsia complicated by intrauterine growth retardation. The control group consisted of 12 healthy normotensive delivering patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and with normal laboratory tests. Maternal and umbilical serum soluble Fas and FasL concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Increased maternal and umbilical vein serum sFas and increased umbilical vein serum sFasL levels were found in the study group in comparison with the control group. In our study in both groups of patient higher maternal sFas values were observed in comparison with the umbilical cord blood. Further studies are necessary to evaluate the role of Fas/FasL pathway in pregnancies complicated by preeclampsia and intrauterine growth retardation.

Objective: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients., Patients and Methods: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.

The purpose of this study was to evaluate maternal serum angiotensin I, angiotensin II and aldosterone level, plasma renin activity, angiotensin converting enzyme activity in pregnancies complicated by preeclampsia with and without intrauterine growth retardation. The study was carried out on 26 patients with singleton pregnancy complicated by preeclampsia (group P) and 12 preeeclamptic patients with preeclampsia complicated by intrauterine growth retardation (group PI). The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and normal laboratory tests (group K). Decreased angiotensin I level and decreased plasma renin activity in maternal blood in preeclamptic patients were found to be lower in comparison with the control group. Decreased plasma angiotensin II levels in maternal blood in preeclamptic patients were found to be lower in comparison with the control group. Maternal aldosterone levels were lower in both study groups in comparison with the healthy controls. Elevated serum angiotensin-converting enzyme activity in preeclamptic patients without IUGR was found to be higher in comparison with the healthy controls and with the preeclamptic patients with IUGR. Our results and other reports point out the significant role of RAAS activity in the pregnancy complicated by preeclampsia.

The aim of this study was to compare the immunoreactivity of angiotensin-II receptor type 1 (AT1R) in the vascular endothelial cells of human placental vessels in normal and preeclamptic pregnancies. Immunohistochemistry was used to examine the localization of AT1R in the vascular endothelium of human placental vessels. In preeclamptic patients without intrauterine growth retardation (IUGR) the mean histological index H score was significantly higher, but significantly decreased in patients with preeclampsia complicated by IUGR in comparison with the control group. Immunolocalization of AT1R in vascular endothelial cells in our study supports the view that angiotensin II may play a role in the regulation of vascular tone and vascular resistance and the actions of other vasoactive factors, vasodilators or vasoconstrictors. However, our results confirmed that AT1R immunoreactivity is elevated in vascular endothelial cells of human placenta from pregnancies complicated by preeclampsia, suggesting a higher activity of the renin-angiotensin-aldosterone system (RAAS) in women with preeclampsia. On the other hand reduced immunoreactivity of AT1R in placental vascular endothelial cells in pregnancy complicated by preeclampsia with IUGR may result from chronic higher RAAS activity and may suggest the decreased ability to compensate and the inability to restore the normal balance between vasodilators and vasoconstrictors. These results may also reflect destructive changes and dysfunction of the vascular endothelium in preeclamptic pregnancy with IUGR., (Copyright 2003 S. Karger AG, Basel)