Maternal plasma levels of cytokines in normal and preeclamptic pregnancies and their relationship with diastolic blood pressure and fibronectin levels

BACKGROUND: To determine the plasma concentrations of placental growth factor (PLGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), soluble tumor necrosis factor alpha receptor (sTNFp55), interleukin-2 receptor (IL-2R), and interleukins 6 and 10 (IL-6, IL-10) in normotensive and preeclamptic women, and to evaluate the correlations between these cytokines and the diastolic blood pressure and fibronectin levels. METHODS: A prospective case-control study. Thirty-five women with preeclampsia were compared with 34 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained and plasma levels of PLGF, VEGF, TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 were measured by an enzyme-linked immunoassay and fibronectin by a radial immundiffusion technic. RESULTS: In preeclampsia PLGF and VEGF levels were significantly lower, and TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 levels were significantly higher than in normotensive pregnancy (p < 0.001). The plasma levels of PLGF and VEGF significantly decreased, whereas TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 levels significantly increased with the increments in diastolic blood pressure and fibronectin levels (p < 0.001). CONCLUSIONS: Altered concentrations of various cytokines might explain the shallow placentation and endothelial cell dysfunction described in preeclampsia. The clinical severity of preeclampsia seems to correlate with the severity of the cytokine abnormalities.     

Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia.

OBJECTIVE: Altered production of nitric oxide by the vascular endothelium may influence the pathogenesis of preeclampsia. The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, and peripheral circulation of preeclamptic pregnancies compared with normotensive controls. METHODS: Fifteen women with preeclampsia were compared with 16 women with normotensive pregnancies. At cesarean, blood samples were taken from the uterine vein draining the placental site, the umbilical vein, and the antecubital vein after delivery of the baby but before delivery of the placenta. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS: Nitric oxide metabolites were higher in the uteroplacental (P < .01), fetoplacental (P < .001), and peripheral (P < .02) circulations in samples from preeclamptic pregnancies compared with control pregnancies. In samples from the fetoplacental circulation only, nitric oxide metabolite levels were negatively correlated with gestational age (r = -.489, P < .01) and birth weight (r = -.544, P < .004). Nitric oxide metabolite levels were not significantly correlated with blood pressure, placental weight, or maternal age. CONCLUSION: In established preeclampsia, production of nitric oxide was higher in the uteroplacental, fetoplacental, and peripheral circulation than in normotensive pregnancies. This increase may be part of a compensatory mechanism to offset the pathologic effects of preeclampsia.     

Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia

OBJECTIVES: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity. METHODS: Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked immunoassay. Platelet aggregation was induced by the agonist agents adenosine diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich plasma by aggregometry. RESULTS: Plasma concentrations of active TGF-beta(1) were significantly higher in preeclamptic women (10.41+/-2.07ng/mL) compared with normotensive pregnant women (7.01+/-3.29ng/mL). Platelet number and platelet agonist-induced aggregation percent were significantly lower in patients with preeclampsia than in healthy pregnant women. A significant correlation was observed between TGF-beta(1) plasma levels and platelet agonist-induced aggregation percent as between plasma levels of TGF-beta(1) and platelet number in preeclamptic patients. CONCLUSION: The association between impairment in platelet responsiveness and higher levels of TGF-beta(1) in the plasma of patients with preeclampsia suggests that this cytokine may play a role in the pathophysiological events of preeclampsia that are dependent on platelet activation.     

Maternal circulating nitrite levels are decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

OBJECTIVE: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. MATERIALS: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks' gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. RESULTS: Maternal circulating nitrite levels in nonpregnant women (1.13 +/- 0.22 microM) were significantly higher than those in the first-trimester pregnant women (0.68 +/- 0.13 microM), second-trimester pregnant women (0.65 +/- 0.13 microM), third-trimester pregnant women (0.48 +/- 0.17 microM), first puerperal week women (0.36 +/- 0.16 microM), and fourth puerperal week women (0.67 +/- 0.17 microM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 +/- 0.17 microM) and third-trimester pregnant women (0.48 +/- 0.17 microM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the groups. CONCLUSION: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.     

Bioactivity of serum hCG in preeclampsia

OBJECTIVE: To compare hCG levels, obtained by biologic and immunologic means, in women with normal pregnancies and women with preeclampsia. METHODS: Peripheral blood samples from women in the third trimester with preeclampsia (n = 30) or normal pregnancies (n = 30) were assayed for immunoactive and bioactive hCG (mouse Leydig cell testosterone production assay). RESULTS: Serum bioactive hCG levels tended to be lower than normal, and immunoactive hCG levels tended to be higher in women with preeclampsia, but the differences were not statistically significant. However, the ratio of bioactive to immunoactive hCG was significantly lower than normal for preeclamptic women (0.70 +/- 0.28 vs. 1.15 +/- 0.35 for normotensive pregnant women [mean +/- standard deviation], P <.001). CONCLUSION: The ratio of bioactive to immunoreactive serum hCG is lower among preeclamptic than among normotensive pregnant women.     

Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex

OBJECTIVE: The aim of the present study was to evaluate the effects of fetal gender on serum human chorionic gonadotropin (hCG) and testosterone in normotensive and preeclamptic pregnancies. METHODS: The study consisted of 137 women with singleton pregnancies in the third trimester. Seventy-three pregnancies were uncomplicated; among those were 35 male and 38 female fetuses. Sixty-four pregnancies were complicated by preeclampsia; among those were 33 male and 31 female fetuses. Human chorionic gonadotropin and total testosterone were measured in maternal peripheral blood. RESULTS: In male-bearing pregnancies, maternal hCG and testosterone serum levels were significantly higher in preeclamptic than normotensive mothers (P <.001). In female-bearing pregnancies, testosterone levels were significantly higher in preeclamptic than normotensive mothers (P <.001), whereas the hCG levels were not significantly different. Male-bearing preeclamptic women had significantly higher testosterone levels than female-bearing preeclamptic women (P <.02), whereas the hCG levels were not significantly different. In uncomplicated pregnancies the hCG levels were significantly higher in female-bearing than in male-bearing mothers (P <.005), whereas the testosterone levels were not significantly different. CONCLUSION: In preeclamptic pregnancies with male fetuses, the maternal serum hCG levels were significantly higher than in uncomplicated pregnancies. Total testosterone levels were significantly higher in pregnancies with either gender and significantly higher in male-bearing than in female-bearing pregnancies. This may indicate an androgen influence on the pathophysiologic mechanism of preeclampsia.     

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia,and their relation with severity of disease

Abstract

Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants.

Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version.

Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p?<?0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p?<?0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age.

Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.     

The relation of maternal serum eNOS,NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction

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.     

Increased expression levels of E-cadherin,cytokeratin 18 and 19 observed in preeclampsia were not correlated with disease severity

Introduction

Preeclampsia is a pregnancy-specific disorder and placental factor(s) contribute to the pathogenesis of preeclampsia. Turnover of villous trophoblast is affected by impaired placental perfusion in preeclampsia. Expression and localisation of cadherins and cytokeratins are involved in the pathogenesis of preeclampsia. However, studies describing the associations between cadherins and cytokeratins in preeclampsia are limited. The aim of this study was to investigate the expression of E-cadherin, N-cadherin, cytokeratin 18 and cytokeratin 19 in placentae from women with preeclampsia in order to determine whether their expression differs with disease severity.

Methods

29 preeclamptic placentae and 25 normotensive placentae were included in this study. The expression of E-cadherin, cytokeratin 18, cytokeratin 19 andN-cadherin was quantified by immunohistochemistry and western blotting.

Results

E-cadherin, cytokeratin 18 and cytokeratin 19 were expressed predominantly in the syncytiotrophoblast of the placenta and the expression of E-cadherin, cytokeratin 18 and cytokeratin 19 was significantly increased in preeclampsia compared to normotensive pregnancies. However, there was no significant difference in expression between severe preeclampsia and mild preeclampsia. In addition, there was no difference in the expression of N-cadherin between preeclampsic and normotensive pregnancies.

Discussion

Our data demonstrated increased expression of E-cadherin, cytokeratin 18 and cytokeratin 19 in the syncytiotrophoblast of preeclamptic placentae, but this increase was not correlated with disease severity.

Conclusion

Our data suggests that E-cadherin and cytokeratins are involved in the pathogenesis of preeclampsia.     

Circulating and placental endoglin concentrations in pregnancies complicated by intrauterine growth restriction and preeclampsia

Inadequate trophoblast invasion and spiral artery remodeling leading to poor placental perfusion and hypoxia are believed to underlie preeclampsia (PE) and intrauterine growth restriction (IUGR). Recent studies implicate increased circulating endoglin as a contributor to the pathogenesis of PE. The objective of this study was to determine whether placental and circulating endoglin concentrations are altered in pregnancies complicated by intrauterine growth restricted (IUGR) infants and to address the role of hypoxia on the regulation of placental endoglin. We analyzed 10 placentas each from normal pregnant (NP), PE, and IUGR subjects. Endoglin levels were 2.5-fold higher in preeclamptic placentas compared to NP (15.4+/-2.6 versus 5.7+/-1.0, p<0.01). In contrast, endoglin levels were similar in NP and IUGR placentas (5.7+/-1.0 vs 5.9+/-1.1, p=NS). Placentas from pregnancies with both PE and IUGR exhibited endoglin levels comparable to the PE group and significantly different from normotensive pregnancies with and without IUGR pregnancies (mean 14.9+/-4.0, n=9, p=0.013). Soluble endoglin concentrations in maternal plasma were comparable in NP and IUGR, but higher in women with PE (n=10 per group, p<0.05). Despite a 2-fold increase in hypoxia inducible factor, HIF-1alpha, we did not observe endoglin upregulation in NP, PE, or IUGR placental villous explants exposed to hypoxia (2% oxygen). In contrast to PE, placental or circulating endoglin is not increased in normotensive women delivering small, asymmetrically grown (IUGR) infants at term. The placentas of women with IUGR appear to be fundamentally different from PE women with respect to endoglin, despite the proposed common pathology of deficient trophoblast invasion/spiral artery remodeling and poor placental perfusion.     

Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors

OBJECTIVE: Imbalance between angiogenesis-related factors is closely related to the development of preeclampsia. The objective was to estimate the most effective and accurate predictive biomarker among levels and ratios of angiogenesis-related factors, including soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin, placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1), in women who subsequently developed preeclampsia. METHODS: A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-beta1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women. RESULTS: Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-beta1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-beta1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-beta1) were significantly higher than in normotensive women (P<.001) and even greater in severe preeclampsia with preterm delivery compared with mild preeclampsia with term delivery (P<.05). At equivalent sensitivity (85%), the false-positive rate was 45% for sFlt-1, 41% for soluble endoglin, 33% for sFlt-1/PlGF, 21% for soluble endoglin/TGF-beta1, and 10% for the combined ratio. After adjusting for potential confounding factors, the risks for developing preeclampsia were as follows: odds ratio (OR) 6.9 [95% confidence interval 2.3-20.7] for sFlt-1 level, 7.1 [2.3-21.7] for soluble endoglin level, 6.8 [2.4-19.4] for sFlt-1/PlGF, 38.8 [9.8-154.3] for soluble endoglin/TGF-beta1, and 74.8 [17.6-316.7] for the combined ratio. CONCLUSION: The combined ratio of angiogenesis-related factors showed the lowest false-positive rate and the highest OR for prediction of preeclampsia, indicating that it may provide more effective prediction of development of preeclampsia. LEVEL OF EVIDENCE: II.     

Plasma malondialdehyde, superoxide dismutase, sE-selectin, fibronectin, endothelin-1 and nitric oxide levels in women with preeclampsia

OBJECTIVE: The purpose of this study was to determine plasma malondialdehyde (MDA), superoxide dismutase (SOD), soluble E-selectin (sE-selectin), fibronectin, endothelin-1 (ET-1) and nitric oxide (NO) levels in women with preeclampsia and to find out the relations of diastolic blood pressure with these variables. STUDY DESIGN: We performed a case-control study consisting of randomly selected 34 healthy pregnant women and 35 patients diagnosed as preeclampsia. Lipoperoxidation was ascertained by the formation of MDA. SOD activity was determined by the method of Sun et al. Plasma concentration of NO was estimated using colorimetric assay. Plasma ET-1 and sE-selectin were measured by enzyme-linked immunosorbent assay (ELISA). A nephelometric method for fibronectin quantitation was used. RESULTS: The mean plasma level of MDA was significantly higher and SOD was significantly lower in preeclamptic pregnancies (P<0.001). Plasma concentrations of fibronectin, sE-selectin and ET-1 were significantly increased, whereas NO was significantly decreased in women with preeclampsia than normotensive women (P<0.001). CONCLUSION: Increased plasma levels of MDA, fibronectin, sE-selectin, ET-1, and decreased plasma levels of NO and SOD in preeclamptic patients suggest that poorly perfused fetoplacental unit is the origin of oxygen free radicals and lipid peroxides.     

Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus.

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.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation.

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.     

Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment.

OBJECTIVE: The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity. STUDY DESIGN: Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women. RESULTS: Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05). CONCLUSION: Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.     

Anti-hypertensive drugs alter cytokine production from preeclamptic placentas and peripheral blood mononuclear cells.

OBJECTIVE: Antihypertensive drugs are administered to women with preeclampsia to control blood pressure and fluid overload. Whether they modulate placental or circulating cytokine production in women with preeclampsia is unknown. This study examines the effect of pharmacological doses of antihypertensive drugs on the production of IL-10, tumor necrosis factor alpha (TNF-alpha), and IL-6 in placental tissue and peripheral blood mononuclear cells (PBMCs) from women with preeclampsia. METHODS: Term placenta samples (n = 6) and PBMCs from whole blood (n = 6) were obtained from women with preeclampsia. Both villous explants and PBMCs were cultured with increasing concentrations of antihypertensive drugs (clonidine, diazoxide, hydralazine, and furosemide). The dose effect of drugs on the production of placental and circulating cytokines IL-10, TNF-alpha, and IL-6 was examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data suggest that clonidine can stimulate anti-inflammatory IL-10 production from PBMC while decreasing pro-inflammatory TNF-alpha, whereas low doses of hydralazine increased the production of IL-10, TNF-alpha, and IL-6 from preeclamptic PBMCs. There was a reduction in IL-10, TNF-alpha, and IL-6 production with increasing doses of clonidine and hydralazine by placentas in preeclampsia. IL-10, TNF-alpha, and IL-6 production from preeclamptic placenta and PBMCs were inhibited by diazoxide and furosemide. CONCLUSIONS: Antihypertensive drugs may alter Th1/Th2 cytokine balance in preeclamptic tissues in vitro.     

Measurement of the total antioxidant response in preeclampsia with a novel automated method

OBJECTIVES: Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. STUDY DESIGN: Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. RESULTS: Statistically significant differences (determined using Student's t-test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31 +/- 0.12 mmol versus 1.06 +/- 0.41 mmol Trolox eq./L; 30.2 +/- 17.83 micromol/L versus 18.1 +/- 11.37 micromol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8 +/- 14.3 micromol/L versus 38.8 +/- 9.6 micromol/L). CONCLUSIONS: We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia.     

Twin pregnancy and preeclampsia

INTRODUCTION: Preeclampsia is a pregnancy-specific disorder of humans which rates among one of the major cases of maternal and fetal morbidity and mortality. Etiology of preeclampsia is still largely unraveled and treatment is syndrome specific. OBJECTIVE: Evaluation of the incidence of preeclampsia in twin pregnancies and comparison of selected clinical characteristics among preeclamptic and non-preeclamptic twin pregnancy patients. METHODS: Retrospective analysis of 194 normotensive and 25 preeclamptic patients with twin pregnancies admitted to the Lublin State Hospital Nr 4 between January 1st 1992 and December 31st 1997. Patients were matched for gravidity, parity, maternal age and selected biochemical parameters. RESULTS: Preeclampsia occurred two times more frequently in nulliparous women (68% vs 32%). Gravidas with preeclampsia had significantly higher serum uric acid levels than their non-preeclamptic counterparts (6.7 +/- 0.3 vs 4.3 +/- 0.1; p < 0.001). Hypertension, proteinuria and edema coexisted concomitantly in 52% of preeclamptic patients. CONCLUSIONS: 1. Preeclampsia complicates one tenth of twin pregnancies. 2. In preeclamptic women nulliparas were two times more frequent. 3. In preeclamptic women is significantly higher level of uric acid.     

Maternal,placental and fetal exposure to bisphenol A in women with and without preeclampsia

Objectives: We aimed to investigate potential association between the exposure of bisphenol A (BPA) and preeclampsia. Methods: Concentrations of BPA were assessed in 58 pregnancies including 35 normotensive and 23 preeclamptic women, using a highly sensitive gas chromatography–mass spectrometry (GC-MS) method. Results: BPA was detected in maternal blood, fetal blood and placental tissue; and actual concentrations of BPA were determined. Interestingly, significant accumulation of BPA in the placentas of women with preeclampsia compared to normotensive women has been shown. Conclusions: This is the first study to highlight a significant correlation between preeclampsia and a high accumulation of BPA in the placenta.     

Plasma, urinary, and salivary 8-epi-prostaglandin f2alpha levels in normotensive and preeclamptic pregnancies

OBJECTIVE: Our purpose was to measure and compare plasma, urinary, and salivary concentrations of 8-epi-prostaglandin F(2alpha) (8-isoprostane) in women with normotensive pregnancies and the respective concentrations in pregnancies complicated by preeclampsia. STUDY DESIGN: Plasma, urinary, and salivary 8-isoprostane levels were measured in pregnant women with preeclampsia (n = 40), normotensive pregnant women (n = 20), and nonpregnant women (n = 10). One-way analysis of variance was used to determine significant differences. RESULTS: Plasma free 8-isoprostane concentrations were increased in women with severe preeclampsia (342 +/- 50 pg/mL), in comparison with nonpregnant women (129 +/- 17 pg/mL) and normotensive pregnant women (150 +/- 11 pg/mL; P =.003, and.0001, respectively). Urinary excretion of 8-isoprostane was slightly but not significantly decreased in preeclampsia (1200 +/- 227 pg/mL), in comparison with urinary excretion in nonpregnant women (1625 +/- 364 pg/mL) and normotensive pregnant women (2149 +/- 432 pg/mL). Salivary concentrations of 8-isoprostane were increased in normotensive women (496 +/- 113 pg/mL), in comparison with nonpregnant women (150 +/- 27 pg/mL) but were not related to preeclampsia (419 +/- 96 pg/mL; P 相似文献