Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.     

Serum lipid peroxidation and antioxidant potential levels in hyperemesis gravidarum

Hyperemesis gravidarum (HEG) is a severe form of nausea and vomiting with unknown etiology. Recent studies have suggested that there might be an etiologic role for HELICOBACTER PYLORI (HP) in HEG. HP is a Gram-negative bacterium that colonizes the gastric mucosa, increases the generation of reactive oxygen species (ROS), and decreases plasma antioxidants such as ascorbic acid. The aim of this study was to investigate plasma ROS activities and antioxidant status, and their relationship with HP infection, in HEG womens. Twenty-five HEG women, 20 gestational age- and gravida-matched healthy pregnant controls, and 15 nonpregnant women were examined for specific immunoglobulin G (IgG) against HP, serum malondialdehyde (MDA) as a measure of lipid peroxidation, and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CT). Compared with controls, the seropositivity of HP for IgG was significantly higher ( P < 0.01) in pregnancies with HEG. When three study groups (including both HP + and HP- patients) were compared with each other with respect to the study parameters, MDA concentration increased significantly in pregnant women when compared with control group (nonpregnant women; P < 0.01), as well as in HEG compared with healthy pregnant women ( P < 0.01). The SOD, GSH-Px, and CT activity were increased in the group of normal pregnant women versus the nonpregnant group ( P < 0.01), but decreased significantly in the group of HEG pregnant women ( P < 0.01). Serum MDA levels and SOD, GSH-Px, and CT activity were not affected by the seropositivity of HP for IgG in either group ( P > 0.05). The results of the present study suggest that HEG is an oxidative stress condition, as reflected by the increased ROS activity and decreased antioxidant status, regardless of HP infection.     

Relationship between erythrocyte catalase and serum adenosine deaminase activities in eclampsia

Objective. To examine the relationship between antioxidant status and T-cell activation in the pathogenesis of eclampsia by measuring the activities of erythrocyte catalase, an enzyme of antioxidant mechanism, and serum adenosine deaminase (ADA), regarded as a marker of T-cell activation.

Methods. A total of 60 patients [20 eclamptic (E) pregnant women, 20 healthy pregnant (HP) women and 20 non-pregnant (NP) women] were included in the study. Maternal venous blood samples were obtained from each patient during weeks 28–37 of gestation, and biochemical analyses of catalase activity in erythrocytes and ADA activity in serum were carried out.

Results. Erythrocyte catalase activity was significantly lower and serum ADA activity was significantly higher in the E pregnant women when compared with the HP women and NP women (P <0.001). No significant correlation was observed between erythrocyte catalase activity and serum ADA activity.

Conclusions. Erythrocyte catalase and serum ADA activities may at least in part contribute to the pathogenesis of eclampsia. However, more studies are needed to verify and clarify the relationship between antioxidant status and T-cell activation in eclampsia.     

Glutathione peroxidase activity in normal and preeclamptic placentas

OBJECTIVE: The decrease of placental glutathione peroxidase (GSH-Px) activity may lead to exacerbation of lipid peroxidation in preeclamptic placentas. DESIGN: The aim of the study was the determination of GSH-Px activity in placentas from normal and preeclamptic pregnancies (with and without intrauterine growth retardation-IUGR). MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 24 normal pregnancies (group K), 26 pregnancies complicated by severe preeclampsia-PE (group PE) and 23 pregnancies complicated by severe PE and IUGR (group PEI). The activity of GSH-Px was determined using a spectrophotometric method and expressed as IU/g protein. Comparative analysis was performed using u Mann-Whitney test. RESULTS: Mean activity of GSH-Px (MGSH-Px) in the PEI group--5.38 +/- 1.59 (M +/- SD), was significantly lower (p < 0.001) as compared to MGSH-Px in the group K (7.22 +/- 1.21). MGSH-Px in the PE group (6.47 +/- 1.31) was lower than MGSH-Px in the group K, but this difference was not statistically significant (p > 0.05). MGSH-Px in the group PEI was significantly lower (p = 0.023) as compared to MGSH-Px in the PE group. CONCLUSIONS: The activity of GSH-Px is decreased in placentas from pregnancies complicated by severe PE and IUGR. Received results may indicate that the decrease of placental GSH-Px activity may be involved in pathogenesis of IUGR in preeclamptic pregnancies.     

Increased Maternal Serum and Cord Blood Fibronectin Concentrations in Preeclampsia are Associated with Higher Placental Hyaluronic Acid and Hydroxyproline Content

Background. Total or cellular fibronectin (FN) determinations have been used to differentiate between normal and preeclamptic pregnants. The purpose of this study was to examine the relationship between maternal serum FN levels and the extracellular matrix molecule contents of placental tissue, such as FN, hyaluronic acid (HA) and hydroxyproline (HP) levels. Material and Methods. We obtained maternal blood samples and placental tissue samples from healthy (n = 17, controls) and preeclamptic pregnants (n = 29). We also obtained cord blood samples for FN and HA determination from the same patients. FN and HA concentrations in the placenta and maternal and cord blood were measured by and enzyme-linked immunosorbent assay and HP contents in the placenta were measured by a colorimetric assay. Results. FN levels in maternal serum, cord blood, and placenta were significantly higher in preeclamptics than in controls (p<0.001, p<0.001 and p<0.05, respectively). HA concentrations in the cord blood and placenta were found to be elevated in preeclamptics (p<0.05 and p<0.01). Preeclamptics had significantly higher placental HP levels than controls (p<0.001). Similar statistically significant results were obtained when the pregnant subjects classified as nulliparous and multiparous. There was no difference in ECM molecule levels between nulliporous and multiparous women in preeclamptic pregnant group. In regression analysis maternal serum FN levels were correlated with placental HA and HP levels (p<0.01 and p<0.01). There was a positive correlation between cord blood FN and both placental HP (p<001) and HA levels (p<0.01). FN levels in maternal serum, cord blood, and placenta were also negative correlated with fetal birth weight (p<0.01, p<0.05 and p<0.05, respectively). Conclusion. FN in maternal serum, cord blood, and placenta is increased with elevated placental HA and HP levels, probably reflecting placental basement membrane alterations during preeclampsia.     

Fractional excretion of angiogenic factors in women with severe preeclampsia

OBJECTIVE: We estimated the fractional excretions of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor, and placental growth factor of severely preeclamptic women at the time of disease clinical manifestation. METHODS: Levels of free sFlt-1, vascular endothelial growth factor, and placental growth factor were measured by immunoassay from time-matched serum-urine samples from 64 women in the following groups: nonpregnant reproductive aged (n = 9), healthy pregnant controls (n = 13), mildly preeclamptic women (n = 15), and women with severe preeclampsia (n = 27). Urinary concentrations of angiogenic factors were normalized to creatinine and fractional excretions calculated. Correlations were estimated between fractional excretions of angiogenic factors, albuminuria, nonspecific proteinuria and urine protein-to-creatinine ratio. RESULTS: Severely preeclamptic women had more than double urinary vascular endothelial growth factor (P = .01) and fractional excretion of vascular endothelial growth factor compared with mildly preeclamptic women (P = .007) or pregnant controls (P < .001). Serum, urine and fractional excretion levels of sFlt-1 were much higher among severely preeclamptic women compared with all the other pregnant groups (P < .001). Conversely, severely preeclamptic women had lower serum placental growth factor levels compared with healthy pregnant women (P < .05) and mildly preeclamptic groups (P < .05). Severely preeclamptic women had increased fractional excretions of placental growth factor, albumin, proteinuria, and random urine total protein/creatinine ratio. Among severely preeclamptic women there was no correlation between proteinuria and fractional excretion of vascular endothelial growth factor (r = 0.30, P = .127) or sFlt-1 (r = 0.35, P = .07). There was a significant correlation between fractional excretion for placental growth factor, random urine total protein/creatinine ratio (r = 0.60, P = .002), and nonspecific proteinuria (r = 0.50, P = .01). CONCLUSION: Severe preeclampsia is characterized by increased fractional excretion of angiogenic factors and especially of vascular endothelial growth factor, likely reflecting 2 separate phenomena that may have additive effects: "endogenous" renal production and glomerular "leakage."     

Ceruloplasmin and antioxidative enzymes in pre-eclampsia

Objective: To evaluate diagnostic value of ceruloplasmin together with other enzymatic and nonenzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and uric acid) and to evaluate the level of oxidative stress in patients with pre-eclampsia (PE) and compare it with normal pregnancy.

Methods: In this prospective study, antioxidative markers were investigated in two groups of pregnant women: patients with pre-eclampsia (n?=?32) and the healthy pregnant women (n?=?60). The following antioxidative markers and enzymes were evaluated: serum ceruloplasmin levels, uric acid, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).

Results: Serum levels of ceruloplasmin, uric acid and SOD were significantly higher in the PE group compared to the control group. Serum levels of GSH-Px were not significantly higher in the PE group compared to the control group. Serum ceruloplasmin and serum uric acid have the best diagnostic accuracy for oxidative stress in PE and are more accurate compared to antioxidative enzymes -SOD and specially more accurate than GSH-Px.

Conclusions: Serum ceruloplasmin level may have significant role as the markers of oxidative stress in pre-eclampsia especially when used in combination with uric acid levels.     

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.     

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.     

The effect of Trolox-vitamin E analog on placental lipid peroxidation with physiologic pregnancies and pregnancies complicated by pre-eclampsia

There are suggestions that free radicals are involved in some dysfunctions observed in preeclampsia. In this study we have examined the effect of Trolox (water soluble vitamin E analog) on placental lipid peroxidation. Placentas from 20 normal and 20 preeclamptic woman were used in this study. Lipoperoxidative process was measured by means of Okhawa method. The level of lipid peroxides in preeclamptic placentas is higher than in normal placentas. In normal placentas 20 microM, of Trolox caused the greatest fall in MDA level (about 25%) in comparison with the control MDA level (only with peroxidative system without Trolox). In preeclamptic placentas the greatest fall in lipooxygenation process (about 14%) was caused by 25 microM. of Trolox. The influence of Trolox on the level of lipid peroxides in preeclamptic placentas is less effective in comparison with normal placentas.     

Lipid and protein peroxidation process and catalase activity in pre-eclamptic placenta

There are some suggestions that free radicals are involved in some dysfunctions observed in preeclampsia. In this study we have examined the antioxidant status of preeclamptic placentas. We have used placentas obtained from normal pregnant women and women with preeclampsia. Lipoperoxidative process was measured by means of Okhawa method. Sedlak method was used to measured the total thiol groups. The catalase activity was measured by means of Pffeifer method. The results show that the catalase activity decreases, the amount of MDA increases and the total amount of thiol groups is smaller in preeclamptic placentas. The level of lipid peroxides in preeclamptic placentas is about 1.8 times higher in comparison with normal placentas. The decreased level of total thiol groups in preeclamptic placentas can be caused by a more intensive process of protein peroxidation. Catalase is less active in preeclamptic placentas. It can be due to lower activity of antioxidant systems or the destruction of antioxidant systems by reactive oxygen species. The results of our experiments confirm lower antioxidant status in preeclamptic placentas and suggest that peroxidative reaction may cause many dysfunctions associated with preeclampsia.     

Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia

OBJECT: The aim of this study was to evaluate the lipid and protein oxidation and antioxidant function in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. METHOD: The study was carried out in 30 patients with mild preeclampsia, 30 with severe preeclampsia, and in 50 normotensive pregnant women during the third trimester of pregnancy. Lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls and some of the antioxidants were measured by spectrophotometric methods. One-way analysis of variance, chi-square test and Pearson correlation test were used for the statistical analyses. Logistic regression procedures were used to calculate odds ratios (OR). RESULTS: Lipid peroxides in serum, placenta and decidua basalis and protein carbonyls in serum were significantly increased, and vitamin E and total carotene levels in serum were significantly decreased especially in women with severe preeclampsia compared with mild preeclampsia and controls. A significant correlation was detected between diastolic blood pressure and lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls. Furthermore, there was significant correlation between antioxidant vitamins and lipid and protein oxidation products in severe preeclamptic patients. Also, logistic regression analysis showed that changes in serum, placental and decidual lipid peroxides and serum protein carbonyls, vitamin E and total carotene concentrations were significantly associated with preeclampsia. CONCLUSION: Our findings suggest that lipid and protein oxidation may be an important factor in the pathogenesis of preeclampsia. Since antioxidant vitamins are significantly decreased in both severe and mild preeclamptic pregnants, early supplementation with antioxidants may be beneficial in preeclamptic patients.     

The impact of platelet functions and inflammatory status on the severity of preeclampsia

Objective: To find out whether there is a correlation between the extent of platelet activation and inflammation and the severity of preeclampsia (PE) in the third trimester of pregnancy.

Methods: Forty-one women with PE (n?=?23 severe, n?=?18 mild) and 80 normotensive pregnant (NP) women were included in the study. Their blood samples were obtained and interleukin (IL)-8 and IL-10 levels measured by an enzyme-linked immunosorbent assay. Basal CD61 and CD62P expressions on CD41-positive platelets were analyzed with the use of flow-cytometry. Platelet aggregation was induced by adenosine diphosphate and determined by aggregometry.

Results: CD62P expression was increased in severely preeclamptic women, and the platelet aggregation was decreased in both mildly and severely preeclamptic women in comparison with NP women. However, CD61 expression was similar among the groups. An enhanced inflammatory response was seen in severely preeclamptic women demonstrated by increased levels of IL-8 and decreased levels of IL-10. However, the intensity of platelet activation did not correlate directly with the change in plasma levels of IL-8 and IL-10 in preeclamptic women.

Conclusions: Platelets may have a role in the inflammatory response in PE. However, the severity of inflammation is found to be independent from the intensity of platelet activation in preeclamptic women. This seems to be related to mechanisms causing alterations of cytokine levels such as IL-8 and IL-10, rather than platelet activation.     

Serum and placental interleukin-18 are elevated in preeclampsia

OBJECTIVES: Interleukin-18 (IL-18) is a proinflammatory cytokine with pleiotrophic qualities and its roles in pregnancy, labor onset and pregnant complications have been proposed. However, the alterations of serum and placental IL-18 have been less investigated. The objective of the current investigation was to detect IL-18 concentrations in serum and placentas from patients with preeclampsia and women with normal pregnancy. METHODS: 27 patients with preeclampsia and 28 women with normal pregnancy were recruited. Blood and placental samples were taken and IL-18 concentrations in serum and placental homogenate were analyzed by enzyme-linked immunosorbent assay (ELISA). The levels of IL-18 in serum and placenta were compared between preeclampsia and control. RESULTS: Both serum and placental levels of IL-18 were significantly increased in preeclampsia as compared with control (P=0.014 and 0.003, respectively). Serum and placental levels of IL-18 were not significantly different in preeclamptic women who received dexomethasone and those who did not (P=0.223 and 0.330, respectively). Serum and placental IL-18 levels were not significantly different between preeclamptic women who delivered before 36 complete gestational weeks and those who delivered after 36 complete weeks (P=0.616 and 0.869, respectively). There were no significant differences in serum and placental IL-18 between women with mild preeclampsia and those with severe preeclampsia (P=0.056 and 0.357, respectively). CONCLUSIONS: Increased serum and placental levels of IL-18 were observed in preeclampsia. Those associations may offer insight into the pathogenesis of the disease.     

子痫前期并发脏器受累的孕妇血清及胎盘氧化应激损伤水平研究

目的:探讨分析并发不同脏器受累的子痫前期孕妇血清及胎盘氧化应激损伤水平。方法:选择2012年12月—2014年12月于福建医科大学附属协和医院产科住院分娩的30例子痫前期并发脏器受累的孕妇作为研究组,30例子痫前期未并发脏器受累的孕妇作为对照1组,另选同期正常晚期妊娠孕妇30例作为对照2组。应用紫外比色法检测血清及胎盘组织中谷胱甘肽过氧化物酶(GPX)活性、过氧化氢酶(CAT)活性、脂质过氧化终产物丙二醛(MDA)水平;WST法(Total Superoxide Dismutase Assay Kit with WST-1)检测血清及胎盘组织中超氧化物歧化酶(SOD)的活性水平。结果:1研究组及对照1组孕妇血清及胎盘组织中GPX、CAT、SOD活性水平均低于对照2组,且研究组均低于对照1组,差异均有统计学意义(P0.05)。2研究组及对照1组孕妇血清及胎盘组织中MDA水平均高于对照2组,且研究组高于对照1组,差异均有统计学意义(P0.05)。3研究组及对照1组孕妇血清及胎盘组织中MDA水平与GPX、CAT及SOD活性水平均呈负相关(P0.05);对照2组孕妇血清及胎盘组织中MDA水平与GPX、CAT及SOD活性水平未见明显相关性(P0.05)。结论:血清及胎盘氧化应激损伤增强可能是子痫前期发病的重要因素,且可能促使子痫前期孕妇并发脏器受累,血清及胎盘组织中抗氧化酶活性水平下降可能是血清及胎盘氧化应激损伤水平升高的原因。     

Assessment of lipid peroxidation intensification in normal and preeclamptic placentas

OBJECTIVE: Free radical induced lipid peroxidation (LP) in the placenta has been suggested as a possible pathogenetic factor of preeclampsia (PE). DESIGN: The aim of the study was to assess LP intensification by the measurement of lipid peroxidation products (LPP) content in placentas from normal and preeclamptic pregnancies. MATERIALS AND METHODS: The investigations comprised placentas obtained immediately after delivery from 24 normal pregnancies [group K], 26 pregnancies complicated by severe PE without intrauterine growth restriction (IUGR) [group PE] and 23 pregnancies complicated by severe PE and IUGR [group PEI]. LPP content was measured by the quantitative determination of thiobarbituric acid reactive substances (TBA-RS) amounts in studied placentas. Used TBA test was calibrated with malondialdehyde (MDA) and results were expressed as MDA equivalent in nmol/mg protein. Comparative analysis was performed using U Mann-Whitney and median tests. RESULTS: Mean placental level of LPP (MLPP) in the group PE-2.45 +/- 0.39 (M +/- SD) was significantly higher (p < 0.001) as compared to MLPP in the group K (1.58 +/- 0.24). MLPP in the PEI group (2.81 +/- 0.65) was higher (p < 0.001) than MLPP in the group K as well as MLPP in the group PE but statistical significance of the latter difference was lower (p = 0.032). CONCLUSIONS: The intensification of LP in placentas from pregnancies complicated by severe PE is IUGR dependent and higher than in placentas from normal pregnancies. Obtained results may indicate that higher degree of LP intensification in preeclamptic placentas may be involved in PE pathogenesis.     

Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia

Neutrophil gelatinase-associated lipocalin (NGAL) concentrations, a product of neutrophils, were investigated in normal and preeclamptic pregnancies. Prospectively collected data and late second trimester (24-26 weeks) serum samples from 48 women who subsequently developed preeclampsia (PE) and 96 control women with uncomplicated pregnancies were compared. Serum NGAL values, as determined by quantitative sandwich enzyme immunoassay, were significantly increased in the preeclamptic compared to the control women: 76.9 ng/ml (interquartile range 39.7-96.5) versus 16.0 ng/ml (interquartile range 11.2-24.4) (p<0.001), and were positively correlated to blood pressure and proteinuria, showing a high sensitivity (75%) and specificity (94.5%). The results suggest that serum NGAL might be involved in the pathophysiology of PE and could be a marker for this syndrome.     

Soluble Flt-1 as a diagnostic marker of pre-eclampsia

BACKGROUND: Serum levels of soluble fms-like tyrosine kinase (sFlt-1) increase in pre-eclampsia (PE). Aims: To determine whether concentrations of serum sFlt-1 can differentiate PE or superimposed PE (SPE) from gestational hypertension (GH) or chronic hypertension (CH). METHODS: Blood was collected from pregnant women being investigated for hypertension (blood pressure of > 140 and/or 90 mmHg). Normotensive (NP) and pre-eclamptic (PE-C) control ranges were measured. RESULTS: Patients with evolving hypertension in pregnancy eventually fell into four groups: GH (n = 14), PE (n = 7), CH (n = 9) and SPE (n = 9). Patients who later developed pre-eclampsia had a higher sFlt-1 (PE: 2.61 ng/mL and SPE: 2.77 ng/mL, respectively) than GH (P < 0.001) or CH (1.05 ng/mL, P = 0.11). Women with established PE at recruitment (PE-C; (n = 18) (3.13 ng/mL; interquartile range (IQR): 2.14-4.17 ng/mL) had a median sFlt-1 higher than NP (n = 18) (0.47 ng/mL; IQR: 0.11-0.89) (P < 0.0008). Patients with GH compared to NP had a slight increase (1.33 ng/mL, P < 0.003). Using a sFlt-1 cut-off of > or = 1.9 ng/mL yielded a sensitivity of 94% (95% confidence interval (CI) 73-100%) and specificity of 78% (95% CI 64-82%). CONCLUSIONS: sFlt-1 was elevated in women with PE compared to NP. The sFlt-1 also differentiated women destined to develop PE among those who presented with a diagnostic rise in maternal blood pressure. The sFlt-1 test is a useful diagnostic test for PE.     

Association between the growth arrest-specific 6 (Gas6) gene polymorphism c.834 + 7G>A and preeclampsia

Objective: Preeclampsia (PE) is a hypertensive disease of pregnancy complicating 2–8% of all pregnancies. The exact pathophysiology still remains unknown. Growth arrest-specific 6 (Gas6) is a member of the vitamin K-dependent protein family and it has been suggested as a novel atherothrombotic risk factor with anti-angiogenic and pro-atherogenic properties. The goal of the our study was to investigate the relationships between the c.834?+?7G?>?A polymorphism of GAS6, plasma Gas6 levels and PE.

Methods: A total of 150 women, including 82 preeclamptic pregnant women and 68 normotensive pregnant (NP) women, were recruited in the current study. Blood samples were taken from all participitants. Plasma Gas6 levels measured by an enzyme-linked immunosorbent assay. GAS6 polymorphism was determined using a PCR-RFLP method.

Results: The plasma Gas6 levels of preeclamptic patients were significantly lower than those of NP women (8.65?±?3.70?ng/ml and 10.89?±?4.23?ng/ml respectively, p?<?0.001). The GG genotype was the most prevalent, and the risk of PE was 3.5-fold higher in pregnant women with GG genotype compared to woman with AA genotype (p?<?0.01). The A allele was less frequent in preeclamptic patients than in control subjects (OR?=?2.118, 95% CI?=?1.330–3.371, p?<?0.001).

Conclusions: Our results suggest that GAS6 c.834?+?7G?>?A polymorphism may have a pivotal role in the pathogenesis of PE suggesting that the A allele has a protective role for PE.     

Oxidant-antioxidant system changes relative to placental-umbilical pathology in patients with preeclampsia.

OBJECTIVE: It is speculated that lipid peroxidation is responsible for the pathologic changes that occur in the uteroplacental vasculature of women with preeclampsia. The aim was to investigate this proposed relationship. MATERIALS AND METHODS: The prospective study involved 90 pregnant women. Thirty had mild preeclampsia, 30 had severe preeclampsia, and 30 were healthy pregnant women (controls). The data collected for each case were umbilical cord and placental pathologies, plasma malondialdehyde (MDA) level, and levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in erythrocytes. Group findings were compared. RESULTS: The mean MDA level in the severe preeclampsia group was higher than the corresponding findings in the mild preeclampsia and control groups (p < 0.001 for both). Also, the MDA level in the mild preeclampsia group was significantly higher than was the control level (p < 0.001). The mean SOD activity level in the severe preeclampsia group was lower than the corresponding results in the mild preeclampsia and control groups (p < 0.001 for both). The mean GSH-Px levels in the mild and severe preeclampsia groups were both significantly lower than was the corresponding finding in the control group (p < 0.01). Compared to the control group, both preeclampsia groups had significantly higher frequencies for placental infarction, villous fibrosis, increased numbers of syncytial nodes, and thickening of vessel walls and lumen obliteration (p < 0.001 for all). Villous fibrinoid necrosis, perivillous fibrosis, and increased villous vascularization were also significantly more frequent in both preeclampsia groups than in the control group, but the differences for these parameters were smaller (p < 0.01 for all). Examination of the samples from the placental ends of the umbilical cords revealed significantly higher frequencies of endothelial irregularity, endothelial shedding, and basal membrane thickening in both preeclampsia groups than in those of the control group (p < 0.001). The same findings were noted in the middle sections of the cords (p < 0.001). At the fetal ends of the umbilical cords, both preeclampsia groups had higher frequencies of endothelial irregularity than did the control group (p < 0.001); however, the frequencies of the more severe pathologic findings (endothelial shedding, basal membrane thickening) in the three groups were similar. CONCLUSION: The frequencies of pathologic changes in the placenta and umbilical vessels of women with preeclampsia parallel the severity of this condition. These changes also parallel plasma levels of MDA, the end product of lipid peroxidation.