Marinobufagenin levels in preeclamptic patients: a preliminary report

Preeclampsia is a disorder resulting in significant fetomaternal complications with no definitive pharmacological intervention. A bufadienolide, marinobufagenin, has been implicated in the etiology of preeclampsia. We investigated both the blood and urine levels of marinobufagenin in preeclamptic and control subjects. Preeclamptic and normotensive pregnant women were recruited at various gestational age periods. Blood and urine specimens were obtained and analyzed for marinobufagenin levels and creatinine. The former determination was performed utilizing a new, novel chemifluorescent enzyme-linked immunosorbent assay. The marinobufagenin levels were higher in preeclamptics than in the controls in both serum and urine at various gestational age periods. Additionally, the mean level of marinobufagenin in the preeclamptic group was significantly greater than in controls in both blood and urine specimens ( P?相似文献   

Antioxidant nutrients and lipid peroxide levels in Thai preeclamptic pregnant women

OBJECTIVE: To compare the antioxidant nutrients and lipid peroxide levels in preeclampsia and normal pregnant women. METHODS: Antioxidant nutrients (vitamin A and E) were measured by high-pressure liquid chromatography, vitamin C was measured by the dinitrophenyl hydrazine method, lipid peroxides were measured by the malondialdehyde method in 20 severe preeclampsia, 30 mild preeclampsia and 60 normal pregnant women as controls. RESULTS: Vitamin C levels in severe and mild preeclampsia were significantly less than those in control group. The corrected vitamin E and vitamin A levels were significantly decreased only in severe preeclampsia. While the lipid peroxide levels in both mild and severe preeclampsia were significantly increased when compared with the nomal pregnancy. CONCLUSIONS: Preeclampsia is associated with the imbalance between lipid peroxides and antioxidant nutrients (vitamin C and E). The imbalances favour lipid peroxides with the increasing severity of preeclampsia.     

Promoter hypomethylation and increased maspin expression in preeclamptic placentas in a Chinese population

ObjectivePreeclampsia is thought to begin with shallow trophoblast invasion and inadequate spiral artery remodeling. Maspin, a tumor-suppressor gene, plays a regulatory role in trophoblast invasion and motility. The tissue-specific methylation of the maspin promoter can regulate maspin gene expression in various cancers. We sought to detect maspin gene expression and assess the degrees of methylation of maspin promoter regions in preeclamptic placentas in the Han Chinese population and to investigate the potential role of maspin in the pathophysiology of preeclampsia.MethodsWe conducted RT-PCR, immunohistochemistry and western blotting to characterize maspin gene expression and protein levels in the placentas from normal and preeclamptic pregnancies. Finally, using methylation-specific PCR and bisulfite sequencing PCR, we detected the degrees of methylation of the promoter regions of maspin in each of the two studied groups.ResultsMaspin expression was increased at the mRNA and protein levels in the preeclamptic placentas compared to the control group. Maspin immunohistochemical staining revealed positive staining in the syncytio-cytotrophoblast layers and more diffuse staining in the preeclamptic group. The mean methylation level of the analyzed promoter region was significantly hypomethylated in the preeclamptic placentas compared to the control placentas, pointing to a negative relationship between maspin promoter methylation and gene expression.DiscussionHypomethylation of the maspin promoter results in increased expression of maspin in preeclamptic placentas, which suggests a negative relationship between maspin methylation and maspin expression in this Han Chinese population. Thus, maspin is likely involved in the etiology of preeclampsia.     

Immunohistochemical expression of Annexin A5 in preeclamptic placentas

Objective

To study the expression of Annexin A5 (A5) in relation to preeclampsia using immunohistochemical Tissue Microarray (TMA) technique.

Study design

Case-control study of 66 singleton preeclamptic (PE) patients matched for gestational age (GA) at delivery with 63 normotensive controls with normally grown fetuses. Immunohistochemical expression of A5 and other population characteristics were compared between the two groups using Chi-square, One-way ANOVA, Spearman’s Correlation, and Linear Regression.

Results

The two groups were similar for maternal age and rate of corticosteroid administration, but differed for nulliparity, Body Mass Index (BMI), blood pressure, presence of placental histological lesions, and placental weight. Expression of A5 was similar in PE and controls (p = 0.10); however it was found to be lower in PE cases complicated by fetal growth restriction (FGR, n = 34) compared with matched controls (n = 55) (p = 0.04). An inverse correlation was found between A5 and GA in cases but not in controls (p = 0.04 vs p = 0.71). The association was even more significant in the subgroup of PE complicated by FGR (p = 0.02). A5 expression was not influenced by blood pressure, proteinuria, or placental weight.

Conclusions

Annexin A5 expression seems to be related only to FGR and not to PE or its clinical severity.     

The expression of heparanase in normal and preeclamptic placentas

Objective: Heparanase plays a central role in processes of placentation. Abnormal placentation may result in inadequate uteroplacental blood flow, leading to unsuccessful pregnancy outcome and preeclampsia. We aimed to evaluate heparanase expression in placentas of preeclamptic patients.

Materials and methods: Placental tissue samples were collected immediately after delivery from 9 preeclamptic patients and 3 healthy controls at term, and were analyzed by immunohistochemistry, western blot analysis and real-time PCR, with regard to the presence of heparanase

Results: Immunohistochemistry staining for heparanase did not differ between normal and preeclamptic placental sections. On the other hand, western blot analysis revealed increased expression of heparanase in preeclpamptic placentas compared to controls, p?=?0.001. Similarly, RT-PCR analysis showed also an increased expression of heparanase m-RNA compared to health controls, p?=?0.005.

Conclusion: Heparanase is over expressed in preeclamptic placentas compared to normal healthy controls, suggesting its role in the development of preeclampsia.     

Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: A mechanism by which the placenta communicates with the maternal endothelium

Introduction

Preeclampsia is characterized by maternal endothelial dysfunction. While the mechanisms leading to preeclampsia are unclear, a factor(s) from the placenta is responsible for triggering the disease. One placental factor implicated in triggering preeclampsia is trophoblast debris which may transmit pathogenic signals from the placenta to endothelial cells. In this study, we investigated whether trophoblast debris from preeclamptic placentae triggered endothelial cell activation.

Methods

Trophoblast debris from preeclamptic or normotensive placentae, or trophoblast debris from normal placental explants that had been cultured with preeclamptic (n = 14) or normotensive sera (n = 14) was exposed to endothelial cells. Activation of the endothelial cells was quantified by cell surface ICAM-1 and U937 adhesion to endothelial cells. The levels of IL-1β, pro-caspase-1 and active caspase-1 in the trophoblast debris were measured.

Results

Compared to controls, the levels of ICAM-1 and U937 adhesion to endothelial cells were significantly increased following exposure of the endothelial cells to trophoblast debris from preeclamptic placentae or placentae treated with preeclamptic sera. The levels IL-1β, pro-caspase-1 and active caspase-1 were significantly increased in both trophoblast debris from preeclamptic placentae and placentae treated with preeclamptic sera.

Discussion

These results provide the first direct evidence that trophoblast debris produced from preeclamptic placentae or placentae treated with preeclamptic sera can activate the endothelium.

Conclusions

Trophoblast debris from preeclamptic but not normotensive placentae can induce endothelial cell activation. This may be one mechanism by which the preeclamptic placenta communicates with the maternal endothelium to induce activation of the endothelium.     

Glycosylation pattern and axin expression in normal and IUGR placentae

Objective: The aim of this study was to investigate the protein glycosylation pattern and AXIN1 protein expression in human placentae of normal pregnancies and compare them with placentae of pregnancies complicated with intrauterine growth restriction (IUGR).

Methods: A total of 38 placentae (17 placentae of IUGR fetuses from singleton pregnancies and gestational age-matched 21 control placentae from normal singleton pregnancies) were collected from the Clinical Hospital Sveti Duh, Department of Gynecology and Obstetrics, Zagreb, Croatia. Gestational age was determined according to the last menstrual period (LMP) and by ultrasound measurements. Expression of glycoproteins was measured by Western blotting with SNA, UEA-I, PHA-E and DBA lectins as probes whereas expression of AXIN1 was determined by immunohistochemistry.

Results: Comparison of detected sugars revealed differences in protein glycosylation between normal and IUGR placentae. Higher expression of AXIN1 protein located mostly in the cytoplasm of syncytiotrophoblast and to a lesser extent in its nuclei was found in IUGR placentae.

Conclusion: Results of our study suggest that changes in glycoprotein content may contribute to restricted placenta growth and development. Higher expression of AXIN1 protein in IUGR placentae indicates a role of Wnt/β-catenin signaling pathway in pathology of placental development.     

Immunohistochemical study of annexin V expression in placentae of preeclampsia

We investigated the clinical significance of annexin V in the placentae with preeclampsia and found: (1) annexin V was detected on trophoblasts in the placentae and the staining intensity of annexin V in the placentae from such patients was reduced when compared to normal placentae; (2) as expression of annexin V was reduced, the gestosis index from patients with preeclampsia was elevated and the standard deviation value in the infant's standard weight was decreased; plasma level of the fibrin degradation products and thrombin-antithrombin III complex from patients were elevated as the expression of anexin V was reduced. These results suggest that the reduced expression of annexin V in the placentae from patients with preeclampsia may lead to a hypercoagulable state in the intervillous space and may be associated with the development of intrauterine growth restriction.     

Capillary blood glucose screening for gestational diabetes: a preliminary investigation

Home glucose monitoring with the use of reflectance meters is an important adjunct in the care of pregnant women with insulin-dependent diabetes. The accuracy of reflectance meters for the assay of capillary glucose specimens has been well documented. The present preliminary study was undertaken to determine the utility of outpatient screening for gestational diabetes mellitus with the use of a reflectance meter (Accu-Chek, Boehringer Mannheim Co.). One hundred twenty-five patients in our high-risk practice had a standard 50 gm glucose load at 26 to 28 weeks' gestation. Capillary glucose values were measured on site with the Accu-Chek. Venous plasma glucose levels were measured by the central laboratory chemistry analyzer. While the laboratory (x) and meter (y) glucose determinations between the two sets of values were highly correlated (R = 0.89, p less than 0.001), there was a significant difference in their average values (x = 111.74, y = 136.35, p less than 0.0001). With the use of a receiver operator characteristic curve, a meter value of 160 mg/dl was determined as the optimal threshold for performing a 3-hour glucose tolerance test. The sensitivity and specificity with the use of a meter value of 160 mg/dl were 93% and 96%, respectively, for detecting an abnormal screening test in venous plasma (greater than or equal to 135 mg/dl). A total of 32 glucose tolerance tests were performed, with four patients included who had venous values less than 135 mg/dl. All eight patients with gestational diabetes mellitus were correctly identified. These data suggest that a glucose reflectance meter can be used for accurate outpatient screening of gestational diabetes mellitus. The potential advantages of capillary blood glucose screening include both cost and efficiency. Patients with abnormal screening values can be promptly identified and scheduled for a follow-up 3-hour glucose tolerance test.     

Endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism and expression in North Indian preeclamptic women

BackgroundPathophysiological processes in preeclampsia (PE) are influenced by genetic factors, nitric oxide synthases seem to play important roles, although their expression in and their role is still unclear. To better characterize the host genetic factors determining the susceptibility to PE, we evaluated the influence of polymorphisms (Glu298Asp) in the endothelial nitric oxide synthase (eNOS) gene on the risk of developing PE by checking the expression level.MethodsWe conducted a hospital-based case-control study including 300 women with preeclampsia and 200 healthy pregnant women. Their blood samples were analyzed for levels of nitric oxide, eNOS gene polymorphism and expression. eNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction with control β-Actin gene mRNA levels.ResultsThe mRNA expression of eNOS gene was found to be significantly lower in blood (P < 0.05) from women with PE compared to that from normal pregnancies. The total nitric oxide levels (P < 0.001) were decreased in study Group as compared to healthy pregnant patients. The intergenotypic variation of nitric oxide levels in preeclamptic women was found to be significant (P < 0.001).ConclusionsThese results indicate the relationship between reduced nitric oxide levels and eNOS gene polymorphism leading to its altered expression in preeclamptic women.     

DNA microarrays detect the expression of apoptosis-related genes in preeclamptic placentas

AIMS: To investigate the expression of apoptosis-related genes in preeclamptic placentas and the possible mechanism of the regulation process. METHODS: Complementary DNA microarrays were employed to compare gene expression profiles of five preeclamptic and five normal placentas. RESULTS: Among the 368 genes detected over 35% showed an over 2-fold difference of expression between preeclamptic placentas and normal placentas. Many genes involved in cell cycle or apoptosis were more highly expressed in preeclamptic placentas than in normal placentas. The expression of many immune-activation genes in preeclamptic placentas was also higher than that in normal placentas. Additionally, many cytokine receptor/kinase genes were also induced in preeclamptic placentas. CONCLUSIONS: The change in expression of cell apoptosis-related genes in placentas might be involved in the pathogenesis of preeclampsia, while the activation of the immune system might be one cause of this change.     

Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study

Preeclampsia is a disease unique to pregnancy that contributes substantially to maternal and fetal morbidity and mortality. The condition has been thought to be one of hypoperfusion in which increased vascular resistance characterizes the associated hypertension. This study was designed to test an alternative hypothesis, that preeclampsia is characterized by high cardiac output. In a blinded longitudinal study of nulliparas with uncomplicated pregnancies, cardiac output was measured serially by Doppler technique. Cardiac output was elevated throughout pregnancy in patients who became preeclamptic (P = .006). Six weeks postpartum, the hypertension of the preeclamptic subjects had resolved but cardiac output remained elevated (P = .001) and peripheral resistance remained lower than in the normotensive subjects (P = .001). This study demonstrates that preeclampsia is not a disease of systemic hypoperfusion and challenges most current models of the disease based on that assumption.