Granulocyte superoxide anion production and regulation by plasma factors in normal and preeclamptic pregnancy

Data on the respiratory burst activity of granulocytes from healthy and preeclamptic women have remained contradictory. To investigate the role of reactive oxygen species in the etiology of preeclampsia we measured superoxide anion generation by granulocytes from non-pregnant, healthy, and preeclamptic women. We also examined the reciprocal effects of heat-inactivated and non-inactivated plasma on superoxide production. Superoxide generation was measured by ferricytochrome-c reduction. Superoxide production induced by either phorbol-12,13-dibutirate or N-formyl-methionyl-leucyl-phenylalanine was significantly decreased in granulocytes from normal pregnant women compared with non-pregnant and preeclamptic women. The phorbol-12,13-dibutirate-induced superoxide generation by granulocytes from non-pregnant and preeclamptic women was significantly inhibited by plasma from healthy pregnant women. The N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production by granulocytes from non-pregnant and preeclamptic women was suppressed only by non-inactivated plasma, not heat-inactivated plasma from healthy pregnant women. Plasma from preeclamptic women did not influence the phorbol-12,13-dibutirate- and N-formyl-methionyl-leucyl-phenylalanine-induced superoxide production by control granulocytes. The phorbol-12,13-dibutirate-induced superoxide generation by granulocytes from healthy pregnant women was significantly increased by the effect of plasma from non-pregnant and preeclamptic women, but when stimulating with N-formyl-methionyl-leucyl-phenylalanine only non-inactivated plasma caused the same enhancement. These data indicate that reduced superoxide generation in normal pregnancy may be caused by maternal immunosuppressive factors present in plasma. The failure to reduce superoxide production in preeclampsia may be partly responsible for the endothelial dysfunction characteristic of that condition.     

Cell-derived microparticles and complement activation in preeclampsia versus normal pregnancy

BACKGROUND: Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. OBJECTIVES: To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. METHODS: Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP], immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and activator molecules were also determined. RESULTS: Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. CONCLUSIONS: We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles.     

The role of endothelium in normal pregnancy and pregnancy complicated by preeclampsia]

Endothelial cell dysfunction is thought to play a role in preeclampsia and the reduced production by vascular endothelial cells of the antiaggregatory and vasodilatory factors is well documented. The present study was designed to evaluate endothelial cells function in preeclamptic and healthy pregnant subjects. The nitric oxide plasma concentration in women with preeclampsia was significantly lower as compared with normotensive pregnant women. A significant increase in ET concentration was found in preeclamptic women as compared with normal pregnant patients and normal non-pregnant. The plasma concentrations of von Willebrand factor were significantly increased in healthy pregnancy as compared with preeclamptic patients. The results of our study demonstrate a significant endothelial cells damage in preeclamptic patients. Whether these observations contribute to the vascular pathophysiologic features of preeclampsia remains to be proved.     

Plasma Hemopexin Activity in Pregnancy and Preeclampsia

Objective: Plasma hemopexin activity, associated with increased vascular permeability, was evaluated in healthy pregnant and non-pregnant women and in pre-eclamptic women. Methods: Hemopexin activity and the hemopexin inhibitor, extracellular ATP, were assayed in plasma from pregnant (n?=?10), preeclamptic (n?=?9), and non-pregnant women (n?=?10) using standard methods. Abdominal fascia tissue fragments from preeclamptic and pregnant women were immunohistochemically stained for vascular ecto-apyrase or ecto-5′nucleotidase. Results: The data show significantly enhanced Hx activity exclusively in plasma from pregnant women and significantly enhanced plasma ATP in pre-eclamptic women compared with the other groups. Dephosphorylation of preeclamptic plasma resulted in reactivation of Hx activity. Fascia tissue-samples from preeclamptic women showed reduced ecto-apyrase activity and enhanced ecto-5′nucleotidase activity compared to pregnant women. Conclusion: Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.     

Plasma hemopexin activity in pregnancy and preeclampsia.

OBJECTIVE: Plasma hemopexin activity, associated with increased vascular permeability, was evaluated in healthy pregnant and non-pregnant women and in pre-eclamptic women. METHODS: Hemopexin activity and the hemopexin inhibitor, extracellular ATP, were assayed in plasma from pregnant (n = 10), preeclamptic (n = 9), and non-pregnant women (n = 10) using standard methods. Abdominal fascia tissue fragments from preeclamptic and pregnant women were immunohistochemically stained for vascular ecto-apyrase or ecto-5'nucleotidase. RESULTS: The data show significantly enhanced Hx activity exclusively in plasma from pregnant women and significantly enhanced plasma ATP in pre-eclamptic women compared with the other groups. Dephosphorylation of preeclamptic plasma resulted in reactivation of Hx activity. Fascia tissue-samples from preeclamptic women showed reduced ecto-apyrase activity and enhanced ecto-5'nucleotidase activity compared to pregnant women. CONCLUSION: Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.     

Effect of normal and preeclamptic plasma on superoxide-anion production of neutrophils from healthy non-pregnant women

This study has examined whether production of superoxide-anion by granulocytes differs between non-pregnant, healthy pregnant and preeclamptic pregnant women. First, we assessed superoxide-anion production in 13 non-pregnant women, 11 healthy pregnant women and 14 preeclamptic pregnant women. Then, we examined the effect of plasma samples of healthy pregnant and preeclamptic pregnant women on superoxide production by neutrophils separated from healthy pregnant women. Superoxide generation was measured by ferricytochrome-c reduction. Phorbol-12,13-dibutyrate- and n-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide-anion production was significantly decreased in healthy pregnant women's granulocytes compared with non-pregnant women. There was no significant difference between granulocyte superoxide-anion production in preeclamptic pregnant and non-pregnant women. When neutrophils from non-pregnant women were incubated in plasma from healthy pregnant women, the granulocyte phorbol-12,13-dibutyrate-stimulated superoxide-anion production was significantly inhibited. With the same stimulator, there were no significant differences between superoxide-anion production of neutrophils incubated in autologous, non-pregnant and preeclamptic pregnant plasma. If n-formyl-methionyl-leucyl-phenylalanine was used for stimulation, there were no significant differences in the superoxide-anion production of granulocytes in either group. Granulocyte superoxide-anion production decreases during pregnancy; this decrease does not occur in preeclampsia, and may cause endothelial damage. It is conceivable that there are unidentified factors in maternal circulation which inhibit superoxide-anion production by granulocytes in healthy pregnant women.     

Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia,and their relation with severity of disease and fetal birth weight

Objective: The aim of the present study was to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses compared with normal pregnancy. We also sought to determine whether there was a correlation between these markers with severity of preeclampsia and fetal birth weight. Methods: The study population consisted of maternal age, gestational age, and body mass index matched 138 pregnant women; 56 normotensive healthy pregnant women (group 1), 42 women with mild preeclampsia (group 2), 40 women with severe preeclampsia (group 3). Results: Plasma interleukin (IL)-8 and C-reactive protein (CRP) levels were significantly higher in group 3 than group 1 (p?<?0.05). Plasma IL-4, IL-12, and interferon (IFN)-γ levels were similar in all groups. Although plasma IL-8 and CRP levels of mild preeclamptic group were higher than control group and lower than severe preeclamptic group, the differences were not statistically significant. There was a positive correlation between IL-12 and fetal birth weight in severe preeclamptic group (p?<?0.05). Conclusions: Elevated maternal serum pro-inflammatory cytokine IL-8 and CRP in severe preeclamptic women compared with normal pregnant women supports the hypothesis that preeclampsia is associated with increased inflammatory responses.     

Evaluation of the macula,retinal nerve fiber layer and choroid in preeclampsia,healthy pregnant and healthy non-pregnant women using spectral-domain optical coherence tomography

Objective: To evaluate the macular, retinal nerve fiber layer (RNFL) and choroidal thickness alterations by using spectral-domain optical coherence tomography (SD-OCT) in preeclampsia and compare with healthy pregnant and healthy non-pregnant controls. Method: The study population included healthy pregnant control group (n: 25), healthy non-pregnant control group (n: 26) and study group with preeclampsia (n: 27). Retinal thickness parameters were measured by SD-OCT. Results: There was a statistically significant difference among all of the groups for choroidal thickness (p?p?p?p?=?0.004). Conclusions: This study revealed that choroidal thickness measured using SD-OCT increased in women with preeclampsia and healthy pregnant women but the increase in choroidal thickness in preeclampsia was lower than the healthy pregnant controls. This lower rise in choroidal thickness can be generally attributed to the markedly increased systemic vascular vasospasm secondary to preeclampsia.     

Activated protein C resistance in Turkish women with severe preeclampsia

The purpose of this study was to investigate the occurrence rate of APC resistance (APC-R) with severe preeclampsia in Turkish women. Thirty-two consecutive women having severe preeclampsia were included in the study. Thirty-two healthy pregnant women served as the control group. APC-R assays were performed in the third trimester of pregnancy, and 3 and 9 months after delivery. APC-R was demonstrated in the third trimester, 3 months and 9 months after delivery in 27 (84.4%), 23 (71.9%) and 5 (15.6%) of 32 preeclamptic patients, respectively. APC-R rates were significantly higher in preeclamptic group than in normal pregnant women in the third trimester of pregnancy (p < 0.05). Decreased mean APC activity and also increased APC-R rate was still persisting in preeclamptic group for 3 months after delivery. Nine months after delivery, the mean APC activity and also APC-R rates approached to the normal pregnant women; however, there was a significant difference between both groups (p < 0.05). Our results indicate that acquired APC-R may be a contributory factor in the pathogenesis of preeclampsia.     

Hyperhomocysteinaemia: a risk factor for preeclampsia?

Preeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels.Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP).In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence of the 677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17).In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene.     

Serum levels of leukocyte functional antigen-3 in pregnancy and preeclampsia.

BACKGROUND: Adhesion molecules have been demonstrated to be involved in placental growth and development in normal pregnancy. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate serum levels of the adhesion molecule Leukocyte Functional Antigen (LFA)-3 in healthy, non pregnant, female controls, healthy pregnant women, and preeclamptic women. METHODS: In our study we included 45 healthy, non pregnant, female controls, 45 healthy pregnant women, and 45 preeclamptic women. An enzyme-linked immunosorbent assay was used to determine serum levels of LFA-3. Results were correlated to clinical data. RESULTS: The median LFA-3 serum level in healthy, non pregnant, female controls was 0.2 (range 0 to 8.6) ng/mL. LFA-3 serum levels in healthy pregnant women were 4.8 (range 0 to 18) ng/mL and were significantly elevated compared to healthy, non pregnant, female controls (Mann-Whitney U-test, p=0.004). A cut-off level of 4.8 ng/mL was selected according to the 75th quantile of serum levels measured in the panel of healthy, non pregnant, female controls. In preeclamptic women, whose pregnancies had to be terminated due to exacerbation of preeclamptic symptoms, LFA-3 serum levels above the cut-off level were seen in 14/27 (52%) cases. In contrast, preeclamptic women, who went into spontaneous labor showed elevated LFA-3 serum levels in 17/18 (95%) cases (chi-square test, p=0.002). LFA-3 serum levels revealed a statistically significant influence on the odds of termination of pregnancy due to exacerbation of preeclamptic symptoms (unconditional logistic regression, p=0.02) with an odds ratio of 0.1 (95% CI, 0.006 to 0.7) by every doubling of LFA-3 values. CONCLUSIONS: Our results suggest that LFA-3 expression is upregulated in healthy pregnant women compared to healthy, non pregnant, female controls. Failure of LFA-3 upregulation in preeclampsia is associated with an increased risk for termination of pregnancy due to exacerbation of preeclamptic symptoms.     

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women

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.     

Cytokine expression in peripheral blood lymphocytes indicates a switch to T(HELPER) cells in patients with preeclampsia

We sought to determine whether cytokine expression in peripheral blood mononuclear cells is altered in patients with preeclampsia and in patients with a history of recurrent spontaneous abortion (RSA). Twenty-four patients with preeclampsia and twenty patients with a history of RSA were included into the study. Two control groups consisted of twenty healthy pregnant and twenty healthy non-pregnant women. The intracellular expression of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined in peripheral blood mononuclear cells (PBMCs) by flow cytometry as a measure of cytokine production. IL-2 synthesis was significantly elevated in the third trimester in preeclamptic patients in comparison with the control group. Non-pregnant women with RSA showed a significantly lower expression of IFN-gamma compared to the non-pregnant control group. Our data suggest an abnormal immune response in preeclamptic patients characterised by a shift to a predominantly Th1-type immunity.     

Tissue kallikrein activity in pregnancy

To determine tissue kallikrein (TK) activity in black African women with hypertensive disorders of pregnancy; 140 women were recruited and divided into the following groups: group A--35 preeclamptic women, group B--35 mild to moderate hypertensive pregnant women and group C--35 normotensive pregnant women, and group D--35 normotensive non-pregnant healthy women. The activity of tissue kallikrein was determined from a random untimed urine sample using a selective, synthetic chromogenic tripeptide substrate having the sequence H-D-Val-Leu-Arg-pNA (S-2266). Urinary sodium and potassium levels was determined by flame photometry. Tissue kallikrein activity was decreased in women with preeclampsia (1.54 +/- 0.95 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) and mild to moderate hypertensive group (2.03 +/- 0.76 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) compared with normotensive pregnant women. There was also a significant difference in tissue kallikrein activity between the pregnancy groups (1.54 +/- 0.95 vs 2.03 +/- 0.76 ngTK/microg protein; p < 0.001). No difference in tissue kallikrein activity was observed between normotensive pregnant and normotensive non-pregnant healthy women (3.05 +/- 0.83 vs 3.14 +/- 0.88 ngTK/microg protein; p = 0.51). There was no difference in the excretion of urinary sodium and potassium in pregnancy groups compared to normotensive pregnant group. Tissue kallikrein activity is decreased in hypertensive disorders of pregnancy.     

Uterine Catecholamines in Normal and Hypertensive Human Pregnancy

The uterine tissue content of the adrenergic transmitter norepinephrine decreases during normal gestation, as part of a functional uterine denervation. Uterine tissue catecholamines were measured in normal and hypertensive human pregnancy. Myometrial samples were obtained at hysterectomy in nonpregnant patients, or by wedge biopsy at the time of cesarean section, in normal and preeclamptic pregnant patients. Biopsies were taken of both placental and non-placental bed tissue in the pregnant patients. All samples were analyzed for catecholamines by a radioenzymatic assay. There was a significant decrease in uterine norepinephrine and dopamine, but no change in epinephrine in normal pregnant patients when compared with non-pregnant patients. The decrease in dopamine and norepinephrine was greater in the placental bed, suggesting a local augmentation of this process by the placenta. There was an increase in uterine dopamine and norepinephrine in patients with preeclampsia, but no change in epinephrine, when compared with normal pregnant patients, and this increase was greater in the placental bed. These findings are compatible with the hypotheses of 1) functional uterine adrenergic denervation in normal pregnancy, and 2) increased tissue activity of the adrenergic nervous system in patients with preeclampsia.     

Role of lipid peroxidation and enzymatic antioxidants in pregnancy-induced hypertension

AIMS AND OBJECTIVES: Preeclampsia remains a major cause of maternal mortality and morbidity. It is a leading indication for iatrogenic premature delivery. Oxidative stress is considered to be one of the factors in the disease process. The present study is centered on the concept that elevated levels of lipid peroxidation (malondialdehyde) due to a decline in the efficacy of antioxidant defenses may predispose an individual to preeclampsia. MATERIAL AND METHODS: In the present study we measured lipid peroxidation products (MDA) and the counteracting enzymatic antioxidants. The study comprises 25 healthy non-pregnant women as controls, 25 third trimester normal pregnant women and 25 preeclamptic patients of the same trimester. Estimation of lipid peroxidation by thiobarbituric acid (TBARS) and enzymatic antioxidants were carried out by standard methods. RESULTS: In the preeclamptic group malondialdehyde, a product of lipid peroxidation, was significantly increased while enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were reduced significantly as compared to normal pregnant and non-pregnant controls. CONCLUSION: Increased levels of lipid peroxides and reduced antioxidant activities clearly demonstrate the presence of oxidative stress in preeclampsia.     

正常妊娠和子痫前期患者外周血树突细胞亚群的变化

目的:探讨树突细胞(DCs)及其亚群在正常妊娠和子痫前期患者间的变化,及与Th1/Th2型反应的关系。方法:选取正常妊娠孕妇25例、子痫前期患者17例和正常未孕妇女15例,用流式细胞术检测3组外周血树突细胞及其髓样(MDC)和淋巴样(PDC)亚群,比较其数量和比值在妊娠前后及子痫前期患者的变化,并与Th1/Th2型细胞因子的含量比较。结果:与正常妊娠早期和晚期相比,妊娠中期MDC和PDC数量减少,MDC/PDC比值升高,妊娠早、晚期相比无显著差异。与正常晚期妊娠妇女比较,子痫前期患者PDC数量减少,MDC数量改变不明显,MDC/PDC比值升高,两组相比差异显著。与正常晚期妊娠妇女相比较,子痫前期患者Th1型细胞因子IL-2含量增加,IFN-γ无显著差异,Th2型细胞因子IL-10减少,IL-2/IL-10、IFN-γ/IL-10比值升高。结论:DCs在正常妊娠的不同阶段其数量和亚群发生变化,子痫前期患者出现PDC减少和MDC/PDC比值升高现象,并与Th1/Th2型细胞因子的变化趋势一致。     

Cytokine Production by Monocytes,NK Cells,and Lymphocytes Is Different in Preeclamptic Patients as Compared with Normal Pregnant Women

Objective. To measure cytokine production in ex vivo stimulated leukocyte populations of women with normal pregnancy and those with preeclampsia. Methods. Whole blood from preeclamptic and normal pregnant women was stimulated with LPS or PMA/Ca-ionophore. The percentages of IFNγ and IL-2, 4, and 10 producing lymphocytes and NK cells and the percentages of TNFα, IL-1β, and IL-12 producing monocytes were measured by flowcytometry. Results. In women with preeclampsia, there was a significantly increased percentage IL-4 producing cytotoxic T cells. Also, a significant decreased percentage IL-2 producing T helper cells and IL-12 producing monocytes was seen as compared with normal pregnancy. Conclusion. Th1 cytokine production of lymphocytes and monocytes appears to be decreased in our group of preeclamptic patients compared with normal pregnant women.     

Circadian Variations of Plasma Colloid Osmotic Pressure During the Third Trimester in Normal and Preeclamptic Pregnancies

The present study was performed to assess the changes of plasma colloid osmotic pressure (COP) in preeclampsia, and to clarify the character of circadian variations of plasma COP in preeclampsia. During the third trimester of a normal pregnancy, plasma COP values were 21.0 ± 0.2 at 28-31 weeks' gestation, 19.3 ± 0.5 at 32-35 weeks' gestation and 20.4 ± 0.5 mmHg at 36 weeks or more of gestation. These values were significantly lower than those in normal non-pregnant subjects (23.5 ± 0.6). In preeclampsia, plasma COP values (14.7 ± 0.4) were significantly lower than those in normal pregnancy. A circadian variation of plasma COP confirmed a clear circadian rhythm with the acrophase at afternoon in all subjects, and there were no differences among normal non-pregnant, pregnant and severe preeclamptic women. These results indicate that circadian variations of plasma COP are not influenced by either pregnancy or preeclampsia, though plasma COP in preeclampsia significantly decreases.     

Accumulation of advanced glycation end products in women with preeclampsia: possible involvement of placental oxidative and nitrative stress

Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women. Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta. The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta. The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia.