Immune complexes in preeclampsia and normal pregnancy

We determined in normal nonpregnant (group I) and normal pregnant (group II) women and in patients with preeclampsia (group III): (1) immunoglobulins and complement C3b associated with polymorphonuclear leukocytes and platelet surfaces in an attempt to evaluate the interaction in vivo of immune complexes with the membranes of these cells; (2) the occurrence of circulating immune complexes; (3) the serum levels of immunoglobulins, C3, and C4; and (4) the plasma levels of complement C3d. In patients with preeclampsia (group III), the percentages of polymorphonuclear leukocytes and platelets positive for membrane-bound IgG, IgM, IgA, and C3 were significantly higher than the percentages in groups I and II. In group III, there also was a significant increase in circulating immune complexes, as compared to groups I and II. However, circulating immune complexes were also present in significant amounts in normal pregnancy (group II). The plasma levels of complement C3d were markedly increased in the most severe cases of preeclampsia.     

Detection of calcitonin and parathyroid hormone in the human placenta

Detection of calcitonin and parathyroid hormone in the human placenta at term. In this investigation we proved immunoreactive calcitonin and immunoreactive parathyroid hormone in the maternal side of the human placenta. We used the immunocytochemical staining technique (Peroxidase-Antiperoxidase-method) by Sternberger where different antibodies react. We could see calcitonin and parathyroid hormone mainly in the decidual cells as well as in the cytotrophoblastic cells of the maternal part of the placenta.     

Skeletal muscle ultrastructure in normal pregnancy and preeclampsia

The aim of this study was to assess by quantitative methods whether the assumed metabolic disturbance underlying preeclampsia would be reflected in muscle cell composition of lipid, mitochondria, or glycogen. We have reported mitochondrial dysfunction in preeclampsia, and since accumulation of lipid in skeletal muscle is a feature in mitochondrial disorders, our hypothesis was that preeclamptic women would have an increased content of triglyceride droplets. Quantitative investigation of the skeletal muscle ultrastructure was performed in 10 women with severe preeclampsia and in 6 normotensive pregnant women. Biopsy specimens from musculus rectus abdominis were taken during cesarean section and prepared for electron microscopy. Random pictures were taken by transmission electron microscopy, and point-counting stereology was performed. Preeclamptic women did not have a higher lipid volume fraction than normotensive pregnant women, and we had to reject our hypothesis. On the contrary, there was a tendency towards a lower triglyceride volume fraction in pre eclampsia. We did not detect differences in relative volumes of mitochondria or glycogen in skeletal muscle between the two groups.     

Venous pulse transit time in normal pregnancy and preeclampsia

Uncomplicated pregnancies (n = 16) were evaluated longitudinally and compared to early- (n = 12) and late-onset (n = 14) preeclampsia patients, assessed once at diagnosis. Pulse transit time (PTT), equivalent to pulse wave velocity, was measured as the time interval between corresponding characteristics of electrocardiography and Doppler waves, corrected for heart rate, at the level of renal interlobar veins, hepatic veins, and arcuate branches of uterine arteries. Impedance cardiography was used to measure PTT at the level of the thoracic aorta. In normal pregnancy, all PTT increased gradually (P ≤ .01). Pulse transit time was shorter in late-onset preeclampsia (P < .05) and also in early-onset preeclampsia, with exception for hepatic veins and thoracic aorta (P > .05). Our results indicate that PTT is an easy and highly accessible measure for vascular reactivity at both arterial and venous sites of the circulation. Our observations correlate well with known gestational cardiovascular adaptation mechanisms. This suggests that PTT could be used as a new parameter in the evaluation and prediction of preeclampsia.     

Angiotensin-converting enzyme gene polymorphism in preeclampsia and normal pregnancy

OBJECTIVE: The purpose of this study was to evaluate the angiotensin-converting enzyme gene polymorphism in pregnant women with and without preeclampsia. STUDY DESIGN: Preeclampsia was defined as hypertension and pathologic proteinuria in pregnant women after gestational week 20. Genomic DNA was isolated from leukocytes. The insertion-deletion polymorphism in intron 16 of the angiotensin-converting enzyme gene was detected in DNA samples with the use of the polymerase chain reaction. Chi-squared and Student t tests were used for statistical analysis. RESULTS: In preeclampsia (n=51 women) angiotensin-converting enzyme genotypes were deletion-D (DD) in 16 women (31%), insertion-I (II) in 12 women (24%), and insertion-deletion in 23 women (45%); in the control group (n=71), the angiotensin-converting enzyme genotypes were DD in 21 women (30%), II in 17 women (24%), and insertion-deletion in 33 women (46%). Angiotensin-converting enzyme genotype distribution and allelic frequencies were not different between groups. CONCLUSION: No difference in the angiotensin-converting enzyme genotype distribution was found between preeclampsia and normal pregnancy. The results showed no association between angiotensin-converting enzyme polymorphism and the development of preeclampsia.     

Calculated capillary hydrostatic pressure in normal pregnancy and preeclampsia

Capillary hydrostatic pressure has been calculated in normal pregnancy and preeclampsia. In humans, capillary hydrostatic pressure cannot be measured directly but may be calculated when the colloid osmotic pressure in plasma and interstitial fluid and interstitial fluid hydrostatic pressure are known (Starling equation). New methods have made it possible to measure the interstitial fluid colloid osmotic pressure and interstitial fluid hydrostatic pressure. In the present study interstitial fluid was collected from the subcutaneous tissue by implanted wicks (wick method), and interstitial fluid colloid osmotic pressure was determined. Interstitial fluid hydrostatic pressure was recorded by the wick-in-needle technique. Capillary hydrostatic pressure was calculated in 10 women in the first trimester and 10 in the third trimester of normal pregnancy, in 15 patients with mild preeclampsia, and in 13 women with severe preeclampsia. In normal pregnancy, capillary hydrostatic pressure increased by about 30% between the first and third trimesters. In mild preeclampsia, capillary hydrostatic pressure values did not differ significantly from those in the third trimester of normal pregnancy. However, in severe preeclampsia capillary hydrostatic pressure was significantly lower (40%) than in mild preeclampsia. Whether the low capillary hydrostatic pressure is caused by the severe general vasospasm seen in this condition or is a secondary event is unknown.     

Hypocalciuria of preeclampsia is independent of parathyroid hormone level.

Hypocalciuria is a feature of preeclampsia. The roles of parathyroid hormone (PTH) and vitamin D 1,25(OH)2D3 (calcitriol) in its pathogenesis have not yet been determined. Fourteen preeclamptic women were compared with 12 women with chronic hypertension and 11 normotensives, all in the third trimester. Preeclamptics had the lowest urinary calcium excretion rate (62.1 +/- 32.8 mg/24 hours) compared with chronic hypertensive women (162.6 +/- 97.8 mg/24 hours) and normotensive controls (225.6 = 146.9 mg/24 hours) (P less than .05). Serum PTH was lowest in preeclamptics (9.8 +/- 5.5 pg/mL), in contrast to the chronic hypertensives (18.5 +/- 2.7 pg/mL) and normotensives (16.4 +/- 3.2 pg/mL) (P less than .005). Similarly, urinary cyclic adenosine monophosphate (cAMP) excretion was 2.9 +/- 1.4 mumol/24 hours in the preeclamptics, 5.1 +/- 1.7 mumol/24 hours in the chronic hypertensives, and 4.6 +/- 1.3 mumol/24 hours in the normotensive group (P less than .05). These data suggest that the mechanism of hypocalciuria in preeclampsia is independent of the PTH-calcitriol axis. Therefore, it is suggested that the hypocalciuria of preeclampsia is due to intrinsic renal tubular dysfunction.     

Serum levels of apelin,salusin-alpha and salusin-beta in normal pregnancy and preeclampsia

Objective: The purpose of this study was to investigate the relationship between the serum apelin, salusin-alpha and salusin-beta levels and preeclampsia. Method: Twenty-one healthy pregnant women (control group) and 48 patients with preeclampsia (study group) were included in the study between August 2010 and February 2011. Serum apelin, salusin-alpha and salusin-beta levels of the groups were compared. Results: The patients in the study group were divided into two categories: mild preeclampsia and severe preeclampsia. The mild preeclampsia group consisted of 31 patients, and the severe preeclampsia group consisted of 17 patients. Serum salusin-alpha and salusin-beta levels of the control and study groups were not significantly different (p > 0.05). Apelin levels were statistically significantly higher in the study group. No statistically significant difference was detected between the mild and severe preeclampsia groups in terms of the mean serum apelin levels. Conclusion: The serum levels of apelin were higher in the pregnant women with preeclampsia; however, there was no positive relationship between serum salusin-alpha and salusin-beta levels and the disease. Larger prospective studies are needed to validate our findings.     

Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia

OBJECTIVE: Soluble CD40 ligand is a transmembrane protein shed from activated platelets that is involved in the activation of endothelial cells. Findings that estradiol (E2) has an inhibitory effect on inflammation and platelet function and that serum E2 levels are low in women with preeclampsia prompted us to investigate the association between soluble CD40 ligand and serum E2 levels in normal pregnancy and in preeclampsia. METHODS: A case-control single-center design was used. The sample included 22 women with severe preeclampsia, 22 matched normotensive pregnant women, and 22 nonpregnant women. Enzyme immunoassay was used to measure soluble CD40 ligand. RESULTS: Significantly higher levels of soluble CD40 ligand were detected in the nonpregnant women (23,767 +/- 15,637 pg/mL) and in the women with preeclampsia (21,025 +/- 45,386 pg/mL) than in the normotensive pregnant women (8,292 +/- 5,926 pg/mL) (P = .026). No significant correlation between soluble CD40 ligand levels and E2 levels was observed. CONCLUSION: The higher levels of soluble CD40 ligand detected in women with preeclampsia may indicate an exaggerated activation of platelets and endothelial cells. LEVEL OF EVIDENCE: II-2.     

正常妊娠和子痫前期孕妇血液动力学的季节性变化

目的:探讨不同季节正常孕妇和子痫前期孕妇血液动力学的变化。方法:采用无创妊娠期高血压疾病血液动力学监测系统(MP-PIH)检测150例正常妊娠和110例子痫前期孕妇血液动力学参数,根据其发病季节分为夏季组、过渡季组和冬季组,分析不同季节正常孕妇和子痫前期孕妇血液动力学的变化。结果:(1)冬季正常妊娠组与过渡季正常妊娠组相比,每搏输出量(SV)、心输出量(CO)、血管顺应性(AC)显著升高(P<0.01),外周阻力(TPR)显著下降(P<0.05),心率(HR)及血液黏度(V)无统计学差异(P>0.05);冬季组正常妊娠和夏季组正常妊娠相比,SV、CO、AC显著升高(P<0.05);夏季正常妊娠组与过渡季正常妊娠组相比,各血液动力学指标无统计学差异(P>0.05)。(2)不同季节子痫前期的各项血液动力学指标无明显统计学差异(P>0.05);冬季子痫前期组SV、CO、AC与同季度正常妊娠组相比显著下降(P<0.01);各季度子痫前期组TPR、V与同季度正常妊娠组相比显著升高(P<0.05)。结论:正常妊娠血液动力学随气候变化呈动态平衡;子痫前期孕妇生理性的血液动力自我平衡失调,可能是导致冬季型气候条件下子痫前期发病率增高的原因之一。     

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.