Captopril in severe preeclampsia

Captopril is an inhibitor of angiotensin I converting enzyme and is used for treating intractable chronic hypertension. However, the use of captopril during pregnancy is limited because of reported fetal and neonatal side effects. This study explored the efficacy of sublingual captopril in postpartum management of severe preeclampsia. Captopril controlled the systolic and diastolic pressures within normal range in two patients. The other three patients responded moderately and were switched to hydralazine, clonidine, or nifedipine after 12 hours. The systolic and diastolic pressures of these three patients remained moderately elevated over the 24-hour duration of the study while their pulse rates increased. Captopril did not significantly increase the pulse rate in any of the patients studied, and no other side effects were noted. All patients had normal pressures at their 2- and 6-week postpartum check-up. We conclude that sublingual captopril may be used safely and effectively in managing postpartum hypertension in patients with severe preeclampsia.     

Cytokine genotyping in preeclampsia

PROBLEM: Considering that cytokines are involved in preeclampsia (PE) pathogenesis and that cytokine gene polymorphism may affect cytokine production, our purpose was to investigate the association of PE with tumor necrosis factor (TNF)-alpha (-308), transforming growth factor-beta1 (+10; 25), interleukin (IL)-10 (-1082), IL-6 (-174), and interferon-gamma (+874) polymorphisms. METHOD OF STUDY: Genotyping was performed in women with PE (56 White and 95 non-White women) and in women without obstetric pathology (92 White and 97 non-White women). Data were analyzed by the chi-square or Fisher exact test. We performed a meta-analysis encompassing these and results from other laboratories on the association of TNF-alpha polymorphisms and PE. RESULTS: We observed a lower frequency of the IL-10 -1082-G/G genotype in White women with PE (PE: 5%; Control (C): 15%, P = 0.02) and no association for all other polymorphisms, including meta-analysis of TNF-alpha results. CONCLUSION: Our study suggests that PE is associated with IL-10-(1082) polymorphism but not with TNF-(308) polymorphism. On the basis of meta-analysis, we confirm the need for more studies for the evaluation of cytokine genotype in disease.     

Placental pathophysiology in preeclampsia

The two central pathophysiological themes of preeclampsia are: (1) placental trophoblast dysfunction; and (2) endothelial dysfunction within the maternal systemic vasculature. No single factor has been identified as the cause of preeclampsia, however, substantial evidence suggests that the increased oxidative stress, production of vasoconstrictor agents, altered placental cytokine generation, and the formation of other toxic compounds produced by the placenta promote several forms of endothelial dysfunction in preeclampsia. The effects of such placental factors on maternal vascular cells (e.g. endothelial cells, neutrophils and platelets), combined with pre-existing maternal risk factors (vascular, renal, and metabolic diseases), with immune abnormalities and genetic factors pose substantial risks for developing this disorder during pregnancy. While placental dysfunction may not be the sole cause of preeclampsia, placental dysfunction may trigger, or significantly contribute to the vascular complications associated with preeclampsia.     

Evidence for superantigen involvement in preeclampsia

PROBLEM: Preeclampsia is the leading cause of maternal morbidity and premature fetal delivery in the United States, most likely involving the immune system in disease genesis. In this report, we tested the hypothesis that a superantigen phenomenon is an important factor in the pathogenesis of the disease. METHOD OF STUDY: A semi-quantitative polymerase chain reaction (PCR) was used to assess T-cell receptor (TCR) beta chain variable (Vbeta) regions as an indicator of T-cell expansion in both peripheral blood and basal plate of preeclamptic patients. All the subjects were also molecularly typed to identify their HLA-class II alleles. RESULTS: In peripheral blood of the majority of the patients, there was a high abundance of the Vbeta4 gene family, which was not observed in the control group. Polyclonality of this Vbeta gene family was confirmed by analysis of the Valpha chain and the complementary determining region 3 (CDR3). The majority of patients carried the Human Leukocyte Antigens (HLA)-DRB1*13 allele. CONCLUSION: We present evidence for the existence of a superantigen-like effect in at least a subset of patients with preeclampsia.     

Recent advances in understanding of preeclampsia

Despite intensive research, preeclampsia still accounts for significant morbidity and mortality for the mother and the neonate, especially in developing countries. Recent studies have suggested that excess secretion of a naturally occurring anti-angiogenic molecule of placental origin referred to as soluble fms-like tyrosine kinase-1 (sFlt-1, also referred to as sVEGFR-1) may contribute to the pathogenesis of preeclampsia. sFlt-1 acts by antagonizing two pro-angiogenic molecules - vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Abnormalities in the angiogenic balance have been proposed as having a major role in the molecular cascade leading to proteinuria, hypertension, and endothelial dysfunction. Further evidence supports the hypothesis that angiogenic balance is crucial to differentiation and invasion of cytotrophoblasts. The abnormal placentation and the accompanying hypoxia may, in turn, result in more sFlt-1 production, thus leading to a vicious cycle of sFlt-1 production, eventually causing preeclampsia. These recent discoveries may facilitate the development of novel strategies for the diagnosis and therapy of preeclampsia.     

MicroRNA及其在子痫前期中的作用研究进展

近年来有研究发现一些miRNAs在子痫前期患者的胎盘与正常妊娠胎盘组织中的表达存在显著性差异,推测miRNAs可能在胎盘生长发育过程中发挥了一定的作用,其失衡表达可能参与了子痫前期的发病过程。血清或血浆等体液中稳定存在的miRNAs有望作为妊娠性疾病早期预警诊断的理想的、潜在分子标记,而针对miRNAs设计分子靶向药物的探索为揭示子痫前期发病的机理、制定有效的个体化治疗方案具有重要意义。本文即对有关miRNAs及其在子痫前期发病中的最新研究进展作一综述。     

胎盘发育和子痫前期

胎盘是妊娠期间胎儿和母体之间的桥梁,具有血流灌注、物质交换、免疫耐受和妊娠适应性调节等功能,对保障胎儿发育和母体健康发挥关键作用。胎盘发育不良与子痫前期等妊娠疾病密切相关。在本文中,我们总结了人类滋养层细胞分化和胎盘功能单元构建的最新研究进展,并讨论了可能导致子痫前期发病的因素。     

Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia

The maternal immune system must adapt to tolerate the invasion of the allogeneic feto-placental unit. It is generally accepted that improper adaptation causes pregnancy complications like preeclampsia. The Epstein–Barr virus-induced gene 3 (EBI3) protein is a subunit of immune-modulatory cytokines interleukin 27 (IL-27) and IL-35. EBI3 has been reported to associate with HLA-G. In this small pilot study we find higher decidual EBI3 (p < 0.05) and HLA-G (p < 0.01) mRNA expression in preeclampsia (n = 7) compared to normotensive (n = 8) pregnancies. Whether the higher EBI3 and HLA-G mRNA expression is a consequence or cause of preeclampsia remains to be answered. Further research to determine the effects on IL-27 and IL-35 is needed.     

子痫前期患者系统性氧化应激反应的检测

目的研究子痫前期系统性氧化应激检测方法。方法组织化学染色检测胎盘组织缺氧表现;用胞内活性氧(ROS)探针H2DCFDA及全血染色方法检测中性粒细胞(PMN)胞内ROS水平;用H2O2检测试剂盒检测血清中H2O2水平。结果与正常妊娠胎盘组织比较,子痫前期患者胎盘组织合胞体细胞显著增多;血管破坏,结构不清,局部血管有纤维钙化特征;非孕妇女、正常妊娠妇女及子痫前期患者PMN胞内ROS水平分别为:45.61±12.20、51.02±13.60(P<0.01)、85.10±16.30(P<0.01);而血清H2O2浓度分别为:(24.57±5.17)μmol/L、(26.61±3.25)μmol/L、(39.84±9.67)μmol/L。结论对子痫前期系统性氧化应激进行定性和定量检测结果与疾病发生和发展一致。     

环氧合酶-2在子痫前期患者胎盘组织中的表达

目的研究环氧合酶-2(COX-2)在子痫前期患者胎盘组织中的表达,探讨其在子痫前期发病机制中的作用。方法采用免疫组化SP法检测50例子痫前期患者(轻度30例,重度20例)胎盘组织中COX-2的表达,20例正常孕妇为对照组。应用逆转录多聚酶链反应(RT-PCR)检测30例子痫前期患者及12例正常孕妇的胎盘组织中COX-2mRNA的表达。结果(1)COX-2主要表达于胎盘血管内皮细胞。子痫前期患者COX-2蛋白的表达均明显增高,且随病情严重程度的增加而升高。子痫前期组COX-2蛋白的阳性表达率为63.1%、显著高于对照组(COX-2阳性表达率为23%)(P<0.01)。(2)子痫前期组COX-2mRNA表达水平为0.61±0.25,对照组为0.66±0.71,两组比较,差异无显著性(t=-0.93,P>0.05)。结论COX-2参与了子痫前期胎盘螺旋小动脉动脉粥样硬化。     

Immunology and genetic of preeclampsia

Preeclampsia is a disease characterized by hypertension and proteinuria in the third trimester of pregnancy. Preeclampsia is a major cause of maternal mortality, and fetal death, especially in developing countries, but its aetiology remains unclear. Key findings support a causal role of superficial placentation driven by immune mal maladaptation, which then lead to reduced concentrations of angiogenic growth factors and to an increase in placental debris in the maternal circulation resulting in a maternal inflammatory response. Epidemiological research has consistently demonstrated a substantial familial predisposition to preeclampsia. Unfortunately, the conquest of the genes explaining such a individual susceptibility has been proved to be a hard task. However, genetics will also inform us about causality of environmental factors, and then serve as a tool to prioritize therapeutic targets for preventive strategies.     

Postpartum amaurosis in a woman with severe preeclampsia

The maternal and perinatal fetal prognosis of preeclampsia depends on the gestational age of the fetus at onset, the severity of the disease, the quality of care, and the presence of pre-existent medical conditions. One of the uncommon effects of severe preeclampsia on the eye is sudden loss of vision. The present case report is of a woman with severe preeclampsia exacerbated by delivery that coursed with difficult-to-control arterial hypertension and reversible cortical amaurosis without impaired consciousness or seizures.     

可溶性CD105在早发型子痫前期患者中的表达

目的探讨早发型子痫前期患者可溶性CD105（sCD105）表达的变化和意义。方法选择对照组和早发型子痫前期组各30例,其中32周之前发病患者13例,32周之后发病患者17例;选择在本院行产前筛查后发展为早发型子痫前期的妊娠妇女和对照组各30例。采用酶联免疫吸附分析法（ELISA）测定各组血清sCD105水平。结果对照组和早发型子痫前期组血清sCD105水平的中位数分别为13.45ng/ml和36.35ng/ml,差异有统计学意义（P=0.000）。32周之前发病组和32周之后发病组血清sCD105水平的中位数分别为48.76ng/ml和30.39ng/ml,差异有统计学意义（P=0.02）。对照组和早发型子痫前期组妊娠中期sCD105水平的中位数分别为5.20ng/ml和7.51ng/ml,差异有统计学意义（P=0.003）。32周之前发病组和32周之后发病组妊娠中期血清sCD105水平的中位数分别为8.43ng/ml和5.41ng/ml,差异有统计学意义（P=0.011）。结沦早发型子痫前期患者血清sCD105水平显著增高,发生早发型子痫前期的妊娠中期孕妇的sCD105也显著增高,发病孕周越早血清sCD105水平上升更显著。