Successful management with C1-inhibitor concentrate of hereditary angioedema attacks during two successive pregnancies: a case report

Backgroud Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency of the plasma protein C1 inhibitor (C1-INH). HAE is characterised by the onset of angioedema, which may develop in one or several organs, and may last from a few hours to several days. Oedema of the upper airway can be life-threatening. As a result of hormonal changes, some women experience more frequent angioedema attacks during pregnancy. During pregnancy, antifibrinolytic agents should only be used with caution, and attenuated androgens are contraindicated; therefore, replacement therapy with C1-INH concentrate represents one of few therapeutic options, but it is not widely documented. Case study We report the first case study of the successful management with regular infusions of C1-INH concentrate, of two successive pregnancies in a patient with HAE. During the second half of the first pregnancy, C1-INH was administered on demand at home. For the second pregnancy, on demand treatment was intensified to prophylactic therapy, with once or twice weekly infusions from the middle of the second trimester in order to efficiently control the frequent attacks. Conclusions This report illustrates that HAE can be successfully managed during pregnancy with C1-INH infusions at home. Since the number of crises may vary between pregnancies, the treatment regimen must be adapted to the patient’s need.     

Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer: does ethnicity matter?

AIM: To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature. RESULTS: We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism. CONCLUSION: Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans.     

Decrease and dysfunction of endothelial progenitor cells in umbilical cord blood with maternal pre-eclampsia

BACKGROUND: The pre-eclampsia is characterized by placental defective angiogenesis and maternal vascular/endothelial dysfunction. Recently, the decrease and senescence of endothelial progenitor cells (EPC) has been observed in maternal circulation with pre-eclampsia. Given the essential involvement of EPC in neovascularization and reendothelialization, we investigate whether or not the depletion of EPC is existent in placental/fetal circulation with maternal pre-eclampsia. METHODS: Samples of venous cord blood were collected during the labor of preeclamptic mothers (n = 14) and normotensive controls (n = 10). Circulating EPC were enumerated as AC133+/KDR+ cells via fluorescence-activated cell sorting (FACS) analysis. Additionally, EPC were expanded in vitro and identified by DiI-acLDL uptake and lectin staining by direct fluorescent staining under a laser scanning confocal microscope. EPC proliferation, migration and vasculogenesis activities were determined by MTT, modified Boyden chamber assay and in vitro vasculogenensis assay. RESULT: The placental/fetal circulating EPC numbers were significantly decreased in the pre-eclampsia group compared with the control (median, 200; range, 100-440 cells/mL vs 390; 270-440 cells/mL, P < 0.001), and after in vitro cultivation the numbers of EPC also decreased in pre-eclampsia group (19.5; 5.0-32.0 vs 39.5; 31.2-52.0 EPC/x200 field; P < 0.001). Both circulating EPC and cultivated EPC were inversely correlated with cord blood level of soluble fms-like tyrosine kinase 1 (sFlt-1). In addition, the EPC from patients with pre-eclampsia were significantly impaired in their proliferation, migration and vasculogenesis capacities. CONCLUSION: The present study documented the decrease and dysfunction of placental/fetal circulating EPC in patients with pre-eclampsia. The alteration is probably associated with the increased sFlt-1 levels in the umbilical cord blood.     

STOX1 gene in pre-eclampsia and intrauterine growth restriction

The STOX1 gene, identified as a candidate gene for pre-eclampsia in Dutch women, is placentally expressed and subject to imprinting with preferential transmission of the maternal allele. In our study, STOX1 -Y153H frequencies were similar in 157 women with pre-eclampsia (65%) and in 157 controls (64%) from the general Dutch population. In an isolated Dutch population, a distortion could not be demonstrated in the transmission of STOX1 -Y153H variation from heterozygous mothers to offspring in 50 and 56 families with pregnancies complicated by pre-eclampsia or intrauterine growth restriction, respectively. Our findings do not confirm previous suggestions that STOX1 plays a major role in Dutch women with pre-eclampsia.     

CACNA1H基因敲除对小鼠孤独症样行为及海马神经元形态学的影响

目的研究CACNA1H基因敲除(knockout, KO)对小鼠孤独症样行为及海马神经元形态学的影响。方法25只3~4周龄C57BL/6背景的CACNA1H KO小鼠作为实验组, 26只同年龄同背景的野生型(wild type, WT)小鼠作为对照组。通过三箱实验和旷场实验观察小鼠社交、焦虑和重复刻板行为后测量其脑质量与脑体积, 用尼氏染色法(Nissl staining)观察海马神经元数目。将CACNA1H杂合子小鼠与Thy1-GFP-O小鼠杂交, 构建CACNA1H^-/--Thy1⁺(KO-GFP)及CACNA1H^+/+-Thy1⁺(WT-GFP)小鼠, 观察海马神经元树突棘密度及成熟度。结果三箱实验中, 社交测试阶段, KO小鼠在陌生鼠箱中的时间比空箱更长(F_{1, 14}=95.086, P < 0.05;Post-Hoc: P < 0.05), 探索的偏好指数与对照组相比差异无统计学意义(t=1.044, P>0.05);新社交对象识别测试阶段, KO小鼠在新陌生鼠箱与陌生鼠箱中的时间差异无统计学意义(F_{1, 14}=18.062, P < 0.05;Post-Hoc: P>0.05), 探索的偏好指数低于对照组(t=2.390, P < 0.05)。旷场实验中, KO小鼠在旷场中心活动时间明显少于对照组(t=2.503, P < 0.05), 自梳理时间明显多于对照组(t=-2.299, P < 0.05)。形态学结果显示, KO小鼠脑质量/体质量和脑体积与对照组相比差异均无统计学意义(t=0.356, P>0.05;t=-0.660, P>0.05), 但其海马齿状回区神经元数目较对照组减少(t=2.323, P < 0.05), 且KO-GFP小鼠海马齿状回区树突棘密度较对照组增加(t=-2.374, P < 0.05), 而成熟度差异无统计学意义(t=-1.935, P>0.05)。结论CACNA1H KO小鼠具有孤独症样行为, 可能与海马齿状回区神经元数目减少及树突棘密度增高有关。