Pregnancy-associated plasma protein A in pregnancy-related gynaecologic emergency

Serum concentrations of pregnancy-associated plasma protein A (PAPP-A) were measured in patients with pregnancy-related gynaecologic emergencies including ectopic pregnancy (n = 124) and intrauterine abortion (n = 40). The results were compared with those in normal pregnancy (n = 136) and non-pregnant women (n = 460). In ectopic pregnancy and intrauterine abortion, the PAPP-A levels were lower than in normal pregnancy. In patients with a pregnancy-related gynaecologic emergency PAPP-A was undetectable in 82% of the ectopic pregnancies and in 55% of the intrauterine abortions. Considering the frequency of ectopic pregnancy (35.8%) and intrauterine abortion (52.3%) among all patients with pregnancy-related disorders, the likelihood that a pregnant patient with undectable PAPP-A has an ectopic pregnancy is 30%, and intrauterine abortion is 29%. These results indicate that although PAPP-A levels in ectopic pregnancy and intrauterine abortion are lower than in normal pregnancy, PAPP-A measurement cannot be used to distinguish between ectopic pregnancy and intrauterine abortion.     

妊娠相关血浆蛋白A与异位妊娠的关系

目的:研究异位妊娠与妊娠相关血浆蛋白A(PAPP-A)含量变化之间的关系,为临床诊断提供依据。方法:以唐山市妇幼保健院2003年11月~2004年11月入院且已确诊的180例异位妊娠妇女作为研究对象,选择150例同期来院的同孕龄正常妊娠妇女作为对照。采集空腹肘静脉血2ml,当日离心留置血清,用酶联免疫法(ELISA)测定PAPP-A含量,用化学发光法检测β-HCG。统计分析采用t检验、方差分析、相关性分析。结果:正常妊娠者中PAPP-A的含量高于异位妊娠者,且差别有显著性;不同孕周之间两两比较,PAPP-A不同且差别有显著性;PAPP-A与β-HCG之间存在明显的相关性。结论:正常妊娠者PAPP-A含量明显高于异位妊娠者,且差别具有显著性,可用于临床对异位妊娠患者的辅助诊断。     

孕妇血清内早期血清妊娠相关激素与胚胎停育的相关性

探讨孕早期血清妊娠相关蛋白-A(PAPP-A) 和整合素-金属蛋白酶12分泌期蛋白(ADAM12-s)、催乳素(PRL)和孕酮(P)水平变化及其与胚停育的相关性。应用时间分辨荧光免疫分析法测定患者血清中 PAPP-A、ADAM12-s、PRL和孕酮P表达水平,并对测定结果及孕妇妊娠结局进行统计分析。与正常妊娠组孕妇PAPP-A、ADAM12-s、PRL和孕酮P水平相比,胚胎停育组患者PAPP-A、ADAM12-s、PRL和孕酮P平均中位数水平显著降低,差异具有统计学意义(P<0.05)。正常妊娠组和胚胎停育组孕妇血清内PAPP-A、ADAM12-s、PRL和孕酮P水平与患者的孕周数存在显著的直线相关关系,Person相关系数为正值,(P<0.05)。孕早期孕妇血清 PAPP-A、ADAM12-s、PRL和孕酮(P)含量随孕周数增加而显著上升,可以作为预测胚胎停育的有效临床指标。     

白介素-6对人冠脉平滑肌细胞表达妊娠相关血浆蛋白-A的影响

目的探讨炎症因子白介素-6(IL-6)对人冠脉平滑肌细胞表达妊娠相关血浆蛋白A的影响。方法实验于2005年5月至2006年8月在解放军305医院老年病中心实验室完成。人冠脉平滑肌细胞37℃、5%CO2条件下常规培养。实验用5~7代的细胞,按2.5×105/mL密度接种于25cm2的培养瓶中,24h后换液,生长接近80%融合时进行如下处理:(1)应用质量浓度为10ng.mL-1的IL-6刺激人冠脉平滑肌细胞,分别在共同培养0,2,4,8,24,36h后收集细胞。(2)应用不同质量浓度的IL-6(0,5,10,50ng.mL-1)刺激人冠脉平滑肌细胞,共同培养6h后收集细胞。应用实时荧光定量聚合酶链反应的方法检测细胞内妊娠相关血浆蛋白A基因的表达量。应用SPSS10.0软件进行统计学描述与分析,所得数据用x-±s表示,多组间比较用onewayANOVA检验,两两比较应用SNK法检验,并进行pearson相关分析,P<0.05为差异有显著性意义。结果同剂量白介素-6刺激下,妊娠相关血浆蛋白A的表达量在2h时就开始发生上调,8h达高峰,而后开始下降;在不同剂量白介素-6刺激下,妊娠相关血浆蛋白A的表达量在实验剂量范围内随着白介素-6的剂量加大呈上升趋势。除5ng.mL-1和10ng.mL-1组之间差异无显著性意义(P=0.065),其余组间差异均有显著性意义(P<0.05)。结论炎症因子白介素-6能促进冠脉平滑肌细胞中斑块稳定相关标志物妊娠相关血浆蛋白A的表达,可能是炎症在急性冠脉综合征的发生发展中起重要作用的机制之一。     

Human annulus cells regulate PAPP-A and IGFBP-4 expression,and thereby insulin-like growth factor bioavailability,in response to proinflammatory cytokine exposure in vitro

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase which cleaves IGF binding protein (BP)-4 in the extracellular matrix, making IGF available to nearby cells. We have shown that PAPP-A is present in the human intervertebral disc, and is significantly upregulated in more degenerated discs where increased proinflammatory cytokine levels are present. We hypothesized that increased proinflammatory cytokines present in the degenerating disc might be related to PAPP-A expression. Experiments exposed human annulus cells to IL-1-β or TNF-α to test this hypothesis. Treated cells showed significantly increased PAPP-A in conditioned media versus controls (p?<?0.001). PAPP-A production following exposure to IL-1β was significantly greater in cells derived from more degenerated versus healthier discs (p?=?0.05). PAPP-A gene expression (microarray analysis) was significantly upregulated in IL-1β- or TNF-α-exposed cells (p?=?0.01–0.004). Quantitative RT-PCR confirmed significant upregulation of IGFBP-4 in IL-1β- or TNF-α-exposed cells. Data have potential relevance to future cell-based biologic therapies for disc degeneration.     

妊娠相关血浆蛋白A及其基因IVS6＋95（C／G）多态性与急性冠状动脉综合征的相关性研究

目的研究湖北省十堰地区妊娠相关血浆蛋白A（PAPP-A）及其基因IVS6＋95（C／G）多态性与急性冠状动脉综合征（ACS）的相关性。方法随机选择ACS患者219例,其中男性125例。女性94例．平均年龄63．25岁。健康对照者212例,其中男性114例．女性98例,平均年龄59．66岁。取血液标本．应用荧光探针聚合酶链反应和基因芯片技术对其PAP-A基因IVS6＋95（C／G）多态性进行基因分型,用电化学发光法检测PAPP—A浓度。结果ACS组PAPP—A显著高于对照组[（45．92±18．39）pg／mL vs 5（4．11±0．83）pg／mL],差异有显著统计学意义（P〈0．01）;亚组急性心肌梗死（AMI）组[（82．42±26．41）pg／mL]和不稳定心绞痛（UAP）组[（30．52±12．62）pg,mL]血浆PAPP-A都显著高于对照组,差异有显著统计学意义（P〈0．01）．AMI组与UAP组相比差异也有显著统计学意义（P〈0．01）。ACS组GG、GC、CC基因型频率分别为43．38％、41．09％、15．53％,对照组GG、GC、CC基因型频率分别为50．00％、43．40％、6．60％,差异具有统计学意义（P〈0．05）。G、C等位基因频率在ACS组和对照组分别为63．93％、36．07％和71．70％、28．30％,差异也具有统计学意义（P〈0．05）。在ACS组和对照组．各类基因型人群PAPP—A浓度差异无统计学意义（P〉0．05）。结论PAPP-A及其基因IVS6＋95（C／G）多态性与ACS相关．C等位基因和CC基因型是ACS发病的易感危险因素之一。     

Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients

Background. The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. Methods. 29 HD patients were randomized into two groups: 15 patients were treated orally with 400mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical – TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. Results. Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23±11.94 vs. 11.41±1.94 mIU/L, p<0.001; CRP: 5.20±3.50 vs. 3.40±3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. Conclusion. Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.     

Long-term prognostic utility of PAPP-A and calprotectin in suspected acute coronary syndrome

Abstract

Background. Vascular inflammation plays a key role in the development of acute coronary syndrome (ACS). Pregnancy-Associated Plasma Protein A (PAPP-A) and calprotectin are two of several novel promising markers of inflammation. The present study evaluates the prognostic utility of these two biomarkers in patients with suspected ACS. Methods. Chest pain patients with suspected ACS (N = 871) were consecutively included in a prospective, observational study with a mean follow-up time of 84 months. Blood samples were drawn at admission, prior to treatment with heparin. Results. Total mortality was 38.9%. In univariate analyses, high PAPP-A levels were associated with significant increased mortality. The hazard ratio [HR] in quartile (Q) 3 and Q4 were 1.57 (95% confidence interval (CI), 1.14–2.18), p = 0.006, and 1.41 [95% CI 1.02–1.97], p = 0.040, respectively, as compared to Q1. Calprotectin in the upper quartile (Q4) was associated with total mortality [HR1.94 (95% CI 1.42–2.66)], p = < 0.001, the combined endpoint of death or recurrent myocardial infarction (MI) [HR 1.68 (95% CI 1.26–2.24), p = < 0.001], and recurrent MI [HR 1.60 (95% CI 1.06–2.41); p = 0.024]. However, neither PAPP-A nor calprotectin was found to be an independent predictor of future adverse events. Conclusion. In this study, high levels of PAPP-A and calprotectin were associated with adverse clinical outcome in chest pain patients with clinically suspected ACS. However, neither of the two biomarkers was an independent predictor of long-term prognosis.

Trial registration: ClinicalTrials.gov identifier: NCT00521976.     

冠心病患者血清PAPP-A、PC、hs-CRP水平与冠脉病变程度及预后的相关性研究

目的探讨冠心病(CHD)患者血清妊娠相关血浆蛋白A(PAPP-A)、血浆蛋白C(PC)、超敏C反应蛋白(hs-CRP)水平变化及其与冠脉病变程度、预后的关系。方法研究对象源于2017年10月至2018年10月本院收治的186例CHD患者(纳为疾病组)和同期健康体检志愿者85名(纳为对照组),比较两组血清PAPP-A、PC、hs-CRP水平,冠脉造影评估CHD患者冠脉病变程度,随访疾病组预后,分析不同冠脉病变、不同预后CHD患者血清PAPP-A、PC、hs-CRP水平变化,并进行相关性分析。结果与健康组比较,疾病组血清PAPP-A、hs-CRP水平明显升高,PC水平明显降低,差异具有统计学意义(P<0.05);随着冠脉病变程度加重,CHD患者血清PAPP-A、hs-CRP水平依次明显升高,PC水平依次明显降低,差异具有统计学意义(P<0.05);随访发现共42例发生MACE事件(22.58%),发生MACE事件的CHD患者血清PAPP-A、hs-CRP水平较未发生者明显升高,而PC水平明显低于未发生者,差异具有统计学意义(P<0.05);Pearson相关分析发现,CHD冠脉病变程度、预后与血清PAPP-A、hs-CRP呈明显正相关(r=0.546、0.607,P<0.05),与PC水平呈明显负相关(r=-0.512,P<0.05)。结论CHD患者血清PAPP-A、hs-CRP水平明显升高而PC明显降低,三者与CHD病情程度及预后密切相关,或可作为CHD危险分层和预后评估的有效指标。     

The effect of cigarette or sheesha smoking on first-trimester markers of Down syndrome

Objective  To investigate the influence of cigarette or sheesha smoking on first-trimester markers of Down syndrome.
Design  A prospective observational study.
Setting  Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia.
Population  Women with a singleton pregnancy who were either nonsmokers ( n = 1736) or cigarette smokers ( n = 420) or sheesha smokers ( n = 181).
Methods  Fetal nuchal translucency thickness (fetal NT), maternal serum free beta-human chorionic gonadotrophin (free β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared.
Main outcome measures  Fetal NT, maternal serum free β-hCG, PAPP-A and cotinine measurements.
Results  Compared with nonsmoking women, fetal NT was significantly increased and free β-hCG and PAPP-A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day.
Conclusions  Cigarette and sheesha smoking significantly affect first-trimester markers of Down syndrome (fetal NT, free β-hCG and PAPP-A). Correction for this effect in women who smoke might improve the effectiveness of first-trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first-trimester markers require further studies.