How does measurement of platelet P-selectin compare with other methods of measuring platelet function as a means of determining the effectiveness of antiplatelet therapy?

Measurement of P-selectin on activated platelets as a means of measuring platelet function utilizing the technology described here has the advantage of not requiring immediate access to specialist equipment and expertise. Blood samples are activated, fixed, stored, and transported to a central laboratory for flow cytometric analysis. Here we have compared P-selectin with other more traditional approaches to measuring platelet function in blood and/or platelet-rich plasma (PRP) from patients with acute coronary syndromes on treatment for at least 1 month with either aspirin and clopidogrel or aspirin with prasugrel. The comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y₁₂ antagonists). The P-selectin Aspirin Test revealed substantial inhibition of platelet function in all but three of 96 patients receiving aspirin with clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The results were very similar to those obtained using LTA. There was only one patient with high residual platelet aggregation and low P-selectin expression. The same patients identified as “non-responders” to aspirin also presented with the highest residual platelet activity as measured using the VerifyNow system, although not quite as well separated from the other values. With the Multiplate test only one of these patients clearly stood out from the others. The results obtained using the P-selectin P2Y₁₂ Test in 102 patients taking aspirin and clopidogrel were similar to the more traditional approaches in that a wide scatter of results was obtained. Generally, high values seen with the P-selectin P2Y₁₂ Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP P2Y₁₂ Tests. Similarly, low residual platelet function using the P2Y₁₂ test was seen irrespective of the testing procedure used. However, there were differences in some patients. Prasugrel was always more effective than clopidogrel in inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow), only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP) demonstrating high on-treatment residual platelet reactivity (HRPR) defined using previously published cut-off values. The exception was LTA where there were 11 of 56 patients with HRPR. It remains to be seen which experimental approach provides the most useful information regarding outcomes after adjusting therapies in treated patients.     

携P-选择素抗体靶向微泡评价大白兔睾丸缺血/再灌注损伤的实验研究

目的:探讨携P-选择素抗体靶向脂质微泡评价睾丸完全缺血/再灌注损伤的可行性。方法:制备普通脂质微泡(MB)和携P-选择素抗体靶向微泡(MBp)。30只大白兔随机分成对照组、缺血/再灌注损伤(IRI)0.5 h组、1 h组、2 h组、4 h组,每组6只,在缺血/再灌注术后行MB和MBp的双侧睾丸造影(间隔20 min),经过4～5 min待健侧睾丸实质中MB或MBp完全消失,测量术侧睾丸第一帧超声造影的声强度(F-P,10-5AU)。随后将术侧睾丸取下行免疫组化分析。结果:MBp造影图像显示各IRI组术侧睾丸F-P值分别大于各组的MB(P均0.05),并在2 h[MBp(8.34±1.20)10-5AU,MB(1.87±0.25)10-5AU]最高。对照组术侧睾丸MB、MBp声强度未见明显差异(均为0 AU)(P0.05)。免疫组化示对照组睾丸血管内皮无明显P-选择素表达,而IRI组P-选择素表达增加,并随时间延长而增多。结论:携P-选择素抗体靶向微泡超声造影能够评价睾丸IRI的炎症反应。     

2型糖尿病患者血浆P-选择素和血栓调节蛋白水平变化及其临床意义

目的：通过检测2型糖尿病患者血浆P-选择素和血栓调节蛋白水平变化，探讨检测患者血浆P-选择素和血栓调节蛋白的临床意义。方法：采用ELISA法检测了95例2型糖尿病患者和50例健康对照组血浆P-选择素和血栓调节蛋白水平。结果：2型糖尿病患者血浆P-选择素和血栓调节蛋白水平分别依次升高，且相差显著，与对照组相比有显著性差异（P〈0．01）；2型糖尿病患者血浆P-选择素与血栓调节蛋白水平呈显著的正相关。结论：检测血浆P-选择素和血栓调节蛋白水平，可作为2型糖尿病并发血管病变、病情判定以及治疗效果观察的指标。     

系统性红斑狼疮伴肝,肾损害时血浆P选择素测定意义

为探讨粘附分子Ｐ选择素在系统性红斑狼疮（ＳＬＥ）发病中的作用，本文采用ＥＬＩＳＡ法检测ＳＬＥ患者血浆Ｐ选择素含量。结果表明３０例患者血浆Ｐ选择素平均水平较正常对照明显升高（Ｐ〈０．０１）。其中ＳＬＥ伴肝、肾损害者的血浆Ｐ选择素显著高于不伴有肝、肾损害者（Ｐ〈０．０１），后者与正常对照组相比，也有显著差异。此外，ＳＬＥ患者血浆Ｐ选择素变化与血沉（ＥＳＲ）呈正相关（ｒ＝０．４６７，Ｐ〈０．０１）；但与     

Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration

P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counterreceptor that binds to P-selectin, E-selectin, and L-selectin. To determine its physiological role in cell adhesion as a mediator of leukocyte rolling and migration during inflammation, we prepared mice genetically deficient in PSGL-1 by targeted disruption of the PSGL-1 gene. The homozygous PSGL-1-deficient mouse was viable and fertile. The blood neutrophil count was modestly elevated. There was no evidence of spontaneous development of skin ulcerations or infections. Leukocyte infiltration in the chemical peritonitis model was significantly delayed. Leukocyte rolling in vivo, studied by intravital microscopy in postcapillary venules of the cremaster muscle, was markedly decreased 30 min after trauma in the PSGL-1-deficient mouse. In contrast, leukocyte rolling 2 h after tumor necrosis factor alpha stimulation was only modestly reduced, but blocking antibodies to E-selectin infused into the PSGL-1-deficient mouse almost completely eliminated leukocyte rolling. These results indicate that PSGL-1 is required for the early inflammatory responses but not for E-selectin-mediated responses. These kinetics are consistent with a model in which PSGL-1 is the predominant neutrophil P-selectin ligand but is not a required counterreceptor for E-selectin under in vivo physiological conditions.     

P-selectin-mediated platelet adhesion promotes tumor growth

Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.     

老年人P-选择素与肌钙蛋白T的相关性研究

目的 观察老年人P-选择素和肌钙蛋白T的相关性.方法 80例老年患者分别同时检测P-选择素和肌钙蛋白T,根据肌钙蛋白T的高低将患者分为A组(肌钙蛋白正常组)和B组(肌钙蛋白异常组).分别比较两组P-选择素及与肌钙蛋白T的关系.结果 P-选择素B组明显增高,两组比较差异有统计学意义(P<0.01).单因素分析结果 表明P-选择素和肌钙蛋白T呈正相关(r=0.824,P<0.01).结论 P-选择素较肌钙蛋白T对心脏的敏感性和特异性低,但与肌钙蛋白T联合监测是间接判断冠状动脉病变及心肌损伤的程度和预后的简捷和方便的检测方法 .     

测定血小板表面CD62p评估心房颤动的高血凝状态

目的通过测定心房颤动(房颤)患者血小板表面CD62p了解血小板活化百分率,评估原发病、左房内径(LAD)、年龄和心室率对房颤的血凝状态的影响,以期对临床治疗产生一定的指导作用.方法采用流式细胞仪(FCM)测定房颤组和对照组血小板表面CD62p了解血小板活化百分率.结果除孤立性房颤组外,其它各房颤组血小板活化率均高于对照组(P<0.05).血小板活化率与LAD、年龄有良好的相关性(r分别为0.655和0.508,P值均<0.01),与心室率无相关性.结论血小板活化率和LAD可以作为评估房颤患者高血凝状态的两个重要指标,对指导抗凝治疗有重要意义.     

Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease

Summary.  P-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells and platelets. A number of polymorphisms in the gene encoding P-selectin have been identified. Objectives were to investigate the relationship of soluble P (sP)-selectin with P-selectin gene polymorphisms and coronary artery disease (CAD). Two hundred and forty-nine patients, with extent of CAD characterized by ≥50% stenosis in one or more coronary arteries, and 252 healthy controls were studied. Soluble P-selectin was significantly higher in the patients than controls after adjustment for age, sex and smoking [patients 49.8 (47.5–52.1) ng mL⁻¹; controls 46.7 (44.5–49.1) ng mL⁻¹, P  = 0.03). There was no association of sP-selectin with myocardial infarction (MI) or presence of ≥50% stenosis. The −1817 T/C, −1969 G/A and −2123 C/G (but not the Thr715Pro) polymorphisms were in strong linkage disequilibrium. The Thr715Pro polymorphism was significantly associated with sP-selectin even after adjustment for covariates [TT 48.9 (46.9–50.0) ng mL⁻¹; TP + PP 40.7 (38.1–43.6) ng mL⁻¹, P  < 0.0001]. A significant interaction of Thr715Pro and smoking status was identified in the determination of sP-selectin levels. There was no significant association of genotype at any of the polymorphism in relation to MI or stenosis. The Thr715Pro polymorphisms is associated with plasma sP-selectin. This association is modulated by smoking, although the underlying mechanism remains unclear.     

细胞间黏附分子-1和P-选择素在鼻息肉中的表达

目的:揭示细胞间黏附分子-1(ICAM-1,CD54)和P-选择素(CD62p)在鼻息肉发病机制中的作用.方法:收集鼻息内标本32例,炎性鼻甲黏膜11例,正常鼻黏膜12例作对照,应用FACScan流式细胞仪测定不同标本内表达这两种黏附分子的阳性细胞数量.结果:鼻息肉和炎性鼻甲黏膜ICAM-1和P-选择素的细胞阳性率均明显高于正常鼻黏膜(P＜0.001);鼻息肉和炎性鼻甲黏膜之间ICAM-1和P-选择素的细胞阳性率差异无显著性(P＞0.05);ICAM-1和P-选择素在鼻息肉中的表达有正相关关系(r=0.900 1,P＜0.001).结论:ICAM-1和P-选择素在鼻炎和鼻息肉发病过程中都起了重要作用,在鼻息肉中二者表达有一致性.