肾综合征出血热患者血清sP-选择素动态观察及临床意义

目的探讨肾综合征出血热（HFRS）患者血清可溶性P选择素（SP-选择素）水平的动态变化情况及其临床意义。方法用ELISA检测25例正常人和39例EHF患者四期（发热期、少尿期、多尿期及恢复期）血清sP-选择素水平。结果（1）EHF患者血清sP-选择素水平明显升高,且重症组高于轻症组;（2）少尿期及多尿期血清sP-选择素与血尿素和血肌酐均呈显著正相关（P〈0．01）,血清sP-选择素与外周血血小板数呈显著负相关（P〈0．01）。结论血清sP-选择素作为重要的免疫分子参与HFRS的发病过程,动态检测HFRS患者血清sP-选择素水平,可作为HFRS病情观察的重要指标,同时也可为HFRS发病机制及防治研究提供线索。     

机采血小板保存期内血小板聚集功能和可溶性P-选择蛋白的变化

本研究探讨保存期内的机采血小板的聚集功能和可溶性P-选择蛋白含量的改变。收集20份机采血小板样品，分别在保存期第1天（0—24小时）、第2天（24—48小时）、第3天（48—72小时）、第4天（72—96小时）和第5天（96—120小时）检测血小板的聚集功能和可溶性P-选择蛋白含量。结果表明：以ADP作为诱导剂，保存期内机采血小板的血小板聚集功能降低明显，与第1天组比，组间差异均有统计学意义（P均〈0．01），第4天组的血小板最大聚集率≤3％；血浆可溶性P-选择素含量则随着保存时间的延长逐渐升高，与第1天组比，组间差异均有统计学意义（p均〈0．05）。结论：机采血小板在保存期内存在持续活化，且聚集功能下降明显，从第4天开始几乎已完全丧失对ADP的致聚反应，提示机采血小板的体外保存损伤应该引起高度重视。     

Effect of Differently Fed Farmed Gilthead Sea Bream Consumption on Platelet Aggregation and Circulating Haemostatic Markers among Apparently Healthy Adults: A Double-Blind Randomized Crossover Trial

Fish consumption beneficially affects coagulation markers. Few dietary intervention studies have investigated differently fed farmed fish against these cardio-metabolic risk factors in humans. This double-blind randomized crossover trial evaluated differently fed farmed gilthead sea bream consumption against platelet aggregation and circulating haemostatic markers among apparently healthy adults. Subjects aged 30–65 years, with a body mass index 24.0–31.0 kg/m², consuming less than 150 g cooked fish per week, were recruited in Attica, Greece. Participants were randomized (n = 38, 1:1) to one of two sequences; consumption of fish fed with fish oil diet (conventional fish, CF)/fish fed with olive pomace-enriched diet (enriched fish, EF) versus EF/CF. The primary outcomes were ex vivo human platelet aggregation and circulating plasminogen activator inhibitor-1 (PAI-1) and P-selectin (sP-selectin) concentrations. EF consumption had no significant effect on platelet sensitivity or haemostatic markers compared to CF. Platelet sensitivity to platelet-activating factor (PAF) decreased after CF consumption during the second period (p < 0.01). Plasma PAI-1 and sP-selectin concentrations increased after CF consumption during both periods (p < 0.01 for both). Based on current findings, consumption of enriched farmed gilthead sea bream had no greater effect on coagulation markers in adults compared to the conventionally fed fish.     

Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy

BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.     

Acute effects of hyperglycaemia on plasma concentration of soluble P-selectin and von Willebrand factor in healthy volunteers -a prospective randomised double blind controlled study

This study set out to clarify if isolated hyperglycaemia may directly induce acute endothelial and/or platelet activation as diabetes mellitus is a major risk factor for cardio- and cerebrovascular diseases with thromboembolic complications. 12 healthy volunteers were investigated in a prospective randomised, double blind, three-way cross-over trial with a wash-out period of 21 days. Normoglycemic (4.72 mmol/L), moderate (11.1 mmol/L) or high grade (16.7 mmol/L) glucose clamps were maintained for 6 hours by infusion of glucose, insulin and somatostatin. Volunteers were observed for 24 hours. An increase in soluble (s)P-selectin and von Willebrand Factor (VWF) concentrations, of 26 ± 15% and 21 ± 7%, respectively was observed 24 hours after euglycaemic treatment, of 20 ± 7% and 19 ± 5%, respectively after moderate hyperglycaemia and of 22 ± 13% and 18 ± 7%, respectively after high grade hyperglycaemia at 24 hours (p < 0.6 and p < 0.004 in all periods and p = 0.2-0.9 between periods). In conclusion, acute hyperglycaemia for 6 hours does not increase the platelet and endothelial activation markers sP-selectin and VWF in healthy volunteers.     

创伤患者早期血浆sP--选择素的水平及临床意义

目的　探讨血浆可溶性P—选择素 (sP—selectin)在创伤发生后的变化及其意义。方法　应用双抗体夹心ELISA法分别检测 30例创伤患者及 2 0例健康正常人血浆sP—选择素水平。结果　创伤患者早期血浆sP—选择素水平明显高于正常对照 (P <0 .0 1) ,重症组血浆sP -选择素水平明显高于轻症组 (P <0 .0 1)。结论　初步研究表明在创伤后早期血浆sP -选择素水平在创伤后升高与创伤严重程度密切相关 ,检测血浆sP -选择素对创伤病情判断有一定的参考价值。     

The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke

Introduction

Low-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke.

Material and methods

The study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day).

Results

Hyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed.

Conclusions

HMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity.     

Bone marrow megakaryocytes,soluble P-selectin and thrombopoietic cytokines in multiple myeloma patients

Abstract

The expression of adhesion molecules and other cell-surface molecules is substantial in the communication between plasma cells and bone marrow microenvironment, and may lead to increased proliferation of myeloma cells. Many of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g. thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal aim of our study was to explore the relationship between thrombopoietic cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM patients before and after anti-angiogenic treatment. Forty-four patients (20 female and 24 male) with a newly diagnosed MM were examined in three groups, following a division based on the International Staging System, ISS. Plasma levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by means of ELISA. Bone marrow specimens were studied to determine the number of MKs and the so-called “naked nuclei” (NN), as well as the expression of platelet-derived growth factor (PDGF). The comparison revealed a significantly higher concentration of cytokines and sP-selectin in newly diagnosed MM patients compared to healthy volunteers: for TPO, p?=?0.01, IL-6, p?=?0.0005 and sP-selectin, p?=?0.00008, respectively. Marked differences were observed in the concentration of sP-selectin, expression of PDGF and MKs counts between patients with MM stage I and MM stage III. Statistically meaningful correspondences were also found between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p?=?0.009, p?=?0.004 and p?=?0.0005, respectively. Furthermore, the analysis exhibited some statistically meaningful divergences between initial concentrations of sP-selectin in subgroups with different response after chemotherapy. The initial concentration of sP-selectin in the group of MM patients with complete or partial remission stood at 31.86?±?6.13?ng/ml. In the remaining patients (stable disease), the concentration of sP-selectin amounted to 35.15?±?7.23?ng/ml (p?=?0.048). We found a correlation between sP-selectin and IL-6 (ρ?=?0.57, p?=?0.0004), TPO and IL-6 (ρ?=?0.46, p?=?0.001) as well as sP-selectin and TPO (ρ?=?0.36, p?=?0.043), and sP-selectin and PDGF (ρ?=?0.36, p?=?0.03). Our study has eventually demonstrated that sP-selectin, as a marker of platelet activation, could be a useful marker of maximum response to therapy. Its strong association with another marker like PDGF-AB could further lead to the development of new combinational therapeutic strategies of anti-angiogenic therapy in MM patients.     

A systematic review of evidence for the role of inflammatory biomarkers in bipolar patients

Bipolar disorder (BD) is a neuropsychiatric disorder that is characterized by a phasic course of affective episodes interspersed with a euthymic state. Epidemiological, clinical, genetic, post-mortem and preclinical studies have shown that inflammatory reactions and immune modulation play a pivotal role in the pathophysiology of BD. It is conceptualized that biomarkers of inflammation and immune responses should be employed to monitor the disease process in bipolar patients. The objective of this systematic review is to analyse the inflammatory markers involved in human studies and to explore each individual marker for its potential clinical application and summarize evidence regarding their role in BD. A systematic review of human studies to measure inflammatory markers was conducted, and the studies were identified by searching PubMed/MEDLINE, PsycINFO, EMBASE, and Web of Science databases for peer-reviewed journals that were published until September 2015. In this review, we included peripheral markers, genetic, post-mortem and cell studies with inflammatory biomarker analysis in BD. One hundred and two (102) papers met the inclusion criteria. The pro-inflammatory cytokines were elevated and the anti-inflammatory cytokines were reduced in BD patients, particularly during manic and depressive phases when compared to the controls. These changes tend to disappear in euthymia, indicating that inflammation may be associated with acute phases of BD. Even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of using inflammatory markers in the diagnosis, follow-up and prognosis of patients with BD.