Systemic inflammation and COPD: the Framingham Heart Study

BACKGROUND: The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking. METHODS: Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function. RESULTS: IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV(1) (95% confidence interval [CI], - 61 to - 20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV(1) levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV(1) that was on average 19 mL lower (95% CI, - 37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV(1), and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories. CONCLUSIONS: Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited.     

人工寒潮促发大鼠脑卒中发病前脑血管内皮细胞 粘附分子的变化

 【目的】 探讨人工寒潮促发大鼠脑卒中发病前脑血管内皮细胞粘附分子(CAM)的变化&#65377;【方法】 110只SD大鼠制成双肾双夹肾血管性高血压大鼠模型,分为寒潮和非寒潮两大组,再按血压水平各分为正常血压组&#65380;160 ~ 199&#65380;200 ~ 219和 ≥ 220 mmHg等4个亚组,寒潮箱处理3 d后(每亚组6只大鼠)取视交叉平面脑片,连续切片,每8张取1张切片作免疫组化检测血管内皮的VCAM-1&#65380;ICAM-1&#65380;P-选择素水平,视交叉平面剩余切片及其余脑片连续切片,HE染色,了解是否有卒中病灶&#65377;发生脑卒中者被剔出统计学分析&#65377; 【结果】 在 < 220 mmHg的各血压亚组,寒潮组各级脑血管的VCAM-1&#65380;ICAM-1&#65380;P-选择素的免疫组化阳性信号均比非寒潮组高;在 ≥ 220 mmHg血压亚组,寒潮组各级脑血管的上述指标的免疫组化阳性信号均比非寒潮组低;在非寒潮组,各级脑血管的三个指标的免疫组化阳性信号均随血压升高而升高;在寒潮组,各级脑血管的三个指标的免疫组化阳性信号也随血压升高而升高,然而在血压 ≥ 220 mmHg时转为降低&#65377; 【结论】 长期持续的高血压损害了脑血管内皮的调控功能,在寒潮等外因的诱导下易致脑卒中&#65377;     

A clinical-laboratory approach contributing to a rapid and reliable diagnosis of heparin-induced thrombocytopenia

Introduction

Heparin-induced thrombocytopenia (HIT) remains a very challenging diagnosis. The first objective of this study was to compare the performance of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA. The main purpose was to evaluate the diagnostic utility of the combination of the H/PF4 PaGIA^® with the clinical “4T's” score as a screening strategy.

Materials and Methods

102 patients with clinical suspicion of HIT were classified into risk groups using the 4T's score. The presence of HIT antibodies was assessed by two immunoassays and confirmed by a functional flow cytometric assay.

Results

Comparison of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA demonstrated a comparable technical performance, being an excellent screening test to rule out HIT (negative predictive value or NPV = 100%). According to the 4T's score, HIT was excluded in all low risk patients (NPV = 100%). ELISA optical density levels were significantly different between all risk groups (P-values < 0.01). In contrast, due to the low positive predictive value (22%) and weak positive likelihood ratio (2.6), a positive ID-H/PF4 PaGIA^® result did not considerably increase the probability of HIT.

Conclusion

Our study confirms the combination of the 4T's score with the ID-H/PF4 PaGIA^® as a reliable strategy to rule out HIT. Yet, confirming positive ID-H/PF4 PaGIA^® results by flow cytometry within 1-2 h after blood sampling remains necessary. This novel clinical-laboratory approach can contribute in a rapid and reliable way to the definite diagnosis of HIT.     

急性冠脉综合征患者P-selectin、TF、TFPI水平的研究

目的 探讨急性冠脉综合征患者外周血P-selectin、TF、TFPI水平的变化.方法 应用单克隆荧光抗体标记法和夹心酶联免疫吸附法(ELISA)检测急性冠脉综合征(ACS)组、稳定性劳力型心绞痛(SA)组及对照组外周血中P-选择素(P-selectin)、组织因子(TF)和组织因子途径抑制物(TFPI)水平的变化.结果 ①ACS组、SA组和对照组比较,P-selectin均值之间的差异均具有显著性(P＜0.01),以ACS组中最高,SA组次之,对照组最低.TF、TFPI均值在ACS组中显著增高,较其他两组差异有显著性(P＜0.05),TF、TFPI均值之间的差异在SA组和对照组中差异无显著性(P＞0.05).②P-selectin、TF、TFPI 3种检测指标均值在UA组和AMI组间的差异均无显著性(P＞0.05).③3种因子之间具有良好的相关性.④SA组、UA组和AMI组冠脉病变程度之间的差异均无显著性(P＞0.05).结论 外周血中炎性细胞因子及凝血因子相互作用共同参与了急性冠脉综合征发病过程.     

葫芦巴总皂苷对链脲佐霉素诱导的糖尿病大鼠血小板活化的调节作用

目的:观察葫芦巴总皂苷(TFGs)对链脲佐霉素(STZ)诱导的糖尿病大鼠血小板活化的调控作用。方法:将正常大鼠和糖尿病大鼠随机分为未治疗对照组、治疗对照组、未治疗糖尿病组和治疗糖尿病组。两治疗组采用TFGs治疗4周。治疗结束后,分别检测大鼠体质量、血糖和胰岛素水平,采用流式细胞术检测各组大鼠血小板膜P选择素(CD62P)的表达,采用比浊法检测各组大鼠血小板最大聚集率。结果:与正常大鼠相比,糖尿病大鼠血糖明显升高,体质量和胰岛素水平显著下降,糖尿病大鼠经TFGs治疗后体质量明显增加,血糖下降,胰岛素水平升高;糖尿病大鼠血小板CD62P表达和血小板聚集率明显增高,经TFGs治疗后明显降低。结论:TFGs具有明显抑制STZ糖尿病大鼠血小板活化作用,是一种具有防治糖尿病血管病变作用的降糖药物。     

益肾调督针法对脑缺血再灌注大鼠P-selectin mRNA和蛋白表达的影响

目的:通过观察益肾调督针法对脑缺血再灌注大鼠脑内P-selectin mRNA和蛋白表达的影响,探讨益肾调督针法治疗缺血性脑损伤的机制。方法:采用大鼠局灶性脑缺血再灌注模型,应用原位杂交及免疫组化方法观察脑缺血再灌注时P-selectin mRNA和蛋白表达的变化,以及针刺对其影响。结果:正常组和假手术组大鼠P-selectin mRNA和蛋白在皮质区未见表达,脑缺血再灌注后12 h P-selectin mRNA和蛋白表达增强(P<0.05),针刺可明显抑制脑缺血区皮质P-selectin mRNA和蛋白的表达(P<0.05或0.01)。结论:益肾调督针法对缺血性脑损伤的保护作用机制与针刺抑制脑内P-selectin mRNA的表达从而减少P-selectin蛋白的合成有关。     

冠状动脉搭桥术后心脏炎症因子变化

目的:探讨冠状动脉搭桥术后心脏炎症对心功能的影响。方法:42例稳定型心绞痛患者行体外循环下冠脉搭桥术。体外循环运行前,心脏复跳后5、20min分别取动脉及冠状静脉窦血标本;检测白细胞介素(IL)-6、IL-8、IL-10,细胞间黏附分子-1(ICAM-1)和P-选择素(P-selectin)等炎症因子及乳酸水平。记录术后患者肌酸激酶同工酶(CK-MB)、肌钙蛋白-I变化及血流动力学资料。结果:体外循环前IL-6动脉血水平低于冠状静脉窦血水平(P<0.05)。ICAM-1及P-selectin水平高于冠状静脉窦水平(P<0.05)。主动脉开放心脏复跳后动脉血IL-6、IL-8、IL-10、ICAM-1及P-selectin水平与冠状静脉窦水平差别无统计学意义。主动脉开放后20minIL-6、ICAM-1桡动脉和冠状静脉窦血水平差值(CS-A)与术后12h心排指数呈弱负相关。体外循环前动脉血乳酸水平高于冠状静脉窦水平(差值,-0.14±0.25),再灌注阶段心脏乳酸高于体外循环前水平(差值,5min时,0.36±0.22;20min时,0.14±0.20,与术前比较,P<0.01)。主动脉开放后20min后经心乳酸(CS-A)与术后24、48h心肌酶呈正相关。结论:体外循环冠脉搭桥术后心脏炎症反应与术后心功能损害有关,抑制心肌炎症反应有可能改善术后心功能。     

黄芪提取成分对冲击波致家兔肾损伤模型中P-选择素表达的影响

目的:探讨黄芪抗体外冲击波碎石术(ESWL)致肾损伤的有效成分及作用机制。方法:69只家兔随机分为假处理组、对照组、黄芪总皂苷组、总黄酮组和总多糖组,观察ESWL前后P-选择素(p-selectin)在肾脏的表达及细胞超微结构的改变,测定肾组织丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果:ESWL后p-selectin广泛表达于肾小球、肾小管及肾间质等部位,肾组织MDA含量升高,SOD活性明显下降(P<0.05)。黄芪总皂苷组p-se-lectin阳性率及细胞损伤程度显著降低(P<0.05),MDA含量及SOD活性分别明显低于和高于对照组水平(P<0.05)。黄芪总黄酮与总多糖对p-selectin无抑制作用,二者抗冲击波致肾损伤的能力均不如总皂苷显著。结论:黄芪总皂苷除具有清除自由基的能力外,还可显著抑制黏附分子p-selectin的异常表达,是黄芪抗冲击波致肾损伤的主要效应成分。     

狼疮性肾炎患者血浆中P选择素检测的临床意义

采用双抗体夹心法ＥＬＩＳＡ检测３５例狼疮性肾炎（ＬＮ）患者血浆可溶性粘附分子Ｐ选择素含量，结果发现ＬＮ＇患者血浆Ｐ选择素水平较正常对照增高，其中ＬＮ肾病综合征型和肾功能不全型的上述水平又显高于无症状型和肾炎型。对部分患者进行动态观察，发现经治疗病情改善者血浆Ｐ选择素水平降低。本文证实ＬＮ患者体内不同程度存在内皮细胞、血小板激活状态。检测血浆Ｐ选择素可能对判断或监测ＬＮ患者血栓形成状态、病情进展及活动转归等具有重要意义。     

Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two phenotypically distincts inflammatory systemic diseases. However, SLE and SSc share pathogenic features such as interferon signature, loss of tolerance against self-nuclear antigens and increased tissue damage such as fibrosis. Recently, platelets have emerged as a major actor in immunity including auto-immune diseases. Both SLE and SSc are characterized by strong platelet system activation, which is likely to be both the witness and culprit in their pathogenesis. Platelet activation pathways are multiple and sometimes redundant. They include immune complexes, Toll-like receptors activation, antiphospholipid antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once activated, platelet promote immune dysregulation by priming interferon production by immune cells, providing CD40L supporting B lymphocyte functions and providing a source of autoantigens. Platelets are actively implicated in SLE and SSc end-organ damage such as cardiovascular and renal disease and in the promotion of tissue fibrosis. Finally, after understanding the main pathogenic implications of platelet activation in both diseases, we discuss potential therapeutics targeting platelets.