Ⅱ型糖尿病血浆PAI-1、t-PA检测的意义和结果评价

目的:通过对Ⅱ型糖尿病患者分组(伴血管病变组、胰岛素抵抗组、胰岛素抵抗伴血管病变组、Ⅱ型糖尿病组)检测PAI-1、t-PA抗原及活性,并计算抗原比和活性比,以评价各检测指标的临床价值。方法:采用ELISA法检测PAI-1及t-PA抗原,采用发色底物法检测PAl-1、t-PA活性。结果:189例标本总体患病组及分组后各组的PAI-1活性、t-PA活性及t-PA活性/PAI-1活性比值与正常对照组比较均有显著性差异(P<0.05)。患病组间除t-PA抗原,其余检测显示胰岛素抵抗组、胰岛素抵抗组伴血管病变组与Ⅱ型糖尿病组存在显著性差异(P<0.05)。结论:在上述检测指标中t-PA活性、PAI-1活性反映血管病变的发生较敏感,t PA/PAI-1的活性比值更具临床应用价值。     

Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin

Summary.  Receptors for plasminogen activators present on endothelial cell (EC) surface regulate local plasmin activity. Plasmin generation by human ECs, derived from cerebral cortex, skin and lung, iliac artery, iliac vein, aorta and coronary artery, was studied. The respective ECs were treated with recombinant tissue plasminogen activator (rt-PA) or with recombinant urokinase-type plasminogen activator (ru-PA), washed, plasminogen added and the plasmin generated then assayed. The largest amounts of plasmin were generated by cerebral ECs, under baseline conditions or after exposure to rt-PA or ru-PA ( P  < 0.0001). Exposure to rt-PA also resulted in more plasmin generation than ru-PA in the cerebral ECs ( P  < 0.0001) but not in the other ECs. Heparin enhanced plasmin generation by both rt-PA and ru-PA. Specific antibody against annexin II, a t-PA receptor, blocked plasmin generation by rt-PA. Western blotting showed higher amounts of annexin II on the cell membrane in cerebral ECs. This suggests that expression of annexin II in ECs depends on their location, being greatest in cerebral ECs. In contrast, expression of u-PA receptor was the same for all ECs. This has implications for higher risk of intracranial bleeding during thrombolytic therapy, and for a role of t-PA in neurological development and function.     

蝎毒多肽对大鼠纤溶系统的作用

从蝎毒中获取具有多种药理活性的肽类混合物（简称ＳＶＰ），用下肢血管灌流和整体给药的动物模型，观察对血管灌流液内纤溶酶原激活物（ＰＡ）活性、血浆优球蛋白纤溶活性（ＥＦＡ）、纤溶酶（ＰＬ）活性的影响。结果：１～２０μｇ／ｍｌ灌流３ｍｉｎ和０．８，１．６ｍｇ·ｋｇ－１ｉｐＳＶＰ１ｈ血浆中ＰＡ活性与对照组相比明显升高（Ｐ＜０．０５或Ｐ＜０．０１），这可能与血管内皮细胞释放ＰＡ活性增加有关。     

Adjunctive low-dose doxycycline therapy effect on clinical parameters and gingival crevicular fluid tissue plasminogen activator levels in chronic periodontitis

Objective and design: The present study examined effectiveness of low-dose doxycycline (LDD) in combination with nonsurgical therapy on gingival crevicular fluid (GCF) tissue plasminogen activator (t-PA) levels and clinical parameters in chronic periodontitis (CP) a over 12-month period. Methods: GCF samples were collected, probing depth (PD), clinical attachment level (CAL), gingival index (GI) and plaque index were recorded at baseline, 3, 6, 9 and 12 months. CP patients (n = 65) were randomized to LDD or placebo groups. LDD group received LDD (20 mg) b.i.d for 3-months plus and root planing (SRP), while placebo group was given placebo capsules b.i.d for 3-months plus SRP. GCF t-PA levels were determined by ELISA. Friedman, Wilcoxon and Mann-Whitney test was used for statistical analysis. Results: Significant improvement was observed in all clinical parameters in both groups over 12-month period (p < 0.01). LDD group had lower PD, CAL and GI scores than placebo group at 6, 9 and 12-months (p < 0.05). GCF t-PA levels reduced in both groups over 12-month period (p < 0.01). LDD group had lower GCF t-PA levels than placebo group at 6 and 9-months (p < 0.05). Conclusions: These results provide additional information about usefulness of LDD therapy as an adjunct to nonsurgical therapy in long-term management of periodontitis. Received 8 May 2006; returned for revision 13 June 2006; accepted by J. Di Battista 12 July 2006     

氧化修饰低密度脂蛋白对内皮细胞功能的影响

目的 观察氧化修饰低密度脂蛋白（ox-LDL）对内皮细胞NO／ET-1、t-PA／PAI-1合成、细胞表面细胞间黏附分子-1（ICAM-1）表达的影响。方法 采用培养的人脐静脉内皮细胞（HUVECs），在分另0加入不同浓度ox-LDL（50、100、150、200mg／L）孵育24h后，观察培养液中NO、ET-1、t-PA、PAI-1水平及细胞表面ICAM-1的表达。结果 ox-LDL可显著抑制NO、t-PA的合成。ox-LDL还可明显增加ET-1、PAI-1的分泌及诱导细胞表面ICAM-1的表达。结论 ox-LDL对内皮细胞具有明显的细胞毒作用，它对NO／ET-1、t-PA／PAI-．1及ICAM-1表达的影响可能是其致动脉粥样硬化发生的重要机制之一。     

三七、茜草复方对置铜宫内节育器家兔子宫局部t-PA活性的影响

目的 探讨三七、茜草(SQ)复方治疗置铜宫内节育器(Cu-IUD)所致子宫异常出血的作用机理。方法 制 作家兔置Cu-IUD动物模型,以吲哚美辛作对照,观察SQ复方对置Cu-IUD家兔模型子宫匀浆中组织型纤溶酶原激 活物(t-PA)活性的影响。结果 置Cu-IUD家兔模型子宫匀浆中t-PA的含量增高(P<0．01),经SQ复方治疗后与模 型组比较有显著性差异(P<0．01),说明SQ复方能减少家兔子宫匀浆中t-PA的含量,降低t-PA的活性。结论 SQ 复方通过降低置Cu-IUD家兔子宫内膜局部的纤溶活性而达到止血的目的。     

人组织型纤溶酶原激活剂(t-PA)与绿色荧光蛋白(GFP)在转基因烟草中的融合表达

构建人组织型纤溶酶原激活剂(t-PA)与绿色荧光蛋白(GFP)融合表达的植物表达载体pCA1302NSF-tPA。将重组载体转入根瘤农杆菌GV3101中，通过叶圆盘法转化烟草。转化植株经PCR鉴定整合有t-PA基因，通过荧光显微镜可检测到绿色荧光蛋白(GFP)的表达。     

肺原性心脏病心力衰竭患者的凝血纤溶系统活性变化

目的探讨肺原性心脏病(肺心病)充血性心力衰竭患者凝血纤溶指标的变化及意义。方法测定肺心病充血性心力衰竭患者组织型纤溶酶原激活物(tPA)活性、纤溶酶原激活物特异性抑制物(PAI-1)活性和D-二聚体(DD)含量。结果肺心病心力衰竭组血浆tPA活性较健康对照组降低,而PAI-1活性、DD含量明显升高。不同心功能等级的肺心病心力衰竭患者血浆PAI-1活性、DD含量随着心功能程度的加重而明显升高。结论肺心病充血性心力衰竭患者存在凝血纤溶活性异常,且与心功能程度有关。     

Projected Cost-Effectiveness of Primary Angioplasty for Acute Myocardial Infarction

Objectives. This study sought to evaluate the cost-effectiveness of primary angioplasty for acute myocardial infarction under varying assumptions about effectiveness, existing facilities and staffing and volume of services.

Background. Primary angioplasty for acute myocardial infarction has reduced mortality in some studies, but its actual effectiveness may vary, and most U.S. hospitals do not have cardiac catheterization laboratories. Projections of cost-effectiveness in various settings are needed for decisions about adoption.

Methods. We created a decision analytic model to compare three policies: primary angioplasty, intravenous thrombolysis and no intervention. Probabilities of health outcomes were taken from randomized trials (base case efficacy assumptions) and community-based studies (effectiveness assumptions). The base case analysis assumed that a hospital with an existing laboratory with night/weekend staffing coverage admitted 200 patients with a myocardial infarction annually. In alternative scenarios, a new laboratory was built, and its capacity for elective procedures was either 1) needed or 2) redundant with existing laboratories.

Results. Under base case efficacy assumptions, primary angioplasty resulted in cost savings compared with thrombolysis and had a cost of $12,000/quality-adjusted life-year (QALY) saved compared with no intervention. In sensitivity analyses, when there was an existing cardiac catheterization laboratory at a hospital with ≥200 patients with a myocardial infarction annually, primary angioplasty had a cost of <$30,000/QALY saved under a wide range of assumptions. However, the cost/QALY saved increased sharply under effectiveness assumptions when the hospital had <150 patients with a myocardial infarction annually or when a redundant laboratory was built.

Conclusions. At hospitals with an existing cardiac catheterization laboratory, primary angioplasty for acute myocardial infarction would be cost-effective relative to other medical interventions under a wide range of assumptions. The procedure’s relative cost-ineffectiveness at low volumes or redundant laboratories supports regionalization of cardiac services in urban areas. However, approaches to overcoming competitive barriers and close monitoring of outcomes and costs will be needed.     

Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.