Newborn's fibrinolytic mechanism: components and plasmin generation

Plasminogen activity and antigen, tissue-type plasminogen activator (tPA) activity and antigen, plasminogen activator inhibitor (PAI) activity, and plasmin generation rates were determined in 32 normal newborn plasmas and 25 normal adult plasmas. The newborns showed reduced levels of plasminogen activity and antigen and tPA antigen, and activity, normal levels of PAI activity, and slower plasmin generation rates. The slower generation was shown to be due to the hypoplasminogenemia. The in vitro plasmin generation studies also showed that the newborn needed 11 times the usual concentration of urokinase and 5 times the usual concentration of tPA to achieve the minimal activation rate of the adult.     

Streptokinase,but not tissue plasminogen activator,attenuates platelet aggregation in patients with acute myocardial infarction

Abstract. Objectives. To investigate if tissue plasminogen activator (tPA) and streptokinase given during acute myocardial infarction (AMI) have different effects on platelet aggregation which could contribute to the higher reocclusion rate observed after tPA. Design. Open labelled on consecutive patients. Setting. Coronary care unit. Subjects. Twenty patients with chest pain and ST elevations on an electrocardiogram suggestive of AMI. Interventions. Ten patients were treated with tPA (100 mg 3 h^?1), 10 patients with streptokinase (1.5 × 10⁶ IU 1 h^?1). Main outcome measures. Before, immediately after and 24 h after fibrinolytic therapy, platelet aggregation was estimated with filtragometry and whole blood aggregometry. Fibrinogen, β-thromboglobulin, elastase and the fibrinogen-derived peptide Bβ 30–43 were also measured. Results. The groups were comparable at baseline. Directly after treatment, streptokinase prolonged aggregation time in filtragometry with 112 ± 140 s (P < 0.03) and reduced conductance in whole blood aggregometry by 6.2 ± 6.1 Ω (P < 0.03), both tests indicating inhibited platelet function. Fibrinogen decreased 2.5 ± 1.0 g l^?1 (P < 0.02). In the tPA-treated group corresponding changes were 68 ± 225s (NS) and 2.5 ± 7 Ω (NS) with no significant reduction in fibrinogen. After 24 h, at which time every patient was on acetylsalicylic acid, aggregation was inhibited in both groups as measured by aggregometry. Directly after fibrinolytic treatment, neutrophils were similarly activated in both groups with increments of elastase and Bβ 30–43 by 26 ± 46 μg l^?1 (P < 0.03) and 280 ± 381 pmol l^?1 (P < 0.03) respectively (streptokinase) and by 12 ± 6 μg l^?1 (P < 0.02) and 919 ± 856 pmol l^?1 (P < 0.02) respectively (tPA). Conclusions. Despite similar degrees of platelet and leucocyte activation, streptokinase but not tPA treatment appears to inhibit platelet aggregation. One possible reason could be a streptokinase-induced pronounced decrease of fibrinogen and increase of fibrinogen split products. Therefore, further development of adjuvant antiplatelet therapy could be of clinical importance.     

缺氧复氧对血管内皮细胞分泌tPA、PAI-1的影响及辛伐他汀的干预作用

目的探讨缺氧复氧对血管内皮细胞分泌tPA、PAI-1的影响及辛伐他汀的干预作用，并探讨其可能的机制。方法体外培养人脐静脉内皮细胞株ECV304，使用自制的缺氧小室对ECV304进行缺氧复氧处理。第一组：仅进行缺氧复氧处理。第二组：不同浓度的辛伐他汀（0．1、1．0、5．0、10．0μmol／L）以及10．0μmol／L辛伐他汀＋0．2mmol／L甲羟戊酸预处理ECV304后再行缺氧2h、复氧2h处理．其对照组未加药物。用ELISA法分别检测培养液中tPA、PAI-1的含量。结果复氧2h、4h培养液中tPA浓度明显增加。缺氧2h和复氧2h、4h PAI-1浓度明显增加；5．0、10．0μmol／L辛伐他汀预处理组PAI-1浓度较对照组明显降低；同时用辛伐他汀和甲羟戌酸预处理内皮细胞则以上作用消失。结论缺氧复氧刺激使ECV304分泌tPA、PAI-1增加；辛伐他汀可减少缺氧复氧应激下血管内皮细胞分泌PAI-1，对tPA无影响，减少PAI-1／tPA比值，该作用可被甲羟戊酸逆转。     

组织纤溶酶原激活剂、肝素抑制人工晶体表面细胞学反应的实验对比研究

目的：探讨ｔＰＡ（组织纤溶酶原激活剂）、肝素对人工晶体（ＩＯＬ）表面细胞学反应的抑制作用。方法新西兰大白兔３６只,分别ｔＰＡ、肝素及对照共三组,作晶体囊外摘除及人工晶体植入术。术中分别应用含ｔＰＡ（２５μｇ／０．２ｍｌ）、肝素（１００ＩＵ／ｍｌ）和平衡盐溶液的灌注液。术后１、３、７天和１月各时段取出人工晶体,光学显微镜下观察人工晶体表面的细胞学反应情况,用ＳＡＳ软件包行方差分析。结果ｔＰＡ和肝素组     

Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia

Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet‐derived growth factor receptor β‐positive pericytes and N‐acetylglucosamine oligomers (NAGO)‐positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line‐derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA‐induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.     

丹参酮ⅡA对术后肠黏连大鼠模型防治作用研究

目的研究丹参酮ⅡA对大鼠腹腔术后肠黏连的防治作用并测定大鼠血清中IL-1β、tPA、PAI含量的变化。方法构建大鼠肠黏连模型。70只大鼠随机分为假手术组、模型对照组、丹参酮ⅡA高、中、低剂量组、空白溶剂组、阳性对照药组,每组10只;地塞米松组腹腔注射地塞米松5mg／kg,假手术组及模型组给予等量生理盐水,空白溶剂组给予等量不含丹参酮ⅡA的溶剂。各组大鼠于术前1d、术后1、3、5、7d测定血清中IL-1β、tPA和PAI含量。结果高、中、低剂量组、阳性对照药组血清中IL-1β含量显著低于模型对照组、空白溶剂组与假手术组（P〈0．05）;血清中tPA含量显著高于模型对照组、空白溶剂组与假手术组（P〈0．05）,PAI含量显著低于模型组和空白溶剂组（P〈0．05）,与假手术组相比无显著性差异;高、中、低剂量组、阳性对照药组与模型对照组、空白溶剂组相比,肠黏连程度亦显著性降低（P〈0．001）。结论大鼠腹腔术后腹腔注射丹参酮ⅡA对肠黏连发生有防治作用,其防治作用可能与降低血清中IL-1β、PA1,升高血清中tPA有关。     

Control of extracellular cleavage of ProBDNF by high frequency neuronal activity

Pro- and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect proBDNF or mBDNF, we show that low-frequency stimulation induced predominant proBDNF secretion in cultured hippocampal neurons. In contrast, high-frequency stimulation preferentially increased extracellular mBDNF. Inhibition of extracellular, but not intracellular cleavage of proBDNF greatly reduced high-frequency stimulation-induced extracellular mBDNF. Moreover, high-frequency, but not low-frequency stimulation selectively induced the secretion of tissue plasminogen activator, a key protease involved in extracellular proBDNF to mBDNF conversion. Thus, high-frequency neuronal activity controls the ratio of extracellular proBDNF/mBDNF by regulating the secretion of extracellular proteases. Our study demonstrates activity-dependent control of extracellular proteolytic cleavage of a secretory protein, and reveals an important mechanism that controls diametrically opposed functions of BDNF isoforms.     

Use of Hospital-Based Rehabilitation Services and Hospital Readmission Following Ischemic Stroke in the United States

ObjectiveTo examine the association between hospital-based rehabilitation service use and all-cause 30-day hospital readmission among patients with ischemic stroke.DesignSecondary analysis of inpatient Medicare claims data using Standard Analytical Files.SettingAcute hospitals across the United States.ParticipantsFrom nationwide data, Medicare fee-for-service beneficiaries (N=88,826) aged 66 years or older hospitalized for ischemic stroke between January to November 2010.InterventionsHospital-based rehabilitation services were quantified using Medicare inpatient claims revenue center codes for evaluation (occupational therapy [OT] and physical therapy [PT]), as well as the number of therapy units delivered. Therapy minutes for both OT and PT services were categorized into none, low, medium, and high.Main Outcome MeasuresAll-cause 30-day hospital readmission. A generalized linear mixed model was used to examine the effect of hospital-based rehabilitation services on 30-day hospital readmission, after adjusting for patient and hospital characteristics.ResultsIn fully adjusted models, compared to patients who received no PT, we observed a monotonic inverse relationship between the amount of PT and hospital readmission. For low PT (30 minutes), the odds ratio (OR) was 0.90 (95% confidence interval [CI], 0.83-0.96). For medium PT (>30 to ≤75 minutes), the OR was 0.89 (95% CI, 0.82-0.95). For high PT (>75 minutes), the OR was 0.86 (95% CI, 0.80-0.93).ConclusionHospital-based PT services were associated with lower risk of 30-day hospital readmission in patients with ischemic stroke.