Abstract:
:A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters. The extent of thrombolysis within 90 min was determined as the difference between the radioactivity injected in the jugular vein and that recovered in the heart and lungs. Recombinant t-PA (home-made rt-PA or Activase) infused intravenously over 60 min caused dose-dependent progressive thrombolysis. The results of thrombolytic potency (clot lysis in percent versus dose administered in mg/kg) and of specific thrombolytic activity (clot lysis in percent versus steady state plasma level in microgram/ml) were fitted with an exponentially transformed sigmoidal function y = 100 c/(1 + e-a(ax-eh] and the maximal percent lysis (c), the dose or plasma level at which maximal rate of lysis is achieved (b) and the maximal rate of lysis (z = 1/4 ac.eb) were determined. With rt-PA, these parameters were c = 72 +/- 6% (mean +/- SEM), b = 0.19 +/- 0.08 mg/kg, z = 68 +/- 25% lysis per mg/kg, with corresponding values of 87 +/- 5%, 0.07 +/- 0.03 mg/kg and 150 +/- 38% lysis per mg/kg for Activase (p = NS). Deletion of the finger and growth factor domains in rt-PA (rt-PA-delta FE) was not associated with marked alteration of the thrombolytic potency (c = 90 +/- 30%, b = 0.34 +/- 0.35 mg/kg, and z = 54 +/- 14% per mg/kg), but was associated with a significant reduction of the specific thrombolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Collen D,Lijnen HR,Vanlinthout I,Kieckens L,Nelles L,Stassen JMsubject
Has Abstractpub_date
1991-02-12 00:00:00pages
174-80issue
2eissn
0340-6245issn
2567-689Xjournal_volume
65pub_type
杂志文章abstract::Recent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available fo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1994-09-01 00:00:00
abstract::Circulating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-04-0313
更新日期:2014-01-01 00:00:00
abstract::Platelet counts were evaluated in 714 patients with advanced non-small cell lung cancer (N-SCLC), small cell carcinoma of the lung (SCCL), and colon cancer entered to a clinical trial. Patients had not received prior chemotherapy. Platelet counts were not different in patients who had received radiation therapy prior ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-12-28 00:00:00
abstract::Platelet adhesion and aggregation at the sites of vascular injury are key events for thrombosis and haemostasis. It has been well demonstrated that interaction between glycoprotein (GP) Ibα and von Willebrand factor (VWF) initiates platelet adhesion and contributes to platelet aggregation, particularly at high shear. ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-06-0490
更新日期:2014-02-01 00:00:00
abstract::To identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subject...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::The synthetic peptide SFLLRNPNDKYEPF, identical in sequence to the new amino-terminus of the thrombin receptor generated following cleavage of thrombin, acts a thrombin receptor agonist/activating peptide (TRAP). In this study, Northern blot analysis showed that cultured human vascular smooth muscle cells (HVSMC) expr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also foun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00
abstract::Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-live...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1669921
更新日期:2018-10-01 00:00:00
abstract::Microvascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly i...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-08-30 00:00:00
abstract::Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Vitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and prevention of thrombotic disorders in many countries, despite the recent approval of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs are tightly associated to maintaining the patient within the internationa...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-11-0941
更新日期:2014-09-02 00:00:00
abstract::Proteolysis of connective tissue by enzymes such as PMN-elastase (PMNE) is a crucial step during inflammation and metastasis. Semisynthetic sulfated carbohydrates (SC) were shown to exhibit potent antiinflammatory and antimetastatic activity in vivo. The aim of the present study was to examine whether interferences wi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Despite reports that Tris [tris (hydroxymethyl)aminomethane] affects platelets, it is often used to buffer suspending media. Human or rabbit platelets were washed and resuspended in Tyrode solution containing apyrase and 0.35% albumin. Addition of 15 mM Tris partially inhibited primary aggregation induced by 10 microM...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-04-30 00:00:00
abstract::Bypassing inhibitors in haemophilia patients is limited to activated (a) Factor(F)VII products. We introduced "FVa activity augmentation" as another bypassing strategy and studied effects of an engineered FVa variant designated superFVa. Procoagulant and clot stabilising properties of superFVa and recombinant human (r...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH15-07-0525
更新日期:2016-03-01 00:00:00
abstract::Heparin and low molecular weight heparins stimulate two to three fold the accumulation of an antithrombotic heparan sulfate secreted by endothelial cells in culture. This led us to search for the minimum structural requirements of the heparin molecule able to elicit the enhancement of the heparan sulfate. Fragments we...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::LMWH preparations have been proven to be safe and effective in the out-patient management of acute DVT. Although LMWHs are more expensive than unfractionated heparin, the lack of need for laboratory monitoring of LMWHs and their potential for out-patient treatment more than offsets the drug related cost difference and...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract::Components of the fibrinolytic system were studied in samples of plasma from 15 normal, young women and from 11 women taking oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. Fibrinolytic activity of euglobulins precipitated at pH 5.9 was higher than normal in the horm...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-08-30 00:00:00
abstract::An assay of human antiplasmins has been developed utilizing radial diffusion of plasma from wells cut in plasmin-enriched, fibrinogen-agarose plates. After diffusion the fibrinogen is clotted. Zones of fibrin protected from background fibrinolysis develop as the result of plasma antiplasmin activity. A pooled plasma s...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-04-30 00:00:00
abstract::In proliferative retinopathies, like proliferative diabetic retinopathy and retinopathy of prematurity (ROP), the hypoxia response is sustained by the failure of the retina to revascularise its ischaemic areas. Non-resolving retina ischaemia/hypoxia results in upregulation of pro-angiogenic factors and pathologic neov...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH15-01-0051
更新日期:2015-11-25 00:00:00
abstract::Abnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F.Xa), while both progressive antithrombin and antifactor Xa activities...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-02-28 00:00:00
abstract::Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (APC) by thrombin down-regulates the clotting cascade by limited proteolysis of the procoagulant cofactors Va and VIIIa. In addition to its anticoagulant activity, APC also exhibits potent cytoprotective a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-10-0760
更新日期:2013-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-04-30 00:00:00
abstract::The origin and evolution of venom toxins is a mystery that has evoked much interest. We have recently shown that pseutarin C, a prothrombin activator from Pseudonaja textilis venom, is structurally and functionally similar to mammalian coagulation factor Xa-factor Va complex. Its catalytic subunit is homologous to fac...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-11-0707
更新日期:2005-03-01 00:00:00
abstract::Recombinant factor VIIa (rFVIIa: NovoSeven; Novo Nordisk) has proven efficacy in the treatment of haemophilic patients with inhibitors. This prospective, double-blind study compared rFVIIa (35 vs. 90 microg/kg) in the initiation and maintenance of haemostasis during and after elective surgery. Patients with inhibitors...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-11-01 00:00:00
abstract::A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme acti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
abstract::Pulmonary embolism (PE) may encompass a wide spectrum of severity. To determine whether clinical findings, D-dimer (DD) concentration, and deep vein thrombosis (DVT) shown by lower-limb venous compression ultrasonography (US) might predict the scintigraphic extent of PE, we studied 104 hemodynamically stable consecuti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::Fresh retracted clots are known to be poorly lysable by fibrinolytic agents. We have studied whether lysis of retracted clots could be enhanced by bulk transport in comparison to pure diffusion of plasma containing urokinase (400 IU/ml) into the clots. Cylindrical retracted blood clots were occlusively glued by a poly...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-12-07 00:00:00
abstract::Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesio...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-02-01 00:00:00
abstract::Forty-two patients with total occlusion of a coronary vessel were treated with intracoronary fibrinolytic agents. Four therapeutic protocols were compared: group I received streptokinase (SK) as a continuous infusion; group II and III received SK as a bolus at different doses and group IV received lysplasminogen (Pg) ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-12-30 00:00:00