Abstract：
:Recently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to potently inhibit thrombin and factor Xa. To assess their effect on the fibrinolytic system, we studied the interaction of LMWLs with human plasmin. Enzyme inhibition studies indicate that the three sulfated LMWLs studied inhibit plasmin with IC50 values in the range of 0.24 and 1.3 mM, which are marginally affected in the presence of antithrombin. Similarly, plasmin degradation of polymeric fibrin is also inhibited by sulfated LMWLs. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of chromogenic substrates decreases nearly 70% in the presence of LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. Competitive binding studies indicate that the sulfated LMWLs compete with full-length heparin. Comparison with thrombin-heparin crystal structure identifies an anionic region on plasmin as a plausible sulfated LMWL binding site. Overall, the chemo-enzymatic origin coupled with coagulation and fibrinolysis inhibition properties of sulfated LMWLs present novel opportunities for designing new pharmaceutical agents that regulate complex pathologies in which both systems are known to play important roles such as disseminated intravascular coagulation.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Henry BL,Abdel Aziz M,Zhou Q,Desai URdoi
10.1160/TH09-07-0454subject
Has Abstractpub_date
2010-03-01 00:00:00pages
507-15issue
3eissn
0340-6245issn
2567-689Xpii
09-07-0454journal_volume
103pub_type
杂志文章abstract：:Our previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β₂-glycoprotein I/β₂-glycoprotein I (anti-β₂GPI/β₂GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its dow...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-04-0229
更新日期：2011-12-01 00:00:00
abstract：:Tissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDMAC). Surfactant-treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyuret...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-02-28 00:00:00
abstract：:Both the HEPTEST and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-09-07 00:00:00
abstract：:The frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (less than 45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-02-25 00:00:00
abstract：:Although there is evidence that altitude increases the platelet count, its effect on the platelet precursor stimulating factor, thrombopoietin (TPO), is unclear. Unlike erythropoietin, TPO appears largely unresponsive to exogenous signals. In a study in 16 healthy volunteers, we report the effects of altitude exposure...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-02-0086
更新日期：2005-01-01 00:00:00
abstract：:Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72hr washout and 5-11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验
doi：10.1055/a-1376-0970
更新日期：2021-01-27 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：:A synthetic hirudin55-65 C-terminal fragment analog was evaluated for anticoagulant activity and in models of experimental thrombosis in mice and rats. Intravenous injection caused dose-related inhibition of thrombin and anticoagulation in rat blood samples, protection from thromboembolism in mice and inhibition of st...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-04-08 00:00:00
abstract：:One of the most severe and important complication in the treatment of haemophilia A (HA) patients is the formation of inhibitors. The mechanism that leads to factor (F)VIII inhibitor formation is complicated. Both genetic and environmental factors have been mentioned to play decisive roles. Recently, polymorphisms in ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-06-0425
更新日期：2012-01-01 00:00:00
abstract：:The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated pl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-11-0873
更新日期：2017-05-03 00:00:00
abstract：:The turnover of recombinant pro-urokinase (Rec-pro-UK), recombinant urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) was studied in rabbits and in squirrel monkeys (Saimiri sciureus). Following intravenous injection, urokinase activity disappeared rapidly from the blood. The initial disappearance rate could b...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-08-31 00:00:00
abstract：:Platelets contain, besides alpha- and delta-granules, lysosomes which store glycohydrolases able to degrade glycoproteins, glycolipids and glycosaminoglycans. While several studies have shown that alpha- and delta-granule secretion takes place "in vivo" in humans upon platelet activation, no data are available on the ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:The introduction of venography into patient care was a major advance because it was the first accurate method for the diagnosis of DVT. Compression ultrasound has since become the preferred test for patients with suspected DVT because, unlike venography, it is simple, non-invasive and widely available. Venography has ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH13-07-0562
更新日期：2014-01-01 00:00:00
abstract：:Mouse mesothelium has been examined as a surface for supporting blood flow. We have examined ten pieces of intact mesothelium and ten pieces of damaged mesothelium following 10 min exposure to flowing blood in a Baumgartner chamber. Scanning electron microscopy of the intact specimens demonstrated no adhering blood pl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:Subcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic compli...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-03-04 00:00:00
abstract：:Obesity and non-insulin dependent diabetes are associated with a decrease in fibrinolysis, which is mediated by the plasminogen system. The purpose of the current study was to investigate the role of the plasminogen system in the reduced body weight of the plasminogen deficient (Plg-/-) mice. In this study we have fou...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
abstract：:In order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and seru...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-06-28 00:00:00
abstract：:The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-05-01 00:00:00
abstract：:Two candidate ECAA reference preparations have been calibrated in a multicentre exercise at 14 representative national laboratories to provide reference thromboplastin for a large field study in 16 European countries. Two preparations were required because of the established differences in ISI arising from the two mai...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：1996-12-01 00:00:00
abstract：:Heparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-10-30 00:00:00
abstract：:To add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical t...
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：2000-06-01 00:00:00
abstract：:Emicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a manner similar to FVIIIa. However, details of the emicizumab-antigen interactions have not been reported so far. In this study, we first showed by surface plasmo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-01-0030
更新日期：2017-06-28 00:00:00
abstract：:The effects of etamsylate on human platelet aggregation and ATP release as well as on the arachidonate metabolism by the platelet have been studied. Etamsylate enhanced these platelet functions induced by arachidonic acid (AA), thromboxane A2, collagen and calcium ionophore A23187 but not those induced by ADP and epin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-12-27 00:00:00
abstract：:Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laborato...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:In the present research protein analysis on SDS-polyacrylamide gel electrophoresis (PAGE) has been used to study the glycoprotein pattern of the blood platelets of four members from a family affected by May-Hegglin anomaly. In order to characterize the glycoprotein fractions, lactoperoxidase-iodination and immunopreci...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-12-17 00:00:00
abstract：:Amniotic fluid inhibited the fibrinolytic, amidolytic and esterolytic activity of urokinase. Kinetic studies with AGLMe demonstrated non-competitive inhibition. A major part of the inhibitory activity could be separated from alpha 1-antitrypsin by ion-exchange chromatography on DEAE-Sephadex A-50. Plasminogen activato...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-08-29 00:00:00
abstract：:Hemophilia B is a sex-linked recessive bleeding disorder characterized by the presence of either a decreased amount of normal factor IX (FIX) or the presence of a dysfunctional FIX. We have identified a unique mutation in a family with mild hemophilia B. DNA analysis of family members revealed a single base transition...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：:Prothrombin complex concentrates (PCC) are known to carry a risk of thromboembolism. We have chosen to reassess the problem of detecting in vivo signs of activation of the clotting mechanism by assaying fibrinopeptide A (FpA) after PCC administration in hemophilic patients during bleeding episodes. FpA was significant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-10-31 00:00:00
abstract：:Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1999-09-01 00:00:00
abstract：:Hyperglycaemia impairs fibrinolytic activity on the surface of endothelial cells, but the underlying mechanisms are not fully understood. In this study, we tested the hypothesis that hyperglycaemia causes dysfunction of the endothelial membrane protein annexin A2, thereby leading to an overall reduction of fibrinolyti...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH12-12-0944
更新日期：2013-06-01 00:00:00
