The solution structure of recombinant wild-type hirudin and of the putative active site mutant Lys-47----Glu has been investigated by nuclear magnetic resonance (NMR) spectroscopy at 600 MHz. The 1H NMR spectra of the two hirudin variants are assigned in a sequential manner with a combination of two-dimensional NMR techniques. Some assignments made in our previous paper [Sukumaran, D. K., Clore...

This study aimed to investigate the effects of thrombin released in hematoma after intracerebral hemorrhage (ICH) on the cerebral injury of perihematomal tissues and to evaluate the protection effect of hirudin on the cerebral injury after ICH. We used the autologous uncoagulated blood injection method to prepare the ICH rat model, and all rats were randomly divided into a normal group, an ICH ...

Hirudin and hirulog-1 [D-Phe-Pro-Arg-Pro-[Gly]4-desulphohirudin-(54-65)] abrogate the enzyme activities of alpha-thrombin by binding the enzyme simultaneously at its catalytic centre and fibrin(ogen)-recognition exosite. In contrast, hirugen [hirudin-(54-65)] binds alpha-thrombin solely at the fibrin(ogen)-recognition exosite, and competitively inhibits fibrinopeptide A release. To investigate ...

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after...

OBJECTIVES The effects of ximelagatran, an oral direct thrombin inhibitor (DTI), recombinant hirudin (r-hirudin) and enoxaparin on thrombin generation and platelet activation were studied in humans. BACKGROUND Recombinant hirudin (parenteral DTI) and enoxaparin (low molecular weight heparin) have been demonstrated to be clinically effective in acute coronary syndromes. Ximelagatran is current...

Background Platelets contain several factors that inhibit heparin. This study was designed to assess the heparinneutralizing activity present in acute, platelet-rich arterial thrombi formed at sites of arterial injury in animals. Methods and Results Platelet-rich thrombi (n=3) were induced in pig coronary arteries by balloon catheter-mediated arterial injury. Soluble extracts were prepared from...

T he TIMI-9A1 and GUSTO-11A2 trial preliminary reports, in this issue of Circulation by highly experienced and respected investigators, show unexpectedly high rates of intracranial bleeds (ICBs) associated with administration of two plasminogen activators (streptokinase [SK] and tissue-type plasminogen activator [TPAI) and two intravenously administered anticoagulants (heparin and hirudin). Ano...