AIM To compare the analytical methods used to study the pharmacokinetics of recombinant hirudin in the plasma of rats that had been injected with (125)I-recombinant hirudin. METHODS 2.0 mg/kg (125)I-recombinant hirudin were injected intravenously into rats. The recombinant hirudins in the plasma was analyzed by chromogenic substrate assay, enzyme-linked immunosorbent assay (ELISA), total radi...

The 'H NMR spectrum of the 65-residue protein hirudin is assigned in a sequential manner by using a combination of two-dimensional nuclear magnetic resonance techniques to demonstrate through-bond and through-space (<5-i() connectivities. The secondary structure of hirudin is deduced from a qualitative interpretation of the nuclear Overhauser effects involving the backbone NH, CaH, and CPH prot...

Components of the blood have been proposed as potential therapeutic targets for improving cellular regeneration after injury and neurodegenerative disease. In this work, thrombin is shown to increase endogenous neural progenitor proliferation in the intact murine spinal cord. A local injection of heparin before a spinal cord injury reduces cell proliferation and astrogliogenesis associated with...

The effect of recombinant hirudin and the dosage of heparin on acute platelet-thrombus deposition during carotid angioplasty in anesthetized pigs was prospectively assessed. Fifty-five animals (mean weight, 33.9 kg) were randomized to one of six heparin dosages: heparin boluses of 35, 50, 100, 150, 200, or 250 units/kg followed by a continuous infusion of35, 50, 100, 150, 200, or 250 units/kg/h...

BACKGROUND Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. METHODS...

Awareness is increasing concerning the development of antibodies to heparin-platelet factor 4 complex in both regular hemodialysis patients and those treated with continuous forms of renal replacement therapy. Although the development of antibodies does not result in thrombocytopenia or thrombosis in some patients, most patients present with thrombocytopenia, premature platelet activation, and ...

Background Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinan...

Hirudin, the first specific thrombin inhibitor, which was used clinically, stems from medicinal leeches and is produced today by recombinant technology. R-hirudins have been studied in many clinical trials. R-hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In acute coronary syndromes hirudin a...

BACKGROUND The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND RESULTS Eighty-two patients in this prospective, multicenter study received 1 of 4 intraven...