Effects of the pan-selectin antagonist bimosiamose (TBC1269) in experimental human endotoxemia.

Selectins mediate the adhesion of leukocytes to activated endothelial cells and activated platelets. In addition to these cell-to-cell interactions, they influence the fibrin content and size of venous thrombi in different animal models. However, the exact role of selectins in human endotoxemia still remains unclear.

Recombinant human antithrombin inhibits thrombin formation and interleukin 6 release in human endotoxemia.

We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine production. This was a randomized, double-blind, placebo-controlled study in parallel groups enrolling 30 healthy male volunteers. The active treatment groups received infusions of recombinant human antithrombin to increase antithrombin levels to 200% and 500% before infusion of 2 ng/kg endotoxin (LPS).

Pharmacokinetics (PK) of S/D treated anti-D immunoglobulin after intramuscular injection in healthy volunteers: gender differences in PK.

The aim of this study was to investigate the pharmacokinetic profile of the new solvent/detergent (S/D) formulation of an anti-D IgG preparation, and to evaluate gender differences. RhD-negative subjects (m/f=10/8) received a single i.m.

Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation.

Von Willebrand factor (VWF) is synthesized in endothelial cells, stored in the form of high molecular weight multimers and released after stimulation. After release, the multimers are cleaved by ADAMTS13 (von-Willebrand-factor-cleaving protease). We studied healthy volunteers in a double-blind, placebo controlled inflammation model.

Defects in the prostaglandin system--what is known?

The central role of prostaglandins as local mediators is well accepted. Molecular biology and in particular knock-out mice models teach us a lot on mechanisms and eventual biological consequences. Despite the broad basic knowledge available, human data on defects in the prostaglandin system are extremely rare.

Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin.

Whereas bleeding is the most frequent adverse event encountered in patients receiving glycoprotein (GP) IIb/IIIa inhibitors, there are currently no recommendations for how to treat such patients. The present study tested the hypothesis that infusion of desmopressin (DDAVP) reverses the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors (+l-aspirin). Study group 1 (10 healthy volunteers) received a DDAVP infusion to establish dose-response curves for the in vitro inhibition of platelet function by eptifibatide, abciximab, and tirofiban together with l-aspirin before and after DDAVP.

Changes in von Willebrand factor-cleaving protease (ADAMTS13) activity after infusion of desmopressin.

von Willebrand factor-cleaving protease (ADAMTS13) cleaves von Willebrand factor (VWF) and regulates its physiologic function. To investigate the relation between ADAMTS13 activity and VWF, we compared ADAMTS13 activity with the VWF-related parameters VWF antigen (VWF:Ag), VWF collagen-binding activity (VWF:CBA), VWF-propeptide, proVWF, and VWF multimeric composition in 10 healthy volunteers and 3 patients with type 1 von Willebrand disease before and after infusing 0.3 microg/kg desmopressin.