Effects on primary haemostasis of an anti-inflammatory agent with 5-lipoxygenase and cyclooxygenase inhibitory activity.

Objective: Licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid) has been demonstrated to inhibit cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase. The aim of this study was to investigate the in-vitro effects of licofelone on platelet function. Effects observed were compared with those produced by the classic COX-1 inhibitor aspirin (ASA).

Uraemic medium accelerates proliferation but does not induce apoptosis of endothelial cells in culture.

Background: Chronic renal failure patients exhibit accelerated atherosclerosis, which is associated with a high incidence of cardiovascular death. We investigated the potential effect of uraemic medium on cell proliferation and apoptosis of endothelial cells in culture (ECs), two key processes in the development of atherosclerosis. Phosphorylation kinetics of the mitogen-activated protein kinase (MAPK) p42/44 and p38 were also evaluated.

Uremic medium causes expression, redistribution and shedding of adhesion molecules in cultured endothelial cells.

Background And Objectives: Patients with chronic renal failure show signs of accelerated atherosclerosis and high cardiovascular morbidity and mortality. Recent investigations indicate that uremia is associated with endothelial dysfunction and a microinflammatory state. We assessed changes in the expression of adhesion molecules [ELAM-1, VCAM-1 and ICAM-1], and proteins involved in hemostasis [von Willebrand factor (vWF) and thrombomodulin (TM)] in endothelial cells (ECs) and the corresponding extracellular matrices (ECM), respectively.

Erythropoietin triggers a signaling pathway in endothelial cells and increases the thrombogenicity of their extracellular matrices in vitro.

We demonstrate that exposure of cultured human endothelial cells to rHuEPO resulted in a dose-dependent increase in the tyrosine kinase activity, with phosphorylation of JAK-2 followed by rapid phosphorylation of STAT-5. Simultaneously, rHuEPO induced long-lasting phosphorylation of MAPK p42/44. Activation of this signaling pathways was directly associated with an increase in the thrombogenic properties of the extracellular matrix generated by these cells, when they were exposed to flowing blood.