No abstract

Leukocyte‐endothelial cell interactions play an important role during ischaemia‐reperfusion events. Adhesion molecules are specifically implicated in this interaction process. Since defibrotide has been shown to be an efficient drug in reducing damage due to ischaemia‐reperfusion in many experimental models, we analysed the effect of defibrotide in vitro on leukocyte adhesion to endothelial cells in basal conditions and after their stimulation. In basal conditions, defibrotide (1000 μg ml−1) partially inhibited leukocyte adhesion to endothelial cells by 17.3% ± 3.6 (P < 0.05), and after endothelial cell stimulation (TNF‐α, 500 u ml−1) or after leukocyte stimulation (fMLP, 10−7 m), it inhibited leukocyte adhesion by 26.5% ± 3.4 and 32.4% ± 1.8, respectively (P < 0.05). In adhesion blockage experiments, the use of the monoclonal anntibody anti‐CD31 (5 μg ml−1) did not demonstrate a significant inhibitory effect whereas use of the monoclonal antibody anti‐LFA‐1 (5 μg ml−1) significantly interfered with the effect of defibrotide. This result was confirmed in NIH/3T3‐ICAM‐1 transfected cells. We conclude that defibrotide is able to interfere with leukocyte adhesion to endothelial cells mainly in activated conditions and that the ICAM‐1/LFA‐1 adhesion system is involved in the defibrotide mechanism of action.

No abstract

1. Anaerobic formation of lactate from glucose by isolated perfused rat kidney (411mumol/h per g dry wt.) was three times as fast as in aerobic conditions (138mumol/h per g). 2. In aerobic or in anaerobic conditions, the ratio of lactate production to glucose utilization was about 2. 3. Starvation or acidosis caused a decline of about 30% in the rate of aerobic glycolysis. 4. The rate of formation of glucose from lactate by perfused kidney from a well-fed rat, in the presence of 5mm-acetoacetate (83mumol/h per g dry wt.), was of the same order as the rate of aerobic glycolysis. 5. During perfusion with physiological concentrations of glucose (5mm) and lactate (2mm) there were negligible changes in the concentration of either substrate. 6. Comparison of kidneys perfused with lactate, from well-fed or starved rats, showed no major differences in contents of intermediates of gluconeogenesis. 7. The tissue concentrations of hexose monophosphates and C(3) phosphorylated glycolytic intermediates (except triose phosphate) were decreased in anaerobic conditions. 8. Aerobic metabolism of fructose by perfused kidney was rapid: the rate of glucose formation was 726mumol/h per g dry wt. and of lactate formation 168mumol/h per g (dry wt.). Glycerol and d-glyceraldehyde were also released into the medium. 9. Aerobically, fructose generated high concentrations of glycolytic intermediates. 10. Anaerobic production of lactate from fructose (74mumol/h per g dry wt.) was slower than the aerobic rate. 11. In both anaerobic and aerobic conditions the ratio [lactate]/[pyruvate] in kidney or medium was lower during perfusion with fructose than with glucose. 12. These results are discussed in terms of the regulation of renal carbohydrate metabolism.

No abstract