1,721,008 research outputs found
ß-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelium functions
No full textTo evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied
An in vitro method for evaluating vascular endothelial ADPase activity
No full textSome xenobiotics, known to promote the development of thrombotic phenomena affect vascular endothelium ADPase, a regulatory enzyme that inactivates vase- and platelet-active adenine nucleotides. This proposed new experimental approach represents an improved method of evaluation of vascular endothelial ADPase activity which is assessed by measuring, at pre-established times, the degradation rate of exogenous ADP incubated with aortic bovine patches. The ADP dosage was performed by using a spectrophotometric enzymatic assay. Statistical analyses showed that the method is capable of highlighting the linearity of the ADPase activity time-course, thus indicating that the slopes of time-degradation curves of ADP are a valid index for this endothelial ectoenzyme activity. Results obtained with ADPase inhibiting or stimulating agent confirm that this in vitro method is an efficient tool for estimating the ability of xenobiotics or drugs to modify the nonthrombogenic properties of vascular endothelium
Cigarette smoke inhibits adenine nucleotide hydrolysis by human platelets
No full textCigarette smoking is a recognized risk factor for cardiovascular diseases and has been implicated in the pathogenesis of atherosclerosis and thrombotic events. In athero-thrombotic diseases, the extracellular adenine nucleotides play an important role by triggering a range of effects such as the recruitment and activation of platelets, endothelial cell activation and vasoconstriction. NTPDase, a plasma membrane-bound enzyme, is the most relevant enzyme involved in the hydrolysis of extracellular tri- and di-phosphate nucleotides to adenosine monophosphate, which is further degraded by 5′ectonucleotidase to the anti-thrombotic and anti-inflammatory mediator adenosine. Thus, the preserved activity of these enzymes, regulating the extracellular concentrations of nucleotides, is critical in thromboregulatory functions. In the present in vitro study, performed on human platelets suspended in undiluted or diluted aqueous cigarette smoke extract (aCSE), we demonstrated that undiluted and 1 : 2 diluted aCSE is able to significantly reduce ADP hydrolysis (-24% and 12%, respectively) by intact human platelets. ATP degradation was also reduced (-31%) by undiluted aCSE. Conversely, aCSE did not alter platelet AMP hydrolysis. Results obtained by using N-acetylcysteine, a thiol-containing antioxidant, suggest that stable oxidants present in aCSE are responsible for the platelet NTPDase inhibition induced by aCSE. The decreased adenine nucleotide degradation could play a significant role in the extensive platelet activation and vascular inflammation observed in chronic smokers. © 2008 Informa UK Ltd
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