Biomedical subjects

L Pontiggia

Publications and source records attributed to L Pontiggia.

4 recordsLinked to original sources

PubMed2003

[Antiaggregation: aspirin].

Many randomized trials have shown aspirin as an effective antiplatelet drug for the secondary prevention of cardiovascular events. The NNT (number needed to treat) to prevent 1 vascular event is about 25. The NNH (number needed to harm) inducing one cerebral bleeding is about 1'000, to provoke one severe extracerebral bleeding about 100-200. The primary prevention can be recommended only for high risk patients for cardiovascular events (annual risk of 1-1.5% or more), calculated on the basis of the Framingham data, the Sheffield tables or in analysis of U.S. Preventive Services Task Force. The mechanisms of action, interactions and the "aspirin-resistance" are briefly discussed.

Administration, Oral↗

PubMed2000

Genetics of platelet receptor single-nucleotide polymorphisms: clinical implications in thrombosis.

Several single-nucleotide polymorphisms (SNPs) of platelet receptors have been implicated to be associated with an increased risk of arterial thrombosis; this review focuses on the mechanisms and the clinical significance of two specific single-nucleotide polymorphisms, ie the GP IIIa L33P (=PlA1/2) and the GP Ia 807 C/T. Whereas the mechanism of P1A2 is thought to result from 'gain of receptor function' (and there is still considerable controversy on this subject), the collagen receptor SNP is associated with an increased number of receptors on the platelet surface, thus offering a plausible explanation for the observed increased interaction with collagen and the increased risk of thrombotic events reported in some studies but not in others. Overall, the presently available (controversial) data do still not allow the conclusion that the GPIIIa polymorphism alone represents a cardiovascular risk factor in the general population. A number of mechanisms and a series of studies suggest, however, that it may be a risk factor in certain subgroups of patients or in a number of clinical situations. The GPIa SNP discussed seems to be a mild risk factor that is particularly important in synergism with known risk factors, such as smoking, hypertension, diabetes or proteinuria, etc, which may enhance its contribution to the overall cardiovascular risk.

Angina Pectoris↗

PubMed1998

Inhibition of Na,K-ATPase activity by cGMP is isoform-specific in brain endothelial cells.

cGMP has been shown to either activate or inhibit Na,K-ATPase activity. Using mouse brain endothelial cells which express both ouabain-resistant alpha1 and ouabain-sensitive alpha2 and alpha3 isoforms, we show that cGMP reduces total Na,KATPase activity to about 58%. The inhibition is prevented by the protein kinase G (PKG)-specific inhibitor KT5823, indicating that cGMP-mediated activation of PKG leads to inhibition of the pump. A similar extent of inhibition is obtained with nitric oxide. cGMP-induced inhibition acts mainly on alpha1 isoforms but hardly affects alpha2/alpha3 isoforms. These data suggest that inhibition of Na,K-ATPase activity by cGMP occurs in an isoform-selective manner in brain endothelial cells.

Alkaloids↗

PubMed1997

The extracellular domain of the sodium pump beta isoforms determines complex stability with alpha 1.

Both subunits of the Na,K-ATPase are encoded by several genes giving rise to at least six isozymes. To examine whether beta isoforms assemble with alpha 1 in a selective manner, we have overexpressed wild-type and chimeric beta subunits in L929 cells and examined assembly as a function of resistance towards detergent-mediated dissociation. In the presence of digitonin all beta chimeras coimmunoprecipitate the endogenous alpha 1 subunit. Only beta proteins with the ectodomain of beta 1 coimmunoprecipitate alpha 1 in the presence of Triton X-100. All beta chimeras stimulate Na,K-ATPase activity in L929 cells. These data indicate that the beta subunit ectodomains mediate interactions with alpha 1 and influence the stability of this complex.

Animals↗