supported by nicox
en effet nicox autorise des travaux sur une molécule qui leur appartient ,mème si le developpement interne est abandonné
news reuters tirée certainement de cette publication
2010 Mar 18. [Epub
ahead of print]
HYPERGLYCEMIA-INDUCED PLATELET
ACTIVATION IN TYPE 2 DIABETES MELLITUS IS RESISTANT TO ASPIRIN BUT NOT
TO A NITRIC OXIDE-DONATING AGENT.
Gresele
P, Marzotti
S, Guglielmini
G, Momi
S, Giannini
S, Minuz
P, Lucidi
P, Bolli
GB, Bolli
GB.
Section of Internal and Cardiovascular
Medicine*AbstractObjective. Acute,
short-term hyperglycemia enhances high shear-stress-induced platelet
activation in type-2-diabetes-mellitus (T2DM). Several observations
suggest that platelets in T2DM are resistant to inhibition by aspirin.
Our aim was to assess comparatively the effect of aspirin, a nitric
oxide-donating agent (NCX 4016), their combination, or placebo on
platelet activation induced by acute hyperglycemia in T2DM. Research
Design and Methods. In a double-blind, placebo-controlled, randomized
trial, 40 T2DM patients were allocated to aspirin 100mg, o.i.d., NCX
4016 800 mg, b.i.d., both of them, or placebo, for 15 days. On day 15,
one hour after the morning dose, a four-hour hyperglycemic clamp (plasma
glucose 13.9mmol/l) was performed and blood samples were collected
before and immediately after it for platelet activation and
cyclooxygenase-1 (COX-1) inhibition studies. Results. Acute
hyperglycemia enhanced shear stress-induced platelet activation in
placebo-treated patients (basal closure time 63+/-7.1sec, after
hyperglycemia 49.5+/-1.4sec, -13.5+/-6.3sec, P<0.048); pretreatment
with aspirin, despite full inhibition of platelet COX-1, did not prevent
it (-12.7+/-6.9sec, P=NS vs placebo); on the contrary, pretreatment
with the NO-donor NCX 4016, alone or in combination with aspirin,
suppressed platelet activation induced by acute hyperglycemia (NCX
4016:+10.5+/-8.3sec; NCX 4016 plus aspirin:+12.0+/-10.7sec, P<0.05 vs
placebo for both). Other parameters of shear-dependent platelet
activation were also more inhibited by NCX 4016 than by aspirin, despite
lesser inhibition of COX-1. Conclusions. Acute hyperglycemia-induced
enhancement of platelet activation is resistant to aspirin; a
NO-donating agent suppresses it. Therapeutic approaches aiming at a
wider platelet inhibitory action than that exerted by aspirin may prove
useful in patients with T2DM.
PMID: 20299485
[PubMed - as supplied by publisher]