Object-Platelet isoprostane 8-ISO-prostaglandin F2␣ (8-iso-PGF2␣), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation. Methods and Results-We studied 8-iso-PGF2␣ in platelets from 8 male patients with hereditary deficiency of gp91 phox , the catalytic subunit of NADPH oxidase, and 8 male controls. On stimulation, platelets from controls produced 8-iso-PGF2␣, which was inhibited Ϫ8% by aspirin and Ϫ58% by a specific inhibitor of gp91 phox . Platelets from patients with gp91phox hereditary deficiency had normal thromboxane A 2 formation but marked 8-iso-PGF2␣ reduction compared with controls. In normal platelets incubated with a gp91 phox inhibitor or with SQ29548, a thromboxane A 2 /isoprostane receptor inhibitor, platelet recruitment, an in vitro model of thrombus growth, was reduced by 44% and 64%, respectively; a lower effect (Ϫ17%) was seen with aspirin. Moreover, thrombus formation under shear stress (blood perfusion at the wall shear rate of 1500 s Ϫ1 ) was reduced in samples in which isoprostane formation was inhibited by NADPH oxidase inhibitors. In gp91 phox -deficient patients, agonist-induced platelet aggregation was within the normal range, whereas platelet recruitment was reduced compared with controls. Incubation of platelets from gp91 phox -deficient patients with 8-iso-PGF2␣ dose-dependently (1 to 100 pmol/L) increased platelet recruitment by mobilizing platelet Ca 2ϩ and activating gpIIb/IIIa; a further increase in platelet recruitment was detected by platelet coincubation with L-NAME, an inhibitor of NO synthase. Conclusion-This

Background: Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition.

BackgroundAtherosclerosis is a well known progressive disease that recognizes risk factors such as diabetes, hypertension, smoking, dyslipidemia, and inflammation. Mechanisms underlying atherosclerotic processes during inflammation are not completely understood, but cytokines are also involved, in particular tumor necrosis factor-α (TNF-α). Chronic inflammatory diseases such as rheumatoid arthritis (RA) are commonly associated with atherosclerotic complication. Little is known about the role of treatment of chronic inflammatory disease on the evolution of atherosclerosis in this kind of disease. Usually, evolution of atherosclerosis is monitored by intima-media thickness and the presence of plaques on several arteries such as common carotid.AimThe aim of the study was to monitor atherosclerosis evolution in seven RA patients on common treatment with infliximab (an anti-TNF-α drug) compared with seven RA patients during common treatment but not treated with infliximab.Patients and methodsWe selected 14 patients with RA according to the American College of Rheumatology classification criteria. Seven patients were selected before and after common treatment for RA based on nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and steroids (12 months), and seven patients before and after treatment based on infliximab associated with NSAIDs, methotrexate, and steroids (12 months). Ultrasound vascular imaging was performed to screen intima-media thickness and the presence of atherosclerotic plaques on common carotid artery and identify evolution of atherosclerosis.ResultsAfter 12 months, patients that were treated with infliximab showed significant worsening of atherosclerosis with an increase of intima-media thickness and the presence of further atherosclerotic plaques compared to patients that were treated traditionally and showed a nonsignificant increase of the same parameters.DiscussionTreatment based on anti-TNF-α such as infliximab shows a worsening evolution of atherosclerosis based on our data. If these data are associated with a poor clinical outcome such as atherothrombosis of cerebral vessels and/or coronary vessels, this should be evaluated by further studies.