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Preliminary in vitro and animal studies have shown that verbascoside, a phenolic compound, may have several favourable biological activities, including an influence on endothelial function and on platelet aggregation. We sought to evaluate the effects of verbascoside, biotechnologically produced from plant cell cultures, on human platelet aggregation (PA). The blood from 40 aspirin-naive volunteers with at least one cardiovascular risk factor was preincubated in vitro with verbascoside (1 and 2 mg/dL) and aspirin (100 μM). The blood from 20 patients with a prior diagnosis of coronary heart disease who were chronically assuming aspirin was preincubated in vitro with verbascoside (1 and 2 mg/dL). PA is measured with a light transmission aggregometry and multiplate analyzer. As compared to reference, preincubation with verbascoside resulted in a significant inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced PA (p < 0.01 for both). Verbascoside 2 mg/dL did not show a stronger effect as compared to verbascoside 1 mg/dL (p = 0.4). As expected, the in vitro addition of aspirin reduced AA induced PA (p < 0.01), but not that induced by ADP (p = 0.5). The addition of verbascoside to the blood of aspirin-treated patients did not improve the values of PA after AA stimulus (p = 0.8), whereas it ensured a stronger inhibition after ADP stimulus (p < 0.01). Verbascoside in vitro affects PA by mildly inhibiting aggregation, triggered both by ADP and AA. These preliminary data, while intriguing, require confirmation in subjects receiving verbascoside orally in order to determine whether these findings are clinically relevant.

Objectives The authors sought to compare the effect on inhibition of platelet aggregation (IPA) of prasugrel therapy versus tirofiban bolus with or without a post-bolus short drug infusion in ST-segment elevation myocardial infarction (STEMI) patients. Background The degree and rapidity of IPA after prasugrel alone with or without concomitant glycoprotein IIb/IIIa inhibition in STEMI patients is unknown. Methods A total of 100 STEMI patients randomly received prasugrel 60 mg versus 25 μg/kg tirofiban bolus with or without post-bolus 2-h infusion of tirofiban, with or without concomitant prasugrel. IPA at light transmission aggregometry was performed throughout 24 h. The primary endpoint was IPA stimulated with 20 μmol/l adenosine diphosphate (ADP) at 30 min. Results At 30 min, patients in the prasugrel group showed a significantly lower IPA to 20 μmol/l ADP stimulation as compared with tirofiban-treated patients (36 ± 35 vs. 87 ± 31, p Conclusions Our study shows that prasugrel administration leads to a suboptimal IPA for at least 2 h in STEMI patients. Yet, prasugrel, given in association with a bolus only of glycoprotein IIb/IIIa inhibitor, obviates the need of post-bolus infusion and almost completely abolishes residual variability of IPA after treatment. (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse [The FABOLUS PRO trial]; NCT01336348 )

Objectives This study sought to evaluate the impact of SYNTAX score (SXscore), and compare its performance in isolation and combination with the PAMI (The Primary Angioplasty in Myocardial Infarction Study) score, for the prediction of 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Background Patients with STEMI were excluded from the original SYNTAX score (SXscore) algorithm. Therefore, the utility of using the SXscore in this patient group remains undefined. Methods SXscore was calculated retrospectively in 807 patients with STEMI enrolled in the randomized STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) clinical trials. Clinical outcomes of all-cause death, reinfarction, and clinically driven target vessel revascularization were subsequently stratified according to SXscore tertiles: SXLOW ≤9 (n = 311), 9 16 (n = 262). Results At 1-year follow-up, all clinical outcomes including mortality, mortality/reinfarction, major adverse cardiac events (MACE) (a composite of all-cause death, reinfarction and target vessel revascularization), and definite, definite/probable, and any stent thrombosis were all significantly higher in patients in the highest SXscore tertile. SXscore was identified as an independent predictor of mortality, MACE, and stent thrombosis out to 1-year follow-up. The combination SYNTAX-PAMI score led to a net reclassification improvement of 15.7% and 4.6% for mortality and MACE, respectively. The C-statistics for the SXscore, PAMI score, and the combined SYNTAX-PAMI score were 0.65, 0.81, and 0.73 for 1-year mortality, and 0.68, 0.64, and 0.69 for 1-year MACE, respectively. Conclusions SXscore does have a role in the risk stratification of patients with STEMI having primary percutaneous coronary intervention; however, this ability can be improved through a combination with clinical variables. (Multicentre 2×2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI; NCT00229515)

The considerable affinity of tissue transglutaminase for heparin was the basis for use of heparin-based affinity matrices for enzyme purification. Interaction of transglutaminase with heparin might mimic the physiological binding to membrane heparan sulfates, accounting for the limited but significant fraction of enzyme exposed at cell surface to crosslink ECM proteins. Exploring effects of heparin on transglutaminase activity and stability, we have noted that heparin only slightly affects activity in vitro, but the protein against heat treatment and proteolysis.

This study sought to evaluate the impact of SYNTAX score (SXscore), and compare its performance in isolation and combination with the PAMI (The Primary Angioplasty in Myocardial Infarction Study) score, for the prediction of 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention.Patients with STEMI were excluded from the original SYNTAX score (SXscore) algorithm. Therefore, the utility of using the SXscore in this patient group remains undefined.SXscore was calculated retrospectively in 807 patients with STEMI enrolled in the randomized STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) clinical trials. Clinical outcomes of all-cause death, reinfarction, and clinically driven target vessel revascularization were subsequently stratified according to SXscore tertiles: SX(LOW) ≤ 9 (n = 311), 9SX(MID) ≤ 16 (n = 234), SX(HIGH)16 (n = 262).At 1-year follow-up, all clinical outcomes including mortality, mortality/reinfarction, major adverse cardiac events (MACE) (a composite of all-cause death, reinfarction and target vessel revascularization), and definite, definite/probable, and any stent thrombosis were all significantly higher in patients in the highest SXscore tertile. SXscore was identified as an independent predictor of mortality, MACE, and stent thrombosis out to 1-year follow-up. The combination SYNTAX-PAMI score led to a net reclassification improvement of 15.7% and 4.6% for mortality and MACE, respectively. The C-statistics for the SXscore, PAMI score, and the combined SYNTAX-PAMI score were 0.65, 0.81, and 0.73 for 1-year mortality, and 0.68, 0.64, and 0.69 for 1-year MACE, respectively.SXscore does have a role in the risk stratification of patients with STEMI having primary percutaneous coronary intervention; however, this ability can be improved through a combination with clinical variables. (Multicentre 2×2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI; NCT00229515).

Summary. Background: On top of aspirin, an abciximab bolusonly regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time. Objectives: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry. Patients/Methods: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as ‡ 50% 5 lmol L )1 ADP-induced maximum platelet aggregation. Results: In clopidogrel responders (n = 68), IPA after 20 lmol L )1 ADP at 4 h was 89% ± 13% in the bolus-only arm vs. 92% ± 14% in the bolus + infusion arm (P = 0.011 for non-inferiority). IPA after 5 or 20 lmol L )1 ADP and 5 or 15 lmol L )1 TRAP and the proportion of patients showing ‡ 80% IPA did not differ at any time point, irrespective of clopidogrel responsiveness status. Thirty-day outcomes were similar, whereas hemoglobin (0.91 ±0 .8 vs. 0.5 ±0 .7 gd L )1 ; P = 0.01) and platelet count mean drop (41.7 ± 57 vs. 18.6 ± 34 10 9 L )1 ; P = 0.042) were significantly reduced in the bolus-only arm. Conclusions: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs.

The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron "leakage" during biologic oxidations, action of flavin dehydrogenases and specific membrane associated secretion, as well as by physical activation of oxygen by irradiation, e.g. UV sun-light. Organisms have developed efficient protective mechanisms against excessive accumulation of ROS, which include superoxide anion, hydrogen peroxide and hydroxyl radical, since all these metabolites are highly reactive and affect almost every kind of organism, either directly or through conversion into other derivatives, notably NO-derived radicals or RNS. Depending on their tissue concentration they can either exert beneficial physiologic effects (control of gene expression and mitogenesis) or damage cell structures, including lipids and membranes, proteins and nucleic acids, leading to cell death. In this brief overview we summarize the present state-of-the-art, restricting the discussion to the role of ROS in physiology and pathology, not taking into account RNS. Discussion will focus on basic chemical and biochemical features of ROS, underlining how ROS can promote severe diseases, including neoplastic, cardiovascular and neurodegenerative diseases. This brief discussion should clarify the present huge interest in ROS, in the perspective to develop new and specific therapeutic approaches.