Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the overall study population (n = 562).

<p>Continuous data are given as mean ± SEM.</p><p>Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the overall study population (n = 562).</p

<i>In Vivo</i> and protease-activated receptor-1-mediated platelet activation in patients presenting for cardiac catheterization

<p>Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether <i>in vivo</i> and thrombin receptor activating peptide (TRAP)-stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. <i>In vivo</i> and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. <i>In vivo</i> platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all <i>p</i>≤0.02). Patients with an acute coronary syndrome (ACS; <i>n</i>=125) had significantly higher levels of <i>in vivo</i> MPA than patients without ACS (<i>n</i>=437; <i>p</i>=0.01). In the overall study population (<i>n</i>=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA <i>in vivo</i> and in response to TRAP were similar in patients without and with subsequent ischemic events (all <i>p</i>>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (<i>n</i>=459), stent implantation (<i>n</i>=205) or ACS (<i>n</i>=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, <i>in vivo</i> and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization.</p

Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the subgroup of patients with stent implantation (n = 205).

<p>Continuous data are given as mean ± SEM.</p><p>Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the subgroup of patients with stent implantation (n = 205).</p

Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the subgroup of patients with stent implantation (n = 205).

<p>Continuous data are given as mean ± SEM.</p><p>Soluble CD40 ligand levels (sCD40L) in patients without and with the primary and secondary endpoints in the subgroup of patients with stent implantation (n = 205).</p

Patient characteristics of the overall study population, and of patients with aspirin monotherapy (ASA) vs. dual antiplatelet therapy (ASA+Clo).

<p>Continuous data are shown as mean ± SEM. Dichotomous data are shown as %.</p><p>Abbreviations: ACE, angiotensin converting enzyme; BMI, body mass index; CRP, C-reactive protein; MI, myocardial infarction.</p><p>Patient characteristics of the overall study population, and of patients with aspirin monotherapy (ASA) vs. dual antiplatelet therapy (ASA+Clo).</p

Flow cytometric analysis of platelets and platelet-derived microparticles (PDMP) in PRP following activation with SMLEF bipolar pulses, SMHEF monopolar pulses and thrombin.

<p>A) Representative forward- and side-light scatter profiles of (CD41/CD42b double positive) particles in activated and unactivated PRP samples. The oval indicates the location of the normal forward and side-light scatter distribution for intact platelets; CD41+/CD42b+ particles with lower forward and side light scatter are considered PDMP. B) PDMP as % of all CD41/CD42b double positive particles. Platelet count prior to stimulation was 1095.2 ± 192.9 x 10⁹/L (mean ± SD). C) Percentage of PDMP positive for surface phosphatidylserine as detected by annexin V binding; D) Percentage of platelets positive for surface phosphatidylserine as detected by annexin V binding; E) Percentage of all CD41/CD42b double positive particles positive for surface P-selectin. F) P-selectin mean fluorescence intensity (MFI) per particle. Upper and lower boundaries of boxes represent 25^th and 75^th %tile, whiskers represent 10^th and 90^th %tiles, line indicates median, n = 5. *p<0.05, **p<0.01, ***p<0.001.</p

Differential effects of SMLEF bipolar pulses, SMHEF pulses and thrombin on PRP activation, growth factor release, and cell proliferation.

<p>Differential effects of SMLEF bipolar pulses, SMHEF pulses and thrombin on PRP activation, growth factor release, and cell proliferation.</p

³¹P NMR Spectra (¹H decoupled) of the diastereomers of compound 1 and their racemic mixture.

<p>In the left panel are the P¹,P⁴ regions, and in the right panel are the P²,P³ regions of the spectra. The traces are, from bottom to top: racemic mixture (RM), diastereomer <b>1.1</b>, <b>1.2</b>, <b>1.3</b>, and <b>1.4</b>.</p

Stability and metabolism of the four diastereomers of compound 1 in human plasma at 37 °C.

<p>t_1/2, half-life of first order elimination. For other abbreviations, see Figure 1.</p

Independent influence of behavioral stressors on platelet function.

<p>WBA, platelet count, and plasma epinephrine were increased by each of the three stressors, with a (partial) recovery during recovery. In contrast, while the platelet surface markers showed a gradual increase across the approximately 3-h test battery, there was no consistent increase and recovery caused by the three stressors. Mental, mental stress test; tilt, passive head up tilt table test; exercise, cycle exercise test; B, baseline; S, stress test; R, recovery; x-axes, minutes from first blood sample within test battery; left y-axes, absolute values; right y-axes, data expressed as a percentage of each individual’s mean values across the forced desynchrony protocol; error bars, SEM; P-values, significance for effect of time across full stress test battery (9 time points); *, significance for change between consecutive samples (from baseline to stress test and from stress test to recovery). Note platelet ATP release is not shown (see above text).</p