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Background: Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel's antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome., Methods: We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period., Results: Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p=0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events., Conclusions: PPI co-administration did not influence clopidogrel's antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Thrombin is the most potent platelet activator, and achieves rapid platelet activation even in the presence of antiplatelet therapy. Since activated platelets respond stronger to additional stimuli, the extent of endogenous thrombin generation may in part be responsible for the reported response variability to aspirin and clopidogrel therapy., Patients and Methods: Thrombin generation potential was measured with a commercially available assay, and platelet reactivity was assessed with the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, light transmission aggregometry (LTA), the VerifyNow aspirin and P2Y12 assays, and multiple electrode aggregometry (MEA) in 316 patients on dual antiplatelet therapy undergoing angioplasty and stenting., Results: Peak thrombin, the lag phase and the area under the curve of thrombin generation correlated poorly with on-treatment platelet reactivity by all test systems. High on-treatment residual platelet reactivity (HRPR) in response to arachidonic acid was seen in 33 (10.5%), 41 (13%), and 79 (25.7%) patients by LTA, the VerifyNow aspirin assay, and MEA, respectively. HRPR in response to adenosine diphosphate was seen in 150 (48.1%), 48 (15.3%), 106 (33.7%), and 118 (38.3%) patients by the VASP assay, LTA, the VerifyNow P2Y12 assay, and MEA, respectively. Peak thrombin generation did not differ between patients without and with HRPR by the VASP assay, LTA, the VerifyNow P2Y12 assay and MEA. In the VerifyNow aspirin assay, patients without HRPR had higher peak thrombin generation than patients with HRPR (p=0.01). Finally, patients without and with high peak thrombin generation exhibited similar on-treatment platelet reactivity by all test systems, and high peak thrombin generation occurred to a similar extent in patients without and with HRPR., Conclusion: Response to antiplatelet therapy with aspirin and clopidogrel is not associated with thrombin generation potential., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Short peptidoglycan recognition protein (PGRP-S) is a member of the innate immunity system in mammals. PGRP-S from Camelus dromedarius (CPGRP-S) is found to be highly potent against bacterial infections. It is capable of binding to a wide range of pathogen-associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). The heparin-like polysaccharides have also been observed in some bacteria such as the capsule of K5 Escherichia coli thus making them relevant for determining the nature of their interactions with CPGRP-S. The binding studies of CPGRP-S with heparin disaccharide in solution using surface plasmon resonance gave a value 3.3×10(-7) M for the dissociation constant (Kd). The structure of the heparin bound CPGRP-S determined at 2.8Å resolution revealed the presence of a bound heparin molecule in the binding pocket of CPGRP-S. It was found anchored tightly to the protein with the help of several ionic and hydrogen bonded interactions. Three sulphate groups of heparin S1, S2 and S3 have been found to interact with residues, Arg-31, Lys-90, Thr- 97, Asn-99 Asn-140, Gln-150 and Arg-170 of CPGRP-S. The binding site includes two subsites, S-I and S-II with cleft-like structures. Heparin disaccharide is bound in subsite S-I. Previously determined structures of the complexes of CPGRP-S with LPS, LTA and PGN also showed that their glycan moieties were also held in subsite S-I indicating that heparin disaccharide also represents an important element for the recognition by CPGRP-S.