1,720,975 research outputs found
Is hyperhomocysteinemia an important risk factor of cardiovascular disease?
No full textIn the last couple of decades many studies have been carried
out on the association of moderately high plasma levels
of total homocysteine (tHcy) with coronary artery disease,
cerebrovascular disease, peripheral artery disease and
venous thromboembolism. Most studies showed a positive
association between tHcy and thrombosis risk. However,
despite this, many investigators are still skeptical about the
importance of hyperhomocysteinemia as a thrombosis risk
factor, because some important aspects of the association of
hyperhomocysteinemia with cardiovascular diseases still
need to be clarified.
In the following few lines I will try to explain why I consider
hyperhomocysteinemia a proven risk factor for cardiovascular
diseases and then I'll address the question of
whether or not it is an important risk factor
State of the art of new P2Y12 antagonists
No full textThe interaction of ADP with its platelet receptor P2Y12 plays a crucial role in platelet activation and thrombogenesis. This article reviews the pharmacology and clinical trials of specific antagonists of P2Y12. Clopidogrel is a thienopyridine with proven antithrombotic efficacy, but it has some important drawbacks: (a) it is a pro-drug that needs to be metabolized to its active metabolite; (b) it has a delayed onset and offset of action and (c) there is high inter-individual variability in pharmacological response. Prasugrel is also a thienopyridine, with faster onset of action and a more uniform inhibition of platelet function compared to clopidogrel, accounting for lower incidence of ischemic events in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and higher incidence of both non-CABG-related bleeding complications. Two direct and reversible P2Y12 antagonists, Cangrelor and ticagrelor, are characterized by rapid onset and reversal of platelet inhibition. Cangrelor is not superior to clopidogrel in preventing thrombotic events in patients undergoing PCI. Ticagrelor is superior to clopidogrel in preventing major adverse cardiac events in ACS patients, but, like prasugrel, is associated with a higher frequency of non-CABG-related bleeding complications. A shorter period of drug discontinuation before surgery is necessary in ticagrelor-treated patients compared to clopiodgrel-treated patients to limit the severity of post-surgical bleeding
Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis
Full text linkTwo sisters with inherited, severe platelet dysfunction associated with P2Y12 deficiency displayed a single base pair deletion in their P2Y12 genes (378delC), resulting in a frame-shift and premature truncation of the protein. GL, the son of one of them, displayed mild platelet dysfunction and normal P2Y12 sequence. We hypothesized that the abnormal platelet phenotype of GL is due to haploinsufficiency of his P2Y12 gene. We analyzed genomic DNA from the family by Southern Blotting and real-time (RT) PCR. Southern Blotting results demonstrated that GL has a single P2Y12 allele, inherited from his father. RT-PCR revealed that GL, his mother and aunt have one single intact P2Y12 allele, while his father has two P2Y12 alleles. The single GL P2Y12 allele contains normal sequence, while his mother and aunt have the 378delC allele. The results of this study support our hypothesis and illustrate the platelet phenotype associated with P2Y12 haploinsufficiency
Determination of vitamin K1 in plasma by solid phase extraction and HPLC with fluorescence detection
No full textWe describe a procedure for quantification of vitamin K-1 in human plasma by HPLC. Samples, enriched with a vitamin K derivative as internal standard, were deproteinized, purified on polymeric RP-SPE cartridges and injected into HPLC equipped with a post-column on-line zinc metal reactor and a fluorometric detector. Median level in blood donors (n = 87) was 1.967 nmol/L(0.93-4.01, 5th-95th percentiles), with a significant correlation between plasma levels and age (r = 0.276, p = 0.00958) and a lower (not significant) value in women than in men. This method, easy-to-handle and with a high throughput, can be used to identify covert states of vitamin K intake deficiency in patients thus at risk of alterations in blood clotting or bone mineralization
Effects of some pre-analytical conditions on the measurement of homocysteine and cysteine in plasma.
No full textThe association of hyperhomocysteinemia and hypercysteinemia with the risk of arterial and venous thrombosis is well documented. While it is known that standardized pre-analytical conditions are necessary for reliable measurement of plasma total homocysteine, the effects of pre-analytical conditions on cysteine measurement are less well known. The aim of this study was to evaluate the effects of pre-analytical conditions on the measurement of homocysteine and cysteine. We observed that the concentration of total homocysteine in plasma increased significantly with time (38% after 6 h), whereas total cysteine decreased (5% after 2 h) when blood anticoagulated with ethylenediaminetetraacetic tripotassium salt was kept at room temperature. These changes were minimized when acidic citrate dextrose was used as an anticoagulant and were abolished when blood samples were immediately placed on crushed ice, independently of the anticoagulant. Storage of plasma for 72 h at room temperature induced a small (≅6%), but significant, decrease in cysteine when blood was collected in ethylenediaminetetraacetic tripotassium salt. In contrast, homocysteine was stable in plasma for 72 h, independently of the anticoagulant used. In conclusion, if blood samples for plasma total homocysteine and cysteine measurement cannot be kept on ice, they should be collected in acidic citrate dextrose to minimize the artifactual changes
Contribution of protease-activated receptors 1 and 4 and glycoprotein Ib-IX-V in the G(i)-independent activation of platelet Rap1B by thrombin
No full textThrombin activates human platelets through three different membrane receptors, the protease-activated receptors PAR-1 and PAR-4 and the glycoprotein Ib (GPIb)-IX-V complex. We investigated the contribution of these three receptors to thrombin-induced activation of the small GTPase Rap1B. We found that, similarly to thrombin, selective stimulation of either PAR-1 or PAR-4 by specific activating peptides caused accumulation of GTP-bound Rap1B in a dose-dependent manner. By contrast, in PAR-1- and PAR-4-desensitized platelets, thrombin failed to activate Rap1B. Thrombin, PAR-1-, or PAR-4-activating peptides also induced the increase of intracellular Ca 2+ concentration and the release of serotonin in a dose-dependent manner. We found that activation of Rap1B by selected doses of agonists able to elicit comparable intracellular Ca2+ increase and serotonin release was differently dependent on secreted ADP. In the presence of the ADP scavengers apyrase or phosphocreatine-phosphocreatine kinase, activation of Rap1B induced by stimulation of either PAR-1 or PAR-4 was totally inhibited. By contrast, thrombin-induced activation of Rap1B was only minimally affected by neutralization of secreted ADP. Concomitant stimulation of both PAR-1 and PAR-4 in the presence of ADP scavengers still resulted in a strongly reduced activation of Rap1B. A similar effect was also observed upon blockade of the P2Y12 receptor for ADP, as well as in P2Y12 receptor-deficient human platelets, but not after blockade of the P2Y1 receptor. Activation of Rap1B induced by thrombin was not affected by preincubation of platelets with the anti-GPIbα monoclonal antibody AK2 in the absence of ADP scavengers or a P2Y12 antagonist but was totally abolished when secreted ADP was neutralized or after blockade of the P2Y12 receptor. Similarly, cleavage of the extracellular portion of GPIbα by the cobra venom mocarhagin totally prevented Rap1B activation induced by thrombin in the presence of apyrase and in P2Y12 receptor-deficient platelets. By contrast, inhibition of MAP kinases or p160ROCK, which have been shown to be activated upon thrombin binding to GPIb-IX-V, did not affect agonist-induced activation of Rap1B in the presence of ADP scavengers. These results indicate that although both PAR-1 and PAR-4 signal Rap1B activation, the ability of thrombin to activate this GTPase independently of secreted ADP involves co-stimulation of both receptors as well as binding to GPIb-IX-V
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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