Multiplex analysis of genetic polymorphisms within UGT1A9, a gene involved in phase II of Δ9-THC metabolism

We present a novel multiplex assay for the simultaneous detection of 12 polymorphisms within the UGT1A9 sequence, which codes for enzymes involved in phase II biotransformation. The assay combines a multiplexed amplification step with single-base extension sequencing. The method described here is fast, cost-effective, and easy-to-use, combining the relevant features of screening methods for research and diagnostics in pharmacogenetics. To validate the assay, we tested reproducibility and sensitivity and analysed allele frequencies of 110 Caucasian individuals. Furthermore, we describe combining genetic information of individuals consuming Cannabis sativa products with respective plasma concentrations of a metabolite.

     

Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention

This study assessed the effect of body mass index (BMI) on platelet aggregation after administration of a high loading dose of clopidogrel 600 mg. Blood samples of 402 patients before percutaneous coronary intervention were collected >or=2 hours after administration of clopidogrel 600 mg. Platelet aggregation was measured in response to adenosine diphosphate (ADP; 5 and 20 microM). Patients were categorized as normal weight (BMI <25 kg/m(2)) or overweight (BMI >or=25 kg/m(2)). ADP-induced platelet aggregation was significantly higher in overweight patients than in normal-weight patients (46.0 +/- 21.8% vs 38.2 +/- 19.3% for ADP 5 microM, p = 0.0007; 55.1 +/- 22.7% vs 45.2 +/- 21.7% for ADP 20 microM, p <0.0001). Multivariate analyses demonstrated high BMI as the only independent predictor for increased ADP-induced platelet aggregation (p 相似文献   

Platelet Function Testing in Patients with Acute Coronary Syndrome

In patients with an acute coronary syndrome (ACS), inhibition of the platelet P2Y12 receptor is standard of care. The shortcomings of the most commonly used P2Y12 receptor inhibitor clopidogrel—that is its delayed onset of action, its interindividual response variability, and the phenomenon of high on-treatment platelet reactivity—led to the development of more potent P2Y12 receptor inhibitors (prasugrel and ticagrelor) that proved their superiority in terms of reducing thrombotic events compared to clopidogrel. Available randomized studies that aimed at investigating the value of a personalized antiplatelet treatment regimen based on platelet function monitoring results were negative with regard to the possible benefits of monitoring but were all limited by mainly enrolling elective and stable patients with coronary artery disease. Thus, it still warrants further investigation if a tailored, platelet function guided, antiplatelet therapy in ACS patients with the available P2Y12 receptor inhibitors prasugrel, ticagrelor, and clopidogrel can lead to improved patients outcome.     

Kardiologische Krankheitsbilder

Knowledge of rare but important clinical disease symptoms in cardiology is of vital importance in the daily routine as severe courses of disease as well as death may be prevented by early diagnosis, effective monitoring and timely initiation of an adequate therapy. In this article an important rhythmological disease, arrhythmogenic right ventricular cardiomyopathy, as well as two significant structural diseases, takotsubo (stress-related) cardiomyopathy and aortic aneurysm related to Marfan syndrome, as well as their implications for clinical practice will be presented.     

Current evidence for monitoring platelet reactivity in acute coronary syndrome: A plea for individualized antiplatelet treatment

Although clopidogrel is more effective in preventing thrombotic complications than aspirin alone in a broad spectrum of patients with ischemic heart disease, many of its limitations were recently brought to light including a delayed onset of action and highly unpredictable P2Y₁₂-receptor inhibition. New-generation ADP-receptor antagonists, such as prasugrel and ticagrelor, were designed and developed to overcome these limitations, providing a more rapid, more reliable and more potent P2Y₁₂-receptor inhibition. These pharmacodynamic benefits of new-generation antiplatelet agents were translated into significant clinical advantage among patients with acute coronary syndrome (ACS), especially in preventing stent thrombosis. However, the downsides of the unselected use of novel P2Y₁₂-receptor antagonists include higher risk of bleeding and increased costs. Platelet reactivity testing might become a useful tool to help balance between bleeding and thrombosis with P2Y₁₂-receptor antagonists; however, its role in clinical practice for patients undergoing percutaneous coronary intervention (PCI) remains uncertain. The aim of this viewpoint article is to summarize the currently available evidence supporting a role of platelet function testing in patients with ACS after PCI.