Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress.
View Article and Find Full Text PDFThe severity of side effects that may occur with vitamin K antagonists due to their narrow therapeutic window requires great attention in finding out the most appropriate dose for these drugs. Pharmacogenetic research has now considerably helped clarifying the relationships between genetic variants and sensitivity to such therapy, paving the ground to predictive algorithms that include clinical and genetic variables to establish the best doses to start and maintain an adequate anticoagulation. Pharmacogenetic algorithms indeed aim at identifying tailored regimens, reducing adverse drug reactions and subsequent hospitalizations, optimizing therapeutic efficacy and containing costs.
View Article and Find Full Text PDFThe narrow therapeutic index, the large interindividual variability, and the severity of adverse drug reactions connected with vitamin K antagonists, together with their ample use in medical therapy, have prompted the search for strategies to better assist doctors in the choice of the safest and most effective dose of these drugs. The molecular mechanism by which oral anticoagulants exert their effect is an interference with the bioactivation of vitamin K. This mechanism is therefore the subject of numerous pharmacogenetic studies, aimed at finding the relationship between genetic variants influencing the metabolism or action of the drug and therapeutic outcomes.
View Article and Find Full Text PDFObjectives: As osteoporotic fractures are becoming a major health care problem in countries characterized by an increasing number of older adults, in this study we aimed to compare the incidence and costs of hip fragility fractures in Italian elderly people versus those of major cardiovascular diseases (strokes and acute myocardial infarctions [AMI]) occurring in the whole adult population.
Methods: We analyzed hospitalization records maintained at the national level by the Italian Ministry of Health for the diagnosis of hip fractures (ICD-9-CM codes 820-821), AMI (code 410), hemorrhagic (codes 430, 431, 432) and ischemic strokes (codes 433-434), and TIA (code 435) between 2001-2005. Cost analyses were based on diagnosis-related groups.