Abstract
Cardiovascular diseases are the main causes of death worldwide and the pharmacological treatment implementation has been one of the most responsible for reductions in morbidity and mortality recent decades. Some pharmacogenetic tests are available to healthcare professionals, and increasingly, the regulatory agencies understand the relationship pharmaco-genomics. In this project, beside implementation of pharmacogenetic in a traditional institution, we will investigate the new field of research called pharrmacometabolomics. It can be conceptualized as a set of changes on metabolome resulting from pharmacological treatments and its approach can clarify mechanisms for variations to responses to treatment, or even understand how genetic alterations influence the responses. The main aims are: 1-for pharmacogenetic of warfarin: to compare anticoagulation guided by pharmacogenetic algorithm with traditional anticoagulation and to evaluate the impact of the algorithm on adverse events and cost-effectiveness in patients beginning anticoagulation; 2- for pharmacogenetic of anti-smoking drugs: to assess the effect of polymorphisms with therapeutic efficacy and adverse effects in patients treated with bupropion or varenicline; 3- for polymorphisms involved in nicotine dependence: to associate the effect of these polymorphisms with smoking habit and dependence degree; 4- for pharmacogenetic of antihypertensive drugs: to identify polymorphisms associated with efficacy in the treatment, adverse drug, and treatment resistance; 5- for metabolomic analysis in patients treated with antihypertensives: to identify metabolomic changes induced by the treatment, to associate metabolomic changes with responses to treatment, with adverse effects, with resistant hypertension, or with possible effects of the polymorphisms. Analyses of genotypes will be performed by polymerase chain reaction (PCR) followed by restriction enzyme digestion (RFLP), PCR followed by melting curve analysis (HRM), and by Taqman® OpenArray® technology. Metabolomic analysis will be performed by mass spectrometry. We will include: 200 patients, who initiate anticoagulation with warfarin; 500 smokers treated with bupropion and varenicline; for the analysis of nicotine dependence, 1000 smokers and 1000 control subjects; and 1500 patients with hypertension who were followed for a period of 24 weeks. Our expected results may show: 1- for pharmacogenetic of warfarin: there is not complete knowledge about its viability, thus, our study design may allow effective conclusions about cost-effectiveness. This information may be useful in designing preventive and therapeutic programs of personalized medicine in our public service; 2- for pharmacogenetic of anti-smoking drugs: may show significant associations on better treatment, increasing efficiency and reducing adverse events, an important for dropout and treatment failure; 3- for study of polymorphisms involved in nicotine dependence: may generate useful tools in the prevention, treatment and better understanding of smoking and level of dependency; 4- for pharmacogenetic of antihypertensive drugs: the possibility of personalized treatment and identification of resistant hypertension could result, on clinical and epidemiological scenario, in a reduction of complications due to hypertension and cardiovascular mortality; 5- for metabolomic analysis in patients treated with antihypertensives: may clarify mechanisms for variations to responses to treatment, or even understand how genetic alterations influence the responses. (AU)
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Híbrido de Nanotubos de Carbono e Tetraetilortosilicato de Acesso Restrito a Macromoléculas pela Inserção de Monômeros Hidrofílicos na sua Superficie Externa (Sigilo) BR 10 2020 019364 3 - UNIVERSIDADE FEDERAL DE ALFENAS - UNIFAL-MG ; Universidade Federal de São Paulo (Unifesp) . Henrique Dipe De Faria; Alberto Thalison Silveira; Eduardo Costa De Figueiredo; Isarita Martins Sakakibara; Paulo Caleb Júnior De Lima Santos - January 2020, 01