FARMACOGENÉTICA DO TRATAMENTO DE DIABETE MELITO

Diabetes mellitus is a metabolic disease involving the deficiency or resistance to insulin that triggers to severe micro and macrovascular complications. Both genetic and environmental factors contribute to the complex etiology of main forms of diabetes. The recent advances in molecular genetics contributed to the identification of several loci and candidate genes that are related to the clinically recognized diabetes subtypes. This knowledge has become more important for recognition of diabetic patients with differential response to specific hypoglycemic drugs. In this study, the molecular aspects of the monogenic and polygenic forms of diabetes as well as the pharmacogenetics approach of the drugs commonly used in treatment are reviewed.Diabete melito é uma doença metabólica caracterizada pela deficiência ou resistência de insulina que leva a complicações micro e macrovasculares graves. Fatores genéticos e ambientais contribuem para a etiologia complexa das principais formas de diabete. Os avanços recentes na genética molecular contribuíram para a identificação de vários locos e genes que são relacionados aos subtipos de diabete clinicamente reconhecidos. Este conhecimento tornou-se muito importante para o reconhecimento de pacientes diabéticos com resposta diferencial a fármacos hipoglicemiantes específicos. Neste estudo serão revisados os aspectos moleculares das formas monogênicas e poligênicas da diabete assim como a abordagem farmacogenética dos agentes terapêuticos mais comuns

Circulating cell-free DNA as a biomarker in the diagnosis and prognosis of colorectal cancer

Colorectal cancer (CRC) is a disease without evident clinical symptoms in early stages, leading to late diagnosis and disease management. Current diagnostic and prognostic tools require invasive procedures and circulating molecular biomarkers fail to have optimal sensitivity and specificity. Circulating biomarkers with high clinical performance may be valuable for early diagnosis and prognosis of CRC. The purpose of this review was to investigate the application of circulating cell-free DNA (ccfDNA) in CRC diagnosis and prognosis and the analytical methods used in blood samples in articles published between 2005 and 2016. Based on specific inclusion and exclusion criteria, 26 articles were selected. Most studies used ccfDNA quantification as the molecular biomarker. The analytical method was mainly based on the quantitative polymerase chain reaction (qPCR). Biomarkers based on aberrantly methylated genes (n=6) and ccfDNA integrity/fragmentation (n=2) were also used for the CRC diagnosis. The CRC prognosis used the detection of oncogene mutations, such as KRAS and BRAF, in ccfDNA. Significant differences were found in variables among the studies revealing potential bias. ccfDNA quantification as a diagnostic biomarker for CRC has promising results but it lacks clinical specificity since other diseases present a similar increase in ccfDNA content. However, increasing research in the epigenomic field can lead the way to a clinically specific biomarker for the CRC early diagnosis. As for the analytical method, qPCR and derivatives seem to be a perfectly valid technique. The use of ccfDNA quantification in CRC prognosis seems promising. The attempt to use the ccfDNA quantification in clinical practice may reside in the prognosis using a qPCR technique

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population

Exposure to potentially inappropriate medications in Brazilian elderly outpatients with metabolic diseases

Management of pharmacotherapy in elderly with metabolic diseases is challenging and potentially inappropriate medications (PIMs) are risk factors for drug interactions and adverse events. The exposure to PIMs in elderly outpatients with metabolic diseases and its relationship with polypharmacy and other variables was investigated. PIMs prescribed to 207 elderly patients (aged 60 to 96 years) with metabolic diseases who attended a University Hospital of Sao Paulo city, Brazil, from April/2010 to January/2011, were evaluated. PIMs were detected using both 2003 Beers and 2008 STOPP criteria. The association between PIMs and age, gender and polypharmacy was also examined. 2008 STOPP criteria detected more PIMs (44.4 %) than 2003 Beers criteria (16.0%,

Commencement Program, December (2016)

https://red.mnstate.edu/commencement/1194/thumbnail.jp

Analysis of the mRNA expression of the S100β protein in adipocytes of patients with diabetes mellitus, type 2

OBJETIVO: O presente trabalho objetiva compreender a possível relação do nível de expressão gênica do mRNA da proteína S100β em adipócitos com o diabetes melito do tipo 2, pela comparação de dados de portadores dessa doença com os de indivíduos normoglicêmicos. MATERIAIS E MÉTODOS: Foram selecionadas amostras de tecido adiposo de oito pacientes da Seção de Coronárias do Instituto Dante Pazzanese de Cardiologia (IDPC), sendo quatro do grupo diabetes e quatro do grupo de normoglicêmicos. Essas amostras foram submetidas à técnica de RT-PCR em tempo real. RESULTADOS: Por meio do Test-t de Student para os valores de diferença entre os ciclos threshold (ΔCt), observou-se que houve aumento de aproximadamente 15 vezes (p = 0,015) da expressão do mRNA da proteína S100β nos adipócitos dos indivíduos do grupo diabetes quando comparado aos do grupo controle. CONCLUSÃO: Nossos resultados evidenciam, de forma inédita, coexistência entre o aumento da expressão do gene S100β e a patologia do diabetes melito do tipo 2

Use of the polymerase chain reaction to detect Mycobacterium leprae in urine

Leprosy is an infectious disease caused by Mycobacterium leprae. The polymerase chain reaction (PCR) has been applied to detect M. leprae in different clinical samples and urine seems to be attractive for this purpose. PCR was used to improve the sensitivity for diagnosing leprosy by amplifying a 151-bp PCR fragment of the M. leprae pra gene (PCR-Pra) in urine samples. Seventy-three leprosy patients (39 males and 34 females, 14 to 78 years old) were selected for leprosy diagnosis at a reference laboratory in Maringa, PR, Brazil. Of these, 36 were under anti-leprosy multidrug therapy with dapsone and rifampicin for tuberculoid (TT) and dapsone, rifampicin and clofazimine for borderline (BB) and lepromatous (LL) forms. The control group contained 50 healthy individuals without any clinical history of leprosy. DNA isolated from leprosy patients' urine samples was successfully amplified by PCR-Pra in 46.6% (34/73) of the cases. The positivity of PCR-Pra for patients with the TT form was 75% for both patients under treatment and non-treated patients (P = 0.1306). In patients with the LL form, PCR-Pra positivity was 52 and 30% for patients under treatment and non-treated patients, respectively (P = 0.2386). PCR-Pra showed a statistically significant difference in detecting M. leprae between the TT and LL forms of leprosy in patients under treatment (P = 0.0033). Although the current study showed that the proposed PCR-Pra has some limitations in the detection of M. leprae, this method has the potential to be a useful tool for leprosy diagnosis mainly in TT leprosy where the AFB slit-skin smear is always negative.CAPESCAPE

Relationship of short tandem repeats flanking leptin-melanocortin pathway genes with anthropometric profile and leptinemia in Brazilian individuals

Objective: To investigate the relationship of short tandem repeats (STR) near genes involved in the leptin-melanocortin pathway with body mass index (BMI) and leptinemia. Subjects and methods: Anthropometric variables and leptinemia were measured in 100 obese and 110 non-obese individuals. D1S200, D2S1788, DS11912, and D18S858 loci were analyzed by PCR and high-resolution electrophoresis. Results: Overall STR allele frequencies were similar between the obese and non-obese group (p > 0.05). Individual alleles D1S200 (17), D11S912 (43), D18S858 (11/12) were associated with obesity (p < 0.05). Individuals carrying these alleles showed higher BMI than non-carriers (p < 0.05). Moreover, a relationship between D18S858 11/12 alleles and increased waist circumference was found (p = 0.040). On the other hand, leptinemia was not influenced by the studied STRs (p > 0.05). Conclusions: D1S200, D11S912, and D18S858 loci are associated with increased BMI and risk for obesity in this sample. Arq Bras Endocrinol Metab. 2012;56(1):47-53Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, SP, BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (Fapesp), Sao Paulo, SP, Brazil [01/10708-3]FapespFAPESPCNPq, BrazilCNPq (Brazil