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

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%,

Ocorrência de baixos níveis de gamaglobulina sérica em bezerros que receberam colostro no balde ou nas mães

Transfer of passive immunity in 24 calves fed with colostrum, was studied at the end of the first day of life. Results show that gammaglobulin concentrations in calver were: 2,90 ± 0,32 and 2,12 ± 0,91 for animals fed from mothers or nipple pail, respectively. Among the 24 calves, five presented problems in immunoglobulin absortion.  A transferência de imunidade passada a bezerros foi estudada através da determinação do nível sérico de gamaglobulina, em 20 bezerros do tipo "Mantiqueira" e 4 da raça "Holandesa", variedade malhada de preto. Após os exames laboratoriais do soro sanguíneo coletado às 24 horas de vida, encontrou-se concentração média de gamaglobulina de 2,90 ± 0,32 de soro para os animais que ficaram com as mães e 2,12 ± 0,91 para os alimentados no balde. Dentre os 24 bezerros, cinco apresentaram problemas de absorção de imunoglobulinas

PCR in the diagnosis of cutaneous tuberculosis

Seeking to improve the laboratory diagnosis of Cutaneous Tuberculosis, a study was carried out on the application of PCR technique in macerated, decontaminated (with 4% H2SO4 for elimination of normal microbiot), neutralized (with 4% NaOH) biopsies tissues samples stored at -20°C. Of the 37 samples submitted for study, 16.22% were positive by microscopy for acid-fast bacilli (concentrated method) and in 43.24% the Mycobacterium tuberculosis was isolated in Löwenstein-Jensen medium. Using a M. tuberculosis complex specific primer set (gene sequence for 16S rDNA), the mycobacterial DNA was detected in 24.32% of the biopsies. The sensitivity and specificity of PCR were 43.7% and 90.4%, respectively. Due to low sensitivity and discrepant results between bacteriological techniques and PCR methodology, the samples were repeated in a new PCR with primers for the IS6110 target. The sensitivity and specificity of PCR for the IS6110 target obtained 100% in comparison with the culture method. The results confirm the effectiveness of PCR methodology using primers for the IS6110 gene sequence and permit the PCR method to be applied to frozen cutaneous biopsies sent by services that do not identify the M. tuberculosis by the biology molecular method

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

Molecular identification of Candida dubliniensis isolated from oral lesions of HIV-positive and HIV-negative patients in São Paulo, Brazil

Candida dubliniensis é uma nova espécie recentemente descrita. Este patógeno oral emergente compartilha muitas características fenotípicas e bioquímicas com C. albicans dificultando assim a diferenciação entre elas. As mesmas, porém, mostram-se genotipicamente distintas. Este trabalho tem como objetivo identificar, pela técnica de PCR (Polymerase Chain Reaction), a possível presença de C. dubliniensis dentre amostras isoladas de candidose oral eritematosa, provenientes de pacientes HIV positivos e HIV negativos. Em um total de 37 amostras identificadas anteriormente, por método clássico, como C. albicans encontramos duas amostras de C. dubliniensis (5,4%) utilizando a técnica do PCR. Esta técnica mostrou-se útil, prática e com identificação taxonômica mais acurada.Candida dubliniensis is a new, recently described species of yeast. This emerging oral pathogen shares many phenotypic and biochemical characteristics with C. albicans, making it hard to differentiate between them, although they are genotypically distinct. In this study, PCR (Polymerase Chain Reaction) was used to investigate the presence of C. dubliniensis in samples in a culture collection, which had been isolated from HIV-positive and HIV-negative patients with oral erythematous candidiasis. From a total of 37 samples previously identified as C. albicans by the classical method, two samples of C. dubliniensis (5.4%) were found through the use of PCR. This study underscores the presence of C. dubliniensis, whose geographical and epidemiological distribution should be more fully investigated

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