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

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

Climatology of Precipitation during the Passage of the Double Cyclone

The double-cyclone type is considered to be one of the most important pressure patterns around Japan as it is known to cause severe weather such as heavy rain and strong winds in various parts of the country. In this study, double cyclones are classified into the following three types\u27 Heishin type; Nihonkai-L main type! and Nangan-L main type. They are examined in a climatologic context to assess the regional charac teristics of precipitation amount and intensity, and snowfall after the passage of double cyclone. Furthermore, precipitation characteristics of each type of double cyclone, the Nihonkai and Nangan lows are examined. Precipitation from the NihonkaHow main type tends to be weak, although the precipitation caused by the double cyclone is strong along the southern coast and the Hokuriku region of Japan. For the Heishin type, precipitation is observed at nearly 90% of observation points in the whole country. The ratio of observation points with precipitation is greater in eastern Japan for the NihonkaHow main type. Compared to the Nihonkai low and the Nangan low, the double cyclone tends to cause snowfall more frequently in the whole country. The mean total snowfall amount is the greatest for the Nihonkai-low main type among the threetypes of double cyclone. The Heishin type and the Nihonkai-low main type have a tendency to cause snow storms in the Tohoku region and in Hokkaido. The Nangan-low main type may cause relatively calm snowfall nationwide and even bring snowfall to the southern part of Kanto. Heavy precipitation events tend to occur when the southern low moves nearer to the Japanese islands for all of the three types of double cyclone. Moreover, the southern cyclone tends to be stronger than the northern cyclone

SHEAR ZONE DEVELOPMENT AND FRICTIONAL INSTABILITY OF FAULT GOUGE

ABSTRACT: Earthquakes are typical phenomena of frictional slip of geomaterials in nature. To evaluate slip instability, shear development in a gouge layer or fault material has been investigated. However, the quantitative relationship between slip instability and shear development has not been revealed because of difficulty in quantitative observation of microstructures under high pressure. Hence, we aim to describe shear development in a gouge layer energetically, and discuss the relation between shear development and slip instability. To this end, we calculated shear angles by utilizing experimental data of gouge. As a result, this study reveals that shear bands in a gouge layer develop at lower angles or almost parallel to rock-gouge boundaries toward the occurrence of unstable slip, particularly under low confining pressure. Additionally, variation in Riedel shear angles throughout gouge layers depends on confining pressures: Under low confining pressures, heterogeneous localized shears trigger voluntary increase in strain. On the other hand, under a high confining pressure, gouge layers deform homogeneously, and the whole of samples slips dynamically. Clarification of shear development of geomaterials is useful for evaluating the occurrence of frictional slip such as earthquakes and slope failures

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%,