ABSTRACT
Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.
ABSTRACT
O uso popular, e mesmo o tradicional, não são suficientes para validar as plantas medicinais como medicamentos eficazes e seguros. Para melhor entendimento, é necessário avaliar a relação risco/benefício de seu uso, por meio de estudos toxicológicos. O objetivo desta pesquisa foi estimar a toxicidade aguda do extrato etanólico das cascas secas de Pithecellobium cochliocarpum (Gomez) Macbr através da obtenção da dose letal (DL50) em roedores, e da Concentração letal (CL50) frente à Artemia salina Leach. Foram realizados experimentos por via oral e intraperitoneal utilizando camundongos fêmeas albinos Swiss (Mus musculus) (n=6). Por via oral foram administradas 3 doses (1.000, 3.000 e 5.000 mg Kg-1) e por via entraperitoneal, 5 doses (155, 160, 176, 345,6 e 414,72 Kg-1). Os sinais comportamentais foram avaliados durante uma hora após a administração do extrato, ficando em observação até 48 horas. O número de óbitos foi quantificado para posterior cálculo da DL50. A administração por via intraperitoneal foi realizada em intervalo de 5 minutos para cada animal. Nos ensaios de toxicidade por via oral a solução foi introduzida por via intragástrica através de cânula metálica acoplada a seringa (gavagem) no mesmo intervalo de tempo utilizado pela via intraperitoneal. Os animais do grupo de administração oral apresentaram algumas reações, porém não letais até a dose de 5.000 mg Kg-1. A DL50 para a via intraperitoneal foi 257, 49 mg Kg-1 (muito tóxico, grau 4) (Schuartsman, 1980). A CL50 (543,5 µg Kg-1) demonstrou ser tóxica frente à A. salina. Conclui-se que sob condições agudas de exposição, o extrato do Pithecellobium cochliocarpum é um agente tóxico, devendo ser considerado como tal, dependendo da dose administrada ou absorvida, do etempo e frequência de exposição e das vias de administração.
The popular use, and even the traditional one, is not enough to validate medicinal plants as effective and safe medicines. For a better understanding, it is necessary to assess the risk / benefit ratio of their use through toxicological studies. The aim of this work was to evaluate the acute toxicity of Pithecellobium cochliocarpum (Gomez) Macbr dried bark ethanolic extract through its lethal dose (LD50), in mice, and lethal concentration (LC50) in relation to Artemia salina Leach. Experiments were performed by oral and intraperitoneal route using female Swiss albino mice (Mus musculus) (n = 6). The first three doses were given orally (1,000, 3,000 and 5,000 mg kg-1) and the last five doses were given intraperitoneally (155, 160, 176, 345.6 and 414.72 Kg-1). The behavioral signs were evaluated one hour after administration of the extract, being observed up to 48 hours. The number of deaths was quantified for subsequent calculation of LD50. The intraperitoneal administration was carried out at an interval of 5 minutes for each animal. For the oral toxicity test, the solution was introduced in the digestive system of the animals through a metal cannula coupled to a syringe (gavage) at the same time interval used for the intraperitoneal route. The animals from the oral group presented some reactions, but they were not lethal up to the dose of 5.000 mg kg-1. The LD50 for the intraperitoneal group was 257.49 mg kg-1 (very toxic, grade 4) (Schuartsman, 1980). The LC50 (543.5 mg kg-1) was toxic to A. salina. We can conclude that, under acute conditions of exposure, the Pithecellobium cochliocarpum extract is a poisonous agent and should be considered as such depending on the administered or absorbed dose, the time and frequency of exposure, and the administration routes.
Subject(s)
Animals , Female , Mice , Toxicity , Plant Extracts/analysis , Fabaceae/classification , Plants, Medicinal/classification , Phytotherapy/instrumentationABSTRACT
Sao estudados dois casos de polineuropatia amiloidotica familiar confirmados por biopsia, e apesar de nao haver duvidas quanto ao diagnostico, foi ressaltado o comportamento diferente de uma mesma doencao. Destacam-se as investigacoes realizadas por Corino Andrade, que relatou o primeiro caso portugues da doenca, chamando atencao para a incidencia familiar. Procurou-se, tambem, definir polineuropatia amiloidotica familiar, baseando-se em relatos publicados por varios autores
Subject(s)
Adult , Humans , Male , Amyloidosis , Peripheral Nervous System DiseasesABSTRACT
Os autores chamam atencao para o problema do comprometimento neurologico da esquistossomose mansonica em nosso meio, com areas endemicas, onde milhoes de individuos sao acometidos por esta parasitose. Assinalam a subestimacao destas complicacoes que sao pouco diagnosticadas, apesar das multiplas manifestacoes medulares e encefalicas que surgem nestes casos, embora as lesoes medulares sejam bem mais frequentes e mais sugestivas. Ressaltam a importancia do diagnostico etiologico diante da existencia de possibilidades terapeuticas satisfatorias