ABSTRACT
Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3′, 5′-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.
Subject(s)
Humans , Male , Adenosine , Diabetes Mellitus, Type 2 , Histidine , Insulin , Least-Squares Analysis , Mass Spectrometry , Metabolism , Metabolomics , Principal Component Analysis , Quercetin , Statistics as Topic , Tyramine , Tyrosine , Urocanic Acid , VolunteersABSTRACT
A new nonviral gene vector--urocanic acid-coupled chitosan (UAC) was prepared by the reaction of the activated urocanic acid (UA) with the amine group on the chitosan (CTS). The structure of UAC was confirmed with FT-IR, 1H NMR and element analysis. The influencing factors of substitution values were studied by orthogonal test, and the substitution values of UAC increased with the prolongation of activating time of UA and the increasing ratio of UA to CTS. The condensation ability and the resistance to DNase I of UAC/pDNA were evaluated by agarose gel electrophoresis, and UAC showed good condensation ability with pDNA, well protecting pDNA from the degradation by DNase I. The particle size and zeta potential were evaluated by zetasizer, and the results showed that the UAC/pDNA complex was well stable and could easily enter into cells. The transfection studies were performed with HepG2 cells in vitro. It showed that the in vitro transfection of UAC/pDNA was efficient in HepG2 cells and could express more green fluorescent proteins than that of CTS. So the UAC is easy to prepare and a promising non-viral gene vector.
Subject(s)
Humans , Chitosan , Metabolism , DNA , Genetics , Metabolism , Deoxyribonuclease I , Metabolism , Drug Delivery Systems , Genetic Therapy , Methods , Genetic Vectors , Hep G2 Cells , Particle Size , Plasmids , Transfection , Urocanic Acid , MetabolismABSTRACT
Se presenta el caso de un paciente portador de Hydroa Vacciniforme con una larga historia evolutiva en el que la enfermedad adopta una inusual agresividad, con importantes lesiones cicatrizales en áreas expuestas, secuelas oculares y un excepcional compromiso de áreas cubiertas con lesiones cicatrizales en zona genitoperineal. Se asocia como complicación un linfedema crónico de pene.