RESUMEN
More than 300 variants in 12 genes have been associated with Brugada syndrome (BrS) which has a prevalence ranging between 1:2000 and 1:100,000. Until recently, there has been little knowledge regarding the distribution of genetic variations in the general population. This problem was partly solved, when exome data from the NHLI GO Exome Sequencing Project (ESP) was published. In this study, we aimed to report the prevalence of previously BrS-associated variants in the ESP population. We performed a search in ESP for variants previously associated with BrS. In addition, four variants in ESP were genotyped in a second Danish control population (n = 536) with available electrocardiograms. In ESP, we identified 38 of 355 (10%) variants, distributed on 272 heterozygote carriers and two homozygote carriers. The genes investigated were on average screened in 6258 individuals. This corresponds to a surprisingly high genotype prevalence of 1:23 (274:6258). Genotyping the four common ESP-derived variants CACNA2D1 S709N, SCN5A F2004L, CACNB2 S143F, and CACNB2 T450I in the Danish controls, we found a genotype prevalence comparable with that found in ESP. We suggest that exome data are used in research, as an additive tool to predict the pathogenicity of variants in patients suspected for BrS.
Asunto(s)
Síndrome de Brugada/genética , Canales de Calcio Tipo L/genética , Canales de Calcio/genética , Exoma , Canal de Sodio Activado por Voltaje NAV1.5/genética , Polimorfismo de Nucleótido Simple , Anciano , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/epidemiología , Dinamarca/epidemiología , Electrocardiografía , Femenino , Pruebas Genéticas , Genotipo , Técnicas de Genotipaje , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Piroxicam solid depositions were prepared by means of the solvent deposition technique using different concentrations of microcrystalline cellulose as carrier material. The solvent deposition system (SDS) with drug to carrier ratio of 1:9 had a rapid dissolution rate in vitro. When this SDS was administered perorally to rats with a previous experimentally induced inflammation in their paws, it exhibited a pronounced anti-inflammatory action. X-ray diffraction and infrared (IR) spectroscopy showed no differences in the crystal state of piroxicam in SDS formulation and physical mixture of piroxicam and carrier. The increase in the dissolution rate and consequent enhancement of anti-inflammatory effect of piroxicam in SDS were attributed to the reduced particle size of drug deposited on the carrier and enhanced wettability of the particles brought about by the carrier.
