RESUMO
Using orally administered sucrose as a probe of gastrointestinal permeability, this study focused on determining whether Barrett's metaplasia exhibits a paracellular transepithelial leak to small nonelectrolytes. Subjects in five separate classes (nonendoscoped, asymptomatic controls; endoscoped, asymptomatic controls; gastroesophageal reflux disease without mucosal complications; grossly visible esophagitis; and Barrett's esophagus) consumed a sucrose solution at bedtime and collected all overnight urine. Urine volume was measured and sucrose concentration was determined by high-performance liquid chromatography. Patients with Barrett's were observed to exhibit a transepithelial leak to sucrose whose mean value was threefold greater than that seen in healthy control subjects or patients with reflux but without any mucosal defect. A parallel study of claudin tight junction proteins in endoscopy biopsy samples showed that whereas Barrett's metaplasia contains dramatically more claudin-2 and claudin-3 than is found in normal esophageal mucosa, it is markedly lower in claudins 1 and 5, indicating very different tight junction barriers.
Assuntos
Esôfago de Barrett/fisiopatologia , Permeabilidade da Membrana Celular/fisiologia , Células Epiteliais/metabolismo , Sacarose/farmacocinética , Amilases/sangue , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biópsia , Estudos de Casos e Controles , Claudina-1 , Claudina-3 , Claudina-5 , Claudinas , Células Epiteliais/patologia , Esôfago/citologia , Esôfago/metabolismo , Esôfago/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Metaplasia/metabolismo , Metaplasia/patologia , Metaplasia/fisiopatologia , Sacarose/urina , Junções Íntimas/metabolismo , Junções Íntimas/patologiaRESUMO
When transepithelial permeability of rat distal colon is evaluated on the basis of transepithelial electrical resistance, age does not have an effect. Age likewise did not affect the decrease in resistance brought about by phorbol ester exposure. However, age was shown to correlate with increased transepithelial permeability when diffusion of the nonelectrolyte, D-mannitol, was used as an indicator. A phorbol ester-induced increase in transepithelial permeability to D-mannitol was observed to increase with age. Basal permeability to D-mannitol was significantly higher in older rats when the animals were allowed to age on a high-fat diet. Distance from the rectum was shown to be a potential complicating factor in these studies, since distal colon closer to the rectum was observed to have lower transepithelial permeability. The potential effect of such increased leakiness on the increased frequency of colon cancer in older individuals is discussed.
