Transepithelial leak in Barrett's esophagus.
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.
Mullin
J M
JM
Lankenau Institute for Medical Research, Director of Research, Division of Gastroenterology, Lankenau Hospital, 100 Lancaster Avenue, Wynnewood, Pennsylvania, USA. mullinj@mlhs.org
Valenzano
M C
MC
Trembeth
S
S
Allegretti
P D
PD
Verrecchio
J J
JJ
Schmidt
J D
JD
Jain
V
V
Meddings
J B
JB
Mercogliano
G
G
Thornton
J J
JJ
D000681:Amylases / Q000097:blood; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D016022:Case-Control Studies; D002463:Cell Membrane Permeability / Q000502:physiology*; D062445:Claudin-1; D062465:Claudin-3; D062507:Claudin-5; D057167:Claudins; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013395:Sucrose / Q000493:pharmacokinetics* / Q000652:urine; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology
C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C107466:CLDN5 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062507:Claudin-5; D057167:Claudins; D008565:Membrane Proteins; D013395:Sucrose; D000681:Amylases