TY - GEN
T1 - Noninvasive point-of-care measurement of gastrointestinal permeability
AU - Dorshow, Richard B.
AU - Johnson, J. R.
AU - Debreczeny, Martin P.
AU - Riley, I. Rochelle
AU - Shieh, Jeng Jong
AU - Rogers, Thomas E.
AU - Hall-Moore, Carla
AU - Shaikh, Nurmohammad
AU - Tarr, Phillip I.
N1 - Funding Information:
This work was supported by a Phase II Grand Challenges Exploration Grant from the Bill & Melinda Gates Foundation to Washington University in St. Louis School of Medicine, with a sub-contract to MediBeacon Inc. Dr. Tarr is supported by NIH core grant P30DK052574.
Publisher Copyright:
© 2019 SPIE.
PY - 2019
Y1 - 2019
N2 - The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream in a healthy gut. Tight junctions in this barrier are compromised in many intestinal disorders including inflammatory bowel diseases (such as Crohn's and ulcerative colitis), celiac disease, graft vs host disease, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity in humans. The larger molecular weight sugar, lactulose, is minimally absorbed through a healthy gut. The smaller molecular weight sugar, mannitol or rhamnose, in contrast, is readily absorbed through both a healthy and inflamed gut. Thus, a higher ratio of lactulose to mannitol or rhamnose reflects increased intestinal permeability. However, several issues prevent the widespread use of the dual sugar assay including requirements for lengthy urine collection, transport of specimens under conditions free from contamination and bacterial growth, analysis by sophisticated laboratory equipment, and the associated lengthy turnaround time. In a recent publication, the feasibility of employing a dual fluorescent tracer agent assay to mimic the dual sugar absorption test without the need for specimen collection was reported. This dual fluorophore assay for GI permeability was demonstrated in an indomethacin-induced bowel disease model in rats. However, one of the fluorophores was not entirely biocompatible. Herein is reported a dual fluorophore system that is totally biocompatible, with emphasis on the transdermal detection of the fluorophores, thus enabling the use of the technology for noninvasive point-of-care gastrointestinal permeability determination.
AB - The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream in a healthy gut. Tight junctions in this barrier are compromised in many intestinal disorders including inflammatory bowel diseases (such as Crohn's and ulcerative colitis), celiac disease, graft vs host disease, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity in humans. The larger molecular weight sugar, lactulose, is minimally absorbed through a healthy gut. The smaller molecular weight sugar, mannitol or rhamnose, in contrast, is readily absorbed through both a healthy and inflamed gut. Thus, a higher ratio of lactulose to mannitol or rhamnose reflects increased intestinal permeability. However, several issues prevent the widespread use of the dual sugar assay including requirements for lengthy urine collection, transport of specimens under conditions free from contamination and bacterial growth, analysis by sophisticated laboratory equipment, and the associated lengthy turnaround time. In a recent publication, the feasibility of employing a dual fluorescent tracer agent assay to mimic the dual sugar absorption test without the need for specimen collection was reported. This dual fluorophore assay for GI permeability was demonstrated in an indomethacin-induced bowel disease model in rats. However, one of the fluorophores was not entirely biocompatible. Herein is reported a dual fluorophore system that is totally biocompatible, with emphasis on the transdermal detection of the fluorophores, thus enabling the use of the technology for noninvasive point-of-care gastrointestinal permeability determination.
KW - Dual sugar absorption test
KW - Enteropathy
KW - Fluorescence tracer agent
KW - Gastrointestinal permeability
KW - Point-of-care measurement
UR - http://www.scopus.com/inward/record.url?scp=85073775880&partnerID=8YFLogxK
U2 - 10.1117/12.2507965
DO - 10.1117/12.2507965
M3 - Conference contribution
AN - SCOPUS:85073775880
T3 - Progress in Biomedical Optics and Imaging - Proceedings of SPIE
BT - Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications XI
A2 - Achilefu, Samuel
A2 - Raghavachari, Ramesh
PB - SPIE
T2 - Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications XI 2019
Y2 - 4 February 2019 through 5 February 2019
ER -