TY - GEN
T1 - Application of fluorescent tracer agent technology to point-of-care gastrointestinal permeability measurement
AU - Dorshow, Richard B.
AU - Shieh, Jeng Jong
AU - Rogers, Thomas E.
AU - Hall-Moore, Carla
AU - Shaikh, Nurmohammad
AU - Talcott, Michael
AU - Tarr, Phillip I.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Gut dysfunction, often accompanied by increased mucosal permeability to gut contents, frequently accompanies a variety of human intestinal inflammatory conditions. These disorders include inflammatory bowel diseases (e.g., Crohn's Disease) and environmental enteropathy and enteric dysfunction, a condition strongly associated with childhood malnutrition and stunting in resource poor areas of the world. The most widely used diagnostic assay for gastrointestinal permeability is the lactulose to mannitol ratio (L:M) measurement. These sugars are administered orally, differentially absorbed by the gut, and then cleared from the body by glomerular filtration in the kidney. The amount of each sugar excreted in the urine is measured. The larger sugar, lactulose, is minimally absorbed through a healthy gut. The smaller sugar, mannitol, in contrast, is readily absorbed through both a healthy and injured gut. Thus a higher ratio of lactulose to mannitol reflects increased intestinal permeability. However, several issues prevent widespread use of the L:M ratio in clinical practice. Urine needs to be collected over time intervals of several hours, the specimen then needs to be transported to an analytical laboratory, and sophisticated equipment is required to measure the concentration of each sugar in the urine. In this presentation we show that fluorescent tracer agents with molecular weights similar to those of the sugars, selected from our portfolio of biocompatible renally cleared fluorophores, mimic the L:M ratio test for gut permeability. This fluorescent tracer agent detection technology can be used to overcome the limitations of the L:M assay, and is amenable to point-of-care clinical use.
AB - Gut dysfunction, often accompanied by increased mucosal permeability to gut contents, frequently accompanies a variety of human intestinal inflammatory conditions. These disorders include inflammatory bowel diseases (e.g., Crohn's Disease) and environmental enteropathy and enteric dysfunction, a condition strongly associated with childhood malnutrition and stunting in resource poor areas of the world. The most widely used diagnostic assay for gastrointestinal permeability is the lactulose to mannitol ratio (L:M) measurement. These sugars are administered orally, differentially absorbed by the gut, and then cleared from the body by glomerular filtration in the kidney. The amount of each sugar excreted in the urine is measured. The larger sugar, lactulose, is minimally absorbed through a healthy gut. The smaller sugar, mannitol, in contrast, is readily absorbed through both a healthy and injured gut. Thus a higher ratio of lactulose to mannitol reflects increased intestinal permeability. However, several issues prevent widespread use of the L:M ratio in clinical practice. Urine needs to be collected over time intervals of several hours, the specimen then needs to be transported to an analytical laboratory, and sophisticated equipment is required to measure the concentration of each sugar in the urine. In this presentation we show that fluorescent tracer agents with molecular weights similar to those of the sugars, selected from our portfolio of biocompatible renally cleared fluorophores, mimic the L:M ratio test for gut permeability. This fluorescent tracer agent detection technology can be used to overcome the limitations of the L:M assay, and is amenable to point-of-care clinical use.
KW - Fluorescent tracer agent
KW - enteropathy
KW - fluorescence
KW - gastrointestinal permeability
KW - lactulose to mannitol ratio measurement
KW - optical monitoring
KW - pyrazine
UR - http://www.scopus.com/inward/record.url?scp=84982994749&partnerID=8YFLogxK
U2 - 10.1117/12.2211790
DO - 10.1117/12.2211790
M3 - Conference contribution
AN - SCOPUS:84982994749
T3 - Progress in Biomedical Optics and Imaging - Proceedings of SPIE
BT - Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII
A2 - Raghavachari, Ramesh
A2 - Achilefu, Samuel
PB - SPIE
T2 - Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VIII
Y2 - 15 February 2016 through 16 February 2016
ER -