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  • Differential trafficking of saccharidic probes following aspirin in clinical tests of intestinal permeability in young healthy women.

Differential trafficking of saccharidic probes following aspirin in clinical tests of intestinal permeability in young healthy women.

Clinical and experimental pharmacology & physiology (2013-09-17)
Ivana R Sequeira, Roger G Lentle, Marlena C Kruger, Roger D Hurst
ABSTRACT

The effects of inflammatory changes on the absorption of different-sized probes and their permeability ratios are poorly understood. The aim of the present study was to determine the effects of a pharmacological agent on the permeability of the gut mucosa to saccharidic probes of larger and smaller molecular weight. Permeability was assessed by half-hourly urinary excretion of a combined dose of d-mannitol, l-rhamnose and lactulose following consumption of a single 600 mg dose of aspirin and compared with a placebo in a cross-over study in 20 healthy female volunteers. The temporal patterns of excretion of all probes were bimodal, being best fitted by polynomial functions. The relatively small early peak was evident for at least 4 h for smaller sugars, but was less evident with lactulose, being overshadowed by a larger second peak. These conclusions were further supported by separate analyses of the segments of the temporal plots between 2.5 and 4 h and between 4.5 and 6 h. The forms of these curves did not change significantly following dosing with aspirin. A greater proportion of the total dose of mannitol than rhamnose was excreted over the collection period. Following the consumption of aspirin, the cumulative rate of excretion of the smaller sugars (i.e. mannitol and rhamnose) was significantly reduced whereas that of lactulose was increased over the 6 h collection period. Aspirin has opposite effects on the absorption of larger and smaller probes, influencing the outcome of the test. These results have important consequences for the design and comparison of clinical tests of permeability.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Rhamnose monohydrate, ≥99%
Sigma-Aldrich
Lactulose, ≥95%
Millipore
L-Rhamnose monohydrate, suitable for microbiology, ≥99.0%,

Naturally occurring deoxy sugar that is found primarily in plants and some bacteria

Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Sigma-Aldrich
Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
Sigma-Aldrich
D-Mannitol, tested according to Ph. Eur.
Millipore
Sucrose, ACS reagent, suitable for microbiology, ≥99.0%
Sigma-Aldrich
Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
Millipore
D-Mannitol, ACS reagent, suitable for microbiology, ≥99.0%
Sigma-Aldrich
Lactulose, ≥98.0% (HPLC)
Supelco
Sucrose, analytical standard
Supelco
D-Mannitol, ≥99.9999% (metals basis), for boron determination
Supelco
Mannitol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Rhamnose, natural sourced, 99%, FG
Supelco
Sucrose, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Sucrose, United States Pharmacopeia (USP) Reference Standard
Sucrose, European Pharmacopoeia (EP) Reference Standard
Mannitol, European Pharmacopoeia (EP) Reference Standard
Lactulose, European Pharmacopoeia (EP) Reference Standard
USP
Mannitol, United States Pharmacopeia (USP) Reference Standard
USP
Lactulose, United States Pharmacopeia (USP) Reference Standard
Supelco
Lactulose, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-Mannitol, ACS reagent
Sigma-Aldrich
D-Mannitol, suitable for plant cell culture
Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
D-Mannitol, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
D-Mannitol, meets EP, FCC, USP testing specifications
Sigma-Aldrich
Sucrose, ≥99.5%
Sigma-Aldrich
Sucrose, BioXtra, ≥99.5% (GC)
Supelco
Sucrose, analytical standard, for enzymatic assay kit SCA20