High-Throughput Metabolomics for Discovering Potential Metabolite Biomarkers and Metabolic Mechanism from the APPswe/PS1dE9 Transgenic Model of Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disorder, is the major form of dementia. As AD is an irreversible disease, it is necessary to focus on earlier intervention. However, the potential biomarkers of preclinical AD are still not clear. In this study, urinary metabolomics based on ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was performed for delineating the metabolic changes and potential early biomarkers in APPswe/PS1dE9 (APP/PS1) transgenic mice. A total of 24 differentially regulated metabolites were identified when comparing transgenic mice to wild-type mice using multivariate statistical analysis. Among them, 10 metabolites were significantly upregulated and 14 metabolites were downregulated. On the basis of these potential biomarkers, metabolic pathway analysis found that pentose and glucuronate interconversions, glyoxylate and dicarboxylate metabolism, starch and sucrose metabolism, the citrate cycle, tryptophan metabolism, and arginine and proline metabolism were disturbed in APP/PS1 mice. Our study revealed that levels of endogenous metabolites in the urine of APP/PS1 mice changed prior to the emergence of learning and cognitive impairment, which may be associated with abnormal nitric oxide production pathways and metabolic disorders of monoaminergic neurotransmitters. In conclusion, this study showed that metabolomics provides an early indicator of disease occurrence for AD.

Starch and dietary fiber components are excreted and degraded to variable extents in ileostomy subjects consuming mixed diets with wheat- or oat-bran bread.

The study was conducted to determine if the excretion of starch and dietary fiber components varies in ileostomy subjects consuming diets high or low in dietary fiber. Excretion of starch, enzyme-resistant starch and dietary fiber components was studied in nine human subjects with ileostomies, who consumed (in a crossover design) a wheat bread-based diet (daily intake 274 g starch, 2.4 g enzyme-resistant starch and 14.4 g total dietary fiber) and a high fiber diet based on oat-bran bread (daily intake 243 g starch, 2.7 g enzyme-resistant starch and 40.2 g total dietary fiber). Food and excreta were collected on d 3 and 17. No significant differences in excretion of starch, enzyme-resistant starch or dietary fiber components were found on these 2 d in each dietary period. When subjects consumed the wheat bread-based diet they excreted (mean +/- SD) 3.3 +/- 1.7 g starch and 2.4 +/- 0.4 g enzyme-resistant starch daily, whereas when consuming the oat bran-based diet they excreted 4.5 +/- 3.1 g starch and 2.5 +/- 0.4 g enzyme-resistant starch. During both dietary periods subjects excreted significantly greater amounts of certain dietary fiber polysaccharide residues (fucose, galactose and uronic acid) than they ingested. This indicates a contribution of endogenous and/or microbial material to the dietary fiber value in ileostomy effluents. However, significantly less excretion of some dietary fiber polysaccharide residues, especially glucose residues, during the oat-bran bread-based dietary period was also noted. This was presumably caused by a degradation of mixed-linked (1,3),(1,4)-beta-D-glucans.

Oral cornstarch therapy: is persorption harmless?

Sediments prepared from freshly voided urine of four patients with glycogenosis Ia, or leucine-sensitive hypoglycaemia, on oral cornstarch therapy contained starch granules, evidence for persorption i.e. the incorporation of undissolved starch particles. In these patients, amyluria was more marked than in untreated controls. While cornstarch therapy is successful and causes few side-effects, the possibility of late adverse reactions to persorbed starch should not be disregarded.

Structural and immunochemical analysis of three alpha-limit dextrin oligosaccharides.

Complete structures are described for three urinary oligodextrins from one patient with type II and one patient with type III glycogen storage disease. GLC-MS, direct probe MS, and 1H NMR demonstrate two heptasaccharides and one hexasaccharide containing only alpha 1-4 and alpha 1-6 linkages. The observation that all three oligosaccharides were present in urine of both patients and the occurrence of alpha 1-4 and alpha 1-6 linkages in characteristic sequences indicates that the oligodextrins are limit dextrins derived from alpha-amylolytic degradation of glycogen. The binding affinities of the oligodextrins for a monoclonal antibody (401/6) raised against Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc, were determined by frontal analysis. The highest affinity was exhibited by Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc followed by the two heptasaccharides and the hexasaccharide. The results from quantitative affinity measurements agree with results of structural analysis by physical methods in that all oligodextrins containing the nonreducing terminal sequence, Glc alpha 1-6Glc alpha 1-4Glc . . . , are specifically bound by the antibody with similar affinities, but the affinity is somewhat higher for chains containing the tetrasaccharide sequence Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc at the nonreducing terminal. Utilization of affinity methods offers clear advantages for isolation and characterization of oligosaccharides with very similar structures.