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Urinary 1H-NMR Metabolomics Can Distinguish Pancreatitis Patients from Healthy Controls

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TLDR
This metabolomic investigation demonstrates that this non-invasive technique offers insight into the metabolic states of pancreatitis, although the identified metabolites cannot conclusively be defined as biomarkers of disease, future studies will validate the findings in larger patient cohorts.
Abstract
Context The characterization of the urinary metabolome may yield biomarkers indicative of pancreatitis. Objectives We establish a non-invasive technique to compare urinary metabolic profiles in patients with acute and chronic pancreatitis to healthy controls. Methods Urine was obtained from healthy controls (HC, n=5), inpatients with mild acute pancreatitis (AP, n=5), and outpatients with chronic pancreatitis (CP, n=5). Proton nuclear magnetic resonance spectra were obtained for each sample. Metabolites were identified and quantified in each spectrum; resulting concentrations were normalized to account for differences in dilution among samples. Kruskal-Wallis test, post-hoc Mann-Whitney U tests, and principal component analysis were performed to identify metabolites that discriminate healthy controls, acute pancreatitis, and chronic pancreatitis. Results Sixty metabolites were identified and quantified; five were found to differ significantly (P<0.05) among the three groups. Of these, citrate and adenosine remained significant after validation by random permutation. Principal component analysis demonstrated that healthy control urine samples can be differentiated from patients with chronic pancreatitis or acute pancreatitis; chronic pancreatitis patients could not be distinguished from acute pancreatitis patients. Conclusions This metabolomic investigation demonstrates that this non-invasive technique offers insight into the metabolic states of pancreatitis. Although the identified metabolites cannot conclusively be defined as biomarkers of disease, future studies will validate our findings in larger patient cohorts. Image:  Boxplots of two significant metabolites.

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Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis

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References
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TL;DR: In this review, the differences among metabolite target analysis, metabolite profiling, and metabolic fingerprinting are clarified, and terms are defined.
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'metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological nmr spectroscopic data

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Probabilistic Quotient Normalization as Robust Method to Account for Dilution of Complex Biological Mixtures. Application in 1H NMR Metabonomics

TL;DR: The probabilistic quotient normalization is introduced in this work, which is based on the calculation of a most probable dilution factor by looking at the distribution of the quotients of the amplitudes of a test spectrum by those of a reference spectrum.
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