Flow chart of inclusion of CSF samples.

<p>N – number of CSF samples.</p

Age-specific reference values for CSF glucose, CSF/plasma glucose ratio and CSF lactate.

<p>Reference values are based on the 5^th to 95^th percentile values. The subgroups from the original data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042745#pone.0042745.s001" target="_blank">Tables S1</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042745#pone.0042745.s002" target="_blank">S2</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042745#pone.0042745.s003" target="_blank">S3</a>) were clustered into age groups which are commonly used in daily clinical practice (as used by MeSH, Pubmed).</p>*<p>Reference range after exclusion of CSF samples of patients with an unknown or abnormal plasma glucose (<3.0 mmol/L or >7.8 mmol/L) at the moment of lumbar puncture (only represented if >10% different from to the original value). Numbers between brackets represent values without correction for plasma glucose. ‡Reference range after exclusion of CSF samples with CSF lactate >3000 µmol/L (only represented if >10% different from the original value). Number between brackets represents upper limit without exclusion of CSF samples with CSF lactate >3000 µmol/L.</p

Age-specific CSF glucose, CSF/plasma glucose ratio and CSF lactate values.

<p>(A) CSF glucose concentration in 8,871 samples. CSF samples with CSF glucose >10.0 mmol/L (n = 4) are not shown; (B) CSF/plasma glucose in 4,516 samples. CSF samples with CSF/plasma glucose >1.5 (n = 5) are not shown; (C) CSF lactate concentration in 7,614 samples. CSF samples with CSF lactate >5000 µmol/L (n = 22) are not shown. Lines indicate 5^th and 95^th percentile values.</p

Relation between plasma glucose and CSF glucose.

<p>(A) Relation between plasma glucose and CSF/plasma glucose ratio in 4,508 CSF samples. CSF samples with CSF/plasma glucose ratio >1.5 (n = 5) are not shown. (B) Relation between plasma glucose and CSF glucose in 4,513 CSF samples. The grey areas indicates normoglycemia (plasma glucose >3.0 and <7.8 mmol/L).</p

Summary of literature search for reference ranges of CSF glucose, CSF/plasma glucose ratio and CSF lactate.

<p>N - number of CSF samples included in study; wk(s) – week(s); dys – days; yrs- years; P – percentile.</p

Abnormal compounds present in urine 1D ¹H-NMR spectra from the patients.

<p>The metabolites were identified by comparison of the abnormal resonances to a database of NMR spectra of model compounds <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092452#pone.0092452-Engelke1" target="_blank">[5]</a>. In cases where the overlap of resonances in the 1D spectrum was quite severe, 2D COSY NMR experiments were used to provide additional information and confirm that the metabolite identification based on the 1D spectrum was correct.</p><p>*Spectrum not completed interpreted; s = singlet; d = doublet; t = triplet; q = quartet; m = multiplet; v = various multipets.</p><p>3MCC = 3-Methylcrotonyl CoA carboxylase.</p

PCA scoreplot of the autoscaled data.

<p>Note that the points are coloured according to the observations made by a clinical expert as healthy; healthy, but exogenous metabolites were present; patients diagnosed with IEM; and other patients.</p

Feature contributions visualized in a contribution plot and the original NMR spectra for three abnormal metabotypes.

<p>The abnormal metabolites are related to (A, B) high concentrations of taurine, (C, D) alkaptonuria, and (D, E) paracetamol comsumption. The arrows indicate the resonance corresponding to the middle of a bin. Each bin had a width of 0.04 ppm.</p

The ¹H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study

<div><p>Metabolomics studies of disease conditions related to chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways underlying the pathophysiology of alcoholism. The objective of the present study was to utilize proton nuclear magnetic resonance (¹H-NMR) spectroscopy metabolomics to study the holistic metabolic consequences of acute alcohol consumption in humans. The experimental design was a cross-over intervention study which included a number of substances to be consumed—alcohol, a nicotinamide adenine dinucleotide (NAD) supplement, and a benzoic acid-containing flavoured water vehicle. The experimental subjects—24 healthy, moderate-drinking young men—each provided six hourly-collected urine samples for analysis. Complete data sets were obtained from 20 of the subjects and used for data generation, analysis and interpretation. The results from the NMR approach produced complex spectral data, which could be resolved sufficiently through the application of a combination of univariate and multivariate methods of statistical analysis. The metabolite profiles resulting from acute alcohol consumption indicated that alcohol-induced NAD⁺ depletion, and the production of an excessive amount of reducing equivalents, greatly perturbed the hepatocyte redox homeostasis, resulting in essentially three major metabolic disturbances—up-regulated lactic acid metabolism, down-regulated purine catabolism and osmoregulation. Of these, the urinary excretion of the osmolyte sorbitol proved to be novel, and suggests hepatocyte swelling due to ethanol influx following acute alcohol consumption. Time-dependent metabolomics investigations, using designed interventions, provide a way of interpreting the variation induced by the different factors of a designed experiment, thereby also giving methodological significance to this study. The outcomes of this approach have the potential to significantly advance our understanding of the serious impact of the pathophysiological perturbations which arise from the consumption of a single, large dose of alcohol—a simulation of a widespread, and mostly naive, social practice.</p></div

A summary of the experimental designs, data analysis approaches and main metabolic conclusions of some NMR-based ethanol administration studies.

<p>A summary of the experimental designs, data analysis approaches and main metabolic conclusions of some NMR-based ethanol administration studies.</p