1.
Discovery and Validation of Potential Serum Biomarkers for Pediatric Patients with Congenital Heart Diseases by Metabolomics.
Yu, M, Sun, S, Yu, J, Du, F, Zhang, S, Yang, W, Xiao, J, Xie, B
Journal of proteome research. 2018;(10):3517-3525
Abstract
To identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234 NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy (1H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum metabolites distinguishing PCH from NC were identified by 1H NMR-based metabolomic analysis. The amino acid and choline metabolic pathways were considered to be closely related to PCH. The serum levels of 13 metabolites in these two pathways were further determined by UPLC-MS/MS and observed to be altered significantly in PCH. Taurine, glutamine, and glutamate presented considerable diagnostic value for the diagnosis of PCH (AUROC > 0.80). Logistic regression analysis showed that a combination of four variables, namely, betaine, taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC = 0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and the sensitivity and specificity were 93.9 and 95.2%, respectively. Further double-blind sample prediction showed that the accuracy of the model was 83.8% for 80 unknown samples. Our results showed that the serum amino acid and choline metabolite levels in PCH were changed considerably. The combination of four metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used as potential serum biomarkers in PCH diagnosis, which contributes to the early PCH screening.
2.
Metabolomic profiling of children's brains undergoing general anesthesia with sevoflurane and propofol.
Jacob, Z, Li, H, Makaryus, R, Zhang, S, Reinsel, R, Lee, H, Feng, T, Rothman, DL, Benveniste, H
Anesthesiology. 2012;(5):1062-71
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Abstract
BACKGROUND We recently applied proton magnetic resonance spectroscopy (HMRS) to investigate metabolic consequences of general anesthesia in the rodent brain, and discovered that isoflurane anesthesia was characterized by higher concentrations of lactate, glutamate, and glucose in comparison with propofol. We hypothesized that the metabolomic differences between an inhalant and intravenous anesthetic observed in the rodent brain could be reproduced in the human brain. METHODS HMRS-based metabolomic profiling was applied to characterize the cerebral metabolic status of 59 children undergoing magnetic resonance imaging during anesthesia with either sevoflurane or propofol. HMRS scans were acquired in the parietal cortex after approximately 60 min of anesthesia. Upon emergence the children were assessed using the pediatric anesthesia emergence delirium scale. RESULTS With sevoflurane anesthesia, the metabolic signature consisted of higher concentrations of lactate and glucose compared with children anesthetized with propofol. Further, a correlation and stepwise regression analysis performed on emergence delirium scores in relation to the metabolic status revealed that lactate and glucose correlated positively and total creatine negatively with the emergence delirium score. CONCLUSIONS Our results demonstrating higher glucose and lactate with sevoflurane in the human brain compared with propofol could reflect greater neuronal activity with sevofluane resulting in enhanced glutamate-neurotransmitter cycling, increased glycolysis, and lactate shuttling from astrocytes to neurons or mitochondrial dysfunction. Further, the association between emergence delirium and lactate suggests that anesthesia-induced enhanced cortical activity in the unconscious state may interfere with rapid return to "coherent" brain connectivity patterns required for normal cognition upon emergence of anesthesia.