Medical Mass Spectrometry
Online ISSN : 2432-745X
Print ISSN : 2432-7441
ISSN-L : 2432-7441
Volume 2, Issue 1
Displaying 1-5 of 5 articles from this issue
Preface
Review
  • Emiko Sato
    2018 Volume 2 Issue 1 Pages 2-10
    Published: June 25, 2018
    Released on J-STAGE: September 08, 2020
    JOURNAL FREE ACCESS

    Sarcopenia, the degenerative loss of skeletal muscle mass, is associated with increased morbidity and mortality for patients with chronic kidney disease (CKD), where it is specifically referred to as uremic sarcopenia. However, the details of the abnormal metabolic processes induced by uremic toxins remain unclear. Recently, we clarified the pathogenic mechanisms of uremic sarcopenia using liquid chromatography-mass spectrometry (MS) and MS imaging, which revealed that uremic toxin indoxyl sulfate accumulates in the muscle tissue of CKD model mice. Moreover, capillary electrophoresis MS-metabolomics of a muscle cell line suggested that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including the pentose phosphate pathway, for protection against oxidative stress. This altered metabolic flow leads to downregulation of the tricarboxylic acid cycle resulting in an ATP shortage. In a clinical study, plasma indoxyl sulfate levels were associated with skeletal muscle mass reduction in CKD patients. In this review, I discuss the known pathogenic mechanisms of uremic sarcopenia induced by the uremic toxin indoxyl sulfate with a focus on the consequent metabolic alteration and mitochondrial dysfunction.

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Research Papers
  • Haruhito Tsutsui, Yoshio Muguruma, Takumi Noda, Hiroyasu Akatsu, Noriy ...
    2018 Volume 2 Issue 1 Pages 11-20
    Published: June 25, 2018
    Released on J-STAGE: September 08, 2020
    JOURNAL FREE ACCESS

    An early diagnosis of Alzheimer’s disease can lead to better and more targeted treatment and/or prevention for patients. Employing a pathological diagnosis by non-targeted metabolomics with ultra high performance liquid chromatography-electrospray tandem mass spectrometry, in our previous study, we found significant changes in polyamine metabolites arising from the ornithine cycle in human brain samples of patients with Alzheimer’s disease. In this study, we develop a targeted metabolomics methodology for the separation and detection of compounds derived from the ornithine cycle in human cerebrospinal fluid samples. For the targeted metabolomics, two derivatization reagents (9-fluorenylmethyl chloroformate and 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole) are utilized for sensitive and accurate determination of amine analytes. Validation tests confirm a good linearity of r2>0.99 or more in all calibration curves obtained using internal standards. The developed method is applied for the analysis of preliminary 15 metabolites including polyamine metabolites in cerebrospinal fluid samples classified according to brain autopsy Braak stages regarding to Alzheimer’s disease and compared to a control samples. Utilizing the results obtained for the ornithine cycle, we expect to find a metabolic pathway that would be used as a potential biomarker in the future.

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  • Shigeo Takashima, Kayoko Toyoshi, Nobuyuki Shimozawa
    2018 Volume 2 Issue 1 Pages 21-33
    Published: June 25, 2018
    Released on J-STAGE: September 08, 2020
    JOURNAL FREE ACCESS

    Fatty acids vary in their hydrocarbon chain length and the number and position of the double bonds. In this study, we investigated the principle of the separation of fatty acids by reverse-phase liquid chromatography coupled with negative electrospray ionization mass spectrometry (LC-negative ESI-MS). In particular, we aimed to detect very-long-chain fatty acids (VLCFAs) and to distinguish between isomeric unsaturated fatty acids differing in their double bond positions. We found that both saturated and unsaturated fatty acids are not separated by regular chromatography but instead separated by sequential detachment from the column’s stationary phase, according to the strength of the organic mobile phase. The interaction of the fatty acids with the stationary phase during chromatographic migration had a minor effect on their separation. Unsaturated fatty acid isomers with different double bond positions were found to be separable, and their elution order was determined by the position of the double bonds relative to the omega carbon. We also found that fibroblasts from the patients with peroxisomal disease show characteristic distribution patterns for some fatty acid isomers in the proposed separation method. Our method is, thus, useful for analyzing a wide range of fatty acid species, including VLCFAs and unsaturated fatty acid isomers, to understand the physiological changes in fatty acid metabolism from clinical samples.

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Short Communication
  • Tadashi Ogawa, Jun Ueyama, Takayoshi Suzuki, Masae Iwai, Xiao-Pen Lee, ...
    2018 Volume 2 Issue 1 Pages 34-40
    Published: June 25, 2018
    Released on J-STAGE: September 08, 2020
    JOURNAL FREE ACCESS

    The metabolism of acetamiprid, a neonicotinoid insecticide, in rats was investigated by monitoring time-dependent changes in plasma levels of acetamiprid and its metabolites using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Acetamiprid was administrated to rats intravenously at 7.1–21.7 mg/kg for analysis of plasma at 0–96 h. Acetamiprid and its four metabolites could be detected and tentatively identified in rat plasma samples. Plasma levels only estimated from peak areas of acetamiprid decreased, with a half-life of about 4 h, and were completely eliminated by 24 h. N-[(6-Chloro-3-pyridyl) methyl]-N′-cyano-acetamidine was most strongly detected at 4 h and was missing at 48 h. The peak areas of N-[(6-chloropyridin-3-yl) methyl]-acetamide increased over time, reached the maximum at 12–24 h, and the metabolite was then completely eliminated at 72 h. N-Cyano-N′-methylacetamidine and 6-(methylsulfanyl) nicotinic acid showed almost the same behaviors as N-[(6-chloro-3-pyridyl) methyl]-N′-cyano-acetamidine. These findings suggested that LC-QTOF-MS enabled us to tentatively estimate acetamiprid metabolism in rats and that these four metabolites may also be useful biomarkers for acetamiprid exposure in humans.

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