Organic acids, including L- and D-lactate, explain most but not the entire elevated anion gap in diarrhea-associated metabolic acidosis. Also, D-lactate has been implicated in the neurological symptoms associated with this condition. Less-common organic compounds may influence the anion gap and neurological symptoms. This research aimed to characterize and attempt to identify a previously unidentified compound, Compound X, first noted in diarrheic acidotic calves with elevated anion gap (Omole, 1999).<p>
High performance liquid chromatography (HPLC) was used to measure Compound X in biological fluids from diarrheic and healthy calves; diarrheic piglets, foals, and human infants; and calves experimentally infused with saline or acid. Attempts were made to identify Compound X using HPLC with tandem and Fourier-transform mass spectrometry.<p>
Compound X was significantly higher in diarrheic calf serum (p<0.001) and lower in feces (p<0.001) and rumen fluid (p<0.001) than those fluids from healthy calves. Compound X in serum from acid-infused calves (median peak area ratio = 1.5 1.9) was lower than that of diarrheic calves (median = 4.8) and only slightly greater than that of healthy calves (median = 1.2). Serum Compound X correlated with serum D-lactate in diarrheic and healthy calves combined; however, no such correlation was observed in acid-infused calves. Conversely, a relationship between Compound X and neurological disturbance was present in acid-infused calves, but not in diarrheic calves. In other species, Compound X was highest in diarrheic infants and lowest in diarrheic piglets. Although mass spectrometry and database library searches revealed several compounds as putative matches for Compound X, none of the compounds made sense within the context of acidosis and mammalian biological fluids. Therefore, the identity of Compound X remains unknown.<p>
Compound X has been established as a ubiquitous compound(s) present in the biological fluids of mammals. Compound X may be a normal intestinal compound or bacterial metabolite that crosses the intestinal epithelium during diarrhea. In spite of this, Compound X was associated with the neurological manifestations of D-lactic acidosis. Compound X`s identity was not determined, and some reasons for this and future directions are discussed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-05122010-204756 |
| Date | 13 May 2010 |
| Creators | Barabash, Wade |
| Contributors | Whiting, Susan, Zello, Gordon, Hamilton, Don, Naylor, Jonathan, Lehotay, Denis |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-05122010-204756/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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