Saliva Metabolomics in Dry Mouth Patients with Head and Neck Cancer or Sjögren's Syndrome.

The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren's syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes behind dry mouth with different etiologies, we investigated the metabolic profile of 10 HNC patients, 9 pSS patients and 10 healthy controls using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) metabolomics. Principal component analysis (PCA) revealed different metabolic profiles when comparing all subjects included in the study. Both patient groups showed higher ratios of several pyrimidine nucleotides and nucleosides when compared to controls. This finding may indicate that purinergic signaling plays a role in dry mouth conditions. Moreover, significantly increased levels of DL-3-aminoisobutyric acid were found in HNC patients when compared to controls, and a similar tendency was observed in the pSS patients. Furthermore, a dysregulation in amino acid metabolism was observed in both patient groups. In conclusion, metabolomics analysis showed separate metabolic profiles for HNC and pSS patients as compared to controls that could be useful in diagnostics and for elucidating the different pathophysiologies. The demonstrated dysregulation of pyrimidine nucleotides and levels of metabolites derived from amino acids in the patient groups should be studied further.

Separation of nucleic acid hydrolysis products, purines, pyrimidines, nucleosides, nucleotides, ribonucleic acid hydrolyzates, and mixtures from nucleotide syntheses by column chromatography on amberlite XAD-4.

Amberlite XAD-4 resin has been studied as a support for liquid-solid column chromatography. By coating the resin with triethylammonium bicarbonate, a new and unique separation of nucleic acid components has been achieved. Separations are accomplished with a linear gradient of this buffer from 0.1 to 0.4 M. Separation occurs in the following order: inorganic phosphate, purine or pyrimidine bases, 5'-monophosphates, nucleosides and 5'-diphosphates or 5'-triphosphates; the 2'(3')-monophosphates are eluted after either the 5'mono-, di-or triphosphates. The bases and nucleosides are separated in the order: cytosine, uracil, guanine and adenine. Inorganic phosphate and the nucleotides are eluted in the order: inorganic phosphate 5'-mono, di- and tri-phosphates. Excellent separation of the 5'-monophosphates and the 2'(3')-monophosphates is now possible. In each series of 5'-mono-, di- and tri-phosphates or 2'(3')-monophosphates, the elution order is generally cytidine, uridine, guanosine and adenosine. By use of water instead of coating the resin with triethylammonium bicarbonate, the nucleotides and inorganic phosphate are found in the void volume; adenine is eluted very slowly, whereas adenosine is not eluted. Adenosine is eluted only with ethanol-water (1:3). The method is advantageous in that the recovery is quantitative, the buffer is easily removed, the capacity of the column is large (35 mugmoles pergram of resin), flow-rates are high, the time required is short and separations of combinations of inorganic phosphate, bases, nucleosides and nucleotides are now possible that previously could not be accomplished.