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Title: Studies on the pyridinium crosslinks of collagen
Author: McLaren, Alison M.
ISNI:       0000 0001 3625 4529
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1993
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Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd) were performed to assess the validity of these assays as indicators of bone resorption. The day-to-day variation was low in comparison to the increase in the crosslink excretion caused by arthritic disease. The ratio of Pyd and Dpd to creatinine on first morning samples was highly correlated with total daily output. Nyctohemeral variations in crosslink excretion were significant for a group of healthy male subjects although the magnitude of variations were lower than changes in crosslink excretion caused by arthritic disease. The crosslink excretion rates were also found not to be related to renal impairment either at the glomerular or tubular level. It was observed however that renal impairment caused the excretion of a higher concentration of conjugated Pyd. The urinary pyridinium crosslinks were also found to be potential markers for monitoring the effect of a disease modifying drug on rheumatoid arthritis. The excretion of the crosslinks was found to be significantly higher in patients with osteoporosis compared to healthy controls. Fractures were also found to markedly increase excretion of the crosslinks. A sensitive ELISA was developed which allowed measurement of Pyd in serum and plasma. Structural alterations due to hydrolysis were found to occur in Pyd which meant that the unhydrolysed form of the molecule was inactive towards antibodies raised to the hydrolysed form. In healthy subjects approximately fifteen percent of Pyd is excreted in the form of glucosyl-galactosyl-pyridinoline. The latter compound was measured in patients with renal impairment to determine if there was any intrarenal cleavage of the conjugates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry