School of Engineering and Materials Science
Research Student Awards
PhD Thesis: The biochemical evaluation of chronic venous ulcers in the clinical setting
Author: JAMES, T
Supervisor(s): Dan Bader
Chronic venous ulceration is a poorly understood condition that affects a significant proportion of the elderly. This thesis investigates the role of oxidative stress in venous ulceration by analysing chronic wound fluid collected from patients attending a leg ulcer clinic.
A standardised technique for wound fluid collection has been developed and then used to obtain material that is analysed with a series of standard and novel biochemical assays. The results of these investigations support the theory that chronic wound fluid is a plasma-derived material the composition of which is influenced by local cellular and biochemical activity. It is considered to be representative of the wound milieu.
The antioxidant characteristics of chronic wound fluid are observed to share some characteristics with plasma. However, in addition to a significant contribution from albumin and uric acid, it would appear that some components of the antioxidant system are up-regulated including the enzyme glutathione reductase. The elevated activity of this enzyme contributes to the maintenance of wound fluid thiol levels.
The allantoin: uric acid ratio (AUR), a marker of oxidative stress, is significantly elevated in wound fluid compared to plasma. Similarly, another marker of oxidative stress, the advanced oxidation protein products measure (AOPP), closely linked to oxidative modification of proteins, is also elevated. Both observations support the hypothesis that oxidative stress is contributory to venous ulceration. The concentration of hypoxanthine, xanthine and neutrophil elastase are all significantly higher in chronic would fluid compared to plasma, suggesting that both ischaemia-reperfusion and neutrophils as possible sources for the oxidative stress observed. These observations are consistent with hypotheses implicating while cell trapping in tissue with compromised venous function.