The studies described in this thesis provides the field with valuable data on the potential therapeutic effects of fatty acids and specialized pro-resolving lipid mediators in rheumatoid arthritis... Show moreThe studies described in this thesis provides the field with valuable data on the potential therapeutic effects of fatty acids and specialized pro-resolving lipid mediators in rheumatoid arthritis and osteoarthritis. The omega-6 fatty acid AdA shows potent pro-resolving effects on the production of pro-inflammatory chemoattractantLTB4 with great promise to limit RA disease progression. In contrast to the promising potential therapeutic effects of AdA in RA, the evidence for pro-resolving effects in OA is still scarce. The results of the studies from this thesis show that neither LXA4, LXB4, RvE2 or Mar-1 were able to reduce OA disease activity in the experimental set-up we used. Finally, the studies described in this thesis show the utmost critical importance of the right sample preparation and storage for the intended subsequent analysis. Show less
The focus of this thesis is (oxy)lipid analysis. An introductory overview is given of lipids, lipidomics, and lipid mediators in inflammation; and in subsequent chapters the focus is on... Show moreThe focus of this thesis is (oxy)lipid analysis. An introductory overview is given of lipids, lipidomics, and lipid mediators in inflammation; and in subsequent chapters the focus is on development of lipidomic methods for the analysis of oxidized lipids. This touches on different extraction methods of the (target) analytes, sample handling/preparation and storage, separation techniques, and finally the MS detection/resolution/ specificity etc. These methods are then utilized, mainly on human plasma and synovial fluid (SF) samples. Special focus is on the targeted analysis of hydroxylated fatty acids (hFAs), specialized pro-resolving mediators (SPMs) and their intermediates, and other oxylipids present in inflammation and its resolution in rheumatic diseases. For example, the bioactivity of oxylipids and LMs is highly stereospecific, and some difficulties have arisen in the chromatographic separation and resolution of these stereoisomers using classical reversed phase liquid chromatography tandem MS (RPLC-MS/MS), perhaps sometimes resulting in wrong conclusions being drawn, one isomer being confused with another. The work in this thesis was therefore focused on further development and application of analysis platforms for oxidized lipids; their identification, separation and levels in different matrices. All of which, work that can be further used in inflammatory or rheumatoid research. Show less
