Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

Background: Irritable bowel syndrome (IBS) is a common disorder that affects 10–15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). Methods: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. Results: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. Conclusion: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.

Language legislation in Ireland and the United Kingdom: Exploring the gaps between theory and practice

The central objective in this thesis is to explore the gaps between the normative justifications advanced for language rights and language legislative protection and the effective realisation of those rights and legislative provisions in practice. This objective is achieved by examining the scope and application of language rights and legislative provisions within language legislation in Ireland and the United Kingdom. Drawing on Canadian jurisprudence advocating for language rights to be recognised as “purposeful”, the thesis considers the extent to which Ireland and the United Kingdom have limited the acceptance of positive obligations as they relate to the provision of language services in the public sphere. In arguing that language rights are distinct in nature, the thesis suggests that in order for language rights to be effectively realised, an approach to language rights and language legislation more generally must be underpinned by a substantive vision of equality, otherwise language rights and legislative provisions merely amount to symbolic recognition and vacuous rhetoric as opposed to being substantive and enabling rights and provisions. Having said that, the thesis also recognises and elucidates the practical difficulties that arise in the realisation of language rights and language legislative provisions and in doing so seeks to stimulate further dialogue about the nature and limits of language rights and language legislation.

A kingdom near lost: English military recovery in Ireland, 1600-03

Ireland was rarely a peaceful realm for Elizabeth I, but Hugh O’Neill, Earl of Tyrone and his allies brought the edifice of English power in Ireland to the brink of collapse. The war in Ireland at the end of the sixteenth century devoured money, lives and reputations at a prodigious rate. However seven years of Irish success ended when in 1600 the Queen appointed Charles Blount, Lord Mountjoy as Lord Deputy. Success replaced failure, but only after the new Lord Deputy transformed English strategy and rebuilt the army into an instrument fit for purpose.