Physiology - Journal Articles
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Item The gut microbiota: an amazing technicolour dream coat or the emperor’s new clothes?(John Wiley & Sons Ltd., 2025) O'Halloran, Ken D.Item Homeostasis in the laboratory, the clinic and our academic institutions!(John Wiley & Sons Ltd., 2025) O'Halloran, Ken D.Item Endothelial dysfunction does not occur after acute, elevated homocysteine exposure of the lumen of the iliac artery of the anaesthetised pig(Karger, 2024-10-09) Markos, Farouk; O’Leary, Andrew J.; Noble, Mark I. M.; Ruane-O’Hora, ThereseElevated luminal homocysteine has been linked with cardiovascular disease; however, whether there is a direct effect of homocysteine on blood vessel endothelium is not clear. In this study, the acute effect of luminal homocysteine on iliac artery endothelial function was assessed in the anaesthetised pig. Methods: Hyperhomocysteinaemic blood was injected into an occluded segment of the iliac in the anaesthetised pig for 20 min, and the effect on atrial diameter during the occlusion and during the reactive hyperaemia assessed. Results: No significant changes in arterial diameter or pressure were observed during the incubation period at homocysteine concentrations of 10, 20, 40 and 100 µ<sc>M</sc>. There was also no difference in the magnitude of the iliac diameter increase in the response to reactive hyperaemia when the incubation period was completed. Conclusion: There is no evidence of endothelial dysfunction in response to an acute 20-min elevation in homocysteine in an intact conduit artery.Item Regional and conditional variability of FXR: new lessons on ileal inflammation and gut barrier functions(American Physiological Society, 2024-10-10) Joyce, Susan A.; O’Malley, DervlaItem Characterization of Fabry disease-associated lyso-Gb3 on mouse colonic ion transport and motility(American Physiological Society, 2024) Delprete, Cecilia; Uhlig, Friederike; Caprini, Marco; Hyland, Niall P.; Science Foundation Ireland; Fondazione Cassa di Risparmio in Bologna; Università di Bologna; Horizon 2020Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A leading to the accumulation of globotriaosylceramide (Gb3) and subsequent increase in globotriaosylsphingosine (lyso-Gb3) in different cells and organs, including the gastrointestinal (GI) tract. GI symptoms represent some of the earliest manifestations of FD and significantly impact quality of life. The origin of these symptoms is complex, and the exact mechanisms remain poorly understood. Here, we sought to determine whether lyso-Gb3 contributes to the pathophysiology of GI symptoms associated with FD by examining its effects on mouse colonic ion transport and motility ex vivo using Ussing chambers and organ baths respectively. Lyso-Gb3 significantly increased colonic baseline short-circuit current (ISC). This increase in ISC was insensitive to inhibition of the cystic fibrosis transmembrane conductance regulator and Na-K-Cl cotransporter 1 suggesting that the increase in ISC is Cl- ion independent. This response was also insensitive to inhibition with the neurotoxin, tetrodotoxin. Additionally, pretreatment with lyso-Gb3 did not significantly influence subsequent responses to either veratridine or capsaicin implying that the response to lyso-Gb3 does not involve the enteric nervous system. In terms of colonic motility, lyso-Gb3 did not significantly influence colonic tone, spontaneous contractility or cholinergic-induced contractions. These data suggest that lyso-Gb3, significantly influences ion transport in mouse colon, but that accumulation of Gb3 may be a pre-requisite for the more pronounced disturbances in GI physiology characteristic of FD.