Physiology - Journal Articles
Permanent URI for this collection
Browse
Recent Submissions
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.Item The impact of fatigue on people with Fibromyalgia Syndrome: A survey(Wiley, 2023-07-21) McToal, Martina; McVeigh, Rachel Christina; McVeigh, Joseph G.; Fibromyalgia Support Northern IrelandIntroduction: Fibromyalgia syndrome (FMS) is a common pain syndrome associated with fatigue and anxiety. The aim of this survey was to determine the impact of fatigue on the quality of life (QoL) of people with FMS and to explore the relationships between fatigue, pain, and anxiety. Methods: A postal survey was conducted among support groups. Demographic data were collected and participants were asked to complete the Multi-dimensional Assessment of Fatigue Scale (MAF) and two visual analog scales (VAS) measuring pain and anxiety. Data were analysed using descriptive statistics, and relationships between variables were explored using Pearson's correlation coefficient and Fisher's Exact Probability Test. Ethical approval was granted from Ulster University's research ethics committee. Results: A response rate of 52.5% was achieved (105/200). Fatigue was found to severely impact the QoL of those with FMS. From the MAF, a mean Global Fatigue Index score of 40.7 (range 1 = no fatigue—50 = severe fatigue) was calculated. Fatigue was significantly associated with both pain (r = 0.674) and anxiety (r = 0.546) (both p values < 0.0001), and no significant relationship was found between the duration of FMS and fatigue (r = 0.106; p = 0.320). Conclusion: Fatigue has a major impact on the QoL of patients with FMS. There is a strong relationship between fatigue and other variables such as pain and anxiety. However, there is no relationship between the time since diagnosis and fatigue experienced. Fatigue management should feature highly in any treatment programme for those with FMS.Item Gene co-expression analysis of the human substantia nigra identifies ZNHIT1 as an SNCA co-expressed gene that protects against α-synuclein-induced impairments in neurite growth and mitochondrial dysfunction in SH-SY5Y cells(Springer, 2022-02-17) McCarthy, Erin; Barron, Aaron; Morales-Prieto, Noelia; Mazzocchi, Martina; McCarthy, Cathal M.; Collins, Louise M.; Sullivan, Aideen M.; O’Keeffe, Gerard W.; Science Foundation Ireland; Irish Research Council; HORIZON EUROPE Marie Sklodowska-Curie ActionsParkinson’s disease (PD) is neurodegenerative disorder with the pathological hallmarks of progressive degeneration of midbrain dopaminergic neurons from the substantia nigra (SN), and accumulation and spread of inclusions of aggregated α-synuclein (α-Syn). Since current PD therapies do not prevent neurodegeneration, there is a need to identify therapeutic targets that can prevent α-Syn-induced reductions in neuronal survival and neurite growth. We hypothesised that genes that are normally co-expressed with the α-Syn gene (SNCA), and whose co-expression pattern is lost in PD, may be important for protecting against α-Syn-induced dopaminergic degeneration, since broken correlations can be used as an index of functional misregulation. Gene co-expression analysis of the human SN showed that nuclear zinc finger HIT-type containing 1 (ZNHIT1) is co-expressed with SNCA and that this co-expression pattern is lost in PD. Overexpression of ZNHIT1 was found to increase deposition of the H2A.Z histone variant in SH-SY5Y cells, to promote neurite growth and to prevent α-Syn-induced reductions in neurite growth and cell viability. Analysis of ZNHIT1 co-expressed genes showed significant enrichment in genes associated with mitochondrial function. In agreement, bioenergetic state analysis of mitochondrial function revealed that ZNHIT1 increased cellular ATP synthesis. Furthermore, α-Syn-induced impairments in basal respiration, maximal respiration and spare respiratory capacity were not seen in ZNHIT1-overexpressing cells. These data show that ZNHIT1 can protect against α-Syn-induced degeneration and mitochondrial dysfunction, which rationalises further investigation of ZNHIT1 as a therapeutic target for PD.