Imidazole dipeptides: dietary sources and factors affecting uptake and muscle content

The imidazole dipeptides (ImD); anserine (Ans), carnosine (Cam) and balenine, have been shown to be effective at functioning as H+ ion buffers, with Carn being particularly effective within the physiological pH range. Therefore ImD have been reported to be beneficial to athletes exercising at high intensities, where the activity results in the production and accumulation of H+ ions within skeletal muscle. It has also been hypothesised that these compounds may also be beneficial in reducing the morbidities related to ageing, such as Alzheimer's disease. Humans store ImD in the form of Carn and not as anserine or balenine. However, within the human body Carn production is limited by the ability to degrade uracil in the liver, with (3-alanine being the limiting factor. Therefore the content of the diet has a substantial impact on the level of Carn within human skeletal muscle. This thesis aimed to investigate the variability in ImD with age and in subjects from different geographical locations. The effect of ageing on the muscle content of the ImD was demonstrated through the use of a murine model, where increased age was accompanied with a 45% decline in the ImD levels measured in the tibialis anterior of 60wk old senescence-accelerated male mice (Chapter 9). This is supported by further work (Chapter 14) which showed that elderly European subjects exhibited lower levels of carnosine in the vastus lateralis compared to younger European subjects (15.6mmol·kg-1 dm and 22.4mmol·kg-1 dm respectively). However, in Korean elderly subjects no decline was observed (21.5mmol·kg-1 dm), and this could potentially be explained by different dietary habits, with the elderly Korean subjects consuming larger amounts of protein-rich foods than their European counterparts. Analysis was made of the variation in the carnosine content of the vastus lateralis in subjects from differing geographical locations, and subsequently different cultural diets with varying meat contents, and showed that dietary intake of a diet habitually rich in the ImD could potentially 'over-ride' the decline seen with age in subjects who 'reduce' their meat intake

Perceived anxiety and plasma cortisol concentrations following rock climbing with differing safety rope protocols

Objectives: To examine how different safety rope protocols impact on subjective anxiety and self confidence levels and plasma cortisol concentrations and the relationship between subjective states and cortisol during rock climbing. Methods: Participants (n = 12) were tested in three climbing conditions that were designed to invoke low, moderate and high physical and mental stress. Plasma cortisol concentrations were collected pre and post climbing and participants reported subjective anxiety and self confidence states for each climb. Results: Repeated measures analysis of variances showed significant differences between conditions for somatic anxiety (F2, 22 = 7.74, p = .009), self confidence (F2, 22 = 9.52, p = .001) and change in plasma cortisol concentration (F2, 22 = 3.71, p = .041). Pre planned polynomial comparisons showed these were linear effects somatic anxiety was higher in the higher stress conditions whilst self confidence was lower. Plasma cortisol concentration change was also linear Regression analyses showed cubic relationships between plasma cortisol concentration and cognitive anxiety (R2 = .452), self-confidence (R2 = .281) and somatic anxiety (R2 = .268). Conclusions: There is a relationship between plasma cortisol concentration and subjective anxiety and self-confidence states during rock climbing. Changes in the way the safety rope is organised can impact on anxiety, cortisol concentration and self-confidence during rock climbing

A case–control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics

Abstract Background Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted. Results The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance. Conclusions This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance