Publications by authors named "Steven P Gieseg"

Background And Aims: Atherosclerotic plaques are characterized as being vulnerable to rupture based on a series of histologically defined features, including a lipid-rich necrotic core, spotty calcification and ulceration. Existing imaging modalities have limitations in their ability to distinguish between different materials and structural features. We examined whether X-ray spectral photon-counting computer tomography (SPCCT) images were able to distinguish key plaque features in a surgically excised specimen from the carotid artery with comparison to histological images.

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A key process in the development of atherosclerotic plaques is the recruitment of monocytes into the artery wall. Using spectral photon-counting computed tomography we examine whether monocyte deposition within the artery wall of ApoE-/- mouse can be detected. Primary mouse monocytes were labelled by incubating them with 15 nm gold nanoparticles coated with 11-mercaptoundecanoic acid The monocyte uptake of the particle was confirmed by electron microscopy of the cells before injection into 6-week-old apolipoprotein E deficient (ApoE-/-) mouse that had been fed with the Western diet for 10 weeks.

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CD36 is the key scavenger receptor driving the formation of cholesterol-loaded foam cells, the principal cellular component of atherosclerotic plaques. CD36 is down regulated by 7,8-dihydroneopterin, a potent superoxide and hypochlorite scavenging antioxidant generated by interferon-γ stimulated macrophages. 7,8-dihydroneopterin downregulates CD36 mRNA and protein levels so inhibiting macrophage foam cell formation .

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Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation.

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Background And Aims: Cluster of differentiation 36 (CD36) is a key scavenger receptor in the control of macrophage uptake of oxidised low-density lipoproteins (oxLDL). CD36 expression levels are not down regulated by intracellular cholesterol but are upregulated by oxidised low density lipoprotein (oxLDL) leading to the formation of lipid loaded foam cells, a major constituent of atherosclerotic plaques. We have previous shown that CD36 is down regulated by 7,8-dihydroneopterin, an antioxidant generated by γ-interferon activated macrophages.

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7,8-Dihydroneopterin protects cells intracellularly from oxidative stress-induced death, but its mode of transport across the cell membrane is unknown. Nucleosides, such as guanosine, are transported nucleoside transporters of the equilibrative and concentrative forms. Therefore, the objective of this study was to identify which membrane transporters are responsible for 7,8-dihydroneopterin transport in cells and whether this is necessary for protection against oxidative stress.

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Clinical measurement of neopterin has been extensively used as a marker of inflammation but the in vivo mechanism generating neopterin is poorly understood. Neopterin is described as the oxidation product of 7,8-dihydroneopterin, a potent antioxidant generated by monocyte/macrophages in response to interferon-γ. While peroxyl and hydroxyl scavenging generates dihydroxanthopterin, hypochlorite efficiently oxidises 7,8-dihydroneopterin into neopterin, but this reaction alone does not explain the high levels of neopterin seen in clinical data.

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Objectives: To evaluate pterins as diagnostic biomarkers of exercise-induced stress.

Design: Systematic review of the literature.

Methods: MEDLINE, Scopus and Web of Science were searched in March 2019 for relevant literature.

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We performed a systematic review of the literature to evaluate pterins as biomarkers of mechanical and impact-induced trauma. MEDLINE and Scopus were searched in March 2019. We included in vivo human studies that measured a pterin in response to mechanical or impact-induced trauma with no underlying prior disease or complication.

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Context: Knee arthroplasty surgery is significant trauma, leading to an activated immune system causing inflammation and oxidative stress. Many current biomarkers are invasive, costly, and often slow to analyse, limiting their use for rapid inflammatory measurements.

Objectives: We have examined the use of urinary neopterin and total neopterin in knee arthroplasty patients to non-invasively measure oxidative stress and inflammation from immune system activation.

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Background: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2.

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Neopterin has been extensively used as a clinical marker of immune activation during inflammation in a wide range of conditions and stresses. However, the analysis of neopterin alone neglects the cellular reactions that generate it in response to interferon-γ. Neopterin is the oxidation product of 7,8-dihydroneopterin, which is a potent antioxidant generated by interferon-γ-activated macrophages.

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Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells.

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Background: Coaches continually seek new ways of doing things and also refine existing techniques to improve sporting performance. Coaches are currently experimenting using ischaemic preconditioning (IPC) over consecutive days in the hope of improving competitive performances.

Aims: First, to quantify the physiological impact of 1 week of IPC on simulated Keirin cycling performance.

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The role of CD36 in oxidised low-density lipoprotein (oxLDL) mediated cell death was examined by down regulating the receptor level with the macrophage generated antioxidant 7,8-dihydroneopterin. Down regulation of CD36 protein levels in human monocyte derived macrophages by 7,8-dihydroneopterin corresponded to a decrease in CD36-mRNA. The oxidation products of 7,8-dihydroneopterin, dihydroxanthopterin and neopterin did not significantly down regulate CD36.

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Background And Aims: The efficiency of N assimilation in response to defoliation is a critical component of plant regrowth and forage production. The aim of this research was to test the effect of the internal C/N balance on NO3- assimilation and to estimate the associated cytokinin signals following defoliation of perennial ryegrass ( Lolium perenne L. 'Grasslands Nui') plants.

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Combative sport is one of the most physically intense forms of exercise, yet the effect of recovery interventions has been largely unexplored. We investigated the effect of cold-water immersion on structural, inflammatory, and physiological stress biomarkers following a mixed martial arts (MMA) contest preparation training session in comparison with passive recovery. Semiprofessional MMA competitors (n = 15) were randomly assigned to a cold-water immersion (15 min at 10 °C) or passive recovery protocol (ambient air) completed immediately following a contest preparation training session.

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Objectives: We investigated the level of cardiovascular stress associated with professional rugby union and whether these changes could be explained through external workload systems like GPS and video analysis.

Design: Urine samples (14 in game one and 13 in game two) were collected from professional rugby players before, immediately post- and 36h post-play in two consecutive games.

Methods: Urine was analysed for NT-proBNP by ELISA.

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What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise.

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This study investigated a means of quantifying urinary myoglobin using a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method that is an alternative measure of exercise-induced muscle damage. It also investigated the effect of storage and alkalization on urinary myoglobin stability issues. An RP-HPLC method was validated by precision and repeatability experiments.

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Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase.

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The adsorption of proteins at solid-liquid interfaces is important in biosensor and biomaterial applications. Marine mussels affix themselves to surfaces using a highly cross-linked, protein-based adhesive containing a high proportion of L-3,4-dihydroxyphenylalanine (DOPA) residues. In this work, the effect of DOPA residues on protein adhesion on stainless steel surfaces was studied using a quartz crystal microbalance with dissipation system.

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Rugby union is a physical demanding sport that requires optimum recovery between games to maintain performance levels. Analysis of four unique biochemical markers of stress is measured here to determine which recovery strategy currently in use by a professional team provides the necessary requirements for sustained performance. Urine and saliva samples were collected from 37 professional rugby players before, immediately after and 36 hours after five home games, and analysed by enzyme linked immunosorbent assay and high performance liquid chromatography for urinary myoglobin, total neopterin (NP; NP + 7,8-dihydroneopterin), salivary cortisol and immunoglobulin A.

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Rugby union is a physically intense intermittent sport coupled with high force collisions. Each position within a team has specific requirements which are typically based on speed, size and skill. The aim of this study was to investigate the contemporary demands of each position and whether they can explain changes in psychophysiological stress.

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Background: Rugby is a highly popular team contact sport associated with high injury rates. Specifically, there is a chance of inducing internal lung injuries as a result of the physical nature of the game. Such injuries are only identified with the use of specific invasive protocols or equipment.

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