Christopher W Armstrong - University of Melbourne
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Christopher W Armstrong
University of Melbourne
Publications Authored By Christopher W Armstrong
Blood samples were taken at enrolment, then 1h, 3h and 24h post-enrolment for the examination of cellular, protein and genetic changes. Patients with subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed increased intracellular concentrations of GzmB in all cell populations investigated (CD8(+), CD8(-) and Natural Killer [NK] cells). Infarct patients, however, demonstrated significantly reduced GzmB gene expression and increased circulating MMP-9 and S100A12 levels in contrast to transient ischaemic attack (TIA) patients or healthy controls. Furthermore, a pronounced neutrophilia was noted in the infarct and haemorrhage groups, while TIA patients (n=9) reflected healthy controls (n=10). These findings suggest a spectrum of immune response during stroke. TIA showed few immunological changes in comparison to infarct and haemorrhage, which demonstrated inhibition of GzmB production and a rise in neutrophil numbers and neutrophil-associated mediators. This implies a greater role of the innate immune system. These markers may provide novel targets for inhibition and reduction of secondary injury.
The overwhelming body of evidence suggests an oxidative environment with the minimal utilization of mitochondria for efficient energy production. This is coupled with a reduced excretion of amino acids and nitrogen in general. Metabolomics is a developing field that studies metabolism within a living system under varying conditions of stimuli. Through its development, there has been the optimisation of techniques to do large-scale hypothesis-generating untargeted studies as well as hypothesis-testing targeted studies. These techniques are introduced and show an important future direction for research into complex illnesses such as CFS.
Identified metabolites that were found to be significantly altered between the groups were subjected to correlation analysis to potentially elucidate disturbed metabolic pathways. Our results showed a significant reduction of glutamine (P=0.002) and ornithine (P<0.05) in the blood of the CFS samples. Correlation analysis of glutamine and ornithine with other metabolites in the CFS sera showed relationships with glucogenic amino acids and metabolites that participate in the urea cycle. This indicates a possible disturbance to amino acid and nitrogen metabolism. It would be beneficial to identify any potential biomarkers of CFS for accurate diagnosis of the disorder.