BJA/RCoA Project Grant

The successful applicant for the BJA / RCoA Project Grant was:

Principal Applicant
Dr Carsten Bantel
HEFC-E Clinical Senior Lecturer, Imperial College London

Title
Metabolic Characterisation of Human Models of Burn Pain

Amount
£30,445 conditional on ethical approval

Scientific Abstract
Burn pain is still a significant clinical problem that often defies treatment. One potential reason for this is that - instead of being a single entity - it likely comprises different subtypes, each with different underlying mechanisms. However, mechanism based rather than aetiology based treatments have only just recently emerged as therapeutic concepts. At present the principal obstacle in clinical practice to this approach is the lack of biomarkers to indicate specific pathways. This study aims to close this gap. Therefore, two models of burn pain (thermal heat; ultraviolet-B light (sun-burn) are going to be employed in healthy human volunteers. They will be compared to a widely accepted model of neurogenic inflammation (topical capsaicin). After induction of pain, interstitial fluid will be sampled from the affected skin with microdialysis probes. Sample fluid will be analysed for key metabolites and entire metabolite profiles. In addition, the somato-sensory changes in the skin induced by the respective pain models will be quantified. The resultant values for mechanical hyperalgesia and allodynia as well as the changes in heat and pain thresholds will be correlated with the obtained metabolite signature. The thus identified interactions between metabolites and sensory changes should build the basis for the development of biomarkers for burn pain.
 Final Report from Dr C Bantel (538 KB)
 2014 Report from Dr C Bantel  (51 KB)
 2013 Report from Dr C Bantel (21 KB)



Principal Applicant
Professor Helen Galley
Professor of Anaesthesia & Intensive Care, School of Medicine & Dentistry
University of Aberdeen

Title
Development of a "Glo-Cell" biosensor to investigate the role of zinc in sepsis

Amount
£23,510
Project was originally submitted under the AAGBI/Anaesthesia category but was funded by the British Journal of Anaesthesia (BJA) with the agreement of the Grant Committee.

Scientific Abstract
Sepsis induced organ failure is the main cause of death on the intensive care unit. Oxidative damage to mitochondria, with reduced ATP production, has been consistently described. We propose to develop a biosensor of mitochondrial function using human endothelial cells. Cells will be modified so they express the gene for firefly luciferase, which uses ATP to convert luciferin to light. The light is as a measure of ATP production and thereby mitochondrial function. This biosensor will be used to measure ATP production under conditions of oxidative stress induced by various treatments including conditions mimicking sepsis. The model will be validated using other measures of mitochondrial function and by the effects of several antioxidants which act specifically in mitochondria. We will also determine the performance of the biosensor under conditions of different zinc environments on mitochondrial function under sepsis-like conditions. Zinc depletion has been shown to modulate responses to sepsis and inflammation. The biosensor will enable real time measurements of ATP production and rapid testing of novel interventions for oxidative stress and mitochondrial function. It will have the potential beyond this proposal, for applications in other diseases.

 First Year Progress Report from Prof Galley (49 KB)
 Final Report from Prof Galley (504 KB)