Mitochondrial reactive oxygen species (mROS) play a crucial physiological role in intracellular signalling. However, high levels of ROS can overwhelm antioxidant defences and lead to detrimental modifications in protein, lipid and DNA structure and function. Ischaemia-reperfusion injury is a multifaceted pathological state characterised by excessive production of mROS.
View Article and Find Full Text PDFNociception is the process by which sensory neurons detect and encode potentially harmful environmental stimuli to generate behavioral responses. Nociceptor neurons exhibit plasticity in which their sensitivity to noxious stimuli and subsequent ability to drive behavior may be altered by environmental conditions, injury, infection, and inflammation. In some cases, nociceptor sensitization requires regulated changes in gene expression, and recent studies have indicated roles for post-transcriptional mechanisms in regulating these changes as an aspect of nociceptor plasticity.
View Article and Find Full Text PDFCSL040 is a soluble, recombinant fragment of the complement receptor 1 (CR1) extracellular domain that acts as an inhibitor of all three pathways of the complement system. Systemic toxicity, toxicokinetics (TK), and pharmacodynamics (PD) of CSL040 were assessed in two-week intravenous (IV) bolus studies in Han Wistar rats and cynomolgus monkeys. Recovery from any effects was evaluated during a four-week recovery period.
View Article and Find Full Text PDFThe clinical utility of hemoglobin-based oxygen carriers (HBOC) is limited by adverse heme oxidative chemistry. A variety of tyrosine residues were inserted on the surface of the γ subunit of recombinant fetal hemoglobin to create novel electron transport pathways. This enhanced the ability of the physiological antioxidant ascorbate to reduce ferryl heme and decrease lipid peroxidation.
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