The haemodynamic responses to tracheal extubation at the end of surgery were compared with those occurring at tracheal intubation in 12 patients undergoing major elective surgery. Arterial cannulation was performed and heart rate (HR), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) were measured before induction of anaesthesia, before tracheal intubation, at the end of surgery and 1, 3 and 5 min after tracheal extubation. Laryngoscopy was avoided at the end of surgery. At all but the first of these stages, venous blood was obtained for measurement of plasma concentrations of adrenaline and noradrenaline. Rate-pressure product (RPP) was derived from SAP x HR. After tracheal intubation there were significant (P less than 0.05) increases in HR, DAP, RPP and in plasma concentrations of both adrenaline and noradrenaline. After extubation, only HR and adrenaline concentration at 5 min after extubation increased significantly compared with measurements at the end of surgery.
Proteolysis-inducing factor, a cachexia-inducing tumour product, is an N-glycosylated peptide with homology to the unglycosylated neuronal survival peptide Y-P30 and a predicted product of the dermcidin gene, a pro-survival oncogene in breast cancer. We aimed to investigate whether dermcidin is pro-survival in liver cells, in which proteolysis-inducing factor induces catabolism, and to determine the role of potentially glycosylated asparagine residues in this function. Reverse cloning of proteolysis-inducing factor demonstrated B100% homology with the dermcidin cDNA. This cDNA was cloned into pcDNA3.1 þ and both asparagine residues removed using site-directed mutagenesis. In vitro translation demonstrated signal peptide production, but no difference in molecular weight between the products of native and mutant vectors. Immunocytochemistry of HuH7 cells transiently transfected with V5-His-tagged dermcidin confirmed targeting to the secretory pathway. Stable transfection conferred protection against oxidative stress. This was abrogated by mutation of both asparagines in combination, but not by mutation of either asparagine alone. These findings suggest that dermcidin may function as an oncogene in hepatic as well as breast cells. Glycosylation does not appear to be required, but the importance of asparagine residues suggests a role for the proteolysis-inducing factor core peptide domain.
DCD and PIF-CP are proliferation and survival factors in prostate cancer cells subjected to stressors found in the prostate cancer microenvironment. Thus, DCD and specifically PIF-CP are potential targets for the treatment of prostate cancer.
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