Project (M.P.P.) - Simon Fraser University, 2006. / Theses (Master of Public Policy Program) / Simon Fraser University. Also issued in digital format and available on the World Wide Web.

published_or_final_version / Nursing Studies / Master / Master of Nursing

Hepatic ischaemia-reperfusion injury occurs when patients undergoing liver operations such as liver transplantation, tumour resection and shock. Intravenous and intrathecal administration of morphine can be used to provide analgesia prior or after liver surgery. It has been reported that systemically administered morphine conferred protective effect on numerous organs, including heart, brain and kidney. The focus of my research is to investigate the effect of intravenous and intrathecal morphine preconditioning on normal and cirrhotic livers. Further, PI3K/Akt, STAT3 and HO-1/iNOS pathways had been shown to ameliorate hepatic ischemia-reperfusion injury. Hence, we aim to investigate these possible signaling pathways associated with morphine mediated hepato-protection. A partial hepatic ischaemia reperfusion injury model in rats was used. The experiments were divided into two series: one involved in normal livers and the other one involved in cirrhotic livers. For the normal livers, morphine at different doses were administrated intravenously or intrathecally prior the onset of ischaemia, and the experiments were repeated with previous intravenous administration of naloxone methiodide (opioid receptor antagonist), or wortmannin (Akt inhibitor), respectively. For the cirrhotic livers, morphine at optimal doses were injected intravenously or intrathecally prior the onset of ischaemia. Those rats with only induced hepatic ischaemia-reperfusion injury only were marked as control groups. The effect of morphine preconditioning on hepatic architecture, apoptosis and liver function were evaluated respectively by hematoxylin-eosin (H&E) staining, Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) staining, the expression of cleaved Caspase-3, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the expression of phosphorylated Akt, phosphorylated JAK2, phosphorylated STAT3, HO-1 and iNOS were detected by Western Blot to determine the signaling pathways involved by intravenous and intrathecal morphine preconditioning. The normal livers series presented intravenous and intrathecal morphine preconditioning at the 100μg/kg, 10μg/kg, respectively, better persevered hepatic architecture when compared with control groups. The degree of liver cell apoptosis and expression of cleaved caspase-3 were also reduced by intravenous and intrathecal morphine preconditioning. In additional, intravenous and intrathecal morphine preconditioning ameliorated hepatocellular damage by reducing ALT&AST release. Moreover, the expressions of phosphorylated Akt and its downstream protein STAT3 were significantly increased by intravenous and intrathecal morphine preconditioning, compared with their respective control groups. The hepato-protective effect of intravenous and intrathecal morphine preconditioning was reversed by naloxone methiodide or wortmannin pretreatment. The similar pattern of protection was observed in cirrhotic livers. Both intravenous and intrathecal morphine preconditioning protected hepatic architecture much better than control groups. They also attenuated hepatic apoptosis degree and hepatocellular enzyme release. Furthermore, the expression of HO-1 was up-regulated, whereas the expression of iNOS was down-regulated by intravenous and intrathecal morphine preconditioning. In summary, this study provided evidence that intravenous and intrathecal morphine preconditioning could attenuate hepatic ischaemia-reperfusion injury in normal and cirrhotic livers. The involvement of opioid receptors, Akt/STAT3 pathway and HO-1 pathway might be the underlying mechanisms of morphine hepato-protection. Finally, the protective effect of morphine preconditioning might provide a potential therapeutic approach for clinical usage. / published_or_final_version / Anaesthesiology / Master / Master of Philosophy

No description available.

Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however, its mechanism of action remains elusive. Our results demonstrate a novel finding wherein IVIg treatment induces a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and that the liver is the organ of increased IL-11 transcription. Furthermore, we show that IL-11Rα knockout mice, although initially protected, become resistant to protection by IVIg during experimental autoimmune encephalomyelitis (EAE) and develop disease with a similar incidence and severity as control-treated IL-11Rα-/- mice. The inability of IVIg to prevent EAE in IL-11Rα-/- mice correlated with a failure of this agent to decrease IL-17 production by myelin-reactive T-cells in the draining lymph nodes. Finally, we show that IL-11 can directly inhibit IL-17 production by lymph node cells in culture. Together, these results implicate IL-11 as an important immune effector of IVIg in the amelioration of EAE.

Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however, its mechanism of action remains elusive. Our results demonstrate a novel finding wherein IVIg treatment induces a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and that the liver is the organ of increased IL-11 transcription. Furthermore, we show that IL-11Rα knockout mice, although initially protected, become resistant to protection by IVIg during experimental autoimmune encephalomyelitis (EAE) and develop disease with a similar incidence and severity as control-treated IL-11Rα-/- mice. The inability of IVIg to prevent EAE in IL-11Rα-/- mice correlated with a failure of this agent to decrease IL-17 production by myelin-reactive T-cells in the draining lymph nodes. Finally, we show that IL-11 can directly inhibit IL-17 production by lymph node cells in culture. Together, these results implicate IL-11 as an important immune effector of IVIg in the amelioration of EAE.

The purpose of this research was to compare the design of Dose Error Reduction Software (DERS) between smart pumps to determine which features affect the ability of nurses to safely and efficiently program intravenous medications. A high-fidelity usability experiment was conducted. Twenty-four Registered Nurses completed a series of infusion tasks, in a simulated clinical environment, using three smart pumps (Cardinal Alaris System, BBraun Infusomat, and Hospira Symbiq). Results found significant differences in nursing performance across the smart pumps. Nurses were more likely to override clinically inappropriate soft limit alerts when using BBraun Infusomat, than when using Hospira Symbiq or Cardinal Alaris System. Furthermore, when asked to program an infusion over a specific duration, nurses were found to make significantly more parameter entry errors when using Hospira Symbiq than when using Cardinal Alaris System. Results from this study will help set DERS design principles, and assist hospitals during their procurement processes.

The purpose of this research was to compare the design of Dose Error Reduction Software (DERS) between smart pumps to determine which features affect the ability of nurses to safely and efficiently program intravenous medications. A high-fidelity usability experiment was conducted. Twenty-four Registered Nurses completed a series of infusion tasks, in a simulated clinical environment, using three smart pumps (Cardinal Alaris System, BBraun Infusomat, and Hospira Symbiq). Results found significant differences in nursing performance across the smart pumps. Nurses were more likely to override clinically inappropriate soft limit alerts when using BBraun Infusomat, than when using Hospira Symbiq or Cardinal Alaris System. Furthermore, when asked to program an infusion over a specific duration, nurses were found to make significantly more parameter entry errors when using Hospira Symbiq than when using Cardinal Alaris System. Results from this study will help set DERS design principles, and assist hospitals during their procurement processes.

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.