The rates in Japan of cardiac arrest and death during anesthesia and surgery due to all etiologies as well as those totally attributable to anesthesia are comparable to those of other developed countries.

One-lung ventilation induced inflammatory responses of the bronchial epithelia in the dependent lung and the nondependent lung during thoracic surgery. In addition, these inflammatory responses were more augmented in the dependent lung than in the nondependent lung.

To assess the effect of sevoflurane anaesthesia on hepatocellular integrity, we measured plasma concentrations of glutathione S-transferase (GST) before anaesthesia and 1, 3, 6 and 24 h after the end of anaesthesia in 41 healthy, Japanese patients undergoing elective, body surface surgery. Sevoflurane (approximately 1.0 MAC) was delivered in 50-66% nitrous oxide in oxygen via a circle system, with a fresh gas flow of 6 litre min-1. Ventilation was spontaneous in all patients. Mean duration of anaesthesia was 101 min. Concentrations of GST increased significantly 1 h after the end of anaesthesia (P = 0.0075), but this was not significantly different from preoperative concentrations at 3, 6 and 24 h. Three patients developed a large secondary increase in GST concentrations at 24 h. The increase observed at 1 h was probably a result of reduced total liver blood flow; the mechanism for the secondary increase at 24 h is unclear but the possibility that products of sevoflurane biotransformation are responsible cannot be excluded.

Substance P (SP) acting through substance P receptor (SPR) increases the proliferation of glioblastoma cells. At the molecular level, stimulation of SPR in human U373 MG glioblastoma cells results in phosphorylation of mitogen-activated protein kinases ERK1/2. Examination of the underlying mechanism reveals that SPR mediates ERK1/2 phosphorylation in a calcium-dependent manner. Surprisingly, blockade of epidermal growth factor receptor (EGFR), which is transactivated by SPR, has a minimal effect on SPR-mediated ERK1/2 phosphorylation. However, SPR-mediated ERK1/2 phosphorylation is significantly reduced by the Src kinase inhibitor PP2. Interestingly, ERK1/2 in U373 MG cells is also activated by several other mitogenic G protein-coupled receptors (GPCRs) including alpha(1B)-adrenergic, M(3)-muscarinic, and H(1)-histaminergic in an Src-dependent manner. We conclude that c-Src is a mediator of SP-stimulated ERK1/2 phosphorylation in human U373 MG glioblastoma cells.

I/R injury is the main cause for hepatic dysfunction and failure after liver transplantation and liver resection. Therefore, reduction of I/R injury is the most important goal to improve the outcome of these procedures. Olprinone is a newly developed selective phosphodiesterase III inhibitor, which has been reported to ameliorate renal I/R injury in rats. However, no clear evidence for the actions of olprinone on inflammatory response after hepatic I/R injury has been disclosed thus far. Our study was designed to evaluate the action of olprinone on the hepatic I/R injury in rats. Olprinone increased the cyclic adenosine monophosphate level in injured liver tissue and ameliorated the liver injury after hepatic I/R. Moreover, olprinone suppressed the activation of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB, cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), and intercellular adhesion molecule 1 expression in liver after hepatic I/R. These observations suggest that olprinone protects liver against I/R injury via the elevation of cyclic adenosine monophosphate level and suppression of intercellular adhesion molecule 1 expression and cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), possibly by interfering with the signaling pathways of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB in rats.