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Abstract: Human non-functioning pituitary adenomas cause hypopituitarism or the compression of adjacent structures. At present, there is no available medical treatment for these tumours. The Notch3 pathway has an important role in the progression of non-functioning pituitary adenomas. We found, using reverse transcriptase–polymerase chain reaction, that Notch3 mRNA was significantly upregulated in clinically non-functioning pituitary adenomas, and, using Western blotting, that Notch3 protein was expressed at a higher level in non-functioning pituitary adenomas than in normal human pituitary tissue. In addition, using immunohistochemistry, we observed that Notch3 is highly expressed in the cytoplasm of adenoma cells compared to normal pituitary cells. These results suggest that the overexpression of Notch3 mRNA and protein by non-functioning pituitary adenomas may facilitate the growth of these tumours. Our results provide the first comprehensive analysis of Notch3 mRNA and protein overexpression in non-functioning pituitary tumours. This study provides new insights into the pathogenesis of human non-functioning pituitary adenomas and implicates the Notch3 pathway as a molecular therapeutic target for their treatment. [Copyright &y& Elsevier]

Abstract: Brain ischemic postconditioning is the induction of brief periods of ischemia–reperfusion during the early stages following ischemia, and it has been shown to produce neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. Glutamate excitotoxicity is one cause of postischemic neuronal death. Glutamine synthetase (GS) is an enzyme that is expressed in glial cells and may affect glutamate excitotoxicity. We induced global ischemia in rats and performed postconditioning with 6 cycles of 10seconds reperfusion and 10seconds reocclusion before final reperfusion. Hematoxylin and eosin staining revealed extensive neuronal loss (44.0±2.8% cell survival) in the hippocampal CA1 region. Ischemic postconditioning decreased neuronal death (82.0±5.6% cell survival; p <0.05). Western blotting revealed significantly increased GS expression in the hippocampus for the ischemia–reperfusion group over time compared with the sham group (p <0.05). Ischemic postconditioning resulted in significantly increased (p <0.05) GS expression compared with both the sham and ischemia–reperfusion groups, suggesting that upregulation of GS expression after ischemia constitutes a neuroprotective mechanism. [Copyright &y& Elsevier]

Abstract: The objective of this study was to examine the prognostic significance of health-related quality of life (HQOL) parameters combined with baseline clinical factors in patients undergoing neurosurgery for treatment of meningioma. A total of 147 patients (61 male, 86 female; mean age 43years, range 5–77years) who underwent resection of a meningioma between January 2002 and December 2004 were studied. HQOL was evaluated using a modified questionnaire based on the World Health Organization Quality of Life-100 Scale and the Karnofsky Performance Scale. The relationships between HQOL and clinical history, radiological findings, extent of resection, histological grade and recurrence were investigated using multivariate analysis. The mean HQOL score was 73.94±1.79 for preoperative patients with meningioma, 84.88±2.14 for postoperative patients, and 91.13±1.61 for healthy controls. HQOL for patients with meningioma was significantly lower than that for normal controls (P <0.001), and postoperative patients had a more satisfactory HQOL than preoperative (P <0.05). Cox proportional hazards analysis showed that significant predictors of health-related quality of life were tumor size, extent of surgical excision, and histologic grade. Multivariate backward logistic regression yielded the regression equation HQOL=119.1097 – 1.5002X 3 – 8.6650X 6 – 10.4210X 7 (R=0.7466; where X 3 is tumor size, X 6 is extent of surgical excision, and X 7 is the histologic grade of the tumor). This equation can be used preoperatively to predict the HQOL of meningioma patients after neurosurgery. A specialized HQOL questionnaire for patients with meningioma provides useful information when planning the operative procedure, and may make it more likely that patients have a satisfactory HQOL after surgery. [Copyright &y& Elsevier]