Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells.

The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 µmol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 µmol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE2, and LTB4 in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE2, and LTB4 production.

Maintenance of quality in a small cardiac surgical unit.

BACKGROUND: The purpose of this study was to evaluate the outcome of cardiac surgery at Allamanda Hospital which is a small private hospital carrying out less than 100 operations per year. METHODS: Data on patients undergoing cardiac surgery since 2002 were prospectively entered into a database. An analysis of this data is presented and compared with national and international benchmarks for results from larger national and international cardiac surgery units. RESULTS: From October 2002 to March 2007, there were 360 patients who underwent cardiac surgery in a small private cardiothoracic surgical unit (average of 80 patients per year). The average logistic EuroSCORE, Cleveland Clinic and Parsonnet Scores for the patients were 13%, 5.7 and 13.4, respectively. The mean logistic EuroSCORE observed in this study of 13% was substantially higher than those of other published series and institutions. The Allamanda results were compared with those from the European database (EuroSCORE), the STS and the Victorian National Cardiac Surgery Database. The overall observed mortality at Allamanda of 7.5% was lower than predicted by the mean logistic EuroSCORE of 13%. In comparison with the Victorian database, there was no significant difference in mortality for low-risk (additive EuroSCORE 0-3) and medium-risk (4-6) groups. Patients in the high-risk group with additive EuroSCOREs>or=7 were similarly divided into categories of three additive EuroSCOREs. There was no significant difference in any of the categories in the high-risk group. There was a greater proportion of high-risk (additive EuroSCORE>or=7) patients in the Allamanda series (P<0.0001). Patients in the Allamanda series were older (mean age 70.1) than the other published series (P<0.0001). The mean logistic EuroSCORE for the mortality group was 35.9+/-29.4% (6.4-65.3%). CONCLUSION: Low volume cardiac surgery can be undertaken safely in a small Australian private cardiothoracic unit with acceptable results. The trend towards improved outcomes for high-risk patients in larger institutions suggests that such patients undergoing elective procedures should be given the option of doing so in a larger centre. Ongoing quality assurance programs are equally important for large and small cardiac surgical units with participation in a national or international cardiac surgery database.