MPP+-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress

Accumulating evidence suggests that endogenous dopamine may act as a neurotoxin and thereby participate in the pathophysiology of Parkinson’s disease (PD). Cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of PD due to its ability to generate reactive oxygen species (ROS). Inhibition of COX-2 leads to neuroprotection by preventing the formation of dopamine-quinone. In this study, we examined whether dopamine mediates 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in primary ventral mesencephalic (VM) neurons, an in vitro model of PD, and if so, whether the protective effects of COX-2 inhibitors on dopamine mediated MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis result from the reduction of ROS. Reserpine, a dopamine-depleting agent, significantly reduced VM neurotoxicity induced by MPP+, whereas dopamine had an additive effect on MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis. However, inhibition of COX-2 by a selective COX-2 inhibitor (DFU) or ibuprofen significantly attenuated MPP+-induced VM cell toxicity and VM dopaminergic cell apoptosis, which was accompanied by a decrease in ROS production in VM dopaminergic neurons. These results suggest that dopamine itself mediates MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis in the presence of COX-2

A comparative thematic review of vocational leadership literature from the USA, Great Britain and Australia

Vocational education and its leadership is an important sphere of economic activity worldwide and is being impacted by several trends including: the increasing significance and centrality of skills development in today’s economies; economic trends associated with globalisation (internationalisation of education and emergence of global labour markets); and demographic trends resulting in ageing populations and workforces. Leadership in vocational education contexts is crucial to the economic success of this sector. The aim of this paper is to provide a comparative thematic review of the research and literature on leadership in vocational education between the USA, Great Britain and Australia posed by the research question, ‘What are the key leadership issues facing vocational education and training sectors in the USA, Great Britain and Australia?’ This study contributes to the research and literature by identifying key impact factors for vocational education leadership in these nations over the last 13 years. Results from the comparative review established the following three key issues: a concern over equity and diversity; the importance of change management; and leadership skills and their development. Although leadership competencies are the subject of some debate there appears to be a broad consensus that leaders are developed not only by formal courses, but more importantly by on-the-job experiential learning. The future development of leaders within vocational education is discussed in relation to the implications for policy and practice, and suggestions for future research are provided

Serum deprivation and re-addition: Effects on cyclooxygenase inhibitor sensitivity in cultured glia

A number of drugs were assessed for their ability to inhibit stimulus-evoked prostanoid synthesis in cultured glia. These drugs included non-selective cyclooxygenase (COX) inhibitors and those considered to be selective for the inducible isoform of this enzyme (COX-2). Experiments were carried out on normal cultures and those which had been maintained in serum-free growth medium for four days then re-exposed to serum for a further seven days. All of the drugs tested elicited concentration-dependent inhibitions of arachidonic acid (AA)-stimulated thromboxane B2 (TXB2) accumulation in normal cultures with the following rank order of potency: indomethacin > piroxicam > nimesulide = NS398 > ibuprofen ≫ aspirin > paracetamol. In cultures which had been deprived of serum for four days, basal and AA-stimulated TXB2 production was considerably reduced, as was the amount of COX immunoreactivity determined by Western blotting. Basal and AA-stimulated TXB2 production together with COX immunoreactivity were restored to control levels by the re-addition of serum to serum-deprived cultures for 7 days. In these cultures, the rank order of potency was: indomethacin > piroxicam ≫ ibuprofen > nimesulide = NS398 ≫ aspirin > paracetamol; however, there were marked charges in the apparent IC50 values for particular drugs. Indomethacin, piroxicam and aspirin were very similar to control, but the potencies of ibuprofen (3-fold), NS398 (30-fold) and nimesulide (40-fold) were found to be decreased when compared to control. Paracetamol, on the other hand, was found to be almost 3-fold more potent under these conditions. Glia appear to express a COX with a novel sensitivity to particular inhibitors following serum deprivation and re-addition