A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice.

The tripeptide, glutathione (glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.

Role of dopamine D3 and serotonin 5-HT1A receptors in l-DOPA-induced dyskinesias and effects of sarizotan in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease

Sarizotan, a 5-HT1A agonist with additional affinity for D3 and D4 receptors, has been demonstrated to have anti-dyskinetic effects. The mechanism by which these effects occur is not clear. Using unilateral 6-hydroxydopamine-lesioned rats that received chronic intraperitoneal (ip) administration of L-3,4-dihydroxyphenylalanine (L-DOPA) we investigated the involvement of D3 and 5-HT1A receptors in the effects of sarizotan on contraversive circling and abnormal involuntary movements (AIMs). Before sensitization by chronic L-DOPA treatment (12.5 with 3.25 mg/kg benserazide ip, twice daily for 21 days), no effect of the selective D3 agonist, PD128907 (1 or 3 mg/kg ip), or the selectiveD3 antagonist,GR103691 (0.5 or 1.5 mg/kg ip), was observed. Treatment with sarizotan (1 or 5 mg/kg ip) dosedependently inhibited the L-DOPA-induced contraversive turning and AIMs. In co-treatment with the 5-HT1A antagonist, WAY100635 (1 mg/kg ip), sarizotan failed to affect this behaviour, confirming the prominent 5-HT1A receptor-mediated mechanism of action. In the presence of PD128907 (3 mg/kg ip), the effects of sarizotan on contraversive turning, locomotive dyskinesia and axial dystonia, but not on orolingual and forelimb dyskinesia, were blocked. On its own, PD128907 had no effect on the behavioural effects of L-DOPA except that it tended to reduce orolingual and forelimb dyskinesia. GR103691 had no effect on its own or in combination with sarizotan. These data identify an involvement of D3 receptors in the action of sarizotan on some, but not all L-DOPA-induced motor side effects. This selective involvement is in contrast to the more general involvement of 5-HT1A receptors in the anti-dyskinetic effects of sarizotan.

Popular culture : a resource for writing in secondary English classrooms

This chapter explores how a secondary English teacher working with students aged 14-15 enabled them to use their popular culture practices as a resource for writing. The chapter provides examples of conventional classroom situations in which this teacher created a space for students to bring their own semiotic resources to bear on the curriculum. It argues the need for English teachers to become sensitized to the complex literacy practices in which their students engage outside school and to the ways these practices are bound up with their social relationships and sense of identity. The discussion challenges conventional understandings of ‘reading’, ‘writing’, ‘speaking’, and ‘listening’ as components of the English curriculum, arguing that a more contemporary understanding of literacy must take into account the multi-modal practices in which students engage in beyond school.

Combining the forces of science and conservation to turn around the fortunes of shorebirds

At the start of the 21st century the majority of migratory wader (shorebird) populations are faced with serious threats. This commonly results from the continuous destruction of wetlands, their key habitat. Healthy wetlands are highly biodiverse and extremely vulnerable, and as functioning ecosystems particularly important for us humans for a sustained livelihood (artisanal fisheries, small-scale farming) and our well-being (effective water filtering and cleaning systems). In many parts of the world, wetlands have been seen as wastelands, or even as a source of threat (malaria). Many freshwater wetlands have been drained for agricultural use and mudflats have been reclaimed for settlement and urbanization. Wetlands are continuously squeezed by economic development and increasingly used for recreational activities, and their resources are, in general, notoriously overexploited.

Shear-free perfect fluids with a solenoidal electric curvature

We prove that the vorticity or the expansion vanishes for any shear-free perfect fluid solution of the Einstein field equations where the pressure satisfies a barotropic equation of state and the spatial divergence of the electric part of the Weyl tensor is zero.

Making sense of business intelligence : proposing a socio-technical framework for improved decision making in not-for-profit organisations

The authors of this paper argue that human intuition alone cannot be relied upon for strategic decision making in today’s business environment and that quality data intelligence is an imperative. The proposed project described in this paper is research-in-progress, action design research (ADR), to implement an appropriate information systems (IS) enabling enhanced organisational decision making. ADR is a new research method that draws on action research and design research in an organisational setting. In phase 1 of the project, a sociotechnical ‘sense-making’ approach is used to gather and analyse information and decision needs in a not-for-profit (NFP) association, Connections ACT. In phase 2, requirements are designed and modelled to build a conceptual framework that guides NFPs in improving business performance and reporting capability. Phase 3 is the evaluative stage when the framework is reflected upon and refined, with intervention in the organisation’s processes as a promising outcome.