Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a "proof of concept clinical trial" further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18:3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-alpha, IL-1 beta) was increased and anti-inflammatory TGF-beta markedly decreased with loss of membrane n-6 fatty acids linoleic (18:2n-6) and arachidonic acids (20:4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-beta, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS.

Grid effects

Zaha Hadid's Kartal Pendik Masterplan (2006) for a new city centre on the east bank of Istanbul proposes the redevelopment of an abandoned industrial site located in a crucial infrastructural node between Europe and Asia as a connecting system between the neighbouring areas of Kartal in the west and Pendik in the east. The project is organised on what its architects call a soft grid, a flexible and adaptable grid that allows it to articulate connections and differences of form, density and use within the same spatial structure [1]. Its final overall design constitutes only one of the many possible configurations that the project may take in response to the demands of the different areas included in the masterplan, and is produced from a script that is able to generate both built volumes and open spaces, skyscrapers as well as parks. The soft grid in fact produces a ‘becoming’ rather than a finite and definitive form: its surface space does not look like a grid, but is derived from a grid operation which is best explained by the project presentation in video animation. The grid here is a process of ‘gridding’, enacted according to ancient choreographed linear movements of measuring, defining, adjusting, reconnecting spaces through an articulated surface rather than superimposed on an ignored given like an indifferent colonising carpet.