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

Reconsidering the origins of protest in South Africa: some lessons from Cape Town and Pietermaritzburg

Protest politics in South Africa has a long history and has been deployed differentially in different historical moments. Whereas protests formed an important vehicle during the fight against apartheid, their rebirth and propulsion to the centre of the struggles in the post-apartheid dispensation have come as a surprise to many. A majority of these protests, so-called ‘service delivery protests’, are reported as emanating from communities’ dissatisfaction with municipal service delivery as well as problems relating to lack of communication between council and councillors on the one hand and citizens on the other. In this article, we interrogate data from five study sites located in Cape Town and Pietermaritzburg. While we found support for the importance of service delivery, our data contradicts many widely held assertions as regards what causes these protests. We were able to show, for example, that these so-called ‘service delivery protests’ may actually emanate from reasons that extend beyond service delivery. Since our data indicates that levels of participation in Cape Town are higher than in Pietermaritzburg on the one hand, illustrating perhaps the different provincial contexts, there is also variation between the relatively high participation rates of the ‘black African’ sites of Langa and Khayelitsha, on the one hand, and the lower rates of the ‘coloured’ site of Bonteheuwel, on the other, which we ascribe to the disengagement of the community in Cape Town, from both local and national politics.Department of HE and Training approved lis

IMP Dehydrogenase Inhibitors as Immunomodulators

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74880/1/j.1749-6632.1993.tb35869.x.pd

Individual Differences in Cerebral Blood Flow in Area 17 Predict the Time to Evaluate Visualized Letters

Sixteen subjects closed their eyes and visualized uppercase letters of the alphabet at two sizes, as small as possible or as large as possible while remaining “visible.” Subjects evaluated a shape characteristic of each letter (e.g., whether it has any curved lines), and responded as quickly as possible. Cerebral blood flow was normalized to the same value for each subject, and relative blood flow was computed for a set of regions of interest. The mean response time for each subject in the task was regressed onto the blood flow values. Blood flow in area 17 was negatively correlated with response time (r = -0.65), as was blood flow in area 19 (r = -0.66), whereas blood flow in the inferior parietal lobe was positively correlated with response time (r = 0.54). The first two effects persisted even when variance due to the other correlations was removed. These findings suggest that individual differences in the activation of specific brain loci are directly related to performance of tasks that rely on processing in those loci.Psycholog

At risk of being risky: The relationship between "brain age" under emotional states and risk preference.

Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10-25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the "brain age" of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that "brain age" across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception - a pattern exemplified greatest in young-adults (ages 18-21). The results are suggestive of a specified functional brain phenotype that relates to being at "risk to be risky.

Of “raisins” and “yeast”: mobilisation and framing in the East German revolution of 1989

There is no shortage of literature on the social movements that arose in East Germany in 1989. Numerous studies have shed light upon the nature, scale and dynamics of the uprising of that year. But on certain issues questions remain. No consensus exists, for example, on the relationship between the “civic groups” (New Forum, Democratic Awakening, etc.) and the street protests of the autumn of 1989. Were these simply two facets of a single movement? Or are they better characterised as two distinct streams within the same movement delta? Did the street protests push the civic movement activists into the limelight? Or is it more accurate to say, with Reinfried Musch, that “the civic movement brought the people onto the streets”?1 This paper considers two contrasting interpretations of these issues, and finds both wanting. An alternative interpretation is offered, one that draws upon Marc Steinberg's “dialogical” development of frame theory

Visual Mental Imagery Activates Topographically Organized Visual Cortex: PET Investigations

Cerebral blood flow was measured using positron emission tomography (PET) in three experiments while subjects performed mental imagery or analogous perceptual tasks. In Experiment 1, the subjects either visualized letters in grids and decided whether an X mark would have fallen on each letter if it were actually in the grid, or they saw letters in grids and decided whether an X mark fell on each letter. A region identified as part of area 17 by the Talairach and Tournoux (1988) atlas, in addition to other areas involved in vision, was activated more in the mental imagery task than in the perception task. In Experiment 2, the identical stimuli were presented in imagery and baseline conditions, but subjects were asked to form images only in the imagery condition; the portion of area 17 that was more active in the imagery condition of Experiment 1 was also more activated in imagery than in the baseline condition, as was part of area 18. Subjects also were tested with degraded perceptual stimuli, which caused visual cortex to be activated to the same degree in imagery and perception. In both Experiments 1 and 2, however, imagery selectively activated the extreme anterior part of what was identified as area 17, which is inconsistent with the relatively small size of the imaged stimuli. These results, then, suggest that imagery may have activated another region just anterior to area 17. In Experiment 3, subjects were instructed to close their eyes and evaluate visual mental images of upper case letters that were formed at a small size or large size. The small mental images engendered more activation in the posterior portion of visual cortex, and the large mental images engendered more activation in anterior portions of visual cortex. This finding is strong evidence that imagery activates topographically mapped cortex. The activated regions were also consistent with their being localized in area 17. Finally, additional results were consistent with the existence of two types of imagery, one that rests on allocating attention to form a pattern and one that rests on activating stored visual memories.Psycholog

CD28 and staphylococcal enterotoxins synergize to induce MHC-independent T-cell proliferation

The bacterial exotoxins staphylococcal enterotoxin A and B (SEA and SEB) mediate disease through their effects on T lymphocytes. In this manuscript we have demonstrated that both SEA and SEB can directly activate purified T cells in the absence of accessory cells as determined by a transition from G0 to G1 and induction of IL-2 receptor expression. However, neither SEA nor SEB alone was sufficient to result in T-cell proliferation. The induction of T-cell proliferation by SEB or SEA required the addition of a second costimulatory signal. This could be provided by either accessory cells or monoclonal antibody stimulation of CD28. As previously reported, T-cell proliferation induced by enterotoxin in the presence of accessory cells was partially inhibited by a blocking antibody against class II MHC. In contrast, in purified T cells when costimulation was provided through CD28, proliferation was not inhibited by class II antibody, and HLA-DR expression was not detectable. In addition, costimulation through CD28 was partially resistant to the effects of cyclosporin A. These results demonstrate that CD28 costimulation is sufficient to induce proliferation of enterotoxin-activated T cells, and that this effect is independent of class II MHC expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29738/1/0000074.pd