Quantification of urinary excretion of ethosuximide enantiomers and their major metabolites in the rat.

A chiral gas chromatographic assay has been developed for quantitative analysis of ethosuximide and its major metabolites in rat urine. The extraction procedure was found to be precise and reproducible. Recovery was in the range of 94-98%, intraday CV(%) was 0.92% for (S)-ethosuximide (50 mug/ml) and 0.51% for (R)-ethosuximide (50 mug/ml). Interday CV(%) was 1.12% for (S)-ethosuximide and 0.72% for (R)-ethosuximide. The limit of detection was determined to be around 0.01 mug/ml for each enantiomer. Following administration of rac-ethosuximide by i.v., i.p. and oral routes, unchanged ethosuximide was detected in urine up to 72h after drug administration. The appearance of all detected metabolites occurred Within 24h of drug administration. Significantly more (S)-ethosuximide was excreted unchanged than (R)-ethosuximide with all three routes studied. A substantial amount of the drug was eliminated as the 2-(1-hydroxyethyl)-2-methylsuccinimide (2 pairs of diastereoisomers). Much less drug was eliminated as the 2-ethyl-3-hydroxy-2-methylsuccinimide with only one diastereoisomer observed. Examination of the one pair of diastereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide that was resolved showed preferential excretion of one isomer. Comparison of both pairs of diastereoisomers showed that one pair was formed in preference to the other with a ratio of approximately 0.8:1. It is concluded that stereoselective metabolism of ethosuximide occurs. Copyright (C) 2001 John Wiley & Sons, Ltd. Author Keywords: chiral pharmacokinetics; ethosuximide enantiomers; metabolism; rat; urinary excretion; gas chromatography

The African National Congress and its Critics: 'Predatory Liberalism', Black Empowerment and Intra-Alliance Tensions in Post-Apartheid South Africa

Post-apartheid South Africa is characterized by centralized, neo-liberal policymaking that perpetuates, and in some cases exaggerates, socio-economic inequalities inherited from the apartheid era. The African National Congress (ANC) leadership’s alignment with powerful international and domestic market actors produces tensions within the Tripartite Alliance and between government and civil society. Consequently, several characteristics of ‘predatory liberalism’ are evident in contemporary South Africa: neo-liberal restructuring of the economy is combined with an increasing willingness by government to assert its authority, to marginalize and delegitimize those critical of its abandonment of inclusive governance. A new form of oligarch power, combining entrenched economic interests with those of a new ‘black bourgeoisie’ promoted by narrowly implemented Black Economic Empowerment policies, diminishes prospects for broad-based socio-economic transformation. Because the new policy environment is failing to resolve tensions between global market demands for increasing market liberalization and domestic popular demands for poverty-alleviation and socio-economic transformation, the ANC leadership is forced increasingly to confront ‘ultra-leftists’ who are challenging its credentials as defender of the National Democratic Revolution which was the cornerstone in the anti-apartheid struggle.

The New Face of Global Hollywood: Black Hawk Down and the Politics of Meta-Sovereignty

This paper uses Ridley Scott’s 2001 film blockbuster Black Hawk Down to examine the claim that popular film is the ‘newest component of sovereignty’. While the topic of the film – the 1993 UN/US intervention in Somalia – lends itself to straightforward politicisation, this paper is equally interested in the film’s production history and its reception by global audiences. While initial reactions to the film focused on its ideological commitments (e.g. racism, collusion between Hollywood and the Pentagon, post-11 September patriotism), these readings continually posed an imagined ‘America’ against ‘the world’. This paper argues that Black Hawk Down is not about sovereignty as traditionally conceived, that is, about national interest shaping global affairs. Rather, Black Hawk Down articulates, and is articulated by, a new and emerging global order that operates through inclusion, management and flexibility. Drawing on recent theoretical debates over this new logic of rule, this paper illustrates how Black Hawk Down invoked much more diffuse, complex and deterritorialized categories than national sovereignty. In effect, Scott’s film goes beyond traditional notions of sovereignty altogether: its production, signification and reception deconstruct simple notions of ‘America’ and ‘the world’ in favour of what Hardt and Negri call ‘Empire’, what Zizek calls ‘post-politics’, and what we refer to as ‘meta-sovereignty’.

Changes in fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.