Jennifer Chan

Mitochondrial toxicity in the era of HAART: evaluating venous lactate and peripheral blood mitochondrial DNA in HIV-infected patients taking antiretroviral therapy.

Nucleoside analogs can induce mitochondrial toxicity by inhibiting the human DNA polymerase γ. This can lead to a wide range of clinical toxicities, from asymptomatic hyperlactatemia to death. Despite their technical and physiological variability, we propose that random venous lactate measurements can be useful to monitor the development of nucleoside-related mitochondrial toxicity. Recently, we have developed an assay that can measure changes in mitochondrial DNA levels in peripheral blood cells. Using this assay we have characterized changes in mitochondrial DNA (mtDNA) relative to nuclear DNA (nDNA) in peripheral blood cells of patients with symptomatic nucleoside-induced hyperlactatemia. Our results demonstrate that symptomatic hyperlactatemia was associated with markedly low mtDNA/nDNA ratios, which were on average 69% lower than HIV-uninfected controls and 45% lower than HIV-infected asymptomatic/antiretroviral naïve controls. A statistically significant (p = .016) increase in mtDNA/nDNA ratio was observed following discontinuation of antiretroviral therapy. The mtDNA/nDNA ratio remained stable among selected patients who reintroduced antiretroviral therapy with stavudine (d4T)-sparing regimens. Of note, the decline in mtDNA preceded the increase in venous lactate levels. More recently we have evaluated changes in the mtDNA/nDNA ratio in relation to selected antiretroviral drug regimens in a cross-sectional study on a non-random sample of participants within the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program. Eligible patients had continuously received saquinavir plus ritonavir with either nevirapine (n = 20), lamivudine (n = 15), d4T (n = 53) or lamivudine + d4T (n = 69), for 4 to 30 months. d4T-sparing regimens were associated with a higher median mtDNA/nDNA ratio than d4T-containing regimens (p = .016), despite the fact that study patients had received d4T-containing regimens for a shorter median time than patients taking d4T-sparing regimens (13 versus 25 months, p = .002). In summary, mtDNA levels are significantly decreased among patients who develop symptomatic, nucleoside-related hyperlactatemia, an effect reversed upon therapy discontinuation. Furthermore, mtDNA/nDNA ratios were statistically significantly lower in patients taking d4T-containing regimens than in those taking selected d4T-sparing regimens in a population setting. These results suggest that measurement of this parameter should be investigated as a potential clinical management tool.

Between efficiency, capability and recognition: competing epistemes in global governance reforms

This article examines global governance reforms as a site of contestation between three different ‘truths’/epistemes (the market, human rights principles, and cultural identity) in terms of the competing principles of efficiency, capability, and recognition. Nancy Fraser’s conceptions of participation parity and a dialogical approach of recognition to examine diverse global governance reform proposals are used to argue that a neo‐liberal developmentalist approach (Washington Consensus at the core and development on the edges) and a human developmentalist approach (human rights on top without challenging a neo‐liberal core)—both built upon a paradigm of redistribution—fall short of addressing the crisis of recognition. What is needed is more than a question of more funds, but rather a fundamental recognition and representation of the majority developing world as equal partners in global governance. Education in postdevelopmentalism takes on the broader significance of cultural revival as resistance to market fundamentalism.

An ABCA1-independent pathway for recycling a poorly lipidated 8.1 nm apolipoprotein E particle from glia

Lipid transport in the brain is coordinated by glial-derived lipoproteins that contain apolipoprotein E (apoE) as their primary protein. Here we show that apoE is secreted from wild-type (WT) primary murine mixed glia as nascent lipoprotein subspecies ranging from 7.5 to 17 nm in diameter. Negative-staining electron microscropy (EM) revealed rouleaux, suggesting a discoidal structure. Potassium bromide (KBr) density gradient ultracentrifugation showed that all subspecies, except an 8.1 nm particle, were lipidated. Glia lacking the cholesterol transporter ABCA1 secreted only 8.1 nm particles, which were poorly lipidated and nondiscoidal but could accept lipids to form the full repertoire of WT apoE particles. Receptor-associated-protein (RAP)-mediated inhibition of apoE receptor function blocked appearance of the 8.1 nm species, suggesting that this particle may arise through apoE recycling. Selective deletion of the LDL receptor (LDLR) reduced the level of 8.1 nm particle production by approximately 90%, suggesting that apoE is preferentially recycled through the LDLR. Finally, apoA-I stimulated secretion of 8.1 nm particles in a dose-dependent manner. These results suggest that nascent glial apoE lipoproteins are secreted through multiple pathways and that a greater understanding of these mechanisms may be relevant to several neurological disorders.

Scaling up the Ebola Response: What we Learned from AIDS Activism

Volume 1 | Issue 1 Scaling up the Ebola Response: What we Learned from AIDS Activism Chan J* Department of Educational Studies, Faculty of Education, University of British Columbia, Canada *Corresponding author: Chan J, Department of Educational Studies, Faculty of Education, University of British Columbia, Canada, Fax: (604) 822-4244, Tel: (604) 731-8822, E-mail: Jennifer.chan@ubc.ca Review Article Open Access

Civil Society and Global Citizenship in Japan

If modern Japan is about a process of ideology making as Carol Gluck suggests, the comment by Andrew Barshay perhaps best sums up the struggle of civil society in Japan, to strive from state-subject to state-citizen relations. If a tennosei ideorogii, disseminated by an elaborate, but loose network of ideologues and institutions, represented both “internal psychological constriction and external political submissiveness,”1 the role of Japanese civil society, I argue, lies precisely in undoing that ideology by constructing new values as well as institutions for the expressions of citizenship.