Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats

BACKGROUND/AIMS: It is well documented that levels of plasma non-transferrin-bound iron (NTBI), a particularly toxic form of iron, are increased in iron overload disorders. In light of the pathogenetic importance of NTBI in chronic iron overload, we have studied the ability of new orally active iron chelators to promote the biliary excretion of iron originating as plasma 55Fe-NTBI. METHODS: Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of 55Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a single intragastric dose of iron chelator. These chelators were the novel hydroxypyridin-4-one compounds CP102, CP41, and their respective pro-drugs CP117 and CP165. RESULTS: The cumulative recovery of 55Fe in bile of normal rats was increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165, respectively. In iron overloaded rats, these compounds increased the cumulative recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had a choleretic effect, were metabolized by the liver as demonstrated by HPLC study of bile, and were not cytotoxic since normal plasma transaminase levels were maintained at the end of the experiments. CONCLUSIONS: These chelators have potential interest for the treatment of iron overload conditions and may offer advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1)

Migration, Precarization and the Democratic Deficit in Global Governance

This article attempts to provide a critical understanding of the dual signification of “precarity”. It explores what “precarity” as a concept may potentially offer to studies of the changing contemporary political economy of migration. It discusses shifting trends in global migration and point to tendencies for a possible convergence between “South” and “North”, “East” and “West”. Based on a review of current advances in research, it discusses, with reference to the classical work of Karl Polanyi, the potential for a contemporary “countermovement” which would challenge the precarity of migrants. Bringing forward the issue of the “space for civil society” the article addresses a still lingering democratic deficit in the global governance of migration.Policy ImplicationsThe article is relevant to policymakers, trade unions and civil society organizations. It contributes to the understanding of policy making processes in emerging multilevel global governance and focuses on issues of precarization, migration, and the implementation and accountability of human, migrant and labour rights.</p