Thyroid hormone export from cells: contribution of P-glycoprotein

Verapamil inhibits tri-iodothyronine (T-3) efflux from several cell types, suggesting the involvement of multidrug resistance-associated (MDR) proteins in T-3 transport. The direct involvement of P-glycoprotein (P-gp) has not, however, been investigated. We compared the transport of I-125-T-3 in MDCKII cells that had been transfected with mdr1 cDNA (MDCKII-MDR) versus wild-type MDCKII cells (MDCKII), and examined the effect of conventional (verapamil and nitrendipine) and specific MDR inhibitors (VX 853 and VX 710) on I-125-T-3 efflux. We confirmed by Western blotting the enhanced expression of P-gp in MDCKII-MDR cells. The calculated rate of I-125-T-3 efflux from MDCKII-MDR cells (around 0.30/min) was increased twofold compared with MDCKII cells (around 0.15/min). Overall, cellular accumulation of I-125-T-3 was reduced by 26% in MDCKII-MDR cells compared with MDCKII cells, probably reflecting enhanced export of T-3 from MDCKII-MDR cells rather than reduced cellular uptake, as P-gp typically exports substances from cells. Verapamil lowered the rate of I-125-T-3 efflux from both MDCKII and MDCKII-MDR cells by 42% and 66% respectively, while nitrendipine reduced I-125-T-3 efflux rate by 36% and 48% respectively, suggesting that both substances inhibited other cellular T-3 transporters in addition to P-gp. The specific MDR inhibitors VX 853 and VX 710 had no effect of I-125-T-3 efflux rate from wild-type MDCKII cells but reduced I-125-T-3 export in MDCKII-MDR cells by 50% and 53% respectively. These results have provided the first direct evidence that P-gp exports thyroid hormone from cells.

Ethical perspectives of the Australian live export trade

Objective To examine the ethical perspectives of the Australian live export trade. Design and method The perspectives of farmers and other industry personnel, overseas consumers, the Australian public, veterinarians and the assumed interests of transported animals are compared in relation to the ethical consequences. Animal welfare, societal, personal and professional ethics are identified and the ratification of different perspectives considered. Results and conclusions There are positive and negative aspects of the trade for each stakeholder group, and the overall position adopted by any individual reflects their perspective of the balance of these components. The debate as to whether Australia should continue with the trade will be best served by consideration of the interests of all parties in the trade, including the consumers and animals, which are among the most affected by the trade. There is a need for further research to address the major welfare problems for the animals, an openness to inspection on the part of the trade and balance in media reporting.

Export processing zones and growth triangle development: The case of the BIMP-EAGA, Southeast Asia

Exorts processing zones (EPZs) and growth triangles have been two common Asian initiatives to increase wealth and regional competitiveness in the world economy. Since they are seldom analysed jointly, this paper investigates their mutuality in the development process. Taking the problematic case of the Brunei-Indonesia-Malaysia-Philippines East ASEAN Growth Area (BIMP-EAGA) triangle, we explore the role of EPZs in enhancing regional collaboration, competitiveness, and domestic linkages. Despite the triangle's weak economic complementarities, its processing zones are found capable of advancing development by furthering opportunities in regionalisation/localisation of production. Latterly, trade and investment liberalisation within ASEAN raises broad questions about the rationale of EPZs and growth triangles. Zone-triangle nexuses will require rethinking as, under different regulatory conditions, the zones compete more directly across ASEAN and also with global rivals. Copyright © 2005 John Wiley & Sons, Ltd.