1127 IS THERE NEED TO A NEW HEPATITIS B VACCINE SCHEDULE IN CHILDREN WITH CELIAC DISEASE?

Abstract

Material and Methods: We complexed Cu (MS Nordion) to L-histidine (Sigma) and verified the extent of complexing with chromatography. 3.7–5.5 MBq of complexed Cu-histidine was injected into healthy Long-Evans Agouti (LEA) rats, as well as mutant Long-Evans Cinnamon (LEC) rats lacking Atp7b. Radioactivity was measured in bile, blood and organ tissues after times ranging from 1h to 24h. Furthermore, rats were subjected to dynamic microPET imaging for up to 24h. The effect of acute or chronic liver injury on handling of Cu-histidine complex was determined in LEA rats treated once or repeatedly with CCl4. To identify further mechanisms in targeting of Cu, we studied Cu complexed to hepatocyte-specific ligands. Finally, dynamic microPET imaging was performed in LEC rats after transplantation of healthy hepatocytes isolated from LEA rats. Results: Cu was efficiently complexed to histidine. The complex was incorporated largely in the liver and kidney of animals followed by rapid excretion of radiocopper in bile of healthy LEA rats and not in diseased LEC rats. MicroPET data showed a mean time to peak liver activity of 13±2 min in LEA rats, but in LEC rats hepatic SUV (standard uptake value) increased over the entire period of investigation. Dynamic microPET imaging for 30–60 min was sufficient to show divergent patterns of Cu accumulation in WD (+ 35%) and loss of Cu in the healthy state (−10%). In CCl4-treated LEA rats, the kinetics or magnitude of hepatic copper excretion were unchanged or significantly different from LEC rats, respectively (p < 0.05). Enhanced hepatic targeting of Cu complexed with ligands to asialoglycoprotein receptor showed greater fractional biliary copper clearances from the liver (p< 0.05). Moreover, the assay demonstrated correction of Atp7b deficiency in LEC rats repopulated with healthy hepatocytes from LEA rats. Conclusion: Hepatic targeting of Cu will be effective for identifying abnormality in biliary copper excretion. This assay will facilitate management of Wilson’s disease.