Crystal structure of calf spleen purine nucleoside phosphorylase complexed to a novel purine analogue.

The combined use of a rapid virtual screen of a small fragment library together with a single point enzyme assay has been used for the discovery of novel PNP inhibitors. The availability of readily soakable crystals of bovine PNP has allowed the approach to be experimentally validated by determining the crystal structure of one of the inhibitor-PNP complexes. Comparison of the experimentally determined binding mode with that predicted by the virtual screening shows them to be similar. This represents a starting point for the growth of the ligand into a higher affinity inhibitor.

Canalicular cholestasis due to amiodarone toxicity. A definite diagnosis obtained by electron microscopy.

A case of jaundice due to canalicular cholestasis during amiodarone therapy is reported. A definite diagnosis was attained by ultrastructural evidence of a phospholipidosis pattern, a characteristic amiodarone-induced injury. Jaundice occurred within the third month of therapy. Serum bilirubin levels continued to increase in the two weeks following drug withdrawal. A slow decrease was observed in the following three months. Only four cases of jaundice associated with amiodarone therapy have been reported until now.