Treatment of acute hepatic encephalopathy (HE): Lactulose-neomycin versus placebo. Randomized bioequivalence assay

29 HEPATIC COPPER DISTRIBUTION IN WILSON’S DISEASE AND HEPATIC COPPER OVERLOAD GO Binale. SKS Srai.‘O Eostein Departments of Protein and Molecular Biology and ‘Medicine. Royal Free Hospital School of Medicine, London, UK. Th- elevated liver copper (Cu) levels found in Wilson’s dise;;e (WD) are thought to be responsible for hepatotoxicity, but Cu overload secondary to other liver disease is not toxic. It has been suggested that differences in hepatic distribution of the metal are responsible. We have used differential centrifugation and gel-filtrationto investigate the subcellular distribution of Cu in WD, hepatic Cu retention secondar) to cholestasis Cu and normal liver. In all livers n?ost of the post-nuclear was found in the supernatant and there were no gross differer,c:j in the distributionof Cu in the other fractions. In none of the livers were lysosomes a major site of Cu storage. Gel-filtration of supernatants resolved three peaks in all livers. In livers with normal Cu levels CuZn superoxide dismutase was the major Cu binder, whilst WD and livers with elevated Cu >75% of the Cu was associated with metallothionein. In contrast to previous results, which suggest that Cu in WD is predominantly lysosomal, we have shown that the majority of freely soluble copper is present in the supernatant, where it is associated with metallothionein and furthermore there are no clear differences between Cu distribution in WD and other diseases with elevated Cu levels. It appears that gross differences in Cu distribution are not responsible for the toxicity of Cu retention in WD. 31 EXPRESSIONOF THE CANALICULAR SULFATETRANSPORT SYSTEMIN XENOPUSLAEVIS OOCYTES

P. Biwk-sqe, B. Le Fail, C. Balabiud aml ALT grrq, Lab. Intwacticns Cellulaires. lhiversit6 de Bordeaux II. Bordeam.

sectiars. Different typesof sinumidswerecksmvedinearhrodrle~ to dleir: a) size (large, meal. s-&l). b) decreeofczpillariztiar, c) ti extentof &rage, particularlyto endothelial cells (in+zgular thi&mss, overloading withdensek&es, blebs. digitatims, ~QZS..). In regemrative areas. sinzoick weregmzallydifficultto i&ify mqst tbi&medliver-Al plates. Rusewecbzmedwere verysmll, fed capillarized and~presmtedvaykg~ of &x~~&ity. Particularly ti er&tklid ceils. lhis wasat timssoseverethatcnlytkpFesence of Fkn,&Oi~cell rY#Em~ aCdihgmntsof~t~ inS!fJlllUXSS~ttestedthe fonwr existence of simsoids. It is clear Vat themIpholagv of sinsoidsin cimimticnahls is adcmprisesodm fedthsnjust exh-enely hew capillarizaticm. lhe factthatthereismaFhol~icalevidew oftkgadadisappearare of sinwids in regereratiwareas c&d cmtrib.& to the Mive thickming of livewell plahr tick

32 TREATMENT OF ACUTE LACTULOSE-NEOMYCIN

HEPATiC VERSUS

ENCEPHALOPATHY HE) : PLACEBO. RAND0 L IZED

M. Bissiq. B. Haqenbuch, P.J. Meier Division of Clinical Pharmacology, Department of Medicine, University Hospital, CH-8091 Zurich We have recently demonstrat+ed functional expression of the hepatocyte Na /bile acid cotransporter in Xenopus laevis oocytes (J. Biol. In this studv we used Chem. 265, 5357. 1990). the same approaih as a first step towaras “expression cloning” of the gene encoding the canalicular HCO-/SO= oxchange system (Am. J. Physiol. 253, 6461: 1947). Injection of rat liver poly (A) RNA into the oogytes resulted in the functional expression of Na independent SO’ uptake *within 2-4 days. The expressed SO’ ufltake system -
The association laolulose-neomycin is frequently used as treatment for acule HE although its elfiiienoy has never been proved by randomized studv. Furthermore. this treatment is oooriv . . tolerated