New concepts in bilirubin and jaundice: Report of the Third International Bilirubin Workshop, April 6-8, 1995, Trieste, Italy

✍ Scribed by C Tiribelli; J D Ostrow

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 343 KB
• Volume: 24
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510240551

✦ Synopsis

three strains of mutant rats with congenital conjugated The workshop covered three major areas: Unconjuhyperbilirubinemia. (2) The roles of the classical and gated bilirubin (UCB) chemistry and physical chemistry; newer molecular biological approaches to identification UCB transport and intracellular trafficking; and evaluaof these transporters were contrasted, and their limitation and therapy of neonatal and congenital hyperbilitions were discussed. (3) The relative roles of the multirubinemias. Findings of studies in the chemistry and ple carriers in UCB transport under different conditions physical chemistry area were as follows. (1) Nuclear and substrate concentrations were discussed. (4) Cytomagnetic resonance (NMR) studies of highly enriched solic UCB-binding proteins (e.g., ligandin) were shown 13 COOH mesobilirubin in water-dimethyl sulfoxide systo promote transcellular movement of UCB by solubiliztems indicated that the pK a values of the carboxyl ing and transporting the pigment in the aqueous phase groups are 4.2 and 4.9, respectively. This finding differs while limiting binding of UCB to the relatively immobile from some reports that suggest that the two pK a values membranes of cell organelles. (5) Mechanisms were prein aqueous systems are near or above pH 7.0. (2) Consented for translocation of UDP-glucuronic acid (UDtrasting views of the hydrophobic interactions of UCB PGA) into the lumenal location of UDPGA transferase with bile salts were presented: one suggested that multiin the endoplasmic reticulum, as well as the enhanceple bile salt monomers bind to one UCB molecule; the ment of this process by N-acetyl-glucosamine. Studies other suggested that UCB binds to the nonpolar surface in the neonatal and congenital jaundice area were as of helical bile salt micelles. (3) Structures were proposed follows. (1) Criteria were reviewed for initiating treatfor the varied calcium and copper bilirubinate salts ment of neonatal jaundice, emphasizing the primacy of formed at various pH values and cation/UCB ratios. (4) serum bilirubin levels, gestational age, and hemolysis Studies of binding of UCB to human serum albumin as risk factors for kernicterus. (2) New methods were (HSA) showed marked diminution of UCB-binding affinpresented for frequent, automated monitoring of serum ity as albumin and chloride concentrations increased. bilirubin levels and breath CO levels as an index of rates (5) A unique UCB derivative, bilirubin-C10-sulfonic acid, of formation of UCB from heme. (3) The current status was identified as the major bile pigment in bullfrog bile. and limitations of new approaches to treatment of se-(6) New methods were presented for removal of impurivere unconjugated hyperbilirubinemia were discussed: ties from preparations of bile salts and UCB. Findings hepatocyte transplantation and gene therapy, still in the of studies in the transport area were as follows. (1) Four stage of development in animal models, have provided putative basolateral and two putative canalicular hepaonly partial and temporary relief of hyperbilirubinemia; tocytic transporters of UCB and related organic anions extracorporeal liver assist devices have had some sucwere described. Special emphasis was given to the adencess in initial human studies; and inhibition of heme osine triphosphate (ATP)-dependent canalicular multioxygenase (HO) with metalloporphyrins, especially tin specific organic anion transporter that is defective in mesoporphyrin, which markedly decreases bilirubin production for prolonged periods, is a new alternative Abbreviations: UCB, unconjugated bilirubin; NMR, nuclear magnetic resonance; NOE, to phototherapy. (4) The ontogeny of the two HO isonuclear Overhauser enhancement; DMSO, dimethyl sulfoxide; TC, taurocholate; CMC, criti-zymes was contrasted in the liver, spleen, kidney, and cal micellar concentration; CD, circular dichroism; Bf, concentration of unbound UCB; Kf,