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Titolo:
NEW CONCEPTS IN BILIRUBIN AND JAUNDICE - REPORT OF THE 3RD-INTERNATIONAL-BILIRUBIN-WORKSHOP, APRIL 6-8, 1995, TRIESTE, ITALY
Autore:
TIRIBELLI C; OSTROW JD;
Indirizzi:
UNIV TRIESTE,DEPT BBCM,LIVER STUDY CTR,VIA GIORGERI 1 I-34127 TRIESTEITALY DEPT VET AFFAIRS,LAKESIDE MED CTR CHICAGO IL 00000 NORTHWESTERN UNIV,SCH MED CHICAGO IL 00000
Titolo Testata:
Hepatology
fascicolo: 5, volume: 24, anno: 1996,
pagine: 1296 - 1311
SICI:
0270-9139(1996)24:5<1296:NCIBAJ>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
FULMINANT HEPATIC-FAILURE; EXTRACORPOREAL LIVER ASSIST; ORGANIC-ANION TRANSPORT; CARRIER-MEDIATED TRANSPORT; PLASMA-MEMBRANE VESICLES; UDP-GLUCURONIC ACID; MICROCARRIER-ATTACHED HEPATOCYTES; RESISTANCE-ASSOCIATED PROTEIN; HEME OXYGENASE INHIBITOR; SERUM ALBUMIN COMPLEXES;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
272
Recensione:
Indirizzi per estratti:
Citazione:
C. Tiribelli e J.D. Ostrow, "NEW CONCEPTS IN BILIRUBIN AND JAUNDICE - REPORT OF THE 3RD-INTERNATIONAL-BILIRUBIN-WORKSHOP, APRIL 6-8, 1995, TRIESTE, ITALY", Hepatology, 24(5), 1996, pp. 1296-1311

Abstract

The workshop covered three major areas: Unconjugated bilirubin (UCB) chemistry and physical chemistry; UCB transport and intracellular trafficking; and evaluation and therapy of neonatal and congenital hyperbilirubinemias. Findings of studies in the chemistry and physical chemistry area were as follows, (1) Nuclear magnetic resonance (NMR) studiesof highly enriched (COOH)-C-13 mesobilirubin in water-dimethyl sulfoxide systems indicated that the pK(a) values of the carboxyl groups are4.2 and 4.9, respectively, This finding differs fi om some reports that suggest that the two pK(a) values in aqueous systems are near or above pH 7.0, (2) Contrasting views of the hydrophobic interactions of UCB with bile salts were presented: one suggested that multiple bile salt monomers bind to one UCB molecule; the other suggested that UCB binds to the nonpolar surface of helical bile salt micelles, (3) Structures were proposed for the varied calcium and copper bilirubinate salts formed at various pH values and cation/UCB ratios, (4) Studies of binding of UCB to human serum albumin (HSA) showed marked diminution of UCB-binding affinity as albumin and chloride concentrations increased. (5) A unique UCB derivative, bilirubin-C10-sulfonic acid, was identified as the major bile pigment in bullfrog bile. (6) New methods were presented for removal of impurities from preparations of bile salts and UCB. Findings of studies in the transport area were as follows, (1) Four putative basolateral and two putative canalicular hepatocytic transporters of UCB and related organic anions were described, Special emphasis was given to the adenosine triphosphate (ATP)-dependent canalicular multispecific organic anion transporter that is defective in three strains of mutant rats with congenital conjugated hyperbilirubinemia. (2) The roles of the classical and newer molecular biological approaches to identification of these transporters were contrasted, and their limitations were discussed, (3) The relative roles of the multiple carriers in UCB transport under different conditions and substrate concentrations were discussed. (4) Cytosolic UCB-binding proteins (e.g., ligandin) were shown to promote transcellular movement of UCB by solubilizing and transporting the pigment in the aqueous phase while limiting binding of UCB to the relatively immobile membranes of cell organelles,(5) Mechanisms were presented for translocation of UDP-glucuronic acid (UD-PGA) into the lumenal location of UDPGA transferase in the endoplasmic reticulum, as well as the enhancement of this process by N-acetyl-glucosamine. Studies in the neonatal and congenital jaundice area were as follows, (1) Criteria were reviewed for initiating treatment ofneonatal jaundice, emphasizing the primacy of serum bilirubin levels,gestational age, and hemolysis as risk factors for kernicterus, (2) New methods were presented for frequent, automated monitoring of serum bilirubin levels and breath CO levels as an index of rates of formation of UCB from heme, (3) The current status and Limitations of new approaches to treatment of severe unconjugated hyperbilirubinemia were discussed: hepatocyte transplantation and gene therapy, still in the stage of development in animal models, have provided only partial and temporary relief of hyperbilirubinemia; extracorporeal liver assist devices have had some success in initial human studies; and inhibition of heme oxygenase (HO) with metalloporphyrins, especially tin mesoporphyrin, which markedly decreases bilirubin production for prolonged periods,is a new alternative to phototherapy, (4) The ontogeny of the two HO isozymes was contrasted in the liver, spleen, kidney, and lung.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/21 alle ore 15:14:28