Abstract

The structures, properties, and metabolism of bilirubin photoisomers and bilirubin photoproducts and the mechanism of phototherapy for neonatal jaundice will be investigated using the Gunn rat as a model for the jaundiced patient. The investigation will include measurements of the therapeutic potential of current light sources and the action spectrum for phototherapy. In addition, the mechanism of bilirubin conjugation and excretion will be studied by examining the biliary excretion and hepatic metabolism of synthetic model compounds in rats. The research will involve chemistry, biochemistry and photobiology and it will provide valuable information for improving the safety and effectiveness of phototherapy and for understanding and diagnosing liver disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026307-07
Application #
3227817
Study Section
(GCN)
Project Start
1980-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

McDonagh, Antony F; Vreman, Hendrik J; Wong, Ronald J et al. (2009) Photoisomers: obfuscating factors in clinical peroxidase measurements of unbound bilirubin? Pediatrics 123:67-76
Zunszain, Patricia A; Ghuman, Jamie; McDonagh, Antony F et al. (2008) Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha. J Mol Biol 381:394-406
McDonagh, Antony F (2008) Photolysis and photoisomerization of bilirubin in serum specimens exposed to room lighting. Clin Chim Acta 393:130;author reply 131
McDonagh, Antony F; Boiadjiev, Stefan E; Lightner, David A (2008) Slipping past UGT1A1 and multidrug resistance-associated protein 2 in the liver: effects of steric compression and hydrogen bonding on the hepatobiliary elimination of synthetic bilirubins. Drug Metab Dispos 36:930-6
McDonagh, Antony F (2007) Bilirubin toxicity to human erythrocytes: a more sanguine view. Pediatrics 120:175-8
McDonagh, Antony F; Lightner, David A (2007) Influence of conformation and intramolecular hydrogen bonding on the acyl glucuronidation and biliary excretion of acetylenic bis-dipyrrinones related to bilirubin. J Med Chem 50:480-8
McDonagh, Antony F; Maisels, M Jeffrey (2006) Bilirubin unbound: deja vu all over again? Pediatrics 117:523-5
McDonagh, Antony F (2006) Ex uno plures: the concealed complexity of bilirubin species in neonatal blood samples. Pediatrics 118:1185-7
Toietta, Gabriele; Mane, Viraj P; Norona, Wilma S et al. (2005) Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A 102:3930-5
Woydziak, Zachary R; Boiadjiev, Stefan E; Norona, Wilma S et al. (2005) Synthesis and hepatic transport of strongly fluorescent cholephilic dipyrrinones. J Org Chem 70:8417-23

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