Hyperbilirubinemia or jaundice affects nearly half of all newborn infants, and because bilirubin can be toxic to newborns, the management of neonatal jaundice is one of the most common problems in pediatrics. The long-term objective is improvement of the safety and efficacy of visible light phototherapy, the most common method used to reduce the serum concentrations of bilirubin in jaundiced newborn infants. Recent work has shown that the most important pathway for bilirubin elimination during phototherapy is the production and excretion of a structural isomer of bilirubin, designated lumirubin. Traditional recommendations for phototherapy are based on maximizing the production of bilirubin photooxidation products or configurational isomers, which were previously thought to be the main route for pigment elimination. Not only would these recommendations fail to optimize phototherapy, but they also involve the use of phototherapy lamps which emit significant irradiation below 450 nm, a portion of the visible spectrum which has been shown to damage DNA in vitro, and therefore may present a long-term hazard to infants treated with phototherapy. Preliminary studies of the spectral dependence of lumirubin formation indicate that wavelengths of light greater than 450 nm are the most effective in the production of lumirubin. The work will investigate the factors controlling the production of lumirubin from bilirubin both in vitro and in vivo, using a new HPLC system which provides rapid quantitative analysis of bilirubin and its photoproducts.
The specific aims are to measure the wavelength dependence of the formation of lumirubin, to determine the effect on lumirubin formation of the binding of bilirubin to human serum albumin in the presence of various ligands, including fatty acids and steroids, to characterize the binding of lumirubin to human serum albumin, and to study the effectiveness of several light sources for the in vivo production of lumirubin and for the treatment of jaundiced infants. If these studies confirm the preferential formation of lumirubin by green light and show a connection between the rate of lumirubin production and the reduction of plasma bilirubin concentration in jaundiced infants, then it will be possible to design a light source for phototherapy which is more effective than currently-used lamps in treatment of neonatal hyperbilirubinemia, and has no emission in the genotoxic region of the spectrum below 450 nm.
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