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Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (Bf), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported Bf values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at Bf only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome. [ABSTRACT FROM AUTHOR]

The homozygous (jj) jaundiced Gunn rat model for hyperbilirubinemia displays pronounced cerebellar hypoplasia. To examine the cellular mechanisms involved in bilirubin toxicity, this study focused on the effect of hyperbilirubinemia on calcium/calmodulin-dependent kinase II (CaM kinase II). CaM kinase II is a neuronally enriched enzyme which performs several important functions. Immunohistochemical analysis of alternating serial sections were performed using monoclonal antibodies for the α and β subunits of CaM kinase II. Measurements were made of the total numbers of stained cells in each of the deep cerebellar nuclei and of Purkinje and granule cell densities in cerebellar lobules II, VI, and IX. The β subunit was present in Purkinje cells and deep cerebellar nuclei of both groups at all ages, but only granule cells which had migrated through the Purkinje cell layer showed staining for β subunit; external granule cells were completely negative. Many Purkinje cells had degenerated in the older animals, and the percent of granule cells stained for β subunit was significantly reduced. The α subunit was found exclusively in Purkinje cells, although its appearance was delayed in the jaundiced animals. Sulfadimethoxine was administered to some jj rats 24 h or ¶15 days prior to sacrifice to increase brain bilirubin concentration. Results showed that bilirubin exposure modulated both α and β CaM kinase II subunit expression in selective neuronal populations, but sulfadimethoxine had no acute effect on enzyme immunoreactivity. Thus, developmental expression of the α and β subunits of CaM kinase II was affected by chronic bilirubin exposure during early postnatal development of jaundiced Gunn rats. [ABSTRACT FROM AUTHOR]

Presents an abstract of the article 'Neutron scattering studies of the dynamic susceptibility in the mixed-valent alloy Ce[sub1-x]Th[subx] at high energy,' by C.-K. Loong, B.H. Grier. S.M. Shapiro, J.M. Lawrence, R.D. Parks and S.K. Sinha.

We have studied the cubic-to-tetragonal phase transition in epitaxial SrTiO[SUB3] films under various biaxial strain conditions using synchrotron x-ray diffraction. Measuring the superlattice peak associated with TiO[SUB6] octahedra rotation in the low-temperature tetragonal phase indicates the presence of a phase transition whose critical temperature is a strong function of strain, with T[SUBC] as much as 50 K above the corresponding bulk temperature. Surprisingly, the lattice constants evolve smoothly through the transition, with no indication of a phase change. This signals an important change in the nature of the phase transition due to the epitaxial strain and substrate clamping effect. The internal degrees of freedom (TiO[SUB6] rotations) evolve independently from the overall lattice shape. [ABSTRACT FROM AUTHOR]