Heat-stress-induced hyperthermia alters CSF osmolality and composition in conscious rabbits.

Amino acids have received increased attention with regard to their thermoregulatory effects and possible role as neurotransmitters within the thermoregulatory system. The purpose of the present work was to evaluate in conscious rabbits the changes in cerebrospinal fluid (CSF) concentration of taurine, GABA, aspartate, and glutamate during exposure to high ambient temperature (50 min, 40 degrees C) to investigate their involvement in heat stress (HS). CSF and plasma osmolality and CSF concentrations of some cations and proteins were also determined. HS animals underwent transient hyperthermia and thereafter fully recovered. This was accompanied by a significant rise in CSF and plasma osmolality, CSF protein, calcium, taurine, and GABA. Artificial CSF osmolality measurements after addition of CaCl(2) or taurine demonstrated that the increased CSF osmolality after HS is accounted for, only in part, by the increased concentrations of either calcium and taurine. It is suggested that, during HS, taurine and GABA are released in the extracellular space of brain tissues in higher amounts, possibly to counteract the resulting hyperthermia.

Bilirubin photoisomerization products in serum and urine from a Crigler-Najjar type I patient treated by phototherapy.

The relative compositions of the photoisomers of bilirubin-1X alpha (4Z, 15Z-bilirubin) in serum and urine of a patient with Crigler-Najjar type I syndrome treated by phototherapy are reported. High-performance liquid chromatography analysis reveals the presence of high serum levels of the configurational bilirubin photoisomer (4Z,15E-bilirubin) before the beginning of phototherapy (between 12 and 16% of the total bilirubin). The configurational photoisomer value increases during phototherapy with blue fluorescent lamps up to a photoequilibrium of about 25%, similar to that obtained in a bilirubin solution in vitro irradiated by the same lamps. This evidence suggests an inefficient serum excretion of the 4Z,15E-bilirubin. Indeed, its average half-life in serum of the Crigler-Najjar patient is found to be about 8 h. No detectable traces of the bilirubin structural isomer, lumirubin, are found in the serum. On the other hand, lumirubin represents the dominant bilirubin isomer excreted in the urine, as both 15Z and 15E configurations. Smaller amounts of 4Z,15E-bilirubin, 4E,15Z-bilirubin and native 4Z,15Z-bilirubin are observed in urine. The presence in urine of 4Z,15Z-bilirubin is probably due to a fast reversion of the configurational photoisomers to their native form. The half-life of the configurational photoisomers in urine kept at 38 degrees C is found to be of the order of a few minutes. Our study indicates that in Crigler-Najjar type I patients, mechanisms exist to excrete all bilirubin photoisomers. The lumirubin pathway seems to contribute markedly to bilirubin excretion in the urine, as occurs in jaundiced babies under phototherapy. However, the contribution of configurational isomers cannot be neglected.

Fibreoptic phototherapy in the management of jaundice in low birthweight neonates.

A fibreoptic phototherapy device has been compared with conventional white and special blue fluorescent phototherapy lamps to evaluate its efficacy in lowering serum bilirubin levels in low-birthweight neonates. Fibreoptic phototherapy was found to be as effective as white light and less effective than blue light, as assessed by (i) the bilirubin concentration after 24 h of phototherapy and at the end of phototherapy, (ii) the duration of phototherapy, (iii) the percentage daily decline rate and (iv) the overall percentage decline rate (p < 0.05). There were no failures of phototherapy and the need for re-exposure was low (4.7% of the total sample), with no difference between groups. The fibreoptic approach represents a promising way to aggregate synergically the most recent optical technologies and develop a modern, efficient and caring phototherapy system for low-birthweight infants.

Quantum yield and skin filtering effects on the formation rate of lumirubin.

Photocyclization of bilirubin to lumirubin in the skin of jaundiced infants exposed to blue-green light irradiation is considered to be the most important process for bilirubin elimination from the organism. The quantum yield phi LR of the bilirubin-->lumirubin photoreaction has been recently measured and found to vary with the excitation wavelength, with a peak at about 520 nm. The quantum yield phi ZE for the strongly competing reversible configurational photoisomerization of bilirubin has also been recently shown to be wavelength dependent and to decrease significantly in the long-wavelength part of the absorption band of bilirubin. These new data are taken into account to model the bilirubin photochemistry in vivo by using a simplified skin optical model based on the Kubelka-Munk theory. The rate kappa LR of formation of lumirubin has been evaluated for the case of a four-layer skin and for monochromatic and narrow-band coloured fluorescent lamps. The effects of long-wavelength increase in phi LR, decrease in phi ZE and skin optical losses all combine to shift significantly the optimal rate of formation of lumirubin towards the green. These results suggest that a significant improvement in phototherapy might be obtained with the introduction of new lamps emitting in the blue-green spectral region between 490 and 510 nm.

Phototherapy for neonatal hyperbilirubinemia.

New light has recently been shed on the way phototherapy reduces bilirubin concentration in icteric infants. The introduction of a high-performance liquid chromatography technique led to the discovery of new photoisomers of bilirubin, the configurational and structural isomers with high and low quantum yields, respectively, and to a renewed interest in the photochemical properties of bilirubin in vitro and in vivo. Circular dichroism and absorption spectroscopies have then shown that bilirubin behaves like a bichromophoric system, with the 2 halves of the molecule strongly interacting in the excited state. This coupling mechanism makes the quantum yields of bilirubin photochemistry wavelength-dependent, with marked effects in the long wavelength edge of the bilirubin absorption spectrum. The photochemistry of bilirubin is substantially similar in icteric rats and babies, and is consistent with what is observed in vitro. However, the metabolism of bilirubin photoproducts in rats sometimes differs quite significantly from that in babies. In particular, only the low quantum yield structural isomer, lumirubin, is efficiently excreted by babies. Although the relative role of the bilirubin photoprocesses in the therapy of hyperbilirubinemia is not yet known with certainty, the structural photoisomerization is generally assumed to represent the main route of bilirubin elimination. As a consequence, the determination of the spectral band that optimizes the process of formation of lumirubin in neonate may represent an important step in the improvement of the clinical protocol of phototherapy. Therefore, in addition to reviewing the most recent data on bilirubin photochemistry and the metabolism of bilirubin products, this article presents a computation of the optimal light for lumirubin formation. The combined effects of long-wavelength photochemistry of bilirubin and skin attenuation show that the optimal spectral range should be between 480 and 510 nm.

Quantum yields for laser photocyclization of bilirubin in the presence of human serum albumin. Dependence of quantum yield on excitation wavelength.

The quantum yield for laser photocyclization of bilirubin to lumirubin in the presence of human serum albumin (phi LR) was measured at five monochromatic excitation wavelengths in the range 450-530 nm. Solutions used were optically thin throughout the wavelength range and precautions were taken to exclude contributions from photocyclization of bilirubin XIII alpha impurities. The values obtained (7.2-18 x 10(-4] were lower than those previously reported and showed the following wavelength dependence: 457.9 less than 488.0 less than 501.7 less than 514.5 approximately equal to 528.7. However, the rate of lumirubin formation, normalized to constant fluence, decreased with wavelength over the same wavelength range and no evidence was found that photoisomerization of bilirubin to lumirubin is faster with green (514.5 or 528.7 nm) than with blue (457.9 or 488.0 nm) light. The stereoselectivity of the configurational isomerization of bilirubin to 4Z,15E and 4E,15Z isomers also was studied. This reaction became less regioselective for the 4Z,15E isomer with increasing wavelength. The observed wavelength dependence of phi LR and of the [4E,15Z]: [4Z,15E] ratio at photoequilibrium are consistent with an exciton coupling model in which intramolecular energy transfer can occur between the two pyrromethenone chromophores of the bilirubin molecule in the excited state. Relative rates of lumirubin formation in vivo at different excitation wavelengths and constant fluence were estimated for different optical thicknesses and for different skin thicknesses. These estimates suggest that the recently reported clinical equivalence of blue and green phototherapy lights probably reflects the marked variation of skin transmittance with wavelength more than wavelength-dependent photochemistry. The calculations also indicated that the optimal wavelength for phototherapy is probably on the long wavelength side of the bilirubin absorption maximum.

Laser investigation of bilirubin-photobilirubin photoconversion.

The reversibility of the configurational photoisomerization process of bilirubin (BR) with laser lines in the blue-green spectral region is investigated. Photoisomerization efficiency of BR is found to depend strongly on wavelength, and to decrease when the excitation wavelength is increased from blue to green. Reversion of BR photoisomers (identical to photobilirubin, PBR) back to native BR is demonstrated for several laser lines by irradiating PBR/BR mixtures with wavelengths greater than the excitation wavelengths. Green lines turn out to be very efficient for PBR----BR reversion. The PBR concentrations at photoequilibrium, obtained from the spectrophotometric data, are in close agreement with the corresponding values measured with the high performance liquid chromatography technique in the case of 10 nm bandwidth filtered light reported in the literature. The 457 nm blue laser line produces 32% PBR concentration at photoequilibrium; only 14, 7, and 3% PBR concentrations are produced by the blue-green lines at 488, 501, 514 nm, respectively. The effect on the photostationary PBR/BR mixture of successive irradiations with different wavelengths, and the influence of the wavelength sequence are reported. In the case of blue lines our results support the assumption of the first-order kinetics for the BR in equilibrium PBR photoreaction. Departures are observed with green-lines (501, 514 nm). The present results, together with the i) good clinical efficiency reported for fluorescent green lamps; and ii) slow elimination of configurational photoisomers in infants, tend to confirm the lumirubin-pathway as the main mechanism for phototherapy, and call for clinical investigation of narrow-spectrum lamps with peak emission wavelength in the (biologically safer) 480 divided by 530 nm range.