Radiative Relaxation Quantum Yields for Synthetic Eumelanin

We report absolute values for the radiative relaxation quantum yield of synthetic eumelanin as a function of excitation energy. These values were determined by correcting for pump beam attenuation and emission reabsorption in both eumelanin samples and fluorescein standards over a large range of concentrations. Our results confirm that eumelanins are capable of dissipating >99.9% of absorbed UV and visible radiation through nonradiative means. Furthermore, we have found that the radiative quantum yield of synthetic eumelanin is excitation energy dependent. This observation is supported by corrected emission spectra, which also show a clear dependence of both peak position and peak width on excitation energy. Our findings indicate that photoluminescence emission in eumelanins is derived from ensembles of small chemically distinct oligomeric units that can be selectively pumped. This hypothesis lends support to the theory that the basic structural unit of eumelanin is oligomeric rather than heteropolymeric.

Observations of QSO J2233-606 in the Southern Hubble Deep Field

The Hubble Deep Field South (HDF-S) Hubble Space Telescope (HST) observations are expected to begin in 1998 October. We present a composite spectrum of the QSO in the HDF-S held covering UV/optical/near-IR wavelengths, obtained by combining data from the Australian National University 2.3 m telescope with STIS on the HST.(1) This intermediate-resolution spectrum covers the range 1600-10000 Angstrom and allows us to derive some basic information on the intervening absorption systems which will be important in planning future higher resolution studies of this QSO. The QSO J2233 - 606 coordinates are alpha = 22(h)33(m)37(s).6, delta = -60 degrees 33'29 (J2000), the magnitude is B = 17.5, and its redshift is z(em) = 2.238, derived by simultaneously fitting several emission lines. The spectral index is alpha = -0.7 +/- 0.1, measured between the Ly alpha and Mg II emission lines. Many absorption systems are present, including systems with metal lines redward of the Ly alpha emission line at z(abs) 2.204, 1.942, 1.870, 1.787 and a few very strong Ly alpha features at z(abs) = 2.077, 1.928, without similarly strong metal lines. There is a conspicuous Lyman limit (LL) absorption system that is most likely associated with the z(abs) = 1.942 system with a neutral hydrogen column density of N-HI = (3.1 +/- 1.0) x 10(17) cm(-2). There is some evidence for the presence of a second LL absorber just to the blue of the conspicuous system at z = 1.870. We have employed a new technique, based on an analysis of the shape of the observed spectrum in the region of the LL absorption, to explore the properties of the gas. We tentatively conclude that this system might have suitable characteristics for measuring the deuterium-to-hydrogen (D/H) ratio.

Hydromorphone-3-glucuronide: Biochemical synthesis and preliminary pharmacological evaluation

Hydromorphone-3-glucuronide (H3G) was synthesized biochemically using rat liver microsomes, uridine-5'-diphosphoglucuronic acid (UDPGA) and the substrate, hydromorphone. Initially, the crude putative H3G product was purified by ethyl acetate precipitation and washing with acetonitrile, Final purification was achieved using semi-preparative high-performance-liquid-chromatography (HPLC) with ultraviolet (UV) detection. The purity of the final H3G product was shown by HPLC with electrochemical and ultraviolet detection to be > 99.9% and it was produced in a yield of approximate to 60% (on a molar basis). The chemical structure of the putative H3G was confirmed by enzymatic hydrolysis of the glucuronide moiety using P-glucuronidase, producing a hydrolysis product with the same HPLC retention time as the hydromorphone reference standard. Using HPLC with tandem mass spectrometry (HPLC-MS-MS) in the positive ionization mode, the molecular mass (M+1) was found to be 462 g/mol, in agreement with H3G's expected molecular weight of 461 g/mol. Importantly, proton-NMR indicated that the glucuronide moiety was attached at the 3-phenolic position of hydromorphone. A preliminary evaluation of H3G's intrinsic pharmacological effects revealed that following icy administration to adult male Sprague-Dawley rats in a dose of 5 mu g, H3G evoked a range of excitatory behavioural effects.including chewing, rearing, myoclonus, ataxia and tonic-clonic convulsions, in a manner similar to that reported previously for the glucuronide metabolites of morphine, morphine-3-glucuronide and normorphine-3-glucuronide.

Evaluation of an immunoassay (EMIT) for mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatography assay

Mycophenolic acid is an immunosuppressant administered as a bioavailable ester, mycophenolate mofetil. The pharmacokinetics of mycophenolic acid have been reported to be variable. Accurate measurement of concentrations of this drug could be important to adjust doses. The aim of this study was to compare the enzyme-multiplied immunoassay technique (EMIT [Dade Behring; San Jose, CA, U.S.A.]) for mycophenolic acid with a high-performance liquid chromatographic (HPLC) assay using samples collected from renal transplant recipients. The HPLC assay used solid phase extraction and a C18 stationary phase with ultraviolet (UV) detection (254 nm). The immunoassay required no manual sample preparation. Plasma samples (n = 102) from seven patients, collected at various times after a dose, were analyzed using both methods. Both assays fulfilled quality-control criteria. Higher concentrations were consistently measured in patient samples when using EMIT. The mean (+/- standard deviation [SD]) bias (EMIT-HPLC) was 1.88 +/- 0.86 mg/L. The differences in concentrations were higher in the middle of a dosage interval, suggesting that a metabolite might have been responsible for overestimation. Measurement of glucuronide concentrations by HPLC demonstrated only a weak correlation between assay differences and glucuronide concentrations. If the crossreacting substance is active, EMIT could provide a superior measure of immunosuppression; if inactive, further work is needed to improve antibody specificity. In conclusion, it was found that EMIT overestimates the concentration of mycophenolic acid in plasma samples from renal transplant recipients compared with HPLC analysis.