Biodistribution of 4-[(14)C]cholesterol-AmBisome following a single intravenous administration to rats.

A biodistribution study of 4-[(14)C]cholesterol-AmBisome; a unilamellar liposomal preparation of amphotericin B was conducted to support a radiolabeled human study. The radioactive plasma concentration profile (as measured in microg-Eq/ml of cholesterol) was best fit to a sum of three exponentials that yielded alpha-, beta-, and gamma-half-life estimates of 3.0 +/- 0.3, 11.8 +/- 3.7, and 113.4 +/- 32.4 h, respectively. Clearance and the steady state volume of distribution were 4.9 +/- 0.2 ml/h/kg and 341 ml/kg. Recovery data collected up through 96 h demonstrated mass balance and indicated that although the elimination profile in both urine and feces were incomplete, the dominant route of elimination (<2% in urine versus 33% in feces) was feces, presumably via biliary excretion of intact liposome and/or cholesterol. The liver, spleen, and lungs, organs of the reticuloendothelial system known for their rapid uptake of liposomes, presented with the highest levels of radioactivity. Levels in the kidney were 15% of that found in the liver and lungs.

Hydrolysis kinetics of photoexcited 6-methoxyquinoline in aqueous acetonitrile solutions.

6-Methoxyquinoline undergoes pseudo-first-order hydrolysis and its conjugate acid, second-order proton abstraction by hydroxide ion, in the lowest excited singlet state. The proton transfer kinetics in water containing acetonitrile up to a mole fraction of about 0.1 have been evaluated as a function of acetonitrile concentration. At mole fractions above 0.13 of acetonitrile, proton transfer does not occur. At mole fractions below 0.1 steady-state and pulsed-source fluorimetries show the rate constant for hydrolysis to decrease exponentially with the mole fraction of acetonitrile. This is believed to be due to penetration of the aqueous solvent cage of the 6-methoxyquinoline by acetonitrile rather than to specific solvation by the organic cosolvent. The rate of neutralization of the conjugate acid by hydroxide ion is found to vary only slightly and depends on the bulk dielectric properties of the solvent.

Determination of accurate and thermodynamically significant pH in alcohol/water solutions.

2-Hydroxybiphenyl demonstrates proton transfer in the lowest excited singlet state in alcohol/water mixtures as well as in pure water. The dissociation reaction of the directly excited neutral molecule is strongly solvent dependent and independent of solution acidity. The reprotonation of the conjugate base, however, depends predominantly on the acidity of the solution and only on the bulk dielectric constant of the solvent. The linear relationship between the ratio of the relative fluorescence efficiencies of 2-hydroxybiphenyl and its conjugate base and the hydrogen ion concentration is obtained only if proper Bronsted activity factors are included in the relationship. These factors can be calculated from classical electrostatics and are simple powers of the activity coefficients that would be derived from Debye-Hückel theory and which are necessary to convert the formal hydrogen ion concentration to hydrogen ion activity. With this approach it is possible to calculate pH from hydrogen ion concentration in alcohol/water solutions containing mole fractions of methanol, ethanol, isopropyl alcohol, and t-butyl alcohol up to 0.5, 0.3, 0.1, and 0.05, respectively.

Formation and operation of a captive insurance company for malpractice coverage.

With the onset of the "malpractice crisis" of spiralling insurance costs in the 1970s, many medical groups began viewing self-insurance as a viable alternative to conventional carriers. Captive insurance companies are not without their risks, but continue to hold promise for controlling escalating insurance costs and providing a positive cash flow for the parent company.

Characterization of avian reoviruses isolated from the synovia and breast blister.

Reoviruses Texas, S 1133, UMI 203, and WVU 2937 induced swelling of the foot pad and inflammatory changes in the synovial membranes when inoculated in the foot pad of 2-week-old gnotobiotic chicks. From differences in virus neutralization as measured with geometric mean (R) value, all four viruses are subtypes of a single serotype. The cell-associated and cell-released virus growth curves were similar, with a lag phase of about 15 hours and a log phase of 15 to 21 hours. Viral RNA synthesis reached a peak in 5 hours and was active at 14 hours but not at 18 hours. In 90 minutes at 60 C the titer of each virus had decreased about 4 logs.