Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.     

Densification of tungsten and titanium carbides and their mixtures with nickel during heating under high pressure

Conclusions An experimental study was made of the densification kinetics and changes in hardness of powders of the carbides WC and TiC produced by the SHS method, during heating to 1800°C under high pressure, of up to 80 kbar. During heating to 1800°C sintering with relative densities of 98–99% were obtained in a few minutes at pressure of 50 kbar and higher with the WC powder and 35 kbar and higher with the TiC powder. Densification experiments on the same powders with 6 wt. % Ni additions yielded similar results.Translated from Poroshkovaya Metallurgiya, No. 7(223), pp. 28–32, July, 1981.     

Reactions of OH and eaq- adducts of cytosine and its nucleosides or nucleotides with Cu(II) ions in dilute aqueous solutions: a steady-state and pulse radiolysis study

The reactions of OH and eaq- adducts of cytosine, cytidine and deoxycytidine in the presence of Cu(II) ions have been studied by product analysis and pulse radiolysis. The product analysis studies show that the degradation of the base is enhanced in N2O-saturated conditions in the presence of Cu(II) ions and the major radiolytic products are Cu(I), cytosine glycols and 5(6)-hydroxycytosine. It is also interesting to note that the yields of Cu(I) are equivalent to cytosine degradation yields, which suggests that the interaction of the OH adducts with Cu(II) ions restricts the radical recombination reactions (known to be the major physicochemical repair process) which partly regenerate the parent cytosine. The rate constants of the reactions of cytosine OH adducts with Cu(II) ions determined by pulse radiolysis lie between 10(7) and 10(8) dm3 mol-1 s-1. The growth in the transient absorption spectra of cytosine OH adducts in the range 330-400 nm, observed in the presence of copper(II) ions in free and complexed state, suggests formation of copper radical adduct which decays by water insertion at the copper-carbon bond to give glycol as the major product. Such copper radical adduct formation was also observed in the case of cytidine and deoxycytidine. The protonated electron adducts (at the hetero atoms) of cytosine, cytidine and deoxycytidine transfer electrons to the Cu(II) ions with rate constants of 10(8) and 10(9) dm3 mol-1 s-1. Here no adduct formation is observed. The steady-state results show that such electron transfer reactions regenerate the parent molecules themselves. Hence such electron transfer reactions do not contribute to enhanced base degradation in the presence of copper ions.     

Reactions of Molybdenum and Tungsten Carbides with Oxygen at High Temperatures

The interaction of Mo₂C, W₂C and WC with O₂ has been measured between 1300 and 2100 K and 10⁻⁴ and 40 mbar O₂. The weight loss of the carbides is very similar to that of Mo or W, respectively. The reason for this is a metallic surface layer produced on the samples by a fast CO reaction. Its thickness is reduced again by the evaporation of volatile oxides. The superimposition of these two reactions finally results in a steady state with a constant layer thickness between 0.1 and 100 μm. The layer growth and steady state conditions can be calculated from literature data for binary systems. The theoretical values are in agreement with experimental results and show similar trends. Formerly Visiting Scientist at the Max-Planck-Institut     

Reactions of gold(III) ions with ribonuclease A and methionine derivatives in aqueous solution

1. Addition of Au(III) (as chloroaurate) to folded ribonuclease A causes the formation of aggregates, as shown by chromatography and extreme broadening of the 270 MHZ 1H NMR spectrum. 2. When RNAase is partially unfolded Au(III) causes oxidation of methionines to the sulphoxide, and leads to almost complete unfolding (at molar equivalent ratios). 3. Reactions between model methionine derivatives and Au(III) show that the oxidation involves the production of Au(I)-methionine species. The stability of these complexes is dependent on the availability of free NH2 groups which catalyse their disproportionation.     

Corrosion of 310 stainless steel in H2- H2O- H2S gas mixtures: Studies at constant temperature and fixed oxygen potential

Corrosion of SAE 310 stainless steel in H₂-H₂O-H₂S gas mixtures was studied at a constant temperature of 1150 K. Reactive gas mixtures were chosen to yield a constant oxygen potential of approximately 6 × 10^-13 Nm^-2 and sulfur potentials ranging from 0.19 × 10^-2 Nm^-2 to 33 × 10^-2 Nm^-2. The kinetics of corrosion were determined using a thermobalance, and the scales were analyzed using metallography, scanning electron microscopy, and energy dispersive X-ray analysis. Two corrosion regimes, which were dependent on sulfur potential, were identified. At high sulfur potentials (P _{S 2} ± 2.7 × 10^-2 Nm^-2) the corrosion rates were high, the kinetics obeyed a linear rate equation, and the scales consisted mainly of sulfide phases similar to those observed from pure sulfidation. At low sulfur potentials (P _{S 2} ± 0.19 × 10^-2 Nm^-2) the corrosion rates were low, the kinetics obeyed a parabolic rate equation, and scales consisted mainly of oxide phases. Thermochemical diagrams for the Fe-Cr-S-O, Fe-Ni-S-O, Cr-Ni-S-O, and Si-Cr-S-O systems were constructed, and the experimental results are discussed in relation to these diagrams. Based on this comparison, reasonable corrosion mechanisms were developed. At high sulfur potentials, oxide and sulfide phases initially nucleate as separate islands. Overgrowth of the oxide by the sulfide occurs and an exchange reaction governs the corrosion process. Preoxidation at low oxygen potentials and 1150 K is beneficial in suppressing sulfidation at high sulfur potentials. Formerly a Senior Scientist with Materials and Molecular Research Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.     

The three-dimensional NMR solution structure of alpha-cobratoxin at pH 7.5 and conformational differences with the NMR solution structure at pH 3.2

The 3D solution structure of alpha-cobratoxin, a neurotoxin purified from the Naja naja siamensis snake venom, has been determined by Nuclear Magnetic Resonance spectroscopy, in conjunction with distance geometry and restrained molecular dynamics, at pH 7.5. A total of 490 distance restraints were obtained from NOE intensities and 25 phi dihedral angle restraints deduced from J-coupling data. The generated structures are well defined with root mean square deviations from a geometrical mean structure of 0.107 +/- 0.036 nm for the backbone atoms and 0.128 +/- 0.073 nm for the side-chain atoms (considering residues 1 to 66 minus 26 to 35). A comparison between the generated structures at pH 7.5 and the mean NMR solution structure at pH 3.2 revealed that the 3D structure of alpha-cobratoxin is more compact at neutral pH. This major difference is mainly due to the pH-dependent conformational variations of three residues His18, Thr44 and Thr59.     

Effectiveness of salt, pH, and diacetyl as inhibitors for Escherichia coli O157:H7 in dairy foods stored at refrigeration temperatures

The behavior of Escherichia coli O157:H7 inoculated in 10% rehydrated nonfat dry milk adjusted to pH levels between 3.8 and 5.4 with lactic acid, salt levels of 0 to 6%, and diacetyl levels of 0, 5, and 10 micrograms/g was determined at 4 and 12 degrees C. Cell populations were determined by surface plating on tryptic soy agar after 7 and 35 days of incubation. Survival was also determined using retail cultured diary products. E. coli O157:H7 did not survive in skim milk at pH 3.8 and was reduced by 3 log cycles at pH 4.1, regardless of salt, diacetyl, and temperature levels. At pH levels above 4.4, survival was observed at lower salt concentrations for up to 35 days at both 12 and 4 degrees C. The organism grew (up to a 2.2-log increase) at pH 5.0 at 2% salt levels after 35 days of storage at 12 degrees C. Diacetyl at a concentration of 10 ppm had no effect on survival and growth. In all but one case, E. coli O157:H7 was inactivated in yogurt, sour cream, and buttermilk at a rate similar to or greater than what was consistent with the acidified skim milk data. Also consistent with the skim milk data, growth occurred in two of the three cottage cheese samples at 12 degrees C after 7 days but not after 35 days or at 4 degrees C, when a 1- to 2-log decline was observed.     

Reactions of hafnium nitride with molybdenum,tungsten, and tantalum

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