No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

Melphalan (the synthetic product of nitrogen mustard and L-phenylalanine) is an alkylating agent and is the drug of choice in the treatment of multiple myeloma. The bioavailability of melphalan is variable but factors affecting its absorption and the mechanism(s) by which the drug crosses the intestinal epithelium are not known. A sensitive assay for melphalan in plasma (down to a concentration of 2ng.ml^-1) has been developed. The method, involving solid phase extraction and derivatisation with o-phthalaldehyde followed by reversed-phase high-performance liquid chromatography, was applied to the study of melphalan pharmacokinetics in multiple myeloma patients. Bioavailability ranged from 0.16 to 1.37 in nine fasting patients and peak plasma concentrations of melphalan ranged from 8.0 to 170 ng.ml^-1 and occurred 0.5 to 2.0 hours after an oral dose of 10mg. When melphalan was taken with food (three patients) a mean reduction of 40% in bioavailability was observed. Significant correlations (P< 0.05) were observed between bioavailability and melphalan plasma concentrations in single samples drawn at 0.5, 1.0 and 2.0 hours. There was no significant correlation between renal function and melphalan absorption, distribution or elimination. A second peak was observed in the distribution phase of six of the eleven plasma concentration-time curves when melphalan was administered intravenously. The secondary peak may be attributed to either melphalan redistribution or enterohepatic circulation. An <i>in vitro</i> method (modified Ussing technique) was developed to investigate melphalan transport across rat and human small intestine. There was no evidence for the Na⁺-coupled (active) transport of melphalan in these tissues. The rate of melphalan transfer was non-saturable and values of apparent mass transfer coefficients were comparable with the diffusional contribution to the intestinal transport of amino acids The results indicate that passive diffusion is the major process responsible for the transfer of melphalan across intestinal epithelium.

The main objective of this study was to investigate the nature of farinograph absorption (FA) in CWRW flours which is typically lower than CWRS wheats. FA for CWRW genotype samples ranged from 54 - 65%. Phloroglucinol assay of pentosan content (PC) proved to be accurate and precise. The most highly correlated parameters to FA were volume fractions of large (or small) flour particles determined by laser diffraction, protein content, starch damage and water soluble PC. Correlations to FA for these factors were in the range r = 0.40 to 0.68. A promising 4-variable regression model of FA prediction (R2 = 0.64) was developed. CWRW wheats tended to be low in FA due to low levels of wheat hardness, protein content, or PC. Increasing the levels of these parameters by breeding would likely practically improve FA of future CWRW cultivars. An extended abstract is included at the end of this thesis.

No description available.

The adsorption kinetics exhibited by selected charge mutants of T4 lysozyme at silanized silica surfaces were monitored with in situ ellipsometry. Mutant lysozymes were produced by substitution of lysine (Lys) with glutamic acid (Glu). Each substitution resulted in a decrease in the net charge of the protein by 2 units. The wild type lysozyme of net charge +9, and two mutants of net charge +7 and +5 were obtained from E. coli strain RR1 . Adsorption kinetics recorded at hydrophilic and hydrophobic interfaces were compared to the kinetic behavior predicted by two simple models for protein adsorption. One was a three-rate-constant model allowing for reversible adsorption followed by conversion to an irreversibly adsorbed form, and was analyzed under three different conditions. The first condition allowed the adsorption rate (k₁) and the desorption rate (k₋₁) to be variable while the surface-induced conversion rate (s₁) was assumed constant. The second condition assumed k₁ and k₋₁ constant instead of S₁, and the third allowed all kinetic rate constants to be variable. The second model allowed for irreversible adsorption into one of two states directly from solution. Both models suggested that substitution of Lys with Glu in the backbone of T4 lysozyme facilitates the adsorption of the protein at these interfaces. Proteins apparently adsorbed at the interfaces more tightly and occupied a greater interfacial area with substitution of Lys with Glu, and these effects were related to the location of the substitutions relative to other charged residues of the protein, and not to net charge. / Graduation date: 1995