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T J Franz

Publications and source records attributed to T J Franz.

39 records · Page 3Linked to original sources

Free radical oxidation of (E)-retinoic acid by prostaglandin H synthase.

Cooxidative metabolism of all-trans (E)-retinoic acid (RA) by prostaglandin H synthase was investigated employing ram seminal vesicle microsomes (RSVM) or purified, RSVM-derived enzyme. RA was shown to undergo hydroperoxide [H2O2 or 5-phenyl-4-penten-1-yl hydroperoxide (PPHP)]- or arachidonic acid-dependent cooxidation by microsomal prostaglandin H (PGH) synthase as evidenced by UV spectroscopic analysis of reaction mixtures. Cooxidation of RA by microsomal or purified PGH synthase, using PPHP as substrate, was characterized by uptake of dioxygen which was first order with respect to enzyme concentration. Dioxygen uptake was inhibited by the peroxidase reducing substrate 2-methoxyphenol. In addition, O2 uptake was inhibited by the spin trap nitrosobenzene. ESR spin trapping studies, using alpha-phenyl-N-tert-butylnitrone (PBN) as the spin trap, demonstrated the formation of RA-PBN adducts, characterized by hyperfine coupling constants of alpha H = 3.2 G and alpha N = 15.8 G. Reverse phase HPLC analysis of reaction mixtures demonstrated the formation of 4-hydroxy-RA, 5,6-epoxy-RA, 4-oxo-RA, (13Z)-retinoic acid, and other geometric isomers which were identified on the basis of cochromatography with synthetic standards, UV spectroscopy, and/or mass spectrometry. Mechanisms are proposed for the hydroperoxide-dependent, PGH synthase-catalyzed oxidation of RA that are consistent with these results.

Animals↗

Bioavailability of clobetasol propionate in different vehicles.

Topical clobetasol propionate is widely used for the treatment of psoriasis. One formulation of clobetasol propionate, Skin Cap, was thought by some practitioners and patients to be more effective than other formulations. Differences in corticosteroid bioavailability could account for differences in efficacy. The purpose of this study is to compare the relative bioavailability of clobetasol propionate from Skin Cap to two FDA-approved formulations of clobetasol propionate (Olux foam and Temovate scalp application). The bioavailability was assessed by measuring the percutaneous absorption of clobetasol propionate in vitro on scalp skin, using the human cadaver skin model. There was no significant difference in the percutaneous absorption of clobetasol propionate between Olux foam and Skin Cap (2.09 and 1.93% at 48 h, respectively) or between Olux foam and Temovate scalp application (3.70 and 3.46%, respectively) when applied under unoccluded conditions. Under occluded conditions, there was greater absorption of clobetasol propionate from the Olux foam as compared with Skin Cap (4.94 and 1.57%, respectively; p < 0.05). The Skin Cap vehicle does not provide more bioavailable clobetasol propionate than currently available, FDA-approved products. Other differences, including those in patient compliance, could account for the perceived efficacy of the product.

Administration, Cutaneous↗