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D W Miller

Publications and source records attributed to D W Miller.

222 records · Page 13Linked to original sources
PubMedDate not supplied

Microbial transformation of the antihistamine pyrilamine maleate. Formation of potential mammalian metabolites.

Fourteen fungi were found to metabolize pyrilamine (2-[(2-dimethylaminoethyl)(p-methoxybenzyl)amino]pyridine). Two Cunninghamella elegans strains transformed essentially all of the pyrilamine added after 144 hr. After 48 hr of incubation, C. elegans ATCC 9245 metabolized 76% of the antihistamine into methylene chloride-extractable pyrilamine metabolites. These organic-soluble metabolites were isolated by HPLC and the major metabolites were characterized by comparison of their chromatographic, mass, and 1H-NMR spectral properties with those of authentic compounds. The major metabolite was identified as 2-[(2-dimethyloxyaminoethyl)(p-methoxybenzyl)amino]pyridine (N-oxide derivative of pyrilamine). Other metabolites identified were 2-[(2-dimethylaminoethyl)(p-hydroxybenzyl)amino]pyridine, 2-[(2-methylaminoethyl)(p-methoxybenzyl)amino]pyridine, and 2-[(2-methylaminoethyl)(p-hydroxybenzyl)amino]pyridine. These metabolites represent O-demethylated, N-demethylated, and O- and N-demethylated derivatives of pyrilamine, respectively. The mutagenic activities of the N-oxide and the N- and O-dealkylated pyrilamine derivatives, and pyrilamine maleate were measured by reversion of Salmonella typhimurium strains TA97, TA98, TA100, and TA102. Pyrilamine maleate and the three microbial metabolites showed no appreciable mutagenic activity in any of the S. typhimurium tester strains. The metabolism of pyrilamine by 12 other filamentous fungi and yeast strains was much less when compared to C. elegans and ranged from 3.8% to 12.2%. The fungal metabolism of pyrilamine may be useful in predicting results of mammalian metabolism and in readily providing sufficient quantities of metabolites for further toxicological studies.

Aminopyridines↗
PubMedDate not supplied

Testicular microvascular blood flow: alteration after Leydig cell eradication and ischemia but not experimental varicocele.

Testicular microvascular blood flow is known to exhibit vasomotion, or pulsatile flow. In the present study we have used laser-Doppler flowmetry to study microvascular blood flow in the rat testis and to examine the response of the microvasculature to pharmacological stimulation and pathophysiological conditions. With a mean microvascular flow rate of 13.3 +/- 1.7 perfusion units (PU), the mean cycle amplitude was 3.4 +/- 0.6 PU, and the cycle frequency was 10.3 +/- 0.8 cycles per minute. Blood flow parameters did not differ between left and right testes, between scrotal testes and testes in a 35 degree C glass testicle receptacle, or among testicular regions. Perifusion of seminiferous tubules and their vasculature with 0.1 microgram/microliter epinephrine significantly reduced microvascular blood flow and eliminated vasomotion. Elimination of Leydig cells and intratesticular testosterone also eliminated vasomotion but did not significantly alter mean blood flow rates. Thirty days after imposition of experimental left varicocele (ELV) there were no significant changes in microvascular blood flow parameters. Testicular torsion of sufficient degree and duration to destroy spermatogenesis did not induce a change in mean microvascular blood flow rate 24 hours after repair of torsion, but testicular vasomotion was eliminated in the majority of animals. We conclude that microvascular flow is altered in some testicular pathologies and not in others. The mechanisms underlying changes in microvascular blood flow are at present unknown.

Animals↗