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Biomedical subjects

R L Reed

Publications and source records attributed to R L Reed.

95 records · Page 6Linked to original sources
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The current status of family medicine geriatric fellowships.

A questionnaire was sent to directors of all family medicine-affiliated geriatric fellowship programs to characterize trends and changes since institution of ACGME accreditation of fellowships. The number of fellowships has more than doubled since 1986, but few fellows graduate from these programs. There is currently a surplus of fellowship positions; over half of all programs did not recruit a first-year fellow for the 1989 academic year. In 1986, most family medicine-affiliated programs had independent administration. Almost half of the programs are now jointly sponsored with an internal medicine department. These programs are over six times more likely to train internists than family physicians. Although there has been a growth in geriatric training programs over the past three years, the number of family physicians seeking such training remains negligible.

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The role of flavin-containing monooxygenase in the N-oxidation of the pyrrolizidine alkaloid senecionine.

The pyrrolizidine alkaloid, senecionine, is N-oxidized by purified pig liver flavin-containing monooxygenase but not by purified rabbit lung flavin-containing monooxygenase. The activity of the pig liver enzyme toward senecionine was linear with time and amount of enzyme. The oxygenation was not due to some indirect mechanism, such as O2- release from the enzyme, as scavengers of activated oxygen had no effect on product formation. The Km of purified pig liver flavin-containing monooxygenase for senecionine was 0.3 mM. Although senecionine is a substrate for the pig liver enzyme, studies performed with rat liver microsomes suggest that, in this species, cytochromes P-450 catalyze the majority of senecionine-N-oxidation. These experiments included inhibition by chemical inhibitors of P-450, treatment of the microsomes with elevated temperatures, inhibition by anti-NADPH-cytochrome P-450 reductase antibody, the effect of dexamethasone on N-oxidation, and relative amounts of flavin-containing monooxygenase determined by immunoquantitation. These results demonstrate that flavin-containing monooxygenase can be involved in the detoxication of pyrrolizidine alkaloids via N-oxidation, but the relative contribution of flavin-containing monooxygenase and cytochromes P-450 may be species and tissue dependent.

Animals↗
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Bioactivation and detoxication of the pyrrolizidine alkaloid senecionine by cytochrome P-450 enzymes in rat liver.

Rats display a marked sex difference in the oxidation of the pyrrolizidine alkaloid senecionine, especially with respect to N-oxidation. This sex difference was largely eliminated following treatment with dexamethasone. These observations suggested the potential involvement of the male-specific cytochrome P-450 UT-A and the P-450 PCN-E in the metabolism of this pyrrolizidine alkaloid. Reconstituted rat P-450 UT-A exhibited a high rate of N-oxidation (15 nmol min-1 nmol P-450-1) which is almost 3-fold higher than the turnover number observed with male rat liver microsomes. In contrast, rat P-450 UT-A displayed a much lower activity toward necine pyrrole [+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine, DHP) formation (1.0 nmol min-1 nmol P-450-1). The N-oxygenation and pyrrole formation activities displayed by rat cytochromes P-450 PB-B and P-450 BNF-B toward senecionine were low, with rates less than 1 nmol min-1 nmol P-450-1. Rabbit antibody to rat P-450 UT-A inhibited the senecionine-N-oxidation activity of untreated male rat liver microsomes by 60%, with lesser inhibition of DHP production. Rabbit antibody to human P-450NF (the human homologue to rat P-450 PCN-E) was a potent inhibitor of DHP production by untreated male rat liver microsomes. With microsomes from dexamethasone-pretreated rats, anti-P-450NF inhibited DHP and N-oxide production in parallel. We conclude that the large sex difference in senecionine N-oxidation probably is the result of the specificity of P-450 isozymes UT-A and PCN-E.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗