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Biomedical subjects

S D Nelson

Publications and source records attributed to S D Nelson.

At least 235 records · Page 13Linked to original sources
PubMed1976

Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat.

Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

Animals↗
PubMed1976

Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis.

The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.

Acetylation↗
PubMed1975

The rapid identification of a new metabolite of warfarin via a chemical ionization mass spectrometry ion doublet technique.

An ion doublet chemical ionization mass spectrometry technique was utilized for the rapid detection and elucidation of the structure of a new hydroxylated metabolite of the oral anticoagulant warfarin. This technique involves the use of a 50:50 mixture of stable isotope labeled and unlabeled drug. With this procedure ions found in the mass spectrum which are associated with the administered drug can be identified unambiguously. The unknown metabolite from rat liver microsomal preparations was identified as benzylic hydroxywarfarin by reincubating the microsomes with warfarin specifically labeled in the benzylic position and observing the subsequent loss of label in the product. The ion doublet technique was also employed in a single human study, and benzylic hydroxywarfarin was detected and identified.

Animals↗
PubMed1975

Primary and beta-secondary deuterium isotope effects in N-deethylation reactions.

Lidocaine (1), labeled specifically with deuterium in the alpha-methylene (lidocaine-d4,2) and beta-methyl (lidocaine-d6,3) carbon atoms of the terminal amino group, was used to probe the mechanism of oxidative N-deethylation by rat liver microsomes. The reaction rates were determined by measuring the formation of acetaldehyde colorimetrically. This general assay for oxidative N-deethylation reactions has the advantages of being rapid, producing a relatively stable colored derivative and being linear over the range of 0.25-4 mug of acetaldehyde formed per milliliter of incubate. Deuterium substitution at the methylene carbon atoms, the presumed site of initial oxygen insertion, revealed a kH/kD = 1.49 +/- 0.11 and a KmD/KmH = 1.23. Deuterium substitution on the terminal methyl groups showed a kH/kD = 1.52 +/- 0.10 and a KmD/KmH = 0.92. The results are explained in terms of both primary and secondary isotope effects on a possible rate-determining step in the N-deethylation sequence.

Acetaldehyde↗
PubMed1975

HL-A antigens and thyrotoxicosis.

HL-A phenotypes were determined in 60 patients with primary thyrotoxicosis and in 60 age-sex matched controls living in the same region in order to establish the frequencies of ten HL-A antigens in the two populations. HL-A1 was present in 28 patients and 18 controls (X2 equals 2;86, P greater than 0,05); HL-A13 was present in eigth patients and only one control (X2 equals 4.32, 0.05 greater than P greater than 0.025). These findings suggest that HL-A phenotypes may be of value in studies on the aetiology of primary thyrotoxicosis. The statistical significance of these results is discussed as these findings may be due to chance deviations.

Adult↗
PubMed1974

National organ matching and distribution service.

In the first eleven months of the National Organ Matching and Distribution Service 455 kidney transplants were notified. A high proportion of first transplants failed within seven days of operation, probably reflecting low quality of some of the donor kidneys supplied. To improve the results of renal transplantation and to serve the increasing number of potential recipients registered with the service, as well as to obtain the optimum blood and tissue group compatibility of donor and recipient, many more kidneys are needed.

ABO Blood-Group System↗