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Biomedical subjects

S C Mitchell

Publications and source records attributed to S C Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1989

Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.

1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.

Adult↗
PubMed1989

The fate of cimetidine sulphoxide in the guinea pig.

1. An oral dose of cimetidine given to guinea pigs was totally excreted in 3 days, divided equally between urine and faeces. 2. Only 40% of an oral dose of cimetidine sulphoxide was voided in 3 days, the remainder being found in the mesentery and omental tissues. 3. In contrast, 90% of an i.v. dose of cimetidine sulphoxide was excreted in urine in 24 h. 4. Approx. 20% of an oral dose of both cimetidine (17.2%) and cimetidine sulphoxide (24.9%) was secreted in bile during the first day. 5. The major metabolic routes encountered were sulphoxidation and sulphoxide reduction.

Administration, Oral↗
PubMed1988

Poor sulphoxidation ability in patients with food sensitivity.

Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions by using carbocisteine and debrisoquine as probe compounds. The proportion of poor sulphoxidisers (58 of 74) was significantly greater than that of a previously determined normal control population (67 of 200; p less than 0.005). The proportion of poor carbon oxidisers was not significantly different from the controls. Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.

Adult↗
PubMed1988

Trimethylaminuria ('fish-odour syndrome'): a study of an affected family.

1. Beginning with a single propositus, who had been previously diagnosed at the age of 10 as suffering from trimethylaminuria (fish-odour syndrome), both her parents and two sisters were investigated biochemically with respect to their ability to N-oxidize trimethylamine (TMA), both when derived from the diet and when administered exogenously. 2. Both the propositus and a second sister were markedly deficient in their ability to N-oxidize TMA, both when derived from the diet and when given as such; furthermore, both siblings readily developed the symptoms of fish-odour syndrome as characterized by a strong objectionable breath and body odour shortly after the oral administration of TMA (300 mg). 3. At this dose level of TMA, neither of the parents nor the third sister showed any evidence of impaired N-oxidation ability nor did they experience any 'fish-odour' symptoms. 4. With an oral challenge of 600 mg of TMA, both the parents showed a clear impairment of N-oxidation capacity which was not seen in six healthy unrelated volunteers. Both parents experienced a fish-odour syndrome at this level of TMA challenge. 5. The family data support the hypothesis that trimethylaminuria is an inborn error in the ability to N-oxidize TMA which is inherited as an autosomal recessive trait. Furthermore, experience with this family suggests that an oral challenge dose with 600 mg of TMA may be used to identify carriers of the condition.

Adult↗
PubMed1988

Biological consequences of drug sulphoxidation.

The addition of an oxygen atom to the sulphur centre of a compound, with the formation of a polarized S-O moiety, alters the physical and chemical properties of the molecule and can profoundly influence its biological activity, its disposition within the body and its potential fate. Examples are given to illustrate these points.

Animals↗
PubMed1988

The metabolism of 35S-D-penicillamine in man.

1. The excretion and metabolism of 35S-D-penicillamine (200 mg orally) was studied in four healthy male volunteers. 2. The major route of excretion was the urine with 82% of the administered dose being voided over three days (73% during the first 24 h); the remainder was excreted in the faeces. 3. Metabolism occurred via the pathways of S-methylation, N-acetylation and disulphide formation. Extensive degradation of the molecule was observed with the production of large amounts of inorganic sulphate.

Administration, Oral↗
PubMed1987

Odorous urine following asparagus ingestion in man.

The production of odorous urine after the ingestion of asparagus has been shown to occur in 43% of 800 volunteers investigated. This characteristic is reproducible over a 12-month-period and has been shown to remain with individuals for virtually a lifetime. Family studies suggest that the ability to produce the odorous urine is inherited as an autosomal dominant trait.

Female↗
PubMed1987

A genetic polymorphism of the N-oxidation of trimethylamine in humans.

Trimethylamine (TMA) and its N-oxide (TMAO) are normal components of human urine. They are present in the diet and also derived from the enterobacterial metabolism of precursors such as choline. Dietary TMA is almost entirely metabolized to and excreted as TMAO. However, the extent to which TMA undergoes N-oxidation appears to be polymorphic in a British white population study (n = 169). Two propositi were identified with relative TMA N-oxidation deficiency that was further confirmed by oral challenge with TMA (600 mg). The study of the families of the two propositi, as well as those of two identified subjects with trimethylaminuria, under both normal dietary conditions and after oral TMA challenge strongly indicates that the conditions of impaired N-oxidation is inherited as a recessive trait. It is proposed that the N-oxidation of TMA in humans is polymorphic and under single gene diallelic control in which individuals who are homozygous for the variant allele exhibit marked N-oxidation deficiency and trimethylaminuria.

Adolescent↗
PubMed1987

Disclosure of the metabolic retroversion of trimethylamine N-oxide in humans: a pharmacogenetic approach.

Trimethylamine N-oxide (TMAO), which is naturally occurring in dietary marine fish, is well absorbed and excreted apparently unchanged as judged by end-product analysis. Such observations may conceal the fact that the amine N-oxide has undergone a sequence of deoxygenation and oxygenation reactions only to revert to the parental form and be excreted as such--a process that we propose to call metabolic retroversion. To evaluate this phenomenon for TMAO we have investigated the fate of the orally administered substance in healthy volunteers and in four subjects previously phenotyped as having an inherited deficiency with respect to the metabolic N-oxidation of trimethylamine (TMA). Two of these subjects were typed as homozygous affected and the other two as "carriers." If substantial reduction of orally administered TMAO occurs during the course of its postulated retroverted metabolism, it was hypothesized that this would be revealed by the extensive urinary excretion of unoxidized TMA by the four affected subjects. After oral TMAO administration in the four healthy subjects, greater than 94% of the urinary TMA was in the form of TMAO and only less than 4% as the free base. However, after oral TMAO in the two homozygous-affected subjects, unoxidized TMA accounted for 35% and 51%, respectively, of the total urinary TMA, the balance being due to TMAO. For the carrier subjects, TMA accounted for 12% and 16% of the total urinary TMA after TMAO administration. It is thus clear that the urinary excretion of unoxidized TMA is increased greatly in affected subjects with an inherited deficiency of N-oxidation after the oral administration of TMAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Sodium aurothiomalate toxicity and sulphoxidation capacity in rheumatoid arthritic patients.

The association between sulphoxidation capacity and sodium aurothiomalate toxicity was investigated in 65 patients undergoing treatment for rheumatoid arthritis. Of those showing side-effects, 30/37 (81%) were also poor sulphoxidizers compared with only 9/28 (32%) in the group not displaying adverse reactions. A patient with poor sulphoxidation had a nine-fold greater risk of developing toxicity. The prior measurement of sulphoxidation capacity may help to identify those patients most susceptible to the deleterious effects of this drug.

Adult↗
PubMed1987

The metabolism of 14C-labelled trimethylamine and its N-oxide in man.

The metabolism and elimination of 14C-labelled trimethylamine and its N-oxide (100 mg orally) were studied in three male volunteers. For both compounds the urine was the major route of elimination, with 95% of the administered 14C being voided in the first 24 h. No radioactivity was found in expired air. The majority (greater than 95%) of the urinary 14C from both compounds was excreted as trimethylamine N-oxide.

Biotransformation↗
PubMed1987

The chemical nature of the urinary odour produced by man after asparagus ingestion.

1. The pungent urinary odour produced by certain individuals within a few hours of eating asparagus has been shown to be due to a combination of up to six sulphur-containing alkyl compounds identified as methanethiol, dimethyl sulphide, dimethyl disulphide, bis-(methylthio)methane, dimethyl sulphoxide and dimethyl sulphone. 2. The possible roles of S-methylmethionine and asparagusic acid as precursors of these odorous substances are discussed in relation to the known chemistry of the vegetable.

Adult↗
PubMed1986

The case of the black-speckled dolls: an occupational hazard of unusual sulphur metabolism.

A patient who made reproduction antique china dolls complained that wherever she touched the dolls' heads when painting them, black speckles appeared after the subsequent firing. Investigation by means of mass spectrometry and X-ray fluorescence showed that the clay was rich in iron, that the patient's sweat contained volatile sulphides whenever she ate garlic, and that the speckles consisted of iron and sulphur. The patient was shown to be a poor sulphoxidiser and was therefore unlikely to be able to excrete sulphur-containing breakdown products of garlic in her urine. The speckling phenomenon, which is not uncommon in 19th-century china dolls, is an example of an occupational hazard where the risk is to the product rather than the patient.

Adolescent↗