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Biomedical subjects

R H Waring

Publications and source records attributed to R H Waring.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1986

Sulphoxidation of S-carboxymethyl-L-cysteine in the rhesus monkey (Macaca mulatta), cynomologus monkey (Macaca fascicularis), African green monkey (Cercopithecus aethiops) and the marmoset (Callithrix jacchus).

The metabolic pathways giving rise to the urinary metabolites of S-carboxymethyl-L-cysteine have been identified for the rhesus, cynomologus, African green and marmoset species of monkey. The formation of a sulphoxide metabolite from the sulphide precursor is a reaction important in these species. The metabolic profile displayed by the marmoset was distinct from the three Old World species, with the rhesus and cynomologus being similar to man.

Animals↗
PubMed1985

Lack of congruence of S-carboxymethyl-L-cysteine sulphoxidation and debrisoquine 4-hydroxylation in a Caucasian population.

One-hundred-and-twenty volunteers and three families were investigated for possible association between the sulphoxidation of S-carboxymethyl-L-cysteine and the debrisoquine hydroxylation polymorphism. The observed individual variations in these two metabolic reactions were shown not to be concordant (rs = 0.068) and any heritable factors controlling the major aspects of these phenomena do not co-segregate.

Adolescent↗
PubMed1985

The metabolism of phenothiazine in the neonatal calf: identification of drug-polypeptide conjugates from urine.

The presence of a polypeptide conjugate fraction in the urine of young calves after oral dosing with phenothiazine has been confirmed. Four different polypeptide conjugates, containing up to six amino acids attached to phenothiazine or leucophenothiazone via the carboxyl terminal of the chain, have been isolated, characterized and sequenced. In addition, several minor polypeptide conjugates have been observed. The literature pertaining to polypeptide conjugates of drugs has been reviewed and the importance of this metabolic route in neonatal animals discussed.

Amino Acid Sequence↗
PubMed1985

The influence of an experimental liver cirrhosis upon the metabolism of diazepam and imipramine hydrochloride in the rat.

When either diazepam or imipramine hydrochloride was administered orally to rats with thioacetamide-induced hepatic cirrhosis, the biliary and faecal elimination of metabolites was significantly decreased compared with that in normal animals. However, renal excretion of metabolites of diazepam or imipramine was increased in the liver-damaged rats. Experiments in vitro showed that liver homogenates from cirrhotic rats metabolized diazepam or imipramine hydrochloride in qualitatively and quantitatively similar ways to those from normal rats. Clearance of radioactivity from the blood following i.v. administration of either diazepam or imipramine hydrochloride was prolonged in animals with experimental cirrhosis.

Animals↗
PubMed1984

Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in man.

Interindividual variation in the sulphoxidation of S-carboxymethyl-L-cysteine (750 mg p.o.) was investigated in 200 healthy volunteers. Nearly a 100-fold difference was observed between individuals with respect to the amount of sulphoxide metabolites detected in their 0-8 h urine (0.6 to 59.1% recovery). Such a difference was shown to be reproducible over several months in 40 subjects who spanned the entire range of capacities. Cumulative plots and maximum likelihood analysis of the distribution indicated that a bimodal model was most probable. Analysis of pedigree data obtained from 12 families suggested a genetic effect with overlying environmental influences.

Adolescent↗
PubMed1984

The metabolism of S-methyl-L-cysteine in man.

The excretion and metabolism of radiolabelled S-methyl-L-cysteine (150 mg orally) was studied in three male volunteers. The major route of excretion was the urine with 55.9% of the administered radioactivity being voided over three days (33.3% during the first 24 h). Faecal excretion was relatively unimportant (c. 1.4%). The remaining radioactivity was either slowly excreted in the urine over the next 21 d (35S-labelled compound) or exhaled (14C-labelled compounds). Metabolism occurred via the pathways of S-oxidation, N-acetylation and deamination. Extensive degradation of the molecule was observed with the production of large amounts of inorganic sulphate and CO2. The options for the sequence of metabolic degradation of the amino acid derivative are discussed.

Acetylation↗
PubMed1984

D-Penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3.

Sulphoxidation of carbocysteine, a drug structurally similar to D-penicillamine, displays a skewed distribution within a population. In 66 patients with rheumatoid arthritis (RA) a significant association between impaired sulphoxidation and toxicity (p less than 0.001) was found; HLA-DR3, although associated with toxicity (p less than 0.05), appeared to be an independent risk factor of most importance in the group with extensive sulphoxidation. The relative risk of toxicity in a patient possessing either DR3 or impaired sulphoxidation was 25. The prevalence of poor sulphoxidizers within this group of RA patients was increased compared to that in a previous population study and requires further investigation. Our findings explain a number of the toxic phenomena associated with D-penicillamine administration in RA.

Adult↗
PubMed1983

Early changes in thioacetamide-induced liver damage.

Plasma amino acids, serum enzymes, liver glutathione and the hepatic lipid peroxidation capacity of the rat were investigated in acute thioacetamide toxicity. These were examined in parallel with the earliest pathological changes shown by electron microscopy. Plasma arginine levels were significantly lowered 3 h after dosing thioacetamide and by 9 h were indistinguishable. This finding correlates with other workers demonstrating urea cycle damage in alcohol and carbon tetrachloride damaged rat liver. Depressed arginine plasma levels were detectable before any of the biochemical or pathological processes co-examined and as such may prove useful as a sensitive in vivo method for detection of acute liver damage.

Acetamides↗
PubMed1983

The metabolism of S-carboxymethyl-L-cysteine in man: isolation of an ester glucuronic acid conjugate from urine.

A conjugate isolated from urine of human volunteers after an oral dose of S-carboxymethyl-L-cysteine was characterized as a carboxylic acid ester glucuronide. Of the 166 volunteers investigated, 61 gave no detectable drug glucuronide (less than 0.5% administered dose); the remaining 105 showed a unimodal distribution of drug glucuronide excretion accounting for 0.5-11.5% (mean 4.1%, median 3.4%) of the total dose recovered in the 0-8 h urine. No significant variation in subject age, sex or urinary pH was observed between the two groups, but those not excreting urinary glucuronide had significantly higher 0-8 h urine volumes (P less than 0.001), although notable exceptions occurred.

Adult↗
PubMed1983

The metabolism of thioacetanilide in the rat.

The metabolism and acute toxicity of thioacetanilide was studied in the rat. Following intragastric dosage (100 mg/kg), over 90% dose was excreted in urine, predominantly as conjugated metabolites: less than 7% was recovered in the faeces, consisting of unchanged thioacetanilide. N-Acetyl-4-aminophenol sulphate was the major urinary metabolite, with smaller amounts of conjugated 4-hydroxythioacetanilide and unmetabolized thioacetanilide. Biliary excretion amounted to only 3.4% and was N-acetyl-4-aminophenol glucuronide. Although desulphuration was a major metabolic pathway in the rat, no hepatic toxicity (shown by serum enzymes, plasma bilirubin, hepatic glutathione and cytochrome P-450 levels) occurred up to doses of 500 mg/kg. Combination of rapid 4-hydroxylation, absence of sulphoxide formation, and the structural tautomerism exhibited by thioacetanilide may be, in part, responsible for these findings.

Acetanilides↗
PubMed1982

A comparison of the metabolism and elimination of benzanilide and salicylanilide in the rat.

1. The metabolism and elimination of benzanilide and salicylanilide in rats were compared. 2. For both compounds, greater than 70% dose was excreted in urine with 20% in faeces, in 3 days. 3. With [14C]benzanilide and [14C]salicylanilide, 40% and 35% respectively of the 14C was excreted in the bile in 24 h. 4. Benzanilide was metabolized to 4'-hydroxybenzanilide (24%), 2-hydroxybenzanilide (salicylanilide, 19%) and 2'-hydroxybenzanilide (13%), with small amounts of 4-hydroxybenzanilide. 5. Salicylanilide was excreted unchanged (56%) with small amounts of the 5-hydroxy and 4'-hydroxy-derivatives. 6. All metabolites were present as glucuronide conjugates; the free aglycones were not found.

Anilides↗
PubMed1981

A comparison of the in vivo metabolism of phenothiazine and promazine in the neonatal guinea pig.

The in vivo metabolism of promazine and phenothiazine was studied in neonatal guinea pigs aged 1-21 days. Urinary metabolites were estimated for both compounds; marked fluctuations with age were noted, some values being greater than those found for adult animals. Unconjugated phenol (C-oxidation products) levels were very low, although glucuronide excretion was always present; glucuronyl transferase activity did not appear to be limiting, and was present as early as 1 day after birth. Peak sulphoxide excretion showed no correlation with output of other metabolites, suggesting that S- and C-oxidation are not directly linked.

Aging↗