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Biomedical subjects

J A Tillotson

Publications and source records attributed to J A Tillotson.

13 recordsLinked to original sources
PubMed1989

The biological fate of 14C-dimercaptosuccinic acid in monkeys and rabbits.

The biological fate of 14C-labeled dimercaptosuccinic acid (DMSA) in monkeys and rabbits was determined by measuring the 14C activity in their urine, feces, and expired air (14CO2). Monkeys absorbed less than 20% DMSA from three oral dose levels (0.082, 0.16, and 0.5 mmol/kg) of 14C-DMSA, and the rabbits absorbed 32% DMSA or less from an oral dose of 14C-DMSA (0.5 mmol/kg). Although the bioavailability of DMSA was limited in either species, DMSA was detected in the blood of both species within minutes after oral dosing. In either species, most of the radiolabel from the absorbed 14C-DMSA was detected in the urine within 12 hours. We also developed a sensitive assay for directly measuring levels of DMSA (as free thiols) in blood. Intact DMSA was not detected in the blood of the monkeys or the rabbits more than 200 minutes after oral or intravenous dosing at 0.5 mmol DMSA/kg body weight. However, 14C activity in blood and urine of the monkeys was measurable 72 hours after this dose. Differences between measured 14C concentrations and intact DMSA concentrations in the blood suggest the presence of DMSA metabolites that have longer half-lives than DMSA. Consequently, until the biological activities of these compounds are identified, the pharmacokinetic analysis of DMSA may be incomplete.

Animals↗
PubMed1988

The fate of nitroguanidine in the rat.

The metabolism and disposition of nitroguanidine (NG), a component of military propellants and munitions, were examined in the rat. Radiolabeled nitroguanidine [( 14C]NG) was administered orally at doses of 20 and 200 mg/kg and intravenously at a dose of 20 mg/kg. Regardless of the route of administration, the radiolabel was recovered quantitatively in the urine of all animals within 48 hr after dosing. Chromatographic analysis of the urine indicated that the [14C]NG was excreted unchanged; no radiolabel was found in the expired air, feces, or tissues of the treated animals. No sex differences were seen in the disposition of NG. The kinetics of [14C]NG in the blood of the dosed animals was followed. The elimination half-life of NG was on the order of 2 hr. The bioavailability of orally administered NG was 100%; the kinetics of NG in the blood was not dose dependent. Examination of tissues 1 hr after an oral dose of NG showed that NG was evenly distributed throughout the body. Nitroguanidine is a chemical of low toxicity (LD50 greater than 5 g/kg); it is quantitatively absorbed from the gastrointestinal tract, distributed throughout the body, and rapidly excreted in the urine.

Animals↗
PubMed1981

The relationship of the urinary ascorbate metabolites to specific levels of ascorbate supplementation in the monkey.

This study was designed to investigate urinary ascorbic acid (AA) and its metabolites derived from (1-14C) AA administered to trained monkeys fed different levels of ascorbate for extended periods of time. A chromatographic procedure was developed which rapidly separates the urinary compounds into four major fractions with minimal degradation. The distribution of 14C in the four peaks was dependent upon the ascorbate nutritional status of the monkey and remained constant for at least 30 days postlabel. The two major fractions were identified as oxalate and unmetabolized ascorbate. The ascorbate metabolites in the two minor fractions have not been identified. In monkeys maintained on low ascorbate intakes, unmetabolized ascorbate accounted for 10 to 20% and oxalate 25 to 48% of the urinary 14C. The average percentages of 14C in the urine of monkeys fed high levels of ascorbate were 75% for ascorbate and 7% for oxalate. The urine also contained an ascorbate metabolite which degraded during storage and/or chromatography, yielding 14CO2. Ascorbate sulfate was not detected as a urinary metabolite.

Animals↗
PubMed1980

Ascorbic acid requirements of the trained monkey as determined by blood ascorbate levels.

The ascorbate requirements of 4 monkeys were investigated by comparison of the plasma and whole blood ascorbate levels to known amounts of ascorbate supplements. The monkeys were conditioned to the experimental procedures to minimize environmental stress which increases ascorbate requirements. Trained monkeys required 3 and 6 mg AA/kg body weight fed daily to mature and young monkeys, respectively, to maintain blood ascorbate levels proposed as necessary to prevent the development of scurvy. Young monkeys (sexually immature) required twice the amount of the vitamin to maintain acceptable ascorbate levels than did the mature monkeys. Smaller amounts of ascorbate were required by the monkeys to maintain similar blood ascorbate levels when the vitamin was incorporated into the diet in comparison to the single and oral supplement. Only small variations were measured between the plasma and whole blood ascorbate levels in the same monkey. The leucocyte ascorbate levels suggest that the tissue ascorbate concentration may be minimal although the blood ascorbate concentration is in an acceptable range.

Aging↗
PubMed1978

Ascorbate metabolism in the trained monkey.

The metabolic fate of 14C-1-ascorbate was studied in trained monkeys (Macacca fasicularis) by measurement of the 14C in the expired breath, urine, and feces. To minimize stress, each monkey was placed in a restraining primate chair and trained to all experimental procedures prior to the isotope studies. The majority of the 14C-1-ascorbate was absorbed by the trained monkeys and ascorbate turnover increased with increasing plasma levels. The urine of trained monkeys was the major excretion route of 14C-1-ascorbate and its metabolites. less than 2.5% of the 14C-1-ascorbate was oxidized in 24 hr to 14CO2. The 14CO2 production was not changed by diet or the ascorbate nutritional status in the trained monkey. A significant increase in 14CO2 production was measured in an untrained monkey. The metabolic fate of 14C-1-ascorbate in man and the trained monkey was similar. Therefore, the trained monkey could be a study model for ascorbate metabolism in man.

Animals↗
PubMed1977

Urinary riboflavin metabolites in the rat.

Male rats were fed a riboflavin-deficient diet for 25 days and then fed [2-14C]riboflavin to replete their riboflavin pool(s). During a second depletion period, urine and feces were collected and 14C excretion monitored. The urine was chromatographed on R-15 resorcinol resin and 14C was measured in all fractions. The 14C compounds in the individual fractions were shown to be different by thin layer chromatography. The amount of 14C recovered as riboflavin increased after acid hydrolysis of the urine indicating the presence of riboflavin in conjugated forms. All R-15 fractions were found to support growth in a microbiological (L. casei) assay for riboflavin. This suggested that other derivatives, in addition to riboflavin and flavin nucleotides, are biologically active. However, the conjugated compounds were apparently less active, since acid hydrolysis of the urine enhanced its growth-promoting ability of L. casei. One 14C metabolite was identified as urea, thus providing evidence for degradation of the riboflavin molecule. This study has shown that the metabolic fates of riboflavin in the rat include conjugation and extensive degradation.

Age Factors↗