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Biomedical subjects

J W Daniel

Publications and source records attributed to J W Daniel.

At least 19 recordsLinked to original sources

The metabolic fate of sucralose in rats.

The fate of sucralose was investigated in rats following single intravenous or oral doses of 2-1000mg/kg. Following intravenous administration (2-20mg/kg) approximately 80% of the dose was eliminated in urine with 9-16% in the faeces. In contrast, only about 5% of oral doses (10-1000mg/kg) was recovered in the urine, indicating that sucralose is poorly absorbed from the intestinal tract. After both intravenous and oral administration, the radioactivity excreted in urine and faeces was mainly unchanged sucralose. Two minor radioactive urinary components were observed, which together accounted for less than 1% of the administered dose. Rats which had been given high concentrations of sucralose (3%) in the diet for more than 18 months showed a similar metabolic profile, demonstrating that metabolic adaptation of the gut microflora or mammalian enzymes had not occurred during the treatment period.

Administration, Oral↗

Changes in some antinutrients of cowpeas (Vigna unguiculata) processed with 'kanwa' alkaline salt.

The effect on several anti-nutritional factors in cowpeas (Vigna unguiculata L. Walp) was investigated following treatment at 100 degrees C or 121 degrees C with solutions (0.1% w/v) of kanwa rock salt or NaHCO3 in distilled water. The concentration of polyphenols, calculated as tannic acid, was reduced substantially up to 67% under the alkaline conditions employed, but the reduction appeared to be greater (69-79%) at higher temperature. The loss of phytic acid was greater (27-40%) when beans were cooked in NaHCO3 than in kanwa (11-29%). The concentration of reducing sugars was decreased in all treatment groups especially under alkaline conditions. There was no evidence for the formation of lysinoalanine in any of the samples.

Bicarbonates↗

Glutathione-dependent dechlorination of 1,6-dichloro-1,6-dideoxyfructose.

The metabolism of 14C- and 36Cl-labelled 1,6-dichloro-1,6-dideoxyfructose (DCF) was studied in the isolated perfused rat liver system. Dechlorination of DCF occurred in the liver and erythrocytes and was GSH-dependent. The GSH conjugate formed was identified by 13C and 1H n.m.r. as the 6-chlorofructos-1-yl-SG conjugate. It is proposed that the GS- anion attacks the low steady-state concentration of the reactive keto form of DCF and that the conjugate formed cyclizes to the dominant beta-anomer. 6-Chlorofructos-1-yl-SG conjugate of hepatic origin is excreted into bile, whereas that produced in erythrocytes does not enter the liver.

Animals↗

The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay.

The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents and compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation.

Caffeine↗

Cyclic nucleotide responses and radiation-induced mitotic delay in Physarum polycephalum.

The response of the plasmodial levels of cyclic AMP and cyclic GMP in Physarum polycephalum to several putative phosphodiesterase inhibitors and to ionizing radiation has been measured. Isobutylmethylxanthine (2 mM) induces a rapid transient threefold elevation of cyclic AMP alone, with maximum response in about 10 min and return to the base line in about 30 min. Theophylline (2 mM) induces a rapid, sustained twofold elevation of cyclic GMP only. Caffeine (2 mM) and Ro-20-1724 (18 microM) both elicit a rapid transient rise in cyclic AMP, resembling the isobutylmethylxanthine response, and a slow transient elevation of the cyclic GMP level. Of particular interest is the rapid threefold transient elevation of the cyclic AMP, but not of the cyclic GMP, level by gamma radiation. These results (1) emphasize the organism and agent specificity of cyclic nucleotide responses, (2) indicate that the kinetics and apparent refractory response are compatible with the function of previously identified membrane receptor systems, i.e., a blue light receptor and a choleragen receptor mediating cyclic AMP responses, and (3) suggest a relationship between the agent-specific cyclic nucleotide responses and the modification of gamma-radiation-induced delay of mitosis by the same agents, i.e., a decrease in the delay by those which elevate cyclic GMP levels and an increase in the delay by those which elevate only cyclic AMP levels.

1-Methyl-3-isobutylxanthine↗

Safety evaluation of thaumatin (Talin protein).

Thaumatin, the sweet proteinaceous extract of the arils of Thaumatococcus daniellii (Benth.) has been studied for its subacute toxicity in rats and dogs and its ability to produce anaphylactic antibodies following oral administration to rats and normal human subjects. Thaumatin was readily digested prior to absorption in rats and no adverse effects resulted from its continuous administration to rats and dogs at dietary concentrations of 0, 0.3, 1.0 and 3.0% for 13 wk. It was not teratogenic when administered orally to rats at 0, 200, 600 and 2000 mg/kg body weight/day from day 6 to 15 of gestation and was without effect on the incidence of dominant lethal mutations when administered on five consecutive days to male mice at 200 and 2000 mg/kg/day. The lack of mutagenic potential was confirmed in bacterial mutagenic assays with Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98 and TA100) and Escherichia coli WP2, at levels of addition of 0.05-50 mg/plate. In rats, thaumatin was found to be a weak sensitizer, comparable with egg albumen, when administered systemically but to be inactive when administered orally. Prick testing of laboratory personnel who had been intermittently exposed by inhalation to thaumatin for periods up to 7 yr showed that 9.3% (13/140) responded positively to commercial thaumatin, while 30.7% were positive to Dermatophagoides pteronyssinus (house dust mite). None of the subjects who gave a positive skin reaction to commercial thaumatin responded to the plant components remaining after removal of the specific sweet Thaumatin proteins. Challenge tests in man did not demonstrate any oral sensitization. The results indicate that thaumatin when used as a flavour modifier and extender, and partial sweetener, is unlikely to be hazardous at the anticipated level of consumption.

Allergens↗

The physiological disposition of the anti-tussive agent, 1,2,3,4a,9b-hexahydro-8,9b-dimethyl-4-[3-(4-methylpiperazin-1-yl)propionamido]dibenzofuran-3-one dihydrochloride Azipranone, in man, rat, dog and baboon.

1. The absorption, tissue distrigution, elimination and biotransformation of the anti-tussive agent Azipranone labelled with 14C have been investigated after oral dosing to rat, dog, baboon and man and parenteral administration to rat and baboon. 2. Levels of radioactivity in plasma were maximal within 20 min of dosing in the rat and after 1-2 h in the remaining species. The concn. declined thereafter with a half-life estimated at 1, 3-4 and 18-24 h for rat, dog, and baboon and man respectively. 3. Three human volunteers excreted 53, 62 and 70% of the radioactivity in the urine in 96 h while the remaining species excreted 50-70% of the dose in the faeces in the same period. 4. Radioactivity was rapidly and extensively eliminated in the bile of both rat and baboon after administration of [14C]Azipranone. 5. The 24 h urine samples from all species contained ten major and a similar number of minor radioactive components. 6. In hepatic microsomal preparations, biotransformations of Azipranone are catalysed by enzymes requiring both NADPH2 and cytochrome-P450.

Administration, Oral↗

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Hand Injuries↗