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Biomedical subjects

B Stavric

Publications and source records attributed to B Stavric.

At least 37 records · Page 2Linked to original sources
PubMed1986

Elimination of chronically consumed caffeine in the pregnant monkey (Macaca fascicularis).

Characterization of alterations in caffeine elimination during pregnancy is essential in assessing the potential exposure of the fetus to caffeine and its metabolites. Female monkeys (Macaca fascicularis) were exposed to caffeine in their drinking water 7 days/week before, during and after pregnancy. The low exposure (0.15 mg/ml) corresponded to a level sometimes consumed by pregnant women (10-15 mg/kg/day) whereas the high exposure (0.35 mg/ml) was above average human consumption (25-30 mg/kg/day). Blood samples and 24-hr urine samples were collected every 2 weeks throughout dosing. Caffeine and metabolite concentrations in serum and urine were determined by high-performance liquid chromatography. Before pregnancy, geometric mean serum caffeine concentrations were approximately 1.6 and 4.9 micrograms/ml and serum theophylline concentrations were 6.6 and 13.3 micrograms/ml for the low and high dose groups, respectively. During pregnancy, serum caffeine concentrations increased by approximately 100% for both dose groups and, after parturition, declined to prepregnancy concentrations. Serum theophylline concentrations were usually greater than serum caffeine concentrations and did not change during pregnancy. The amount of caffeine and theophylline excreted in the urine over 24 hr increased during pregnancy and returned to prepregnancy levels after parturition. The results of this study indicate that pregnancy decreased caffeine elimination, resulting in a significant increase in serum caffeine levels. The changes in caffeine elimination may be related to alterations in serum estrogen and progesterone levels.

Animals↗
PubMed1985

The fate of chronically consumed caffeine in the monkey (Macaca fascicularis).

The metabolic fate of chronically administered caffeine was examined in monkeys. Caffeine and equal parts of citric acid were added to the drinking water of four female monkeys (Macaca fascicularis). The concentration was gradually increased over a 10-week period to 0.35 mg/ml for three of the monkeys. A monkey that was lactating, but had no infant, was exposed to caffeine in the drinking water at a concentration of 0.30 mg/ml. At these doses, administered for up to 50 weeks, there were no overt signs of toxicity as indicated by food and fluid consumption, body weight, or general condition of the monkey. Mean plasma caffeine concentrations were 3.8, 5.7, and 5.9 micrograms/ml, while mean plasma theophylline concentrations were 11.8, 13.0, and 20.1 micrograms/ml, respectively for the monkeys receiving 0.35 mg/ml. Mean plasma caffeine and theophylline concentrations for the lactating monkey were 10.7 and 21.4 micrograms/ml, while mean milk concentrations were 10.5 and 17.6 micrograms/ml, respectively, indicating that caffeine and its major metabolite theophylline are readily excreted in milk. The high plasma theophylline levels indicate that caffeine metabolism in the monkeys differs from that in humans. Theophylline was the main urinary metabolite. In addition, large amounts of 1.3-dimethyluric acid were excreted in the urine but only traces of this metabolite were found in the plasma. After withdrawal of caffeine, plasma caffeine levels decreased to almost zero in the first 24 hr with a half-life of 5.5 hr, and plasma theophylline levels declined with a half-life of 12.7 hr.

Animals↗
PubMed1984

Automated high-performance liquid chromatographic assay for monitoring caffeine and its metabolites in biological fluids of monkeys consuming caffeine.

A recently reported high-performance liquid chromatographic procedure, using a 5 micron C18 reversed-phase column to separate and quantitate caffeine and seven of its metabolites was modified for use with an automatic sampler to allow the continuous analysis of a large number of samples of various biological fluids obtained from monkeys consuming caffeine. The sensitivity for most metabolites was in the range of 0.1-0.3 microgram/ml from a 0.1 ml sample. The repeatability of the method regarding within-day variations was excellent and the absolute retention time for eight standards differed by less than +/- 0.03 min. Excellent repeatability in the day-to-day assay, with almost quantitative recoveries, was found for most of the analyzed compounds in various biological fluids. The standard deviation for the quantitation of all standards was in a range of 0.41-2.01 micrograms/ml, with the standard error less than 0.02. Using this method an analytical chemist could process between 40 and 60 samples of biological fluids in 24 h. The main metabolite of caffeine in the plasma of the monkey was theophylline, while theophylline and 1,3-dimethyluric acid were the major metabolites in urine. A close correlation was observed for the pattern of metabolites found in plasma and milk.

Animals↗
PubMed1984

Mutagenicity screening of foods. II. Results with fruits and vegetables.

A survey of the mutagenic potential of a wide variety of food products has been initiated with results for 28 different beverages reported previously [Stoltz et al, 1982b]. Here, results for samples of 46 widely consumed fruits and vegetables from six general categories are given. Each sample was concentrated and fractionated by polarity and solubility to give five fractions, each of which was assayed for mutagenic potential with Salmonella typhimurium TA98 and TA100. Although statistical analysis of the data resulted in positive findings for 22 fruit and vegetable samples, only six products (grapes, onions, peaches, raisins, raspberries, strawberries) demonstrated potent mutagenic activity.

Cooking↗
PubMed1982

Mutagenicity screening of foods I. Results with beverages.

Following a number of recent reports on the presence of mutagens in certain foods, a general survey of the mutagenic potential of a wide variety of food products has been initiated. Here, results for samples of 28 widely consumed beverages from 13 general categories are reported. Each sample was concentrated and fractionated by polarity and solubility to give up to seven fractions, each of which was assayed for mutagenic potential with Salmonella typhimurium TA98 and TA100 +/- fortified liver homogenate. Fractions showing evidence of either mutagenicity or toxicity were retested at the same and lower concentrations. The utility of the fractionation procedure and the sensitivity of the screening strategy were established by assaying six beverages spiked with known mutagens prior to fractionation. Statistical analysis of the data resulted in positive findings for seven beverages, although confirmation of these results through analysis of a second sample was obtained only for red wine, grape juice, and instant coffee. The remaining 21 beverages showed no strong evidence of mutagenic activity. For those foods for which the variation among replicate plates was largest, the false-positive rate for the two-stage screening procedure employed was estimated to be less than 1% while the false-negative rate for a beverage inducing a threefold increase in the background mutation rate was conservatively estimated to be limited to 14%.

Beverages↗
PubMed1979

Gas-liquid chromatographic-mass spectrometric determination of alpha- and beta-naphthylamines in FD&C Red No. 2 (amaranth).

A method is described for the simultaneous quantitation of trace amounts of alpha- (alpha-NA) and beta-naphthylamines (beta-NA) with detectability in the 0.1 ppb range and sensitivity of 50 picomoles in certified food grade amaranth (FD&C Red No. 2; C.I. Food Red 9; CI 16185). The amaranth sample is extracted with benzene, and the evoporated residue is derivatized with perfluorooctanoic anhydride. The resulting derivatives are separated by gas-liquid chromatography and identified and quantitated by mass spectrometric monitoring of the m/e at 539.04. The method was used for quantitation of alpha-NA and beta-NA in randomly chosen samples of amaranth. Of 11 samples from different manufacturers, 5 were free of the beta-isomer; the remaining samples contained up to 1.2 ppb beta-NA. The concentration of alpha-NA ranged from no detectable amount to 970 ppb; the majority of the samples contained less than 7 ppb.

1-Naphthylamine↗
PubMed1979

Microdetermination of naphthionic acid in serum and amniotic fluid.

A simple, rapid, sensitive, and reproducible microdetermination of naphthionic acid (NA) in serum and amniotic fluid is described. The detection limit of the method is 1 ng NA in 20 microL serum, and 3 ng NA in 50 microL amniotic fluid. The concentration of nonderivatized NA was measured by fluorescence spectrophotometry (excitation 328 nm, emission 420 nm) of the supernate, after precipitation of proteins with absolute ethanol and heating for 30 min at 75 degrees C. Standard deviations of determinations for 2, 10, and 50 ng NA in 20 microL serum were 10.1, 7.59, and 7.64%, respectively. An analyst can perform about 100 determinations daily; results are available within 2 hr of sampling. A modification of the procedure to permit quantitation of NA in urine is also described.

Amniotic Fluid↗
PubMed1978

Use of the uricase-inhibited rat as an animal model in toxicology.

An accessible, reproducible, and inexpensive animal model for toxicologic evaluation of hyperuricemic conditions has been required for some time. A number of authors have tried to develop such a model by administering high doses of uric acid to various animal species (dog, rabbit, rat) but the potent liver uricase in these species prevented development of sustained hyperuricemia. Johnson et al. [4], Stavric et al. [5], and a number of other investigators [72, 75] successfully used potassium oxonate [63] to block the effect of hepatic uricase and to produce hyperuricemia in rats [4, 5, 68, 69, 72, 74, 76, 80], rabbits [66], mongrel dogs [67], mice [65], and pigs [64]. The oxonate-treated rat can serve as a useful animal model not only in investigation of the uric acid nephropathy, but also in a number of other toxicologic evaluations connected with uric acid. This model has been used to evaluate drugs that affect uric acid excretion, to determine which dietary factors affect serum urates, or to evaluate possible therapeutic agents in certain disorders associated with uric acid. The same model could also be used by behavioral scientists, for whom research on uric acid has become increasingly popular in recent years [33, 137]. The ideal uricase inhibitor for induction of hyperuricemia would be one which is irreversible, noncompetitive, and relatively nontoxic, so that its activity would be independent of high levels of uric acid, and effective inhibition could be attained at low dosage levels. Oxonic acid is not an ideal uricase inhibitor, because it is competitive and is eliminated from the body relatively rapidly. Although relatively nontoxic, oxonic acid and its salts are foreign substances that could interfere with some other metabolic systems. The possibility exists that an ideal, or at least a better inhibitor, could be developed by appropriate substitutions on the molecule of oxonic acid or by introducing different types of compounds such as derivatives of diazohypoxanthines, barbiturates, or similar substances. Until such improvements on the uricase-inhibited rat models are available, potassium oxonate, which is easily obtainable, can be used as an effective inhibitor of uricase in vivo.

Aggression↗
PubMed1976

Shikimic acid.

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Animals↗
PubMed1975

Preservatives and artifical sweeteners.

Twenty saccharin-containing table sweeteners, in the form of tablets, liquids, crystals, or blends, and manufactured or distributed by 15 different companies, were analyzed for their o-toluenesulfonamide (o-TS) content. A previously described procedure for the determination of o-TS in commercial saccharin was found to be applicable to the determination of o-TS in these preparations. o-TS was found in all analyzed samples, in amounts ranging from 57 to 3811 ppm. In some cases the concentration of o-TS varied even from lot to lot from the same manufacturer. One pair of lots contained 57 and 67 ppm o-TS, respectively, while in another 711 and 3003 PPM O-TS were found. Gas-liquid chromatographic patterns of samples from the same distributor (or manufacturer) were similar and characteristic of the brand. Recoveries of o-TS from liquid and tablet preparations were almost quantitative, while recoveries from saccharin blends were in the 95-103% range.

Chromatography, Gas↗