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B Stavric

Publications and source records attributed to B Stavric.

18 recordsLinked to original sources
PubMed1992

An update on research with coffee/caffeine (1989-1990).

The interest in research with coffee has been increasing in recent years, and this has resulted in a surge of publications dealing with a variety of pharmaco-physiological effects of coffee/caffeine. This review attempts to update the information on the research with coffee/caffeine, including epidemiological studies, laboratory investigations and tests with volunteers, published in 1989 and 1990. It groups published articles according to observed or investigated biological effects. The most significant findings and differences between studies are pointed out with brief commentaries on the results. The overall assessment for the safety of drinking coffee and the effect of coffee on human health, based on the literature published in 1989 and 1990, indicates that certain controversial issues are still unresolved.

Animals↗
PubMed1988

Methylxanthines: toxicity to humans. 1. Theophylline.

While there are several comprehensive reviews on the toxic effects of theophylline, caffeine and theobromine in animals, data on the toxicity of these methylxanthines in humans have not been extensively reviewed in one document. This question will be addressed in a series of three papers. This paper provides an overview of the human toxicity of theophylline. Only pertinent and recent information on theophylline toxicity is summarized. In addition, some information regarding the use and benefits of theophylline, the mechanism of its effects and factors that affect variability in its clearance and half-life is also provided. Some problems in the analytical methodology of theophylline, problems that may be responsible for the controversy in the reported dose-response effects, are critically reviewed.

Humans↗
PubMed1988

Methylxanthines: toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines.

This review provides a brief overview of known information on the human toxicity of theobromine and paraxanthine. Theobromine has some pharmacological effects, although these activities are considerably weaker than those of theophylline and/or caffeine, described in parts 1 and 2 of this series (Stavric, Fd Chem. Toxic. 1988, 26, 541 & 645). Paraxanthine, which is not found in plants or foods, is the major metabolite of caffeine in humans, in whom its toxicological potency appears to be very low. This paper gives a brief retrospective view of possible toxicological effects when methylxanthines are taken simultaneously or are present in combination as a result of metabolic transformation. Critical review of toxic manifestations due to exposure to relatively large doses of caffeine and theophylline indicates that such combined exposure may potentiate the toxic effects of either drug.

Animals↗
PubMed1988

Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.

Five surveys, using a previously developed high-performance liquid chromatography procedure to measure caffeine concentrations, indicated great variations in the concentrations of caffeine in tea and coffee. In the study of beverages prepared at home, data on caffeine concentrations in 58 samples of tea and coffee, volumes of cups, and numbers of cups consumed/day, indicated that the range of caffeine intakes for the women participating was 49-1022 mg/day. There were considerable day-to-day variations in caffeine contents in coffee samples from some commercial coffee shops. When 17 samples of five national brands of instant coffee were made into beverages in the laboratory, variations in caffeine concentrations between lots were small but between brands were significant. A considerable range of caffeine concentrations was also found when 12 samples of coffee prepared at work by different individuals using the same jar of instant coffee were analysed. Analysis of tea samples prepared in the laboratory indicated that steeping time had an important influence on resulting caffeine and theobromine concentrations. People preparing their own beverages were found to drink more liquid than the volume offered commerically. The mean caffeine 'contents' of home-made coffee and of coffee prepared by individuals at work were 79.4 and 81.7 mg/cup respectively, indicating a mean intake of approximately 80 mg caffeine/cup. When this amount (80 mg/cup) was used to estimate daily intakes of caffeine from coffee, on the basis of the number of reported cups/day, and the values obtained were compared with the amounts actually consumed by individuals, the potential for misrepresentation of individual consumption became obvious. For example, for subjects consuming three cups of coffee, only 25% would have been correctly categorized in the expected range for the daily intake of caffeine, 39% would have been overestimated and 36% underestimated for the amount of caffeine consumed. These variations in caffeine concentrations and in the volume of coffee consumed have frequently been ignored in examinations of the possible relationship between coffee consumption and various health problems, and this could perhaps partly explain some conflicting results seen in epidemiological studies.

Adult↗
PubMed1988

Methylxanthines: toxicity to humans. 2. Caffeine.

While there are several comprehensive reviews on the toxic effects of methylxanthines in animals, data on the toxicity of these chemicals in humans has not been extensively reviewed in one document. In a previous paper (Stavric, Fd Chem. Toxic. 1988, 26, 541), the toxicity of theophylline was reviewed. This paper, the second of three, is intended to provide an overview of the human toxicity of caffeine. Only pertinent and recent information on caffeine toxicity is summarized. In addition, some information regarding the benefits of caffeine and the mechanism of its effects is also provided. The use, effects and toxicity of caffeine intake are reviewed separately for different segments of the population. Controversy concerning the possible association of caffeine with fibrocystic disease of the breast and over the behavioural effects of the drug is presented briefly.

Caffeine↗
PubMed1988

Adverse pregnancy outcome in the monkey (Macaca fascicularis) after chronic caffeine exposure.

Caffeine and the related methylxanthine theophylline are consumed regularly by pregnant women. In a study originally designed to assess the neurotoxic potential of caffeine in the infant, 40 female monkeys (Macaca fascicularis) were divided into three groups and administered caffeine in their drinking water at concentrations equivalent to 0, 10 to 15 or 25 to 35 mg/kg/day of caffeine 7 days a week. After a period of adaptation to caffeine these monkeys were mated with untreated males. Reproductive failure in the form of stillbirths and miscarriages was observed in the treated groups. Subsequently, 12 control monkeys and 1 low-dose monkey were added to the study and most of the original monkeys rebred. The second round of pregnancies confirmed that the treated monkeys had an increased rate of stillbirths and miscarriages. The precise cause of death of the stillborn infants could not be determined. Maternal weight gain and infant birth weights decreased in a dose-related manner. These results indicate that in utero exposure to methylxanthines (caffeine and/or its major metabolite theophylline) adversely affects pregnancy outcome in the monkey.

Abortion, Veterinary↗
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↗
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.

Explore the source record for details and available documents.

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↗
PubMedDate not supplied

The mutagenicity of saccharin impurities. I. Detection of mutagenic activity.

Sodium saccharin, ortho-toluenesulfonamide and impurities extracted from commercially produced saccharin with water and organic solvents were tested for mutagenicity with strains of Salmonella typhimurium. The organic solvent soluble impurities exhibited strong mutagenic activity for TA98 and slight activity for TA100. Mutagenic activity for S. typhimurium TA98 was demonstrated in extracts of some but not all lots of sodium saccharin produced by both Maumee and Remsen-Fahlberg processes. The significance of the mutagenic impurity to the carcinogenicity of saccharin is discussed.

Drug Contamination↗