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Biomedical subjects

B Stavric

Publications and source records attributed to B Stavric.

At least 19 recordsLinked to original sources
PubMed1995

Investigation of the effect of coffee lipids on serum cholesterol in hamsters.

The effect of coffee total lipids (CTL), coffee non-saponifiable matter (NSM) and coffee diterpene alcohols (DTA) extracted from Coffea arabica beans on serum cholesterol in adult male Syrian hamsters was examined. The animals were fed either a commercial laboratory chow diet (study 1), containing 5% fat and low in saturated fat (1.46 g/100 g diet) and cholesterol (0.03 g/100 g diet) or a semi-synthetic diet (study 2) set in gelatine, containing 10% fat and high in saturated fat (4 g/100 g diet) and cholesterol (0.5 g/100 g diet). The coffee lipid extracts were dissolved in olive oil (concentration either 5 mg CTL, 0.5 mg NSM or 0.5 mg DTA per 250 microliters olive oil) in study 1 and in coconut oil (concentration either 20 mg CTL, 2 mg NSM or 2 mg DTA per 250 microliters) in study 2. A dose of 250 microliters of these solutions was administered daily to hamsters by gavage. Control animals received 250 microliters vehicle only. For serum lipid analysis, blood samples were obtained on days 0, 7 and 14 in study 1 and on days 0, 7, 14 and 21 in study 2. Statistical analyses of the data in Study 1 indicated a tendency for serum total cholesterol and high density lipoprotein-cholesterol to increase with administration of CTL, NSM and DTA. In contrast, in study 2 there were no significant differences in serum lipid levels between control and coffee lipid-treated groups across time. In either study, total serum cholesterol levels of the three coffee lipid groups were not significantly different from each other. These results support the concept that coffee lipids may be hypercholesterolaemic and indicate that diterpenes could be the lipid component responsible for such an effect. However, it appears that this hypercholesterolaemic effect is apparent only when the background diet is low in saturated fat and cholesterol. A high saturated fat/high cholesterol diet may mask the hypercholesterolaemic effect of coffee lipids.

Animals↗
PubMed1995

Evaluation of hamburgers and hot dogs for the presence of mutagens.

Food products derived from heat-treated (fried, broiled, baked) meat may contain traces of mutagenic heterocyclic amine contaminants, some of which are proven carcinogens in rodents. To confirm their presence and range in Canadian foods, and estimate the average human intake of these types of mutagens from frequently consumed heat-processed foods, several commercially prepared fried-beef patties (hamburgers) and hot dogs (weiners) were analysed for their mutagenic capacity. The mutagenicity of the extracts was tested in the Salmonella/microsome assay using strain TA98 with metabolic activation. 16 samples of hamburgers and 14 samples of hot dogs, randomly obtained from 'fast food' commercial establishments or street vendors, were used in this survey. The mutagenic activity of these samples ranged from very low to 1042 revertants/g equivalent for the hamburgers and from non-detectable to 4875 revertants/g equivalent for the hot dogs. The average values were 199 and 424 revertants/g for the hamburgers and hot dogs, respectively. The wide range in mutagenicity was found even for the same type of product obtained from the same outlet at different times. This indicates possible inconsistency in cooking procedures during the preparation of these products. It also shows the difficulty in accurately assessing the intake of mutagenic heterocyclic amines from hamburgers and hot dogs prepared in 'fast food' outlets.

Amines↗
PubMed1994

Role of chemopreventers in human diet.

Recent research has confirmed that many common foods contain nonnutritive components that may provide protection against chronic disease including some forms of cancer. These naturally occurring compounds, which possess anticarcinogenic and other beneficial properties, are referred to as chemopreventers. The predominant mechanism of their protective action is due to their antioxidant activity and the capacity to scavenge free radicals. Among the most investigated chemopreventers are some vitamins, plant polyphenols, flavonoids, catechins, and some components in spices. The majority of chemopreventers are available in and consumed from vegetables, fruits, grains, and tea. Various naturally occurring chemicals in garlic, soybeans, tea, and red wine appear to be responsible for the beneficial effect of these commodities on several chronic diseases. This article will review some recent studies in the search for the beneficial effects of dietary chemopreventers on human health.

Anticarcinogenic Agents↗
PubMed1994

Biological significance of trace levels of mutagenic heterocyclic aromatic amines in human diet: a critical review.

Cooking of protein-rich foods may induce the formation of a series of heterocyclic aromatic amines (HAAs) that have been found to be mutagens and carcinogens. Despite very potent mutagenic activity found in the Salmonella/microsomal assay, this test cannot predict carcinogenic potency of HAAs in rodents and monkeys. Doses used in the feeding studies with animals exceeded by several orders of magnitude the levels of HAAs found in human diet, being approximately 500,000-3,000,000-fold higher than the human dietary levels. A comparison of these levels and their relevance for humans is presented. Differences in metabolic fate of different HAAs due to species and sex of the animals are discussed. These differences could account for the variable cancer-producing potential in different species. A number of still unresolved variables (such as the levels of HAAs in foods, bioavailability, possible synergistic effect from mixtures of HAAs, and metabolic fate and detoxification) preclude reliable assessment of the potential health hazard from HAAs in foods. The difference in the ability of human and animal liver microsomes to bioactivate HAAs and to form DNA adducts causes further uncertainty. The differences due to the hepatic cytochrome P-450-mediated activation of HAA among rats, monkeys and humans may influence susceptibility to cancer from these agents. HAAs occur only in traces in the human diet; however, they are present in many foods consumed daily. The levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) are approximately 100-fold higher than the levels of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). However, their mutagenic potential in the Ames Salmonella assay is reversed. Other in vitro tests, however, indicate similar genotoxicity between IQ, MeIQx and PhIP. Although most feeding studies with HAAs have been conducted with IQ and MeIQ, evidence obtained from a variety of studies indicates the possibility that PhIP may have an active role in the aetiology of human cancer and, therefore, its role as such should be evaluated. The influence of trace levels of HAAs on human health remains to be confirmed.

Amines↗
PubMed1994

Dietary effects on the uptake of benzo[a]pyrene.

It has been established that exposure to polycyclic aromatic hydrocarbons (PAHs), or more specifically benzo[a]pyrene (B[a]P), either by inhalation through cigarette smoking or by contact through occupational exposure of the lungs or skin, can result in cancerous lesions. It appears that the general population consumes more B[a]P from food than from smoking. Despite this, epidemiological studies have not implicated B[a]P from foods as a causative factor in some human cancers. This lack of an epidemiological correlation between cancer incidence and intake of dietary PAHs/B[a]P could be due to some 'protective' or 'detoxification' mechanism. Despite the abundance of literature regarding the food content of B[a]P, there are few data concerning its uptake from foods. In the present study we investigated the intestinal absorption of B[a]P from foods using bile duct cannulated rats and radioactive B[a]P. [14C]B[a]P was first added to solvents such as water, corn oil, liquid paraffin or 50% ethanol, which were the administered by gavage to rats fed diets with or without added carbon. Additionally, food polyphenols such as quercetin and chlorogenic acid were also tested for their effect on the absorption of B[a]P. The results indicated that the excretion of B[a]P in the bile was reduced by water, carbon, quercetin and chlorogenic acid but was potentiated by corn oil. To complement the in vivo studies, some in vitro tests to investigate the efficiency of B[a]P extraction from different foods using water or oil as solvents were also performed. These tests indicated that extraction of B[a]P from foods was affected by the solvent. It is postulated that reduced solubility, physical adsorption and the formation of chemical adducts between B[a]P and some food ingredients, play a sporadic, although still not well determined, role in reducing the absorption of B[a]P from the gut. The results of these studies suggest that B[a]P absorption from the intestinal tract is markedly affected by dietary components, and that this may be a factor that contributes to the lack of an epidemiological correlation between some human cancers and the B[a]P content of foods.

Animals↗
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↗
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↗