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Structural alterations in Candida albicans by caffeine and caffeine salts.

Cytological alterations of Candida albicans following exposure to subinhibitory concentrations of caffeine and caffeine salts were examined by light and transmission electron microscopy (TEM). The effect was different from that induced by ketoconazole. Caffeine and especially caffeine salts caused an increase in unusual modes of proliferation with signs of multiple budding in Candida albicans. Structurally, such yeast cells present some resemblance to Paracoccidioides brasiliensis.

Caffeine↗

[Effect of caffeine on fetal heart rate and caffeine consumption habits in pregnant patients].

Responsiveness to caffeine was studied in early human fetal hearts surviving in nutrient solution. Alterations of the spontaneous contraction rate were followed. Three concentrations (0.01, 0.1 and 1 mmol/l) were applied. In the presence of caffeine there was a significant age- and concentration-dependent increase in fetal heart rate in the period of the 6th to 17th weeks of gestation. Concerning the caffeine consumption habits of pregnant women a questionaire investigation was carried out in 686 cases. 69 per cent of the pregnants regularly drink coffee; 10.7 per cent of them consumes more than 300 mg per day. The authors call attention to the potential harmful effect of caffeine on the fetal heart.

Caffeine↗

Caffeine-induced reduction of the survival of gamma-irradiated HeLa cells and the reversal of the caffeine effect by Escherichia coli RecA protein.

It is confirmed that survival of gamma-irradiated HeLa cells is decreased by post-treatment with caffeine. The caffeine effect is believed to be the result of an inhibition of the repair of gamma-ray-induced DNA damage. In this work we show that the caffeine-induced reduction of the survival of gamma-irradiated HeLa cells is reversed when Escherichia coli RecA protein is introduced into the cells with the aid of liposomes.

Caffeine↗

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↗

Liquid chromatographic method for the simultaneous determination of caffeine and fourteen caffeine metabolites in urine.

An HPLC method has been developed for the separation and the determination of caffeine and its metabolites in urine samples using a one extraction-analysis run and UV detection. The compounds were extracted by liquid-liquid extraction using chloroform-isopropylalcohol (85:15, v/v). Chromatographic separation was accomplished on an ODS analytical column with a mobile phase containing 0.05% acetic acid/methylalcohol (92.5:7.5, v/v). Compounds were monitored at 280 nm. The method was validated for the determination of AFMU, 1X, 1U, 17X and 17U caffeine metabolites required to assess the metabolic activity of the enzymes subject to in vivo caffeine testing. The validated assay was applied to urine samples from ten healthy volunteers. The method was proved to be suitable to assess simultaneously the enzymatic activity of cytochrome P450 CYP1A2 and CYP2A6, as well as N-acetyltransferase and xanthine oxidase.

Adult↗

Lack of inhibitory effect of cimetidine on caffeine metabolism in children using the caffeine breath test.

AIMS: To study the potential drug interaction between cimetidine and caffeine in a group of children who received cimetidine for gastritis. METHODS: The caffeine breath test was carried out prior to the administration of cimetidine and after 2-3 weeks therapy. The children (n = 1) received 300-800 mg cimetidine daily (11-36 mg kg(-1) day(-1)). RESULTS: There was no significant change in the 2 h cumulative labelled CO2 following the administration of cimetidine (mean values 5.61% before and 4.87% during cimetidine; Student's t-test P > 0.2). CONCLUSIONS: Cimetidine did not have an inhibitory effect on the metabolism of caffeine in this group of children studied.

Adolescent↗

The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration.

OBJECTIVE: To examine the effect of various combinations of beverages on hydration status in healthy free-living adult males. METHODS: In a counterbalanced, crossover manner, 18 healthy adult males ages 24 to 39, on four separate occasions, consumed water or water plus varying combinations of beverages. Clinical guidelines were used to determine the fluid allowance for each subject. The beverages were carbonated, caffeinated caloric and non-caloric colas and coffee. Ten of the 18 subjects consumed water and carbonated, non-caffeinated, citrus soft drink during a fifth trial. Body weight, urine and blood assays were measured before and after each treatment. RESULTS: Slight body weight loss was observed on all treatments, with an average of 0.30% for all treatments. No differences (p>0.05) among treatments were found for body weight changes or any of the biochemical assays. Biochemical assays conducted on first voids and 24-hour urines included electrolytes, creatine, osmolality and specific gravity. Blood samples were analyzed for hemoglobin, hematocrit. electrolytes, osmolality, urea nitrogen, creatinine and protein. CONCLUSIONS: This preliminary study found no significant differences in the effect of various combinations of beverages on hydration status of healthy adult males. Advising people to disregard caffeinated beverages as part of the daily fluid intake is not substantiated by the results of this study. The across-treatment weight loss observed, when combined with data on fluid-disease relationships, suggests that optimal fluid intake may be higher than common recommendations. Further research is needed to confirm these results and to explore optimal fluid intake for healthy individuals.

Adult↗

A study of caffeine in tea. I. A new spectrophotometric micro-method. II. Concentration of caffeine in various strengths, brands, blends, and types of teas.

A new spectrophotometric micro-method for the determination of caffeine in tea is described. This method is then used to evaluate the caffeine content of a variety of brands and blends of bagged and loose hot tea prepared in different strengths and by different brewing methods. In addition, the caffeine content of instant tea, ice tea, and Mr. Coffee automatic tea is evaluated.

Caffeine↗

Inhibition of caffeine metabolism by ciprofloxacin in children with cystic fibrosis as measured by the caffeine breath test.

The caffeine breath test was carried out in six children with cystic fibrosis, before and during a course of ciprofloxacin. There was a significant decrease in the 2 h cumulative labelled CO2 exhaled during ciprofloxacin treatment, mean difference (s.d.) -5.2(3.3)%, P < 0.02. The results suggest an inhibition of 3-N-demethylation of caffeine (CYP1A2 enzyme activity) by ciprofloxacin. Ciprofloxacin may cause significant drug interactions in children with cystic fibrosis. The caffeine breath test can be used to study drug interactions involving CYP1A2 in children.

Adolescent↗

Effects of morphine and caffeine on adenosine release from rat cerebral cortex: is caffeine a morphine antagonist.

Morphine (1 mg/kg) enhances the efflux of labelled adenosine and its derivatives from the rat cerebral cortex. Caffeine (40 mg/kg) does not alter either basal purine efflux rates or the enhanced efflux elicited by morphine. The antagonism by caffeine of morphine-evoked inhibition of acetylcholine (ACh) release from the cerebral cortex is unlikely therefore to the the result of an action of caffeine on the opiate receptor but is instead due to an antagonism of the inhibitory effect of released adenosine on ACh release.

Acetylcholine↗

[Determination of caffeine and sodium benzoate contents in caffeine and sodium benzoate injection by P-matrix method].

The contents of caffeine and sodium benzoate injection may be determined by P-matrix method without separation of its components. BSAIC language is used for programming. The average recovery of caffeine is 100.0% and that of sodium benzoate is 99.95%. The variation coefficient of caffeine is 0.40% and that of sodium benzoate is 0.65%. On the basis of recovery rate and data observed it is concluded that this method is accurate, reliable, simple and rapid as compared with the standard pharmacopoeia regulations.

Caffeine↗

Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea.

Oral administration of green or black tea inhibited UVB light-induced complete carcinogenesis in the skin of SKH-1 mice. Green tea was a more effective inhibitor than black tea. Oral administration of decaffeinated green or black tea resulted in substantially less inhibitory activity than did administration of the regular teas, and in one experiment, administration of a high-dose level of the decaffeinated teas enhanced the tumorigenic effect of UVB. Oral administration of caffeine alone had a substantial inhibitory effect on UVB-induced carcinogenesis, and adding caffeine to the decaffeinated teas restored the inhibitory effects of these teas on UVB-induced carcinogenesis. In additional studies, topical application of a green tea polyphenol fraction after each UVB application inhibited UVB-induced tumorigenesis. The results indicate that caffeine contributes in an important way to the inhibitory effects of green and black tea on UVB-induced complete carcinogenesis.

Administration, Oral↗

Isolation of a new dual-functional caffeine synthase gene encoding an enzyme for the conversion of 7-methylxanthine to caffeine from coffee (Coffea arabica L.).

In coffee and tea plants, caffeine is synthesized from xanthosine via a pathway that includes three methylation steps. We report the isolation of a bifunctional coffee caffeine synthase (CCS1) clone from coffee endosperm by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) technique using previously reported sequence information for theobromine synthases (CTSs). The predicted amino acid sequences of CCS1 are more than 80% identical to CTSs and are about 40% similar to those of tea caffeine synthase (TCS1). Interestingly, CCS1 has dual methylation activity like tea TCS1.

Amino Acid Sequence↗

A schedule induction probe technique for evaluating abuse potential: comparison of ethanol, nicotine and caffeine, and caffeine-midazolam interaction.

Previous research has shown that under daily 3h sessions of food schedule-induced drug solution polydipsia (on a fixed-time 1min (FT 1min) schedule, session probes at greater FT values induced comparatively more ml/pellet drinking of solutions of drugs possessing abuse potential (ethanol, cocaine, midazolam) than of vehicle or other drug solutions. The present study extended these findings to nicotine and caffeine, drugs that usually do not function as reinforcers in i.v. self-administration studies with animals, but are known to have reinforcing effects for humans. The positive effects for nicotine and caffeine did not depend upon prior overindulgence in ethanol. Results on the effects of chronic, presession s.c. doses of midazolam could not be interpreted as contributing to the abuse potential of caffeine, but had independent dipsogenic effects. The FT probe technique, as well as schedule-induced i.v. self-administration, are useful methods for discerning the abuse potential of agents which are usually not distinguished by i.v. self-administration methods.

Journal Article↗

First-derivative spectrophotometric and gas-liquid chromatographic determination of caffeine in foods and pharmaceuticals. I. Rapid determination of caffeine in coffee, tea and soft drinks.

A simple and rapid spectrophotometric method is described for the determination of caffeine in coffee, tea and soft drinks. To exclude the irrelevant absorptions, due to the presence of some accompanying naturally occurring ingredients in the analysed multicomponent drinks, the derivative method is found to be superior. Another gas-liquid chromatographic (GLC) procedure for the quantitation of the analeptic agent, in bulk form and in the same drinks, is also investigated. The recovery testing of the proposed methods gives good percentage mean recoveries with relatively low deviations. The results of the methods described are compared with those obtained by direct UV-spectrophotometry as well as by applying an official pharmacopoeial procedure for caffeine.

Beverages↗

Comparison of the caffeine skinned fibre tension (CSFT) test with the caffeine-halothane contracture (CHC) test in the diagnosis of malignant hyperthermia.

We have compared and contrasted two diagnostic tests for Malignant Hyperthermia (MH) - the Caffeine-Halothane Contracture Test and the Caffeine Skinned Fibre Tension Test. Both tests show a strongly positive relationship both with the occurrence of MH reactions and with each other. The former test is more rapid and requires less skill. The latter test can be performed on much less muscle and permits storage of the muscle over prolonged periods of time.

Anesthesia↗

[3H]9-Methyl-7-bromoeudistomin D, a caffeine-like powerful Ca2+ releaser, binds to caffeine-binding sites distinct from the ryanodine receptors in brain microsomes.

[3H]9-Methyl-7-bromoeudistomin D ([3H]MBED), the most powerful Ca2+ releaser from sarcoplasmic reticulum, specifically bound to the brain microsomes. Caffeine competitively inhibited [3H]MBED binding. [3H]MBED binding was markedly blocked by procaine, whereas that was enhanced by adenosine-5'-(beta,gamma-methylene)triphosphate. The Bmax value was 170 times more than that of [3H]ryanodine binding. The profile of sucrose-density gradient centrifugation of solubilized microsomes indicated that [3H]MBED binding protein was different from [3H]ryanodine binding protein. These results suggest that there are MBED/caffeine-binding sites in brain that are distinct from the ryanodine receptor and that MBED becomes an essential molecular probe for characterizing caffeine-binding protein in the central nervous system.

Adenosine Triphosphate↗

The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men.

Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded randomized trials. Each trial included the ingestion of either: 1) CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance test. Blood samples were collected at baseline (-30), 0 (time of treatment ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and 180 min. Area under the curve for glucose and insulin were higher (P < or = 0.05) following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was observed following RCOF compared with DECAF, the effect was less pronounced. Interestingly, DECAF resulted in a 50% lower glucose response (P < or = 0.05) than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not the same. These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes.

Alkaloids↗