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Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat.

There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt p.o.) or vehicle alone. At the end of the study there were 5.65 +/- 0.81 and 1.31 +/- 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P < 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4'-hydroxy-PhIP but more PhIP-4'-O-glucuronide and PhIP-4'-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4' position coupled with enhanced phase 2 conjugation.

Animals↗

Clinically significant pharmacokinetic interactions between dietary caffeine and medications.

Caffeine from dietary sources (mainly coffee, tea and soft drinks) is the most frequently and widely consumed CNS stimulant in the world today. Because of its enormous popularity, the consumption of caffeine is generally thought to be safe and long term caffeine intake may be disregarded as a medical problem. However, it is clear that this compound has many of the features usually associated with a drug of abuse. Furthermore, physicians should be aware of the possible contribution of dietary caffeine to the presenting signs and symptoms of patients. The toxic effects of caffeine are extensions of their pharmacological effects. The most serious caffeine-related CNS effects include seizures and delirium. Other symptoms affecting the cardiovascular system range from moderate increases in heart rate to more severe cardiac arrhythmia. Although tolerance develops to many of the pharmacological effects of caffeine, tolerance may be overwhelmed by the nonlinear accumulation of caffeine when its metabolism becomes saturated. This might occur with high levels of consumption or as the result of a pharmacokinetic interaction between caffeine and over-the-counter or prescription medications. The polycyclic aromatic hydrocarbon-inducible cytochrome P450 (CYP) 1A2 participates in the metabolism of caffeine as well as of a number of clinically important drugs. A number of drugs, including certain selective serotonin reuptake inhibitors (particularly fluvoxamine), antiarrhythmics (mexiletine), antipsychotics (clozapine), psoralens, idrocilamide and phenylpropanolamine, bronchodilators (furafylline and theophylline) and quinolones (enoxacin), have been reported to be potent inhibitors of this isoenzyme. This has important clinical implications, since drugs that are metabolised by, or bind to, the same CYP enzyme have a high potential for pharmacokinetic interactions due to inhibition of drug metabolism. Thus, pharmacokinetic interactions at the CYP1A2 enzyme level may cause toxic effects during concomitant administration of caffeine and certain drugs used for cardiovascular, CNS (an excessive dietary intake of caffeine has also been observed in psychiatric patients), gastrointestinal, infectious, respiratory and skin disorders. Unless a lack of interaction has already been demonstrated for the potentially interacting drug, dietary caffeine intake should be considered when planning, or assessing response to, drug therapy. Some of the reported interactions of caffeine, irrespective of clinical relevance, might inadvertently cause athletes to exceed the urinary caffeine concentration limit set by sports authorities at 12 mg/L. Finally, caffeine is a useful and reliable probe drug for the assessment of CYP1A2 activity, which is of considerable interest for metabolic studies in human populations.

Animals↗

Theophylline reverses haloperidol-induced catalepsy in the rat. Possible relevance to the pharmacological treatment of psychosis.

The effect of theophylline (5, 15, or 30 mg/kg sc) on the catalepsy induced by haloperidol in the rat was studied. Theophylline was shown to induce a dose-dependent inhibition of this catalepsy. These data support the hypothesis that the methylxanthines are dopamine agonists and suggest that coffee, tea, and cola drinks should be avoided by patients undergoing neuroleptic treatment.

Animals↗

Measurement of coffee and caffeine intake: implications for epidemiologic research.

Reported associations between coffee or caffeine intake and benign breast disease, cancers, and cardiovascular diseases have generally been weak and inconsistent. The apparent discrepancies in these studies might be attributable to imprecision in the measurement of coffee and caffeine intake. A study of a random sample of 2,714 U.S. adults disclosed considerable misclassification of total caffeine intake and, to a lesser extent, coffee intake when the estimates were limited to only the number of cups of coffee consumed. Adjustment for the following factors is recommended: amount of caffeinated and decaffeinated coffee consumed both on weekdays and on weekends; the size of the container used; the method used to brew caffeinated coffee; and the amount of caffeine imbibed from tea and soft drinks. Intake of coffee varied markedly between seasons of the year and over time. Random misclassification of coffee and caffeine intake would have the effect of obscuring dose-response relationships to disease incidence.

Adult↗

The beriberi analogy to myocardial infarction.

Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.

Animals↗

Effect of postnatal exposure to caffeine on the pattern of adenosine A1 receptor distribution in respiration-related nuclei of the rat brainstem.

Caffeine, which belongs to the methylxantine family of compounds, is commonly ingested in a range of beverages such as coffee, tea, and cola drinks. It is also used therapeutically and is frequently employed in the treatment of respiratory disturbances in human neonates. The aim of the present work has been to examine the ontogeny of the adenosine A1 receptor system in the brainstem of the newborn rat following postnatal treatment with caffeine to mimic the therapeutic administration of caffeine to premature human infants. The effect of this postnatal exposure to caffeine on the gradual appearance of adenosine A1 receptors was analysed by determining immunohistochemically the distribution of the receptors. The main difference between control animals and animals exposed to caffeine was the transient increase (only at postnatal day 6) in the number of immunopositive neurons in two brainstem areas, the ventrolateral medulla and the rostral dorsolateral pons, in caffeine-treated rat pups, or more specifically, the parabrachial and Kölliker-Fuse nuclei, both of which are classically associated with respiratory control. With previous research highlighting the important role played by the rostral pons in respiratory modulation by the adenosine A1 receptor system, it is thus possible that postnatal exposure to caffeine modulates the ontogeny of the adenosine A1 receptor network. This could imply that the role of caffeine to decrease the incidence of neonatal respiratory disturbances may be due to the earlier than normal development of the adenosinergic system in the brain.

Age Factors↗

School vending machine use and fast-food restaurant use are associated with sugar-sweetened beverage intake in youth.

OBJECTIVE: To examine associations between use of school vending machines and fast-food restaurants and youth intake of sugar-sweetened beverages. DESIGN: A cross-sectional observational study. SUBJECTS/SETTING: From a group randomized obesity intervention, we analyzed baseline data from 1,474 students in 10 Massachusetts middle schools with vending machines that sold soda and/or other sweetened drinks. MAIN OUTCOME MEASURES: Daily sugar-sweetened beverage consumption (regular soda, fruit drinks, and iced tea), purchases from school vending machines, and visits to fast-food restaurants in the preceding 7 days were estimated by self-report. STATISTICAL ANALYSES PERFORMED: Chi(2) and nonparametric tests were performed on unadjusted data; multivariable models adjusted for sex, grade, body mass index, and race/ethnicity, and accounted for clustering within schools. RESULTS: Among 646 students who reported using school vending machines, 456 (71%) reported purchasing sugar-sweetened beverages. Overall, 977 students (66%) reported eating at a fast-food restaurant. Sugar-sweetened beverage intakes averaged 1.2 servings per day. In adjusted models, relative to no vending machine purchases, servings per day increased by 0.21 for one to three purchases per week (P=0.0057), and 0.71 with four or more purchases (P<0.0001). Relative to no fast-food restaurant visits, sugar-sweetened beverage servings per day increased by 0.13 with one visit per week (P=0.07), 0.49 with two to three visits (P=0.0013), and by 1.64 with four or more visits (P=0.0016). CONCLUSIONS: Among students who use school vending machines, more report buying sugar-sweetened beverages than any other product category examined. Both school vending machine and fast-food restaurant use are associated with overall sugar-sweetened beverage intake. Reduction in added dietary sugars may be attainable by reducing use of these sources or changing product availability.

Adolescent↗

Caffeine: a well known but little mentioned compound in plant science.

Caffeine, a purine alkaloid, is a key component of many popular drinks, most notably tea and coffee, yet most plant scientists know little about its biochemistry and molecular biology. A gene from tea leaves encoding caffeine synthase, an N-methyltransferase that catalyses the last two steps of caffeine biosynthesis, has been cloned and the recombinant enzyme produced in E. coli. Similar genes have been isolated from coffee leaves but the recombinant protein has a different substrate specificity to the tea enzyme. The cloning of caffeine biosynthesis genes opens up the possibility of using genetic engineering to produce naturally decaffeinated tea and coffee.

Biotechnology↗

Studies on the effect of polyvinyl pyrrolidone on the activity of chlorhexidine mouthrinses: plaque and stain.

BACKGROUND, AIMS: Polyvinyl pyrrolidone (PVP) was shown in vitro to reduce chlorhexidine induced, dietary staining without affecting the uptake of the antiseptic to the test substrate. The aim of these studies in vivo was to determine whether PVP affected plaque and dietary staining by a low concentration chlorhexidine rinse. METHODS: The plaque and stain studies used a double blind, randomised 6, treatment crossover design involving healthy subjects with a high standard of oral hygiene and gingival health. The rinse formulations under test were: (A) aqueous alcohol (placebo control), (B) 0.03% chlorhexidine, (C) 0.06% chlorhexidine, (D) 0.06% chlorhexidine+1.2% PVP, (E) 0.06% chlorhexidine+5% PVP, (F) 0.06% chlorhexidine+10% PVP. In the plaque study, on day 1 of each period, subjects were rendered plaque free and then rinsed with 15 ml of the test rinse for 60 s. No further tooth cleaning was performed and subjects returned 24 h later for plaque scoring by area. In the stain study, on day 1 of each period, the tongue and teeth of each subject were rendered stain free. Subjects then rinsed under supervision for 60 s with 15 ml of the allocated rinse 8 x a day between 09:00 h and 17:00 h for 3 days. Immediately after each rinse with the test formulation, subjects rinsed for 120 s with 15 ml of warm black tea. Subjects were requested to also drink at least 5 cups of tea or coffee per day. On day 4, stain was scored by area and intensity from designated teeth and dorsum of the tongue. Washout periods were at least 7 days in both studies. RESULTS: Plaque areas were greatest with placebo and least with 0.06% chlorhexidine. Plaque scores increased with increasing concentrations of PVP in the 0.06% chlorhexidine rinse and were significantly higher than 0.06% chlorhexidine without PVP rinse. Tooth stain areas were comparable for placebo, 0.03% and 0.06% chlorhexidine rinses, but significantly reduced with the PVP/chlorhexidine rinses compared to the 0.06% chlorhexidine rinse. Tooth stain intensity was significantly increased with 0.06% chlorhexidine rinses compared to placebo and chlorhexidine/PVP rinses. Tongue stain area and intensity were significantly reduced with 5% and 10% PVP/chlorhexidine rinses compared to 0.06% chlorhexidine rinse. CONCLUSION: PVP, at the concentrations tested, reduced the stain propensity of a 0.06% chlorhexidine rinse but at the expense of some loss of plaque inhibition.

Adolescent↗

Efficacy and safety of herbal stimulants and sedatives in sleep disorders.

World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Herbs are attractive alternative medications to many patients with sleep disorders, who may be averse to using conventional drugs. We review here the most common herbal stimulants and sedatives. Caffeine, in herbal teas, black tea, coffee, soft drinks and pharmaceuticals, is used widely to control sleepiness, but more research is needed on its use in sleep disorders. Ephedra, and its constituent ephedrine, are used in both stimulant and weight loss preparations, sometimes with caffeine; safety concerns have arisen with this practice. Yohimbe is another herb used in stimulant and body-building preparations which has safety concerns. Asian and Siberian ginseng have been traditionally used for fatigue, and have some supportive experimental evidence for this use. Herbal sedatives also have some evidence for efficacy; the observations that certain plant flavonoid compounds bind to benzodiazepine receptors adds interest to their use. Valerian and kava have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows anxiolytic effects. German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination.

Journal Article↗

The gastrointestinal absorption of organically bound forms of plutonium in fed and fasted hamsters.

Values of about 0.005-0.01 per cent were obtained for the absorption in fed hamsters of plutonium ingested as Pu4+ citrate, isocitrate, phytate and malate complexes and Pu3+ ascorbate compared with about 0.003-0.004 per cent for Pu4+ nitrate. Replacing drinking water with tea did not affect the result for Pu4+ nitrate. Fasting hamsters for 8 h before the administration of plutonium citrate increased absorption to 0.1-0.2 per cent. An extra period of fasting for 4 h after administration did not lead to a further increase in absorption. Similar values were also obtained when plutonium citrate was administered after a 24 h fast, followed either by immediate access to food or a further 4 h fast. In hamsters fasted for 24 h before administration of either Pu3+ ascorbate or Pu4+ nitrate, about 6-7 per cent of the ingested plutonium was retained in the gastrointestinal tract after one week. At three weeks after ingestion of Pu3+ ascorbate, gastrointestinal retention had fallen 100-fold without an increase in absorption.

Animals↗

A biological evaluation of DNA damage detected by comet assay in healthy populations residing in areas that differ in lung cancer incidence.

The comet assay was performed to evaluate the effect of environmental exposure between human populations residing in two areas that differ in lung cancer incidence, Saraphi (n = 91) and Chom Thong (n = 94). Three parameters, the tail length, tail intensity, and tail moment, were used to detect DNA damage in peripheral blood and stimulated lymphocytes with and without the DNA repair inhibitor, aphidicolin. Internal standards, cryopreserved isolated lymphocytes, and isolated lymphocytes irradiated with 2 Gy gamma rays, were used to correct the interexperimental variability. Results revealed a significant difference between two populations only when the tail length was used to measure DNA damage. The evaluation of various potential confounding factors, such as gender, pesticide exposure, smoking, alcohol drinking, and fermented tea leaf or betel nut chewing, indicated no significant influence in DNA damage. In conclusion, significant difference in DNA damage, detected only by tail length between the two populations residing in the areas with different incidence of lung cancer, may reflect a nonhazardous level of exposure to toxic substances.

Adult↗

Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial.

BACKGROUND: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. OBJECTIVE: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. DESIGN: Sixty-four healthy volunteers (31 men and 33 women) with a mean (+/-SD) age of 43 +/- 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetière (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk. RESULTS: Consumption of 1 L unfiltered coffee/d for 2 wk significantly raised fasting plasma homocysteine concentrations by 10%, from 12.8 to 14.0 micromol/L. CONCLUSIONS: Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.

Adult↗

Intake of nutrients and food sources of nutrients among the Navajo: findings from the Navajo Health and Nutrition Survey.

Diet has been implicated in the etiology of chronic diseases in many populations, including the Navajo and other American Indian tribes. This report describes the current nutrient intake of the Navajo and identifies the primary food sources of key nutrients. In the Navajo Health and Nutrition Survey, interviewers obtained single 24-h diet recalls from 946 nonpregnant participants age 12-91 between October 1991 and December 1992. Among various sex and age groups, total fat contributed 33-35% of energy and saturated fat contributed 10-11% of energy in the diets. Median fiber intake was 11-14 g/d. Median intakes of vitamin A, vitamin E, vitamin B-6, folate, calcium and magnesium were below sex- and age-specific recommended dietary allowances (RDA) for men and women of all age groups. Intake of vitamin C was below the RDA for men and women age 20 and older. Median iron intake was below the RDA for women under age 60. Fruits and vegetables were each consumed less than once per day per person, as were dairy products. Fry bread and Navajo tortillas, home-fried potatoes, mutton, bacon and sausage, soft drinks, coffee and tea provided 41% of the energy and 15-46% of the macronutrients consumed. Recommendations to increase the intake of essential micronutrients in the Navajo diet are presented.

Adolescent↗

Case-control study of caffeinated beverages and preterm delivery.

Although many women reduce their caffeine consumption once they known they are pregnant, 70-80% of pregnant women still consume caffeine. To evaluate the relation between caffeine consumption and preterm delivery, a case-control study was conducted to identify all preterm (< 37 weeks gestation) infants born to women in selected North Carolina counties from September 1988 through April 1991. Randomly selected full-term, normal-weight livebirths (matched by race and hospital) served as controls. The study population consisted of 408 cases and 490 controls. Telephone interviews with participants assessed the consumption of caffeinated coffee, tea, cola soft drinks, and noncola caffeinated soft drinks, with caffeine consumption measured by the number of daily servings of each beverage and the total milligrams of caffeine. Third-trimester caffeine consumption from all beverages combined showed a nonsignificant inverse association with preterm delivery. Both first- and second-trimester consumption of 1-150 mg/day were associated with a modestly increased risk of preterm delivery, while no association was found at higher consumption levels. Overall, these results do not support an association between caffeinated beverage consumption and preterm delivery, as is true in most previous studies.

Adult↗

Maternal caffeine intake and intrauterine growth retardation.

This study estimates the effect of maternal caffeine consumption throughout pregnancy on fetal growth. We studied 2,714 women who delivered a liveborn infant between 1988 and 1991. Detailed information regarding coffee, tea, and soda drinking during the first and third trimesters of pregnancy was obtained. Average caffeine intake during month 1 of pregnancy was higher than for month 7 (72.4 vs 54.0 mg per day). Consumption of >300 mg caffeine per day during month 1 (adjusted odds ratio = 0.91; 95% confidence interval = 0.44--1.90) and during month 7 (adjusted odds ratio = 1.00; 95% confidence interval = 0.37--2.70) was not associated with intrauterine growth retardation. There was little evidence for any effect modification due to cigarette smoking on the caffeine associations. This study provides evidence that antenatal caffeine consumption has no adverse effect on fetal growth.

Adult↗

Insomnia in general practice: the role of temazepam and a comparison with zopiclone.

The aetiology of insomnia can be conveniently divided into six groups: physical (pain, cough, etc.), physiological (shift-workers etc.), psychological (life events), psychiatric (depression, anxiety, etc.), iatrogenic (stimulant drugs, etc.) and idiopathic (no obvious cause). The four main types of insomnia are: prolonged latency, frequent short awakenings, one or two long awakenings and early morning awakening. Patients' habits that may interfere with sleep are related to: alcohol, smoking, tea and coffee drinking, and bedtime drinks. In a double-blind comparison between temazepam and nitrazepam, both drugs were shown to be effective hypnotics, nitrazepam being better for early morning wakening, although at the expense of more hangover effects. Zopiclone, a new cyclopyrrolone hypnotic, was also compared to temazepam in a double-blind cross-over trial and similar hypnotic effects were recorded with both drugs.

Anti-Anxiety Agents↗

Caffeine reduction as an adjunct to anxiety management.

A reduction in tea and coffee drinking is popularly advocated for the relief of tension and anxiety symptoms, and it was decided to collect empirical data on this matter in the course of normal clinical practice. It was found that patients who made substantial reductions in caffeine drinking also made the greatest improvements in anxiety, irritability, sleep disturbance, headaches and abdominal symptoms. The methodology leaves an ambiguity in the interpretation of this result, but the data provide a useful basis for the design of further studies.

Adolescent↗