Absence Of Caffeine Research Articles

Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50–300mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance.

Molecular genetic study of Pseudomonas aeruginosa DNA repair system

Bacteria Pseudomonas aurginosa, E coli and Stapthylococcus aureus were exposure to different doses of ultraviolet radiation and survival curves drawn for each type, the results show that the bacteria Pseudomonas aurginosa more resistant by UV radiation than Ecoli and Stapthylococcus aureus bacteria. The bacterium Pseudomonas aeruginosa was irradiated with different doses of U.V light via wave length( 254 nm ) for different periods ( 50 , 100 , 150 , and 200 sec ) .It appear that part of irradiated bacterial culture was exposed to sun light and the other part was kept in the dark . The survivors of the cells exposed to the sun light was more than the dark and this ensure possessing the bacterium photoreactivating repair system investigate the excision repair system, the minimal inhibitory concentration ( MIC) of caffeine against bacteria was studied by exposing the bacterium to different concentrations of caffeine (10 , 15 , 20 and 25 mg/ml ) and the MIC was 20 mg/ml , Furthermore the bacterium was exposed to different times of U.V. light in the presence of caffeine and the studying ensure that the survivors of the cells in the medium with caffeine was less than the medium with absence of caffeine and this leads to possess the bacterium excision repair system. To detect the recombination repair system , the bacterium was exposed to the concentrations( 0.1 ,0.2 , 0.3 , 0.4 μg / ml) of acrivlavine and the MIC was 0.3 μg / ml , then the bacterium was exposed to different times of U.V. light in the presence of acrivlavine . The survivors of the cells in the medium with acrivlavine was less compared with the absence of acrivlavine. It would seem that possessing bacterium recombination repair system . sensitivity test of the bacterium against antibiotics was established and the results appeare that it was to the antibiotics Chloramphenicol, Carpencillin, Trimethoprim, Rifampicin The diameters of inhibition were (16,20,17,18) mm respectively and resistant to the antibiotics Amoxicillin, Ampicillin, Clindomycin, Cloxacillin , Nalidixic acid , Cephaloxin , Tetracyclin and Tobromycin. To study SOS repair system the bacterium was mutated with direct mutagens represented with nitrous acid and indirect mutagens represented with U.V. light to isolate Rifampicin and Chloramphenicol mutants. It is quite likely that the sensitivity of bacterium for mutagenesis then possessing SOS repair system .

224 SILDENAFIL ACCELERATES SPERM PENETRATION OF PORCINE OOCYTES IN A CHEMICALLY DEFINED MEDIUM

Sperm capacitation, a cyclic-adenosine monophosphate-dependent phenomenon, is an important initiation step for penetration into oocytes. In porcine IVF, the use of caffeine, as a nonspecific phosphodiesterase (PDE) inhibitor, is common to accelerate sperm capacitation and penetration. The objective of this study was to examine the effects of PDE inhibitors (cilostamide, rolipram, and sildenafil as PDE type 3-, type 4-, and type 5-specific inhibitors, respectively) on the capacitation of boar sperm and the penetration into porcine oocytes in the absence of caffeine and other capacitation inducers in a chemically defined medium. After washing sperm samples collected from an ejaculated sperm-rich fraction of different individual Berkshires, the sperm were resuspended in capacitation inducer-free (theophylline- and adenosine-free) PGM-tac4 (mPGM-tac) at 5 × 105 cells mL–1. The suspension was cultured in mPGM-tac nonsupplemented or supplemented with 2.5 mM cilostamide, rolipram, or sildenafil for 90 min at 39°C in an atmosphere of 5% CO2 in air, and then the capacitation status was assessed by chlortetracycline fluorescence assay. Other sperm suspensions were used to co-culture with denuded in vitro-matured oocytes in the same medium for 8 h in an atmosphere of 5% CO2 in air and fixed, and sperm penetration was then examined. Statistical analyses of results from 4 replicated trials were performed by ANOVA with a Bonferroni-Dunn post hoc test (significance, P < 0.05). In our result from the chlortetracycline fluorescence assay, although the incidence of intact sperm was significantly reduced in the presence of rolipram (54.3%) and sildenafil (52.7%) as compared with controls (66.7%), there were no differences in capacitated sperm among experimental groups (24.3 to 34.3%). The incidence of acrosome-reacted sperm was higher in the presence of cilostamide (17.3%) than in the others (9.0 to 13.0%). High sperm penetration was observed only in the presence of sildenafil (76.6%) as compared with the control (0%) or the presence of rolipram (4.4%) or cilostamide (1.8%). These results demonstrate that inhibition of PDE type 5, but not PDE type 3 and type 4, significantly accelerates the penetration of boar sperm into the oocytes in a capacitation inducer-free chemically defined medium, whereas inhibition of PDE type 3 may induce an acrosome reaction.

Optimización del método captación del radical 2,2-difenil-1-picrilhidrazilo (DPPH) para evaluar actividad antioxidante en bebida de café

Coffee is one of the most consumed beverages in the world, being appreciated for its organoleptic characteristics and more recently for its potential beneficial effects on human health. Coffee is also known to be a rich source of compounds with potent antioxidant activity. The antioxidant activity can be measured with different test and method of capture radical DPPH, is a method used by many authors that have been carried out to assess adaptation in various foods (fruits, juices, coffee, vegetables).This study aim to evaluate the antioxidant capacity, by the DPPH assay, of coffee brew prepared in three commonly used ways (filter, espresso, italian) from different countries of origin (Colombia, Kenya and Ethiopia) and decaffeinated coffee.The optimization results of the test show lower values of absorbance (0.709) when the sample is subjected to centrifugation step (modification to Delgado-Andrade, 2005) with respect to only those that are subjected to agitation (1.609). The antioxidant activity data obtained show a high antioxidant capacity with inhibition percentages above 50%, with the coffee Colombia, Ethiopia and Kenya coffee filter made with values 70.56%, 73.52% and 73.65% respectively.In conclusion, according to the results, we see the need to adapt the methods set out radical capture the characteristics of the food or product evaluated to ensure 100% food antioxidant activity.The antioxidant activity of coffee drinking from different origins is similar and does not vary depending on the presence or absence of caffeine. Moreover, we observed only differences antioxidant activity relating to the type procedure, where coffee type “espresso” has less antioxidant activity (p<0.05) than the other two procedures. It would be interesting therefore recommend the use of the procedures (filter and Italian) for the obtaining of coffee and get a good intake of dietary antioxidants.

A biomathematical model of the restoring effects of caffeine on cognitive performance during sleep deprivation

RationaleWhile caffeine is widely used as a countermeasure to sleep loss, mathematical models are lacking. ObjectiveDevelop a biomathematical model for the performance-restoring effects of caffeine in sleep-deprived subjects. MethodsWe hypothesized that caffeine has a multiplicative effect on performance during sleep loss. Accordingly, we first used a phenomenological two-process model of sleep regulation to estimate performance in the absence of caffeine, and then multiplied a caffeine-effect factor, which relates the pharmacokinetic–pharmacodynamic effects through the Hill equation, to estimate the performance-restoring effects of caffeine. ResultsWe validated the model on psychomotor vigilance test data from two studies involving 12 subjects each: (1) single caffeine dose of 600mg after 64.5h of wakefulness and (2) repeated doses of 200mg after 20, 22, and 24h of wakefulness. Individualized caffeine models produced overall errors that were 19% and 42% lower than their population-average counterparts for the two studies. Had we not accounted for the effects of caffeine, the individualized model errors would have been 117% and 201% larger, respectively. ConclusionsThe presented model captured the performance-enhancing effects of caffeine for most subjects in the single- and repeated-dose studies, suggesting that the proposed multiplicative factor is a feasible solution.

Effects of caffeine on sperm characteristics after thawing and inflammatory response in the uterus after artificial insemination with frozen-thawed boar semen

We previously reported that AI with frozen-thawed boar semen supplemented with caffeine increased the number of uterine sperm by inhibiting migration of polymorphonuclear leukocytes (PMNs) into the uterine lumen, and also improved fertility of gilts and sows. The objective of the present study was to determine the effects of the addition of caffeine to a thawing solution on postthaw sperm quality and uterine inflammatory response after AI with frozen-thawed boar semen. Incubation of frozen-thawed sperm in Modena solution supplemented with 10 mM caffeine for 90 minutes improved (P < 0.05) percentages of progressive motility, straightness, and linearity of sperm movement compared with no caffeine, without causing damage to plasma or acrosomal membranes. Gilts inseminated once with 2 × 109 frozen-thawed sperm suspended in Modena solution with or without caffeine, and gilts that did not receive AI, were slaughtered 4 hours later. Uteri were recovered for analysis of number of uterine PMNs and mRNA expression (quantitative reverse transcription polymerase chain reaction) of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and cyclooxygenase 2 in the endometrium. Caffeine decreased (P < 0.05) both the number of total uterine PMNs and expression of IL-8 mRNA in the endometrium after AI. The amount of IL-8 and cyclooxygenase 2 mRNA after AI in the absence of caffeine were higher than samples from gilts that did not receive AI (P < 0.05), whereas there were no significant differences between treatments in expression levels of tumor necrosis factor-α, IL-1β, IL-6, or monocyte chemoattractant protein-1 mRNA. Pregnancy rate in sows inseminated with sperm supplemented with caffeine (16 of 23; 70%) tended (P < 0.1) to exceed that without caffeine (12 of 26; 46%), but litter size was not affected. In conclusion, the addition of caffeine to the thawing solution inhibited migration of uterine PMNs, probably by downregulating IL-8 mRNA expression in the endometrium.

Physiological effects following administration of Citrus aurantium for 28 days in rats

BackgroundSince ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. MethodFemale Sprague–Dawley rats were dosed daily by gavage for 28days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusionSynephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

DETECTION OF DNA REPAIR SYSTEMS OF THE BACTERIUM PSEUDOMONAS AERUGENOSA

The bacterium Pseudomonas aeruginosa was irradiated with ultraviolete light with wave length ( 254 nm ) for different periods ( 50 , 100 , 150 , and 200 sec ) . part of irradiated bacterial culture was exposed to sun light and the other part was kept in the dark . The survivors of the cells exposed to the sun light was more than in the dark and this ensure possessing the bacterium photoreactivating repair system To investigate the excision repair system, the minimal inhibitory concentration ( MIC)of caffeine against bacteria was studied by exposing the bacterium to different concentrations of caffeine ( 10 , 15 , 20 and 25 mM ) and the MIC was 20 mM , then the bacterium was exposed to different doses of U.V. light in the presence of caffeine and the study ensured the survivors of the cells in the medium with caffeine was less than the medium with absence of caffeine and this refers to possess the bacterium excision repair system. To detect the recombination repair system , the bacterium was exposed to the concentrtions 0.1 ,0.2 , 0.3 , 0.4 µg / ml of acrivlavine and the MIC was 0.3 µg / ml , then the bacterium was exposed to different doses of U.V. light in the presence of acrivlavine . The survivors of the cells in the medium with acrivlavine was less compared with the absence of acrivlavine and this indicate possessing bacterium recombination repair system . To study SOS repair system the bacterium was mutated with direct mutagens represented with nitrous acid and indirect mutagens represented with U.V. light to isolate rifampicin and chloramphenicol mutants. The study ensured the sensitivity of bacterium for mutagenesis then possessing SOS repair system .

A novel POLH gene mutation in a xeroderma pigmentosum-V Tunisian patient: phenotype–genotype correlation

XP occurs at higher frequency in Tunisia (1:10,000) than in Japan (1:22,000) (Hirai et al. 2006) and the United States (1 per million) (Kleijer et al. 2008). XP-V cells are unable to synthesize intact daughter DNA strands on UV-irradiated templates resulting from an inability to carry out translesion synthesis (Lehmann et al. 1975; Masutani et al. 1999). Approximately 20% of XP patients belong to XP-V complementation group (Gratchev et al. 2003). In Tunisia, XP is classified into three clinical forms: severe, intermediate with or without neurological abnormalities, and moderate (Zghal et al. 2006). Previous molecular investigation showed homogeneity of mutational spectrum in XPA and XPC genes (Ben Rekaya et al. 2009; Messaoud et al. 2010a,b). The moderate clinical form of XP is characterized by mild dermatological manifestations, no neurological abnormalities and late onset of skin cancers. The median age of onset is 4 years. Mild skin symptoms and late onset of skin tumours have been already described in XP-V (Tanioka et al. 2007), XP-F (Matsumura et al. 1998) and XP-E patients (Rapic-Otrin et al. 2003). Post-UV cell survival in the presence or absence of caffeine (Itoh et al. 2000), unscheduled DNA synthesis (UDS) and detection of polymerase eta employing Western blot (Tanioka et al. 2007) cannot define exactly the molecular defects are in the polymerase eta. These laboratory assays are used to find out the UV sensitivities of the patients’ cells and the DNA repair status of their cells as

Caffeine Decreases Phospho-Chk1 (Ser317) and Increases Mitotic Cells with Cyclin B1 and Caspase 3 in Tumors from UVB-Treated Mice

Oral administration of caffeine to mice inhibits UVB-induced carcinogenesis, and these results are paralleled by epidemiology studies indicating that caffeinated coffee and tea intake (but not decaffeinated beverage intake) is associated with decreased incidence of nonmelanoma skin cancer. Topical applications of caffeine to the skin of SKH-1 mice that had previously been treated with UVB inhibited subsequent skin tumor development and stimulated apoptosis in tumors but not in nontumor areas of the epidermis. This study sought to determine the basis of these differential effects on tumor versus nontumor sites that can be induced by caffeine, long after all UVB treatment has ceased. The activation status of the ATR/Chk1 pathway in UVB-induced tumors and uninvolved skin was determined by quantitating phospho-Chk1 (Ser317) and induction of lethal mitosis in vivo in the presence and absence of topical caffeine treatment. In the absence of caffeine, we found that UVB-induced tumors often had islands of phospho-Chk1 (Ser317) staining cells that were not present in nontumor areas of the epidermis. Treatment of mice with topical caffeine significantly diminished phospho-Chk1 (Ser317) staining and increased the number of mitotic cells that expressed cyclin B1 and caspase 3 in tumors, consistent with caffeine-induced lethal mitosis selectively in tumors. We hypothesize that compared with adjacent uninvolved skin, UVB-induced skin tumors have elevated activation of, and dependence on, the ATR/Chk1 pathway long after UVB exposure has ceased and that caffeine can induce apoptosis selectively in tumors by inhibiting this pathway and promoting lethal mitosis.

Effects of the adenosine deaminase polymorphism and caffeine intake on sleep parameters in a large population sample.

To evaluate the association between the adenosine deaminase polymorphism, sleep architecture, and caffeine consumption. Genetic association study. NA. 958 participants who underwent polysomnography and genotyping. NA. Individuals carrying the A allele who consumed caffeine in the day prior to polysomnography demonstrated higher sleep efficiency and REM sleep percentage, after adjustment for potential confounders. No effect was observed in the absence of caffeine. Our data support the role of the ADA G22A polymorphism in sleep, and demonstrate for the first time that caffeine may act as a modulator of its functional effects. Name: Epidemiology of sleep disturbances among adult population of the Sao Paulo City. URL: http://www.clinicaltrials.gov/ct2/show/NCT00596713?term=NCT00596713&rank=1. Number: NCT00596713

Pannexin 1 Constitutes the Large Conductance Cation Channel of Cardiac Myocytes

A large conductance (∼300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca(2+) release from the sarcoplasmic reticulum, particularly when augmented by caffeine, has been described previously in isolated cardiac myocytes. A potential candidate for this channel is pannexin 1 (Panx1), which has been shown to form large ion channels when expressed in Xenopus oocytes and mammalian cells. Panx1 function is implicated in ATP-mediated auto-/paracrine signaling, and a crucial role in several cell death pathways has been suggested. Here, we demonstrate that after culturing for 4 days LCC activity is no longer detected in myocytes but can be rescued by adenoviral gene transfer of Panx1. Endogenous LCCs and those related to expression of Panx1 share key pharmacological properties previously used for identifying and characterizing Panx1 channels. These data demonstrate that Panx1 constitutes the LCC of cardiac myocytes. Sporadic openings of single Panx1 channels in the absence of Ca(2+) release can trigger action potentials, suggesting that Panx1 channels potentially promote arrhythmogenic activities.

Caffeine and dithiothreitol delay ovine oocyte ageing

The intracellular glutathione levels and developmental competence of aged oocytes after parthenogenetic activation, somatic cell nuclear transfer and intracytoplasmic sperm injection in the presence or absence of caffeine or dithiothreitol (DTT) were examined. The following results were found: (1) ovine oocytes were fully aged 30 h post-onset of maturation culture; (2) the appropriate concentrations of caffeine and DTT for oocyte culture were 5 mM and 1 mM, respectively; (3) when nuclear transfer-reconstructed embryos were treated with caffeine or DTT following fusion, no increase in the frequency of development to blastocyst was observed (P > 0.05), but the cell numbers of blastocysts increased (P < 0.05); (4) both caffeine and DTT increased the blastocyst formation rates of intracytoplasmic sperm-injected embryos (P < 0.05); (5) caffeine increased the glutathione content of aged oocytes (P < 0.05). The glutathione content of DTT-treated aged oocytes was higher than that of oocytes matured for 36 h (P < 0.05). In conclusion, caffeine and dithiothreitol delay oocyte ageing but only to a limited extent.

Sex-related effects of agmatine on caffeine-induced locomotor activity in Swiss Webster mice

In mammalian brain, agmatine is an endogenous amine that is synthesized through the decarboxylation of l-arginine by arginine decarboxylase. It has been proposed as a new neurotransmitter and/or neuromodulator. It was shown that agmatine had some beneficial effects in animal models of opioid and alcohol addiction. Locomotor stimulant properties of drugs such as ethanol, caffeine, nicotine and amphetamine have been linked to their addictive properties. The present study investigates the effects of agmatine on caffeine-induced locomotor activity both in male and female mice. Adult Swiss Webster mice were used in the study. Locomotor activity was measured for 30 min immediately following caffeine (2.5, 5, 10 and 20 mg/kg, i.p.) or saline treatments. Agmatine (5, 10 and 20 mg/kg, i.p.) were injected 20 min before caffeine (2.5 and 5 mg/kg, i.p.) administration. In both sexes, agmatine (5–20 mg/kg) were also tested for ability to depress or stimulate locomotor activity in the absence of caffeine. Caffeine (5 mg/kg) induced a significant increase in locomotor activity of both male and female mice. There was no significant difference in the locomotor-activating effects of caffeine between male and female mice. Agmatine blocked the caffeine (5 mg/kg)-induced locomotor stimulation dose dependently in male but not female mice. Agmatine had not any effect on the lower dose (2.5 mg/kg) of caffeine in both sexes. These results suggest that agmatine has sex-related inhibitory effects on caffeine-induced locomotor activity in Swiss Webster mice, and male mice are more sensitive than the females to the effect of agmatine.

Enhancing the release and plant uptake of PAHs with a water-soluble purine alkaloid

The effect of a common plant alkaloid, caffeine, on the release and plant uptake of some polycyclic aromatic hydrocarbons (PAHs) in soils was investigated. Cucurbita pepo (ssp. pepo cv. Gold Rush) was grown in PAH-spiked media in the presence and absence of caffeine. Solubility tests initially confirmed the ability of caffeine to dissolve PAHs mixtures of anthracene, phenanthrene, pyrene, benzo[ a]pyrene and benzo[ ghi]perylene. Extraction experiments also highlighted its potential as a PAH-releasing agent from an aged soil. Phytoextraction from a low organic sand medium ( f OC = 0.056 ± 0.03%) indicated a significant enhancement of pyrene uptake with three weeks daily watering with 500 mg L −1 caffeine solution. The average pyrene content of roots was 35.3 and 16.0 μg g −1, in caffeine and non-caffeine set-ups, respectively. In the shoots, the corresponding values were 3.60 and 1.67 μg g −1. Both showed more than twofold increase with caffeine. Caffeine also accumulated mainly in the leaves of the treated samples at 2800 mg kg −1 dry weight. Further tests with a 1-year aged soil ( f OC = 5.2 ± 1%) containing a mixture of phenanthrene and pyrene yielded parallel results. However, lower PAH content in these samples were observed due to the stronger PAHs partitioning in aged-soil matrix. After four weeks of caffeine, phenanthrene in shoots and roots increased by one and a half and four times, respectively. The corresponding enhancements for pyrene were two and a half and three and a half times.

Altered expression of the caffeine synthase gene in a naturally caffeine-free mutant of Coffea arabica

In this work, we studied the biosynthesis of caffeine by examining the expression of genes involved in this biosynthetic pathway in coffee fruits containing normal or low levels of this substance. The amplification of gene-specific transcripts during fruit development revealed that low-caffeine fruits had a lower expression of the theobromine synthase and caffeine synthase genes and also contained an extra transcript of the caffeine synthase gene. This extra transcript contained only part of exon 1 and all of exon 3. The sequence of the mutant caffeine synthase gene revealed the substitution of isoleucine for valine in the enzyme active site that probably interfered with enzymatic activity. These findings indicate that the absence of caffeine in these mutants probably resulted from a combination of transcriptional regulation and the presence of mutations in the caffeine synthase amino acid sequence.

Honeybush (Cyclopia sp.) – A rich source of compounds with high antimutagenic properties

The genus Cyclopia (Fabaceae family) includes a number of shrubs endemic to Cape Fynbos region of South Africa. The most common of these plants is Cyclopia intermedia E. Mey., used together with other Cyclopia species (mainly C. subternata and C. sessiliflora) to manufacture the honeybush herbal tea which has been produced in South Africa roughly since the beginning of the 19th century. Honeybush infusions are gaining popularity due to their characteristic honey-like flavour, low tannin content, absence of caffeine and potential health effects related to their antimutagenic and antioxidant properties. The presented review summarizes information concerning botany, chemistry, biological activity and application of Cyclopia plants.

Pharmacological and Psychological Effects of Caffeine Ingestion in 40-km Cycling Performance

The ergogenic effects of caffeine are well documented. Research has yet to examine any psychological contribution to this effect. To explore the psychological and pharmacological effects of caffeine in laboratory cycling performance. Fourteen male competitive cyclists performed 14 40-km time trials (eight experimental interspersed with six baseline). The experimental phase consisted of two trials for each of four experimental conditions: informed caffeine/received caffeine, informed no treatment/received caffeine, informed caffeine/received placebo, and informed no treatment/received no treatment. Conditions were nonrandomized. ANOVA was used to estimate main effects and interactions for mean values of power, heart rate, blood lactate, and maximal oxygen uptake. Probabilistic inferences for mean power were based on a smallest worthwhile change of 1.5%. Relative to baseline, a very likely beneficial main effect of receiving caffeine (3.5%; 95% confidence interval 1.5 to 5.5%), and a possibly beneficial main effect of being informed of caffeine (0.7%; -0.7 to 2.1%) were observed. A substantial interaction between belief and pharmacology indicated that caffeine exerted a greater effect on performance in conditions when subjects were informed that they had not ingested it, whereas belief exerted a greater influence on performance in the absence of caffeine (2.6%; -0.7 to 5.9%). A possibly harmful negative placebo (nocebo) effect was observed when subjects were correctly informed that they had ingested no caffeine (-1.9%; -4.1 to 0.3%). No clinically significant changes relative to baseline were observed in mean heart rate. Clear and substantial increases in blood lactate were evident after receipt of caffeine. Data for mean oxygen uptake were unclear. Our data support the ergogenic efficacy of caffeine but suggest that both positive and negative expectations impact performance.

Caffeine Deprivation State Modulates Expression of Acquired Liking for Caffeine-Paired Flavours

Previous studies found that caffeine consumers acquired a liking for the flavour of novel caffeinated drinks when these drinks were consumed repeatedly in a caffeine-deprived, but not nondeprived, state. Expression of this acquired liking appeared acutely sensitive to current caffeine deprivation state, but the use of between-subjects designs confounded interpretation of those studies. The present study evaluated these findings further using a within-subject design, with one flavour paired with caffeine (CS + ) and the second with the absence of caffeine (CS-). During four CS + and four CS- training days, 32 moderate caffeine consumers alternatively consumed a novel flavoured drink a CS + paired with caffeine and a CS- flavour paired with placebo. Participants evaluated both drinks before and after training in two motivational states: caffeine deprived and nondeprived. As predicted, pleasantness ratings for the caffeine-paired flavour increased overall. However, this acquired liking was only significant when tested in a caffeine-deprived state. These data are consistent with a conditioned-flavour preference model and imply that expression of acquired liking for a novel caffeinated flavour depends on the need for the effects of caffeine at the time when the drink is evaluated.

43 INVITED Genome and transcriptome analysis of single disseminated cancer cells

We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans.Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP.In vivo ischemia-reperfusion injury was assessed in the thenar muscle by 99mTc-annexin A5 scintigraphy. Forty-two healthy volunteers performed forearm ischemic exercise. In 24 subjects, this was preceded by a stimulus for IP. In a randomized double-blinded design, the subjects received caffeine (4 mg/kg) or saline intravenously before the experiment. At reperfusion, 99mTc-annexin A5 was administered intravenously. Targeting of annexin was quantified by region-of-interest analysis, and expressed as percentage difference between experimental and contralateral hand. In vitro, we assessed recovery of contractile function of human atrial trabeculae, harvested during heart surgery, as functional end point of ischemia-reperfusion injury. Field-stimulated contraction was quantified at baseline and after simulated ischemia-reperfusion, in a paired approach with and without 5 min of IP, in the presence (n = 13) or absence (n = 17) of caffeine (10 mg/l).Ischemic preconditioning reduced annexin targeting in the absence of caffeine (from 13 ± 3% to 7 ± 1% at 1 h, and from 19 ± 2% to 9 ± 3% at 4 h after reperfusion, p = 0.006), but not after caffeine administration (targeting 11 ± 2% and 16 ± 3% at 1 and 4 h). In vitro, IP improved post-ischemic functional recovery in the control group, but not in the caffeine group (8 ± 3% vs. −8 ± 5%, p = 0.003).Caffeine abolishes IP in 2 human models at a dose equivalent to the drinking of 2 to 4 cups of coffee. (The Effect of Caffeine on Ischemic Preconditioning; http://clinicaltrials.gov/ct/show/NCT00184912?order=1; NCT00184912).