Astilbin lowers the effective caffeine dose for decreasing lipid accumulation via activating AMPK in high-fat diet-induced obese mice.

BACKGROUND: Caffeine has an anti-obesity effect, although chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression, amongst other symptoms. The present study aimed to investigate whether the addition of flavonoids such as astilbin can reduce the caffeine dose needed to inhibit obesity. RESULTS: ICR mice (n = 80) were fed with normal diet, high-fat diet (HFD), HFD supplemented with astilbin, caffeine, or astilbin + caffeine for 12 weeks. When diets supplemented with astilbin, 0.3 g kg-1 diet caffeine had the same effect as 0.6 g kg-1 diet caffeine alone, and 0.6 g kg-1 diet caffeine combined with astilbin most effectively inhibited HFD-induced obesity. Astilbin improved the anti-obesity effects of caffeine on lipid accumulation via the activation of AMP-activated protein kinase α (AMPKα). (i) Activated AMPKα decreased lipid biosynthesis by suppressing the activity or mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein 1c and its target gene fatty acid synthase. (ii) Activated AMPKα also up-regulated lipolysis by enhancing the expression of adipose triglyceride lipase and increasing the phosphorylation of hormone-sensitive lipase. (iii) Finally, activated AMPKα increased carnitine acyltransferase and acyl-CoA oxidase activities, which further promoted fatty acid ß-oxidation. CONCLUSION: The results obtained in the present study indicate that astilbin may decrease the effective dose of caffeine needed for an anti-obesity effect and also suggest that it suppresses fat accumulation via the activation of AMPK. © 2020 Society of Chemical Industry.

Sustancias inhibidoras de sueño, hábitos de estudio y rendimiento académico en estudiantes de medicina y enfermería de universidades de la ciudad de Barranquilla, Colombia / Sleep-inhibiting substance, study habits and academic performance in medical and nursing students from universities in the city of Barranquilla, Colombia

OBJETIVO: Determinar el uso de sustancias inhibidoras del sueño, los hábitos de estudio y el rendimiento académico en los estudiantes de II y III semestre de Medicina de universidades de la ciudad de Barranquilla. MÉTODO: Se evaluó una muestra de 463 estudiantes (Universidad Metropolitana 199 estudiantes y en la Universidad Simón Bolívar 264 estudiantes). El instrumento fue diseñado por las investigadoras y validado por un grupo de 10 expertos mediante el método Delphi. Para la evaluación de los resultados se realizó un análisis de tendencia central a cada una de las variables. RESULTADOS: Hubo mayor predominio del rango etario entre los 18-21 años con el 62%; el género de mayor prevalencia fue el femenino un 72,14%; en promedio el 67% de los estudiantes no tienen buenos hábitos de estudio; el 30% consumen sustancias inhibidoras de sueño; la cafeína ocupa el primer lugar, seguido de las bebidas tipo cola y las energizantes; y, el 72,86% indicaron que han obtenido mejores resultados académicos por el consumo de estas sustancias. CONCLUSIÓN: Existe la presencia de un multiconsumo de sustancias inhibidoras de sueño por los estudiantes, situación que pone en riesgo su salud integral

OBJECTIVE: To determine the use of sleep-inhibiting substances, study habits and academic performance in the students of the 2.nd and 3.rd semesters of University Medicine of the city of Barranquilla. METHOD: An assessment was made on a sample of 463 students (Metropolitan University 199 students. and the university Simón Bolívar 264 students). The survey tool was designed by the researchers and validated by a group of 10 experts using the Delphi method. For the evaluation of the results, a central tendency analysis was carried out on each of the variables. RESULTS: There was a greater prevalence (62%) in the age range between 18-21 years. Females had a higher prevalence (72.14%). On average, 67% of students did not have good study habits, with 30% consuming sleep-inhibiting substances, and caffeine occupying the first place, followed by cola-type beverages and energizers. Around three-quarters (72.86%) indicated they have obtained better academic results by consuming these substances. CONCLUSION: There is multiple use of sleep-inhibiting substances by the students, a situation that puts at risk their integral health

Caffeine Exacerbates Postictal Hypoxia.

A stroke-like event follows seizures which may be responsible for the postictal state and a contributing factor to the development of seizure-induced brain abnormalities and behavioral dysfunction associated with epilepsy. Caffeine is the world's most popular drug with ∼85% of people in the USA consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their body and brain during seizures. This preclinical study investigated the effects of acute caffeine on local hippocampal tissue oxygenation pre and post seizure. We continuously measured local oxygen levels in the CA1 region of the hippocampus and utilized the electrical kindling model in rats. Rats were acutely administered either caffeine, or one of its metabolites, or agonists and antagonists at adenosine sub-receptor types or ryanodine receptors prior to the elicitation of seizures. Acute caffeine administration caused a significant drop in pre-seizure hippocampal pO2. Following a seizure, caffeine, as well as two of its metabolites paraxanthine, and theophylline, increased the time below the severe hypoxic threshold (10 mmHg). Likewise, the specific A2A receptor antagonist, SCH-58261, mimicked caffeine by causing a significant drop in pre-seizure pO2 and the area and time below the severe hypoxic threshold. Moreover, the A2A receptor agonist, CGS-21680 was able to prevent the effect of both caffeine and SCH-58261 adding further evidence that caffeine is likely acting through the A2A receptor. Clinical tracking and investigations are needed to determine the effect of caffeine on postictal symptomology and blood flow in persons with epilepsy.

Caffeine regulates GABA transport via A1R blockade and cAMP signaling.

Caffeine is the most consumed psychostimulant drug in the world, acting as a non-selective antagonist of adenosine receptors A1R and A2AR, which are widely expressed in retinal layers. We have previously shown that caffeine, when administered acutely, acts on A1R to potentiate the NMDA receptor-induced GABA release. Now we asked if long-term caffeine exposure also modifies GABA uptake in the avian retina and which mechanisms are involved in this process. Chicken embryos aged E11 were injected with a single dose of caffeine (30 mg/kg) in the air chamber. Retinas were dissected on E15 for ex vivo neurochemical assays. Our results showed that [3H]-GABA uptake was dependent on Na+ and blocked at 4 °C or by NO-711 and caffeine. This decrease was observed after 60 min of [3H]-GABA uptake assay at E15, which is accompanied by an increase in [3H]-GABA release. Caffeine increased the protein levels of A1R without altering ADORA1 mRNA and was devoid of effects on A2AR density or ADORA2A mRNA levels. The decrease of GABA uptake promoted by caffeine was reverted by A1R activation with N6-cyclohexyl adenosine (CHA) but not by A2AR activation with CGS 21680. Caffeine exposure increased cAMP levels and GAT-1 protein levels, which was evenly expressed between E11-E15. As expected, we observed an increase of GABA containing amacrine cells and processes in the IPL, also, cAMP pathway blockage by H-89 decreased caffeine mediated [3H]-GABA uptake. Our data support the idea that chronic injection of caffeine alters GABA transport via A1R during retinal development and that the cAMP/PKA pathway plays an important role in the regulation of GAT-1 function.

ß-Estradiol antagonizes the inhibitory effects of caffeine in BMMSCs via the ERß-mediated cAMP-dependent PKA pathway.

Caffeine negatively mediates bone homeostasis to cause bone loss and even osteoporosis. This phenomenon occurs in postmenopausal women with estrogen deficiency but not in healthy young women. In this study, we determined whether the effects of caffeine on bone homeostasis were antagonized by estrogen and the underlying mechanisms. In particular, because high levels of cAMP, an important second messenger, have been observed in postmenopausal women suffering from osteoporosis, we examined the role of cAMP in the effects of caffeine on bone homeostasis. In vivo study showed that caffeine accelerated bone loss in osteoporotic rats, whereas ß-estradiol blunted the negative effect of caffeine on bone. In vitro study, we harvested bone marrow-derived mesenchymal stromal cells (BMMSCs) from osteoporotic rats. We found that caffeine and ß-estradiol inversely affected BMMCSs proliferation, apoptosis, osteogenic lineage commitment, extracellular matrix synthesis and mineralization. These parameters were assessed according to the expression levels of osteogenic markers, alkaline phosphatase activity and Alizarin red staining. The deleterious effects of caffeine on BMMSCs were blunted by ß-estradiol. The cAMP-dependent PKA pathway was found to be involved in regulating caffeine/ß-estradiol-mediated cell growth, survival and osteogenesis. Additionally, after estrogen receptor (ER) ß knockdown, the antagonistic effects of ß-estradiol on caffeine were nearly abolished. These results indicated that by binding to ERß, ß-estradiol antagonizes the negative impacts of caffeine on cell growth and osteogenic differentiation in BMMSCs through the cAMP-dependent PKA signaling pathway.

Theacrine: A purine alkaloid from Camellia assamica var. kucha with a hypnotic property via the adenosine system.

Theacrine (l,3,7,9-tetramethyluric acid), a purine alkaloid from Camellia assamica var. kucha, has diverse pharmacological properties, including sedative and hypnotic activities, anti-inflammatory and analgesic activities, antidepressant effects, and a protective effect against stress-provoked liver damage. The present study aims to investigate the possible mechanism of the hypnotic activity of theacrine. The results revealed that theacrine significantly enhanced pentobarbital-induced sleep at a dose of 3.0mg/kg (i.g.) in mice. Sleep parameter analysis by EEG and EMG showed that theacrine obviously shortened wake time and increased NREM sleep time and that theacrine almost had no effect on REM sleep. Meanwhile, theacrine markedly attenuated caffeine (a nonselective antagonist of adenosine receptor)-induced insomnia. In pretreatment with the adenosine A1 receptor antagonist DPCPX and the A2A receptor antagonist SCH 58261, theacrine significantly reversed the decrease in sleeping time in pentobarbital-treated mice. In addition, theacrine also markedly increased the adenosine content in the hippocampus of rats. These results suggested that theacrine might mediate the adenosine system to augment pentobarbital-induced sleep.

Antifungal activity and expression patterns of extracellular chitinase and ß-1,3-glucanase in Wickerhamomyces anomalus EG2 treated with chitin and glucan.

In this study, the expression patterns of extracellular chitinase and ß-1,3-glucanase from cultured Wickerhamomyces anomalus EG2 treated with chitin, glucan, and chemical chitinase inhibitors (kinetin, caffeine, and acetazolamide) were investigated using SDS-PAGE. Relationship between enzyme expression and antifungal activity from yeast plays a very important role for biocontrol of phytopathoges. To determine antifungal activity against phytopathogens, W. anomalus EG2 was shown to strongly inhibit hyphal growth of Fusarium oxysporum KACC 40032 and Rhizoctonia solani KACC 40111. Slight chitinase activity was observed 12 h after incubation in both PDB and YPD medium without colloidal chitin. The molecular weight of chitinase was approximately 124 kDa ß-1,3-Glucanase isoenzyme (GN1 and GN2) was observed distinctly on SDS-PAGE gels when laminarin was used as a substrate. ß-1,3-Glucanase isoenzyme was not observed when using glucan-containing high polymer complex (GHPC) as a substrate. Production of chitinase from W. anomalus EG2 was inhibited slightly by acetazolamide. Abnormal and cluster-shaped cells of W. anomalus EG2 were observed in both PDB and YPD medium treated with colloidal chitin. These results indicated that W. anomalus EG2 could be applied commercially as a biological control agent of phytopathogens and as a bioinhibitor of yeast cell growth.

Effects of caffeine on behavioral and inflammatory changes elicited by copper in zebrafish larvae: Role of adenosine receptors.

This study investigated the effects of caffeine in the behavioral and inflammatory alterations caused by copper in zebrafish larvae, attempting to correlate these changes with the modulation of adenosine receptors. To perform a survival curve, 7dpf larvae were exposed to 10µM CuSO4, combined to different concentrations of caffeine (100µM, 500µM and 1mM) for up to 24h. The treatment with copper showed lower survival rates only when combined with 500µM and 1mM of caffeine. We selected 4 and 24h as treatment time-points. The behavior evaluation was done by analyzing the traveled distance, the number of entries in the center, and the length of permanence in the center and the periphery of the well. The exposure to 10µM CuSO4 plus 500µM caffeine at 4 and 24h changed the behavioral parameters. To study the inflammatory effects of caffeine, we assessed the PGE2 levels by using UHPLC-MS/MS, and TNF, COX-2, IL-6 and IL-10 gene expression by RT-qPCR. The expression of adenosine receptors was also evaluated with RT-qPCR. When combined to copper, caffeine altered inflammatory markers depending on the time of exposure. Adenosine receptors expression was significantly increased, especially after 4h exposure to copper and caffeine together or separately. Our results demonstrated that caffeine enhances the inflammation induced by copper by decreasing animal survival, altering inflammatory markers and promoting behavioral changes in zebrafish larvae. We also conclude that alterations in adenosine receptors are related to those effects.

Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction.

The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 µM/0.5 µl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats.

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine.

Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e., relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-primed reinstatement of cocaine-seeking. Adult male and female Wistar rats lever-pressed under a FR 1 schedule for cocaine infusions (0.4mg/kg/inf). After 14 sessions of stable responding in daily 2-h sessions, rats underwent a 21-day extinction period when no drug or drug-related stimuli were present. Rats were then separated into four groups that received PRO (0.5mg/kg) alone (PRO+SAL), ATO (1.5mg/kg) alone (VEH+ATO), control (VEH+SAL) or combination (PRO+ATO) treatments prior to the reinstatement condition. Reinstatement of cocaine-seeking to cues and/or drug injections of cocaine or caffeine was tested after extinction. During maintenance, females self-administered more cocaine than males, but no sex differences were seen during extinction. Females showed greater cocaine-seeking than males after a CAF priming injection. Individual treatment with ATO did not decrease reinstatement under any priming condition; however, the combination treatment decreased cocaine-seeking under the COC+CUES priming condition in males, and both PRO alone and the combination treatment decreased cocaine-seeking in the CAF+CUES condition in females. Overall, PRO alone was only effective in reducing reinstatement in females, while the combination treatment was consistently effective in reducing reinstatement in both sexes.

Fasting activated histaminergic neurons and enhanced arousal effect of caffeine in mice.

Caffeine, a popular psychoactive compound, promotes wakefulness via blocking adenosine A2A receptors in the shell of the nucleus accumbens, which projects to the arousal histaminergic tuberomammillary nucleus (TMN). The TMN controls several behaviors such as wakefulness and feeding. Fasting has been reported to activate the TMN histaminergic neurons to increase arousal. Therefore, we propose that caffeine may promote greater arousal under fasting rather than normal feeding conditions. In the current study, locomotor activity recording, electroencephalogram (EEG) and electromyogram recording and c-Fos expression were used in wild type (WT) and histamine H1 receptor (H1R) knockout (KO) mice to investigate the arousal effects of caffeine under fasting conditions. Caffeine (15mg/kg) enhanced locomotor activity in fasted mice for 5h, but only did so for 3h in normally fed animals. Pretreatment with the H1R antagonist pyrilamine abolished caffeine-induced stimulation on locomotor activity in fasted mice. EEG recordings confirmed that caffeine-induced wakefulness for 3h in fed WT mice, and for 5h in fasted ones. A stimulatory effect of caffeine was not observed in fasted H1R KO mice. Furthermore, c-Fos expression was increased in the TMN under fasting conditions. These results indicate that caffeine had greater wakefulness-promoting effects in fasted mice through the mediation of H1R.

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.

BACKGROUND AND PURPOSE: While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca²âº signalling and Ca²âº sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca²âº signalling and sensitivity. EXPERIMENTAL APPROACH: Airways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase-contrast microscopy. Ca²âº signalling was measured with 2-photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca²âº-sensitive indicator (with or without caged-IP3). Effects on Ca²âº sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca²âº . KEY RESULTS: The TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist-induced Ca²âº oscillations. However, in non-contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca²âº signals in ASM cells. Ca²âº increases mediated by the photolysis of caged-IP3 were also attenuated by chloroquine, quinine and denotonium. In Ca²âº-permeabilized ASM cells, the TAS2R10 agonists dilated MCh- and 5HT-constricted airways. CONCLUSIONS AND IMPLICATIONS: TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca²âº oscillations while simultaneously reducing the Ca²âº sensitivity of ASM cells. Reduction of Ca²âº oscillations may be due to inhibition of Ca²âº release through IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions.

L-theanine partially counteracts caffeine-induced sleep disturbances in rats.

L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.5 mg/kg caffeine and saline, or 7.5 mg/kg of caffeine followed by various doses of L-theanine (22.5, 37.5, 75, or 150 mg/kg). Vigilance states were divided into: wakefulness (W), transition to slow-wave sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). Caffeine significantly increased the duration of W and decreased the duration of SWS and REMS compared to the Control. Although L-theanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5 mg/kg (but not at 75 and 150 mg/kg), it significantly reversed caffeine-induced decreases in SWS. In conclusion, low doses of L-theanine can partially reverse caffeine-induced reductions in SWS; however, effects of L-theanine on caffeine-induced insomnia do not appear to increase dose-dependently.

Cafeína: la droga intelectual que estimula al mundo / Caffeine intellectual drug that stimulates the world

La cafeína es la droga estimulante más aceptada socialmente y a su vez, la menos perjudicial. La cafeína es la droga más popular del mundo. Se ha visto que la promueven en Groenlandia, al pie de la capa de hielos eternos; en el extremo meridional de América del Sur, allí donde las aguas del Cabo de los Hornos azotan los roqueros costeños. La usan los nómadas del desierto del Sinaí y los remotos aldeanos del Tíbet y de la China. En la ex Unión Soviética se consumían cada año centenares de millones de litros que la contienen. La encontramos en grandes cartelones por toda América del Norte, de uno a otro océano, si caminamos por las calles de cualquier ciudad europea, no podemos escapar de su aromática presencia. Es la cafeína, que se encuentra en el café, el té, el mate, el cacao, el guaraná, y en un amplio espectro de bebidas con base de cola. La cafeína, es una sustancia presente en numerosos elementos de la dieta diaria, existen opiniones encontradas con respecto a su uso, ya que muchos de sus efectos son valiosos para la vida diaria. Pero también puede producir efectos nocivos si se la usa en dosis excesivas, como “dependencia” aunque con un síndrome de abstinencia mucho más, benigno que en otro caso. Sus síntomas son dolor de cabeza, irritabilidad y somnolencia. En general, las personas recurren a la cafeína para poder obtener estimulación, ya que disminuye el cansancio y la fatiga. Se comporta como un estimulante del sistema nervioso central, ayudando a la memoria, facilitando la asociación de ideas y mejorando la percepción sensoria, la cafeína en su justa medida permite incrementar la atención y facilita el proceso bioquímico que se desarrolla durante la formación de la memoria en el cerebro. La cafeína se encuentra en semillas como el café, el cacao, la guaraná, o en hojas como el té y la yerba mate.

ABSTRACT : Caffeine is a stimulant drug more socially acceptable and in turn, the less damaging. Caffeine is the world's most popular drug. It has been promoting it in Greenland, at the foot of the permafrost layer, at the southern tip of South America, where the waters of Cape Horn hit coastal rockers. The used by nomads in the Sinai desert and remote village in Tibet and China. In the former Soviet Union were consumed each year hundreds of millions of liters that contain it. It is found in large billboards throughout North America, from one ocean to the other, if we walk through the streets of any European city, we cannot escape its aromatic presence. Is caffeine, found in coffee, tea, mate, cocoa, guarana, and a broad spectrum of cola-based drinks. Caffeine is a substance found in many elements of the daily diet, there are conflicting opinions regarding its use, as many of its effects are valuable life skills. But it can also have harmful effects if used in excessive doses, as "dependency" but with a lot more withdrawal, otherwise benign. Symptoms include headache, irritability and drowsiness. In general, people turn to caffeine stimulation to obtain, since it reduces tiredness and fatigue. It behaves like a central nervous system stimulant, helping memory, facilitate the association of ideas and improving sensory perception, caffeine in perspective can increase attention and facilitates the biochemical process that develops during memory formation in the brain. Caffeine is found in seeds such as coffee, cocoa, guarana, or leaves as tea and yerba mate.

Cafeína: la droga intelectual que estimula al mundo / Caffeine intellectual drug that stimulates the world

La cafeína es la droga estimulante más aceptada socialmente y a su vez, la menos perjudicial. La cafeína es la droga más popular del mundo. Se ha visto que la promueven en Groenlandia, al pie de la capa de hielos eternos; en el extremo meridional de América del Sur, allí donde las aguas del Cabo de los Hornos azotan los roqueros costeños. La usan los nómadas del desierto del Sinaí y los remotos aldeanos del Tíbet y de la China. En la ex Unión Soviética se consumían cada año centenares de millones de litros que la contienen. La encontramos en grandes cartelones por toda América del Norte, de uno a otro océano, si caminamos por las calles de cualquier ciudad europea, no podemos escapar de su aromática presencia. Es la cafeína, que se encuentra en el café, el té, el mate, el cacao, el guaraná, y en un amplio espectro de bebidas con base de cola. La cafeína, es una sustancia presente en numerosos elementos de la dieta diaria, existen opiniones encontradas con respecto a su uso, ya que muchos de sus efectos son valiosos para la vida diaria. Pero también puede producir efectos nocivos si se la usa en dosis excesivas, como ôdependenciaö aunque con un síndrome de abstinencia mucho más, benigno que en otro caso. Sus síntomas son dolor de cabeza, irritabilidad y somnolencia. En general, las personas recurren a la cafeína para poder obtener estimulación, ya que disminuye el cansancio y la fatiga. Se comporta como un estimulante del sistema nervioso central, ayudando a la memoria, facilitando la asociación de ideas y mejorando la percepción sensoria, la cafeína en su justa medida permite incrementar la atención y facilita el proceso bioquímico que se desarrolla durante la formación de la memoria en el cerebro. La cafeína se encuentra en semillas como el café, el cacao, la guaraná, o en hojas como el té y la yerba mate.(AU)

ABSTRACT : Caffeine is a stimulant drug more socially acceptable and in turn, the less damaging. Caffeine is the worlds most popular drug. It has been promoting it in Greenland, at the foot of the permafrost layer, at the southern tip of South America, where the waters of Cape Horn hit coastal rockers. The used by nomads in the Sinai desert and remote village in Tibet and China. In the former Soviet Union were consumed each year hundreds of millions of liters that contain it. It is found in large billboards throughout North America, from one ocean to the other, if we walk through the streets of any European city, we cannot escape its aromatic presence. Is caffeine, found in coffee, tea, mate, cocoa, guarana, and a broad spectrum of cola-based drinks. Caffeine is a substance found in many elements of the daily diet, there are conflicting opinions regarding its use, as many of its effects are valuable life skills. But it can also have harmful effects if used in excessive doses, as "dependency" but with a lot more withdrawal, otherwise benign. Symptoms include headache, irritability and drowsiness. In general, people turn to caffeine stimulation to obtain, since it reduces tiredness and fatigue. It behaves like a central nervous system stimulant, helping memory, facilitate the association of ideas and improving sensory perception, caffeine in perspective can increase attention and facilitates the biochemical process that develops during memory formation in the brain. Caffeine is found in seeds such as coffee, cocoa, guarana, or leaves as tea and yerba mate.(AU)

Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances.

BACKGROUND AND PURPOSE: Spontaneous electrical activity, termed slow waves, drives rhythmic, propulsive contractions in the smooth muscle of the oviduct (myosalpinx). Myosalpinx contractions cause egg transport through the oviduct. Agents that disrupt slow wave pacemaker activity will therefore disrupt myosalpinx contractions and egg transport. Caffeine is commonly used as a ryanodine receptor agonist and has been previously associated with delayed conception. Here we assessed the effects of caffeine on pacemaker activity in the murine myosalpinx. EXPERIMENTAL APPROACH: The effects of caffeine on electrical pacemaker activity were studied using intracellular microelectrode and isometric force measurements on intact oviduct muscle preparations. Responses to caffeine were compared with responses caused by 3-isobutyl-1-methylxanthine (IBMX) and forskolin. KEY RESULTS: Caffeine caused hyperpolarization of membrane potential and inhibited slow wave generation and myosalpinx contractions. The effects of caffeine could be mimicked by the K(ATP) channel agonist pinacidil and antagonized by the K(ATP) channel antagonist glibenclamide. Caffeine is known to inhibit cyclic nucleotide phosphodiesterases (PDEs), leading to an increase in cytosolic cAMP and stimulation of downstream cAMP-dependent mechanisms. The effects of caffeine were mimicked by the PDE inhibitor, IBMX, and the adenylyl cyclase activator forskolin. These effects were also reversed by glibenclamide. CONCLUSIONS AND IMPLICATIONS: These results suggest that caffeine activates K(ATP) channels in oviduct myosalpinx. Since caffeine abolishes slow waves and associated contractions of the myosalpinx, it would have a negative effect on egg transport through the oviduct and may contribute to the documented delayed conception in women consuming caffeinated beverages.

Agrobacterium-mediated silencing of caffeine synthesis through root transformation in Camellia sinensis L.

Tea [Camellia sinensis (L.) O. Kuntze] is a perennial and most popular non-alcoholic caffeine-containing beverage crop. Tea has several constraints for its genetic improvement such as its high polyphenolic content and woody perennial nature. The development of transgenic tea is very difficult, laborious, and time taking process. In tea, regeneration requires minimum 8-12 months. In view of this, attempt has been made in this article to develop a rapid, efficient, and quite economical Agrobacterium-mediated root transformation system for tea. The feasibility of the developed protocol has been documented through silencing caffeine biosynthesis. For this, one-month-old tea seedlings were exposed to fresh wounding at the elongation zone of roots and were inoculated with Agrobacterium tumefaciens cultures carrying a RNAi construct (pFGC1008-CS). The pFGC1008-CS contained 376 bp of caffeine synthase (CS) cDNA fragment in sense and antisense direction with an intron in between. This has made the RNAi construct to produce a hairpin RNA (ihpRNA). The suppressed expression of CS gene and a marked reduction in caffeine and theobromine contents in young shoots of tea seedlings were obtained after root transformation through Agrobacterium infiltration. Such transformation system could be useful for functional analysis of genes in tea like woody and perennial plants.

Mechanisms mediating the ability of caffeine to influence MDMA ('Ecstasy')-induced hyperthermia in rats.

BACKGROUND AND PURPOSE: Caffeine exacerbates the hyperthermia associated with an acute exposure to 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') in rats. The present study investigated the mechanisms mediating this interaction. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were treated with caffeine (10 mg x kg(-1); i.p.) and MDMA (15 mg x kg(-1); i.p.) alone and in combination. Core body temperatures were monitored before and after drug administration. KEY RESULTS: Central catecholamine depletion blocked MDMA-induced hyperthermia and its exacerbation by caffeine. Caffeine provoked a hyperthermic response when the catecholamine releaser d-amphetamine (1 mg x kg(-1)) was combined with the 5-HT releaser D-fenfluramine (5 mg x kg(-1)) or the non-selective dopamine receptor agonist apomorphine (1 mg x kg(-1)) was combined with the 5-HT(2) receptor agonist DOI (2 mg x kg(-1)) but not following either agents alone. Pretreatment with the dopamine D(1) receptor antagonist Schering (SCH) 23390 (1 mg x kg(-1)), the 5-HT(2) receptor antagonist ketanserin (5 mg x kg(-1)) or alpha(1)-adreno- receptor antagonist prazosin (0.2 mg x kg(-1)) blocked MDMA-induced hyperthermia and its exacerbation by caffeine. Co-administration of a combination of MDMA with the PDE-4 inhibitor rolipram (0.025 mg x kg(-1)) and the adenosine A(1/2) receptor antagonist 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-C]quinazolin-5-amine 15943 (10 mg x kg(-1)) or the A(2A) receptor antagonist SCH 58261 (2 mg x kg(-1)) but not the A(1) receptor antagonist DPCPX (10 mg x kg(-1)) exacerbated MDMA-induced hyperthermia. CONCLUSIONS AND IMPLICATIONS: A mechanism comprising 5-HT and catecholamines is proposed to mediate MDMA-induced hyperthermia. A combination of adenosine A(2A) receptor antagonism and PDE inhibition can account for the exacerbation of MDMA-induced hyperthermia by caffeine.

Recent caffeine ingestion reduces adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia.

OBJECTIVES: Caffeine, an adenosine receptor blocker, should theoretically reduce adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia (SVT). We aimed to determine the effect of recent caffeine ingestion on the likelihood of reversion of SVT with adenosine. METHODS: This was a multicenter, case-control study of adult patients with SVT treated with adenosine between September 2007 and July 2008. The primary endpoint was reversion to sinus rhythm (SR) after a 6-mg adenosine bolus, as a function of recent (within 2, 4, 6, and 8 hours) caffeine ingestion. Caffeine ingestion data were collected using a self-administered questionnaire. RESULTS: Of 68 patients enrolled, 52 (76.5%, 95% confidence interval [CI] = 64.4% to 85.6%) reverted after a 6-mg adenosine bolus. There were no significant differences in age, sex, or daily caffeine ingestion between patients who did and did not revert (p > 0.05). However, as a group, patients who did not revert had recently ingested significantly more caffeine (p < 0.05). If caffeine had been ingested less than 2 or 4 hours before the adenosine bolus, the odds of reversion to SR were significantly reduced (odds ratio [OR] = 0.18, 95% CI = 0.04 to 0.93; and OR = 0.14, 95% CI = 0.04 to 0.49, respectively). If caffeine had been ingested less than 6 or 8 hours before the adenosine, the odds of reversion were not reduced (OR = 0.31, 95% CI = 0.09 to 1.02; and OR = 0.31, 95% CI = 0.09 to 1.08, respectively). CONCLUSIONS: Ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduces its effectiveness in the treatment of SVT. An increased initial adenosine dose may be indicated for these patients.