RESUMEN
BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).
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Complejos Atriales Prematuros , Glucemia , Cafeína , Café , Duración del Sueño , Caminata , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complejos Atriales Prematuros/inducido químicamente , Complejos Atriales Prematuros/etiología , Cafeína/efectos adversos , Cafeína/farmacología , Café/efectos adversos , Glucosa , Estudios Prospectivos , Ingestión de Líquidos , Estudios Cruzados , Glucemia/análisis , Duración del Sueño/efectos de los fármacos , Acelerometría , Electrocardiografía Ambulatoria , Automonitorización de la Glucosa Sanguínea , Aplicaciones Móviles , Envío de Mensajes de Texto , Complejos Prematuros Ventriculares/inducido químicamente , Complejos Prematuros Ventriculares/etiologíaRESUMEN
Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent1-3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations, which could influence phenotype through unstable gene silencing rather than DNA change6,7. Here we show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine. Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavourable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance. Caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents.
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Farmacorresistencia Fúngica/genética , Silenciador del Gen , Heterocromatina/genética , Heterocromatina/metabolismo , Schizosaccharomyces/genética , Cafeína/farmacología , Farmacorresistencia Fúngica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Heterocromatina/efectos de los fármacos , Histona Acetiltransferasas/metabolismo , Proteínas Nucleares/metabolismo , Fenotipo , Schizosaccharomyces/citología , Schizosaccharomyces/efectos de los fármacos , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismoRESUMEN
Sleep deprivation (SD) is widely acknowledged as a significant risk factor for cognitive impairment. In this study, intraperitoneal caffeine administration significantly ameliorated the learning and memory (L/M) deficits induced by SD and reduced aggressive behaviors in adult zebrafish. SD led to a reduction in protein kinase A (PKA) phosphorylation, phosphorylated-cAMP response element-binding protein (p-CREB), and c-Fos expression in zebrafish brain. Notably, these alterations were effectively reversed by caffeine. In addition, caffeine mitigated neuroinflammation induced by SD, as evident from suppression of the SD-mediated increase in glial fibrillary acidic protein (GFAP) and nuclear factor-κB (NF-κB) activation. Caffeine restored normal O-GlcNAcylation and O-GlcNAc transferase (OGT) levels while reversing the increased expression of O-GlcNAcase (OGA) in zebrafish brain after SD. Intriguingly, rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, effectively mitigated cognitive deficits, restored p-CREB and c-Fos levels, and attenuated the increase in GFAP in brain induced by SD. In addition, rolipram reversed the decrease in O-GlcNAcylation and OGT expression as well as elevation of OGA expression following SD. Treatment with H89, a PKA inhibitor, significantly impaired the L/M functions of zebrafish compared with the control group, inducing a decrease in O-GlcNAcylation and OGT expression and, conversely, an increase in OGA expression. The H89-induced changes in O-GlcNAc cycling and L/M dysfunction were effectively reversed by glucosamine treatment. H89 suppressed, whereas caffeine and rolipram promoted O-GlcNAc cycling in Neuro2a cells. Our collective findings underscore the interplay between PKA signaling and O-GlcNAc cycling in the regulation of cognitive function in the brain, offering potential therapeutic targets for cognitive deficits associated with SD.NEW & NOTEWORTHY Our observation highlights the intricate interplay between cAMP/PKA signaling and O-GlcNAc cycling, unveiling a novel mechanism that potentially governs the regulation of learning and memory functions. The dynamic interplay between these two pathways provides a novel and nuanced perspective on the molecular foundation of learning and memory regulation. These insights open avenues for the development of targeted interventions to treat conditions that impact cognitive function, including SD.
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Disfunción Cognitiva , Isoquinolinas , Privación de Sueño , Sulfonamidas , Animales , Privación de Sueño/tratamiento farmacológico , Pez Cebra/metabolismo , Cafeína/farmacología , Rolipram , Acetilglucosamina/metabolismo , Procesamiento Proteico-Postraduccional , Cognición , Disfunción Cognitiva/tratamiento farmacológico , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismoRESUMEN
Dominant GNAO1 mutations cause an emerging group of childhood-onset neurological disorders characterized by developmental delay, intellectual disability, movement disorders, drug-resistant seizures and neurological deterioration. GNAO1 encodes the α-subunit of an inhibitory GTP/GDP-binding protein regulating ion channel activity and neurotransmitter release. The pathogenic mechanisms underlying GNAO1-related disorders remain largely elusive and there are no effective therapies. Here, we assessed the functional impact of two disease-causing variants associated with distinct clinical features, c.139A > G (p.S47G) and c.662C > A (p.A221D), using Caenorhabditis elegans as a model organism. The c.139A > G change was introduced into the orthologous position of the C. elegans gene via CRISPR/Cas9, whereas a knock-in strain carrying the p.A221D variant was already available. Like null mutants, homozygous knock-in animals showed increased egg laying and were hypersensitive to aldicarb, an inhibitor of acetylcholinesterase, suggesting excessive neurotransmitter release by different classes of motor neurons. Automated analysis of C. elegans locomotion indicated that goa-1 mutants move faster than control animals, with more frequent body bends and a higher reversal rate and display uncoordinated locomotion. Phenotypic profiling of heterozygous animals revealed a strong hypomorphic effect of both variants, with a partial dominant-negative activity for the p.A221D allele. Finally, caffeine was shown to rescue aberrant motor function in C. elegans harboring the goa-1 variants; this effect is mainly exerted through adenosine receptor antagonism. Overall, our findings establish a suitable platform for drug discovery, which may assist in accelerating the development of new therapies for this devastating condition, and highlight the potential role of caffeine in controlling GNAO1-related dyskinesia.
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Proteínas de Caenorhabditis elegans , Discinesias , Acetilcolinesterasa/metabolismo , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Cafeína/farmacología , Evaluación Preclínica de Medicamentos , Discinesias/tratamiento farmacológico , Discinesias/genética , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/farmacología , Proteínas de Unión al GTP/genética , Mutación , Neurotransmisores/metabolismoRESUMEN
PURPOSE OF REVIEW: Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management. RECENT FINDINGS: Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy. SUMMARY: There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.
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Cafeína , Estimulantes del Sistema Nervioso Central , Cafeína/uso terapéutico , Cafeína/farmacología , Cafeína/administración & dosificación , Humanos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Trastornos de Cefalalgia/tratamiento farmacológico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/metabolismoRESUMEN
Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca2+ uniporter (MCU) enhance Ca2+-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2) Female VSMCs have lower cytosolic Ca2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α1C (CaV1.2), Na+-K+-2Cl- symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5) Sex-dependent differences in Ca2+ signaling mean both sexes ought to be included in experimental design.
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Señalización del Calcio , Músculo Liso Vascular , Femenino , Masculino , Humanos , Señalización del Calcio/fisiología , Músculo Liso Vascular/metabolismo , Calcio/metabolismo , Andrógenos/metabolismo , Estrógenos/metabolismo , Caracteres Sexuales , Células Endoteliales/metabolismo , Cafeína/farmacología , Miocitos del Músculo Liso/metabolismoRESUMEN
Caffeine, a widely consumed stimulant, is known for its effects on alertness and fatigue reduction by blockade of adenosine receptors. While it holds therapeutic potential, its diverse impacts pose risks, particularly in early development. This study explores the developmental effects of caffeine exposure using Caenorhabditis elegans (C. elegans) as a model organism. We investigated morphological and behavioral changes induced by caffeine exposure at the L1 stage and assessed their impact at the L4 stage, which roughly corresponds to human infancy and adolescence, respectively. Caffeine-exposed worms displayed increased body length, body bends, and pharyngeal pumping rates compared to control worms. These findings indicate heightened food-seeking behavior and greater food intake, leading to the observed morphological changes. While caffeine did not affect other locomotor behaviors, its stimulatory effect on growth and development highlights its significance. This study provides insights into the potential impact of early-life caffeine exposure on long-term health and development, offering a foundation for future research in vertebrates to uncover its implications on metabolism and other metrics of health.
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Proteínas de Caenorhabditis elegans , Cafeína , Animales , Humanos , Cafeína/farmacología , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Receptores Purinérgicos P1RESUMEN
PURPOSE: To demonstrate hyperpolarization of 15N-caffeine and report exploratory findings as a potential probe of liver function and perfusion. METHODS: An amorphous formulation of [1,3-15N2]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid-state 15N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home-built RF surface coils. 15N signal decay constants were estimated in H2O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B0, and in the presence of albumin to assess the impact of protein binding. RESULTS: Polarization levels of 3.5% and aqueous T1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15N-MR spectra of the liver region, even with metabolic stimulation by ß $$ \beta $$ -naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent. CONCLUSION: These results establish the feasibility of hyperpolarization of hyperpolarized 15N-caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.
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Cafeína , Hígado , Isótopos de Nitrógeno , Cafeína/farmacología , Cafeína/química , Animales , Ratas , Hígado/diagnóstico por imagen , Hígado/metabolismo , Masculino , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Ratas Sprague-Dawley , Espectroscopía de Resonancia Magnética , Pruebas de Función HepáticaRESUMEN
PURPOSE: Abnormalities in cerebral veins are a common finding in many neurological diseases, yet there is a scarcity of MRI techniques to assess venous hemodynamic function. The present study aims to develop a noncontrast technique to measure a novel blood flow circulatory measure, venous transit time (VTT), which denotes the time it takes for water to travel from capillary to major veins. METHODS: The proposed sequence, venous transit time imaging by changes in T1 relaxation (VICTR), is based on the notion that as water molecules transition from the tissue into the veins, they undergo a change in T1 relaxation time. The validity of the measured VTT was tested by studying the VTT along the anatomically known flow trajectory of venous vessels as well as using a physiological vasoconstrictive challenge of caffeine ingestion. Finally, we compared the VTT measured with VICTR MRI to a bolus-tracking method using gadolinium-based contrast agent. RESULTS: VTT was measured to be 3116.3 ± 326.0 ms in the posterior superior sagittal sinus (SSS), which was significantly longer than 2865.0 ± 390.8 ms at the anterior superior sagittal sinus (p = 0.004). The test-retest assessment showed an interclass correlation coefficient of 0.964. VTT was significantly increased by 513.8 ± 239.3 ms after caffeine ingestion (p < 0.001). VTT measured with VICTR MRI revealed a strong correlation (R = 0.84, p = 0.002) with that measured with the contrast-based approach. VTT was found inversely correlated to cerebral blood flow and venous oxygenation across individuals. CONCLUSION: A noncontrast MRI technique, VICTR MRI, was developed to measure the VTT of the brain.
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Venas Cerebrales , Imagen por Resonancia Magnética , Humanos , Masculino , Adulto , Femenino , Velocidad del Flujo Sanguíneo/fisiología , Venas Cerebrales/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Circulación Cerebrovascular/fisiología , Reproducibilidad de los Resultados , Cafeína/farmacología , Medios de Contraste , Adulto Joven , Procesamiento de Imagen Asistido por Computador/métodos , Hemodinámica , Angiografía por Resonancia Magnética/métodosRESUMEN
Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20 years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long-term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET-1, ICAM-1, VCAM-1, and E-selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM-1. Expression of PDGF-BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT-PCR and western blot. Intracellular Ca2+ density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET-1, ICAM-1, VCAM-1, and E-selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM-1 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF-BB was suppressed by CSB. Intracellular Ca2+ intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.
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Selectina E , Molécula 1 de Adhesión Intercelular , Humanos , Células Endoteliales de la Vena Umbilical Humana , Células Cultivadas , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Selectina E/metabolismo , Benzoato de Sodio/metabolismo , Benzoato de Sodio/farmacología , Becaplermina/farmacología , Cafeína/metabolismo , Cafeína/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismoRESUMEN
Preclinical human skin ageing research has been limited by the paucity of instructive and clinically relevant models. In this pilot study, we report that healthy human skin of different age groups undergoes extremely accelerated ageing within only 3 days, if organ-cultured in a defined serum-free medium. Quantitative (immuno-)histomorphometry documented this unexpected ex vivo phenotype on the basis of ageing-associated biomarkers: the epidermis showed significantly reduced rete ridges and keratinocyte proliferation, sirtuin-1, MTCO1 and collagen 17a1 protein levels; this contrasted with significantly increased expression of the DNA-damage marker, γH2A.X. In the dermis, collagen 1 and 3 and hyaluronic acid content were significantly reduced compared to Day 0 skin. qRT-PCR of whole skin RNA extracts also showed up-regulated mRNA levels of several (inflamm-) ageing biomarkers (MMP-1, -2, -3, -9; IL6, IL8, CXCL10 and CDKN1). Caffeine, a methylxanthine with recognized anti-ageing properties, counteracted the dermal collagen 1 and 3 reduction, the epidermal accumulation of γH2A.X, and the up-regulation of CXCL10, IL6, IL8, MMP2 and CDKN1. Finally, we present novel anti-ageing effects of topical 2,5-dimethylpyrazine, a natural pheromone TRPM5 ion channel activator. Thus, this instructive, clinically relevant "speed-ageing" assay provides a simple, but powerful new research tool for dissecting skin ageing and rejuvenation, and is well-suited to identify novel anti-ageing actives directly in the human target organ.
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Cafeína , Pirazinas , Envejecimiento de la Piel , Humanos , Recién Nacido , Cafeína/farmacología , Senoterapéuticos , Técnicas de Cultivo de Órganos , Proyectos Piloto , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Piel/metabolismo , Envejecimiento , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Biomarcadores/metabolismoRESUMEN
INTRODUCTION/AIMS: The transcranial magnetic stimulation tests of short-interval intracortical inhibition (SICI) by both conventional amplitude measurements (A-SICI) and threshold-tracking (T-SICI) are important methods to investigate intracortical inhibitory circuits, and T-SICI has been proposed to aid the diagnosis of amyotrophic lateral sclerosis. Beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability. The aim of this study was to determine whether these SICI tests are affected by caffeine. METHODS: Twenty-four healthy subjects (13 females, 11 males, aged from 19 to 31, mean: 26.2 ± 2.4 years) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo ingested as chewing gum. A-SICI and T-SICI, using parallel tracking (T-SICIp), were performed before and after chewing gum. RESULTS: There was no significant change in SICI parameters after placebo in A-SICI (p > .10) or T-SICIp (p > .30), and no significant effect of caffeine was found on A-SICI (p > .10) or T-SICIp (p > .50) for any of the interstimulus intervals. DISCUSSION: There is no need for caffeine abstention before measurements of SICI by either the T-SICI or A-SICI measurements.
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Excitabilidad Cortical , Corteza Motora , Femenino , Humanos , Masculino , Cafeína/farmacología , Goma de Mascar , Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Inhibición Neural/fisiología , Estimulación Magnética Transcraneal/métodos , Adulto Joven , AdultoRESUMEN
Caffeine is a widely used drug that broadly affects human cognition and brain function. Caffeine acts as an antagonist to the adenosine receptors in the brain. Previous anecdotal reports have also linked caffeine intake with changes in pupil diameter. By modifying the retinal irradiance, pupil diameter modulates all ocular light exposure relevant for visual (i.e., perception, detection and discrimination of visual stimuli) and non-visual (i.e., circadian) functions. To date, the extent of the influence of caffeine on pupillary outcomes, including pupil diameter, has not been examined in a systematic review. We implemented a systematic review laid out in a pre-registered protocol following PRISMA-P guidelines. We only included original research articles written in English reporting studies with human participants, in which caffeine was administered, and pupil diameter was measured using objective methods. Using broad search strategies, we consulted various databases (PsycINFO, Medline, Embase, Cochrane Library, bioRxiv and medRxiv) and used the Covidence platform to screen, review and extract data from studies. After importing studies identified through database search (n = 517 imported, n = 46 duplicates), we screened the title and abstracts (n = 471), finding 14 studies meeting our eligibility criteria. After full-text review, we excluded seven studies, leaving only a very modest number of included studies (n = 7). Extraction of information revealed that the existing literature on the effect of caffeine on pupil parameters is very heterogeneous, differing in pupil assessment methods, time of day of caffeine administration, dose, and protocol timing and design. The evidence available in the literature does not provide consistent results but studies rated as valid by quality assessment suggest a small effect of caffeine on pupil parameters. We summarize the numeric results as both differences in absolute pupil diameter and in terms of effect sizes. More studies are needed using modern pupil assessment methods, robust study design, and caffeine dose-response methodology.
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Cafeína , Pupila , Humanos , Cafeína/farmacología , Cafeína/administración & dosificación , Pupila/efectos de los fármacos , Pupila/fisiología , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/administración & dosificaciónRESUMEN
A variety of observational studies have demonstrated that coffee, likely acting through caffeine, improves health outcomes in patients with chronic liver disease. The primary pharmacologic role of caffeine is to act as an inhibitor of adenosine receptors. Because key liver cells express adenosine receptors linked to liver injury, regeneration, and fibrosis, it is plausible that the biological effects of coffee are explained by effects of caffeine on adenosinergic signaling in the liver. This review is designed to help the reader make sense of that hypothesis, highlighting key observations in the literature that support or dispute it.
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Cafeína , Café , Humanos , Cafeína/farmacología , Cirrosis Hepática , Adenosina/farmacología , Hígado , Receptores Purinérgicos P1RESUMEN
Fatigue is a non-motor symptom of Parkinson's disease (PD). Adenosine 2A receptor (A2AR) and compromised dopamine neurotransmission are linked to fatigue. Studies demonstrate that A2AR antagonism potentiates dopamine transmission via dopamine receptor D2 (D2R). However, the heterodimer form of A2AR-D2R in the striatum prompted questions about the therapeutic targets for PD patients. This study investigates the effects of caffeine (A2AR non-selective antagonist) plus haloperidol (D2R selective antagonist) treatment in the fatigue induced by the reserpine model of PD. Reserpinized mice showed impaired motor control in the open field test (p < 0.05) and fatigue in the grip strength meter test (p < 0.05). L-DOPA and caffeine plus haloperidol similarly increased motor control (p < 0.05) and mitigated fatigue (p < 0.05). Our results support the A2AR-D2R heterodimer participation in the central fatigue of PD, and highlight the potential of A2AR-D2R antagonism in the management of PD.
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Dopamina , Enfermedad de Parkinson , Humanos , Ratones , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Cafeína/farmacología , Haloperidol/farmacología , Receptores de Dopamina D2 , Estudios Prospectivos , Modelos Teóricos , Receptor de Adenosina A2ARESUMEN
Exposure to chronic caffeine during adolescence has been shown to produce decreased anxiety-like behaviors in rats as well as decreased immobility in the forced swim test (FST) suggesting an antidepressant-like effect. The effects of chronic caffeine on anxiety, however, have been found to be test-dependent and sexually dimorphic. In addition, decreased immobility in the FST has been argued to reflect a shift toward active coping behavior as opposed to an antidepressant-like effect. In order to further characterize the effects of adolescent caffeine exposure, the present experiment assessed the effects of caffeine on marble burying behavior in a two-zone marble burying task. There was no difference in the amount of time rats spent in the two zones failing to support a shift in coping strategy. Caffeine-exposed rats spent less time engaged in marble burying activity and buried slightly fewer marbles, suggesting an anxiolytic effect of caffeine. In addition, caffeine treated rats spent less time engaged in nondirected burying and slightly more time actively engaging with the marbles; however, these effects appeared to be sexually dimorphic as they were driven by larger changes in the females. Overall, these results support an anxiolytic effect of adolescent caffeine, with female behavior appearing to be more affected by caffeine than males.
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Ansiedad , Conducta Animal , Cafeína , Animales , Cafeína/farmacología , Cafeína/administración & dosificación , Masculino , Ansiedad/tratamiento farmacológico , Femenino , Ratas , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Ansiolíticos/farmacología , Ratas Sprague-Dawley , Actividad Motora/efectos de los fármacosRESUMEN
Higher coffee consumption has been associated with reduced dementia risk, yet with inconsistencies across studies. CYP1A2 polymorphisms, which affects caffeine metabolism, may modulate the association between coffee and the risk of dementia and Alzheimer's disease (AD). We included 5964 participants of the Three-City Study (mean age 74 years-old), free of dementia at baseline when they reported their daily coffee consumption, with available genome-wide genotyping and followed for dementia over a median of 9.0 (range 0.8-18.7) years. In Cox proportional-hazards models, the relationship between coffee consumption and dementia risk was modified by CYP1A2 polymorphism at rs762551 (p for interaction = 0.034). In multivariable-adjusted models, coffee intake was linearly associated with a decreased risk of dementia among carriers of the C allele only ("slower caffeine metabolizers"; HR for 1-cup increased [95% CI] 0.90 [0.83-0.97]), while in non-carriers ("faster caffeine metabolizers"), there was no significant association but a J-shaped trend toward a decrease in dementia risk up to 3 cups/day and increased risk beyond. Thus, compared to null intake, drinking ≥ 4 cups of coffee daily was associated with a reduced dementia risk in slower but not faster metabolizers (HR [95% CI] for ≥ 4 vs. 0 cup/day = 0.45 [0.25-0.80] and 1.32 [0.89-1.96], respectively). Results were similar when studying AD and another CYP1A2 candidate polymorphism (rs2472304), but no interaction was found with CYP1A2 rs2472297 or rs2470893. In this cohort, a linear association of coffee intake to lower dementia risk was apparent only among carriers of CYP1A2 polymorphisms predisposing to slower caffeine metabolism.
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Café , Citocromo P-450 CYP1A2 , Demencia , Anciano , Humanos , Cafeína/farmacología , Cafeína/uso terapéutico , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Demencia/epidemiología , Demencia/genética , Factores de RiesgoRESUMEN
Chemical repellents play a crucial role in personal protection, serving as essential elements in reducing the transmission of vector-borne diseases. A biorational perspective that extends beyond the olfactory system as the classical target may be a promising direction to move. The taste system provides reliable information regarding food quality, helping animals to discriminate between nutritious and potentially harmful food sources, often associated with a bitter taste. Understanding how bitter compounds affect feeding in blood-sucking insects could unveil novel molecules with the potential to reduce biting and feeding. Here, we investigated the impact of two naturally occurring bitter compounds, caffeine and quinine, on the feeding decisions in female Aedes aegypti mosquitoes at two distinctive phases: (1) when the mosquito explores the biting substrate using external taste sensors and (2) when the mosquito takes a sip of food and tastes it using internal taste receptors. We assessed the aversiveness of bitter compounds through both an artificial feeding condition (artificial feeder test) and a real host (arm-in-cage test). Our findings revealed different sensitivities in the external and internal sensory pathways responsible for detecting bitter taste in Ae. aegypti. Internal detectors exhibited responsiveness to lower doses compared to the external sensors. Quinine exerted a more pronounced negative impact on biting and feeding activity than caffeine. The implications of our findings are discussed in the context of mosquito food recognition and the potential practical implications for personal protection.
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Aedes , Cafeína , Conducta Alimentaria , Quinina , Gusto , Animales , Femenino , Cafeína/farmacología , Aedes/fisiología , Conducta Alimentaria/efectos de los fármacosRESUMEN
OBJECTIVES: "WKUP GT", a low caffeine beverage consisting of carob, Guarana, Green Tea and Elderberry extracts was studied on attention and cognitive functions post-lunch in a pilot randomized double blind placebo controlled trial. METHODS: Thirty healthy volunteers were included in a crossover design trial, presenting five beverages randomly assigned to the following groups: placebo, "WKUP GT" (single, double or triple doses), or "caffeine" as an active control. Hemodynamic measurements were assessed as safety outcomes. The Cambridge Neuropsychological Test Automated Battery (CANTAB), was used to evaluate the patients when beverages were consumed 30 and 120 min after lunch (respectively Delta30 and Delta120 considering baseline). RESULTS: Drinking "caffeine" or "WKUP GT" after lunch, showed significant improvement (p < 0.05) in rapid visual information processing compared to placebo (Delta120 of "caffeine", "WKUP" single and double). In addition, improvement in Multitasking Test (Delta30 for "WKUP" double, and Delta120 for "caffeine" and "WKUP" triple compared to placebo) was observed. "WKUP" triple also showed significant improvement for "memory" when compared to placebo (Delta120). Compared to "caffeine", WKUP GT did not increase systolic blood pressure. CONCLUSION: "WKUP GT" showed improvements for attention, memory, psychomotor and executive function tasks after lunch without increase in pulse rate.
Asunto(s)
Atención , Cafeína , Cognición , Estudios Cruzados , Almuerzo , Extractos Vegetales , Humanos , Método Doble Ciego , Masculino , Adulto , Atención/efectos de los fármacos , Cognición/efectos de los fármacos , Femenino , Cafeína/administración & dosificación , Cafeína/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Adulto Joven , Pruebas Neuropsicológicas , Voluntarios Sanos , Bebidas , Proyectos PilotoRESUMEN
Alzheimer's disease is a detrimental neurological disorder caused by the formation of amyloid fibrils due to the aggregation of amyloid-ß peptide. The primary therapeutic approaches for treating Alzheimer's disease are targeted to prevent this amyloid fibril formation using potential inhibitor molecules. The discovery of such inhibitor molecules poses a formidable challenge to the design of anti-amyloid drugs. This study investigates the effect of caffeine on dimer formation of the full-length amyloid-ß using a combined approach of all-atom, explicit water molecular dynamics simulations and the three-dimensional reference interaction site model theory. The change in the hydration free energy of amyloid-ß dimer, with and without the inhibitor molecules, is calculated with respect to the monomeric amyloid-ß, where the hydration free energy is decomposed into energetic and entropic components, respectively. Dimerization is accompanied by a positive change in the partial molar volume. Dimer formation is spontaneous, which implies a decrease in the hydration free energy. However, a reverse trend is observed for the dimer with inhibitor molecules. It is observed that the negatively charged residues primarily contribute for the formation of the amyloid-ß dimer. A residue-wise decomposition reveals that hydration/dehydration of the side-chain atoms of the charged amino acid residues primarily contribute to dimerization.