Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients

Introduction Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. Methods Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. Results Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells’ membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. Conclusion Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients. (AU)

Ghrelin prevents lethality in a rat endotoxemic model through central effects on the vagal pathway and adenosine A2B signaling

Accumulating evidence suggest that ghrelin plays a role as an antiseptic peptide. The present study aimed to clarify whether the brain may be implicated ghrelin’s antiseptic action. We examined the effect of brain ghrelin on survival in a novel endotoxemic model achieved by treating rats with lipopolysaccharide (LPS) and colchicine. The observation of survival stopped three days after chemicals’ injection or at death. Intracisternal ghrelin dose-dependently reduced lethality in the endotoxemic model; meanwhile, neither intraperitoneal injection of ghrelin nor intracisternal des-acyl-ghrelin injection affected the mortality rate. The brain ghrelin-induced lethality reduction was significantly blocked by surgical vagotomy. Moreover, intracisternal injection of a ghrelin receptor antagonist blocked the improved survival achieved by intracisternal ghrelin injection or intravenous 2-deoxy-d-glucose administration. Intracisternal injection of an adenosine A2B receptor agonist reduced the lethality and the ghrelin-induced improvement of survival was blocked by adenosine A2B receptor antagonist. I addition, intracisternal ghrelin significantly blocked the colonic hyperpermeability produced by LPS and colchicine. These results suggest that ghrelin acts centrally to reduce endotoxemic lethality. Accordingly, activation of the vagal pathway and adenosine A2B receptors in the brain may be implicated in the ghrelin-induced increased survival. Since the efferent vagus nerve mediates anti-inflammatory mechanisms, we speculate that the vagal cholinergic anti-inflammatory pathway is implicated in the decreased septic lethality caused by brain ghrelin. (AU)

Physio-pathological effects of m6A modification and its potential contribution to melanoma

Methylation of N6-adenosine (m6A) is the most prevalent internal RNA modification and is especially common among the messenger RNAs. These m6A modifications regulate splicing, translocation, stability and translation of RNA through dynamic and reversible interactions with m6A-binding proteins, namely the writers, erasers and readers. RNA methyltransferases catalyze the m6A modifications, while demethylases reverse this methylation. Deregulation of the m6A modification process has been implicated in human carcinogenesis, including melanoma—which carries one of the highest mutant rates. In this review, we provide an up-to-date summary of m6A regulation and its biological impacts on normal and cancer cells, with emphasis on the deregulation of m6A modification and m6A regulators in melanoma. In addition, we highlight the prospective potential of exploiting m6A modification in the treatment of melanoma and non-cancer diseases. (AU)

Remdesivir, la esperanza antiviral frente al SARS-CoV-2 / Remdesivir, the antiviral hope against SARS-CoV-2

El 31 de diciembre de 2019 se detectó en la ciudad de Wuhan (China) un brote neumonía causado por un nuevo coronavirus (SARS-CoV-2). Debido a la elevada capacidad de difusión e infección humana se ha convertido en una nueva pandemia zoónotica. La ausencia de una vacuna ha determinado la búsqueda de fármacos antivirales con capacidad para inhibir la replicación del nuevo virus. De entre ellos, remdesivir, un análogode la adenosina, es el que parece tener un futuro más prometedor. Este fármaco ha mostrado in vitro y en animales una elevada capacidad para bloquear la infección y replicación viralcon unas concentraciones alcanzables en el plasma humano.Aunque todos los estudios se han realizado con el SARS-CoV y el MERS-CoV, parece que por analogía virológica y funcional, remdesivir es de los pocos antivirales con demostrada eficacia. Sin embargo, se precisan estudios y ensayos clínicos en humanospara conocer el resultado de su aplicación en los mismos

On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China). Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic. The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus. Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future. This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma. Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy.However, studies and clinical trials in humans are required to know the result of their application in them

Adenosina frente a antagonistas de los canales del calcio intravenosos en la taquicardia supraventricular / Adenosine versus intravenous calcium channel antagonists for supraventricular tachycardia

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ECG de agosto de 2018 / ECG, August 2018

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Seguridad y eficacia clínica con prasugrel y ticagrelor en síndrome coronario agudo. Resultados de un registro multicéntrico en el mundo real / Safety and efficacy of prasugrel and ticagrelor in acute coronary syndrome. Results of a 'real world' multicenter registry

Introducción y objetivos: La incorporación de los nuevos antiagregantes (NAA) prasugrel y ticagrelor a la práctica clínica está siendo errática. Los datos del mundo real todavía son escasos. Se analizó la tendencia temporal de uso de NAA, su seguridad y eficacia clínica frente a clopidogrel en una cohorte actual de pacientes con síndrome coronario agudo (SCA). Métodos: Estudio multicéntrico observacional retrospectivo de pacientes con SCA ingresados en unidades coronarias incluidos de forma prospectiva en el registro ARIAM-Andalucía entre 2013 y 2015. Se analizaron las tasas de eventos cardiovasculares mayores y hemorragias intrahospitalarias mediante modelos de propensión y regresión multivariante. Resultados: Se incluyó a 2.906 pacientes: el 55% recibió clopidogrel y el 45% NAA. Un 60% presentó SCA con elevación del segmento ST. El uso de NAA se incrementó de forma significativa a lo largo del estudio. El grupo de clopidogrel presentó mayor edad y comorbilidad. La tasa de mortalidad total, el ictus isquémico y la trombosis del stent fue menor con NAA (2 frente a 9%, p < 0,0001; 0,1 frente a 0,5%, p = 0,025; 0,07 frente a 0,5%, p = 0,025, respectivamente). No hubo diferencias en la tasa de hemorragias totales (3 frente a 4%; p = NS). Tras el análisis de propensión, se mantuvo la reducción de mortalidad con NAA (OR = 0,37; IC95%, 0,13-0,60; p< 0,0001) sin incremento en las hemorragias totales (OR = 1,07; IC95%, 0,18-2,37; p = 0,094). Conclusiones: En el mundo real, los NAA se usan de forma selectiva en sujetos más jóvenes y con menor comorbilidad. Su uso se asocia con una reducción de eventos cardiacos mayores, incluida mortalidad, sin aumentar las hemorragias en comparación con clopidogrel (AU)

Introduction and objectives: The incorporation of the new antiplatelet agents (NAA) prasugrel and ticagrelor into routine clinical practice is irregular and data from the 'real world' remain scarce. We aimed to assess the time trend of NAA use and the clinical safety and efficacy of these drugs compared with those of clopidogrel in a contemporary cohort of patients with acute coronary syndromes (ACS). Methods: A multicenter retrospective observational study was conducted in patients with ACS admitted to coronary care units and prospectively included in the ARIAM-Andalusia registry between 2013 and 2015. In-hospital rates of major cardiovascular events and bleeding with NAA vs clopidogrel were analyzed using propensity score matching and multivariate regression models. Results: The study included 2906 patients: 55% received clopidogrel and 45% NAA. A total of 60% had ST-segment elevation ACS. Use of NAA significantly increased throughout the study. Patients receiving clopidogrel were older and were more likely to have comorbidities. Total mortality, ischemic stroke, and stent thrombosis were lower with NAA (2% vs 9%, P < .0001; 0.1% vs 0.5%, P = .025; 0.07% vs 0.5%, P = .025, respectively). There were no differences in the rate of total bleeding (3% vs 4%; P = NS). After propensity score matching, the mortality reduction with NAA persisted (OR, 0.37; 95%CI, 0.13 to 0.60; P < .0001) with no increase in total bleeding (OR, 1.07; 95%CI, 0.18 to 2.37; P = .094). Conclusions: In a 'real world' setting, NAA are selectively used in younger patients with less comorbidity and are associated with a reduction in major cardiac events, including mortality, without increasing bleeding compared with clopidogrel (AU)

Cafeína y cefalea: consideraciones especiales / Caffeine and headache: specific remarks

La cafeína es la droga psicoestimulante más ampliamente utilizada en el mundo. El exagerado consumo de cafeína induce una serie de cambios biológicos y fisiológicos de forma aguda y crónica, que se pueden traducir en déficit cognitivo, depresión, fatiga, insomnio, cambios cardiovasculares y cefalea. El consumo crónico de cafeína promueve un estado pronociceptivo y de hiperexcitabilidad cortical que puede exacerbar una cefalea primaria o desencadenar una cefalea por uso excesivo de analgésicos. El objetivo de la revisión es profundizar en los aspectos fisiológicos de la cafeína y su relación con la cefalea (AU)

Caffeine is the most widely used psychostimulant worldwide. Excessive caffeine consumption induces a series of both acute and chronic biological and physiological changes that may give rise to cognitive decline, depression, fatigue, insomnia, cardiovascular changes, and headache. Chronic consumption of caffeine promotes a pro-nociceptive state of cortical hyperexcitability that can intensify a primary headache or trigger a headache due to excessive analgesic use. This review offers an in-depth analysis of the physiological mechanisms of caffeine and its relationship with headache (AU)

Rol de los receptores de adenosina en la interacción adipocito-macrófago durante la obesidad / Role of adenosine receptors in the adipocyte-macrophage interaction during obesity

La inflamación generada en el tejido adiposo o lipoinflamación, puede contribuir al desarrollo de la resistencia a la insulina. Los mecanismos asociados a la lipoinflamación están relacionados con la función de los adipocitos y los macrófagos presentes en el tejido adiposo. En este contexto, el nivel del nucleósido adenosina está aumentado en individuos con obesidad. Las causas o consecuencias de este aumento no se conocen. Aunque, adenosina al activar a sus receptores (A1, A2A, A2B y A3) es capaz de modular diferencialmente la función de adipocitos y macrófagos, con el fin de evitar la reducción de la sensibilidad a la insulina y generar un estado antiinflamatorio en el individuo con obesidad. En esta revisión proponemos que adenosina podría ser un elemento clave en el desarrollo de nuevas estrategias para el control de la lipoinflamación y homeostasis metabólica a través de la regulación del diálogo adipocito-macrófago (AU)

Lipoinflamation is the inflammation generated in the adipose tissue. It can contribute to the development of insulin resistance. The lipoinflammation-associated mechanisms are related to the function of adipocytes and macrophages present in the adipose tissue. In this regard, the level of nucleoside adenosine is increased in individuals with obesity. Causes or consequences of this increase are unknown. Although, adenosine activating its receptors (A1, A2A, A2B and A3) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialogue (AU)

Understanding pacing postconditioning-mediated cardiac protection: a role of oxidative stress and a synergistic effect of adenosine

We and others have demonstrated a protective role for pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury in the heart; however, the underlying mechanisms behind these protective effects are not completely understood. In this study, we wanted to further characterize PPC-mediated cardiac protection, specifically identify optimal pacing sites; examine the role of oxidative stress; and test the existence of a potential synergistic effect between PPC and adenosine. Isolated rat hearts were subjected to coronary occlusion followed by reperfusion. PPC involved three, 30 s, episodes of alternating left ventricular (LV) and right atrial (RA) pacing. Multiple pacing protocols with different pacing electrode locations were used. To test the involvement of oxidative stress, target-specific agonists or antagonists were infused at the beginning of reperfusion. Hemodynamic data were digitally recorded, and cardiac enzymes, oxidant, and antioxidant status were chemically measured. Pacing at the LV or RV but not at the heart apex or base significantly (P < 0.001) protected against ischemia-reperfusion injury. PPC-mediated protection was completely abrogated in the presence of reactive oxygen species (ROS) scavenger, ebselen; peroxynitrite (ONOO-) scavenger, uric acid; and nitric oxide synthase inhibitor, L-NAME. Nitric oxide (NO) donor, snap, however significantly (P < 0.05) protected the heart against I/R injury in the absence of PPC. The protective effects of PPC were significantly improved by adenosine. PPC-stimulated protection can be achieved by alternating LV and RA pacing applied at the beginning of reperfusion. NO, ROS, and the product of their interaction ONOO− play a significant role in PPC-induced cardiac protection. Finally, the protective effects of PPC can be synergized with adenosine (AU)

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Taquicardia paroxística supraventricular (TPSV): dos presentaciones. Dos aproximaciones / Paroxysmal supraventricular tachycardia (PSVT): two presentations. Two approaches

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Taquicardia supraventricular tipo reciprocante AV incesante y refractaria a cardioversión (AU) / Incesant AV reciprocating supraventricular tachycardia refractory to cardioversion

La taquicardia paroxística supraventricular (TPSV) es la causa más frecuente de emergencia cardiovascular por arritmias en el niño. A pesar de que la mayoría se controlan gracias a las maniobras vagales o el tratamiento farmacológico de primera línea, ante inestabilidad hemodinámica requiere cardioversión sincronizada y estabilización en unidad de cuidados intensivos (AU)

Paroxysmal supraventricular tachycardia (SVT) is the most common cause of emergency cardiovascular by arrhythmias in children. Although most of them are controlled by vagal maneuvers or first—line drug treatment, hemodynamic inestability requires synchronized cardioversion and stabilization in intensive care unit (AU)

Dysregulated innate lymphocytes in patients with primary antibody deficiency treated with intravenous immunoglobulin

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Efectos cardioprotectores del ticagrelor / The cardioprotective effects of ticagrelor

El desarrollo de los inhibidores del receptor plaquetario P2Y12 ha sido fundamental para el tratamiento de los pacientes con síndrome coronario agudo. En los últimos años, múltiples evidencias experimentales y clínicas sustentan que los inhibidores del receptor P2Y12 ejercen efectos pleotrópicos más allá de sus propiedades antiagregantes plaquetarias. La explicación potencial es que, aparte de en las plaquetas, el receptor P2Y12 también se encuentra en una amplia variedad de células y puede modular la respuesta inflamatoria, la función endotelial, el tono vascular y el daño por isquemia/reperfusión. Hay estudios en distintos modelos animales y algún ensayo clínico que han demostrado el potencial cardioprotector de la administración de inhibidores del receptor P2Y12 mediante un mecanismo asociado con la activación de vías de señalización implicadas en la protección miocárdica endógena (p. ej., poscondicionamiento isquémico). Sin embargo, a diferencia de los demás inhibidores del receptor P2Y12, el ticagrelor ha mostrado una vía adicional de cardioprotección a través de mecanismos relacionados con una mayor biodisponibilidad de adenosina, una molécula producida principalmente por las células endoteliales en respuesta a isquemia y con múltiples efectos cardiovasculares beneficiosos. En este capítulo se revisan brevemente las diferencias entre los mecanismos de acción de los distintos inhibidores del receptor P2Y12 y se ahonda en los efectos cardioprotectores atribuidos a estos más allá de su efecto antiagregante, en especial los asociados con la adenosina y derivados únicamente del tratamiento con ticagrelor (AU)

The development of platelet P2Y12 receptor inhibitors has made a crucial difference to the treatment of patients with acute coronary syndrome. In recent years, extensive evidence from both laboratory and clinical studies has established that platelet P2Y12 receptor inhibitors have pleiotropic effects as well as antiplatelet properties. One possible explanation is that the P2Y12 receptor is found on a wide variety of cells in addition to platelets and could, therefore, modulate the inflammatory response, endothelial function, vascular tone, and ischemia-reperfusion injury. Studies in various animal models and a number of clinical trials have demonstrated that the cardioprotective potential of platelet P2Y12 receptor inhibitors is mediated by a mechanism involving the activation of signaling pathways associated with endogenous myocardial protection (e.g. ischemic postconditioning). However, ticagrelor, unlike other P2Y12 receptor inhibitors, has been shown to influence an additional cardioprotective pathway involving mechanisms associated with the increased bioavailability of adenosine, a molecule that is mainly produced by endothelial cells in response to ischemia and which has several beneficial cardiovascular effects. This article briefly reviews the different mechanisms of action of various platelet P2Y12 receptor inhibitors and explores the cardioprotective effects exerted by these compounds in addition to their antiplatelet actions, particularly those effects associated with adenosine, which are uniquely induced by treatment with ticagrelor (AU)

Lactant de dos mesos amb taquicárdia de complex QRS estret / No disponible

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Mechanisms of anaphylaxis beyond IgE

Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators derived from mast cells and basophils. Food allergens are the main triggers of anaphylaxis, accounting for 33%-56% of all cases and up to 81% of cases of anaphylaxis in children. Human anaphylaxis is generally thought to be mediated by IgE, with mast cells and basophils as key players, although alternative mechanisms have been proposed. Neutrophils and macrophages have also been implicated in anaphylactic reactions, as have IgG-dependent, complement, and contact system activation. Not all allergic reactions are anaphylactic, and the presence of the so-called accompanying factors (cofactors or augmenting factors) may explain why some conditions lead to anaphylaxis, while in other cases the allergen elicits a milder reaction or is even tolerated. In the presence of these factors, allergic reactions may be induced at lower doses of allergen or become more severe. Cofactors are reported to be relevant in up to 30% of anaphylactic episodes. Nonsteroidal anti-inflammatory drugs and exercise are the best-documented cofactors, although estrogens, angiotensin-converting enzyme inhibitors, β-blockers, lipid-lowering drugs, and alcohol have also been involved. The mechanisms underlying anaphylaxis are complex and involve several interrelated pathways. Some of these pathways may be key to the development of anaphylaxis, while others may only modulate the severity of the reaction. An understanding of predisposing and augmenting factors could lead to the development of new prophylactic and therapeutic approaches (AU)

La anafilaxia se describe como una reacción aguda, con afectación multisistémica que puede causar la muerte del individuo que la padece, y que es consecuencia de una liberación súbita de mediadores originados en mastocitos y basófilos. Los alérgenos alimentarios son los desencadenantes más frecuentemente relacionados con las reacciones anafilácticas, suponiendo entre un 33 y un 56% de todos los casos y hasta un 81% de las anafilaxias en niños. Se considera que las anafilaxias en humanos están mediadas a través de la IgE, y los mastocitos y basófilos juegan un papel principal. Sin embargo, se han descrito otros mecanismos alternativos. De este modo, otros tipos celulares se han implicado en las reacciones anafilácticas, como es el caso de los neutrófilos o los macrófagos. La activación del complemento o del sistema de contacto, así como mecanismos mediados a través de la IgG, también han sido descritos. No todas las reacciones alérgicas acaban siendo una anafilaxia, de modo que se ha postulado la existencia de factores acompañantes (cofactores o factores potenciadores) que explicarían porque en algunos casos los alérgenos no son capaces de inducir una reacción alérgica o inducen una reacción leve, mientras que en otros casos desencadenan reacciones graves. Los cofactores se consideran relevantes hasta en el 30% de los episodios anafilácticos. En presencia de esos cofactores, las reacciones alérgicas pueden desarrollarse con concentraciones inferiores de alérgeno o ser más grave que en ausencia de ellos. Los antinflamatorios no esteroideos (AINE) y el ejercicio físico son los cofactores mejor conocidos, aunque se han descrito muchos otros, como los estrógenos, los inhibidores del enzima convertidor de la angiotensina, los β-bloqueantes, los hipolipemiantes o el alcohol. Los mecanismos subyacentes en la anafilaxia son muy complejos y múltiples mecanismos parecen estar interrelacionados. Algunos de ellos pueden ser claves en el desarrollo de la anafilaxia, mientras que otros estarían únicamente modulando la gravedad de la reacción. La compresión de estos mecanismos es clave y permitirá el desarrollo de nuevas estrategias profilácticas y terapéuticas en la anafilaxia (AU)

Depresión del segmento ST durante la taquicardia supraventricular. ¿Se debe a la isquemia? / ST-segment depression during paroxysmal supraventricular tachycardia, is ischemia involved?

La aparición de alteraciones significativas de la repolarización durante episodios de taquicardia supraventricular no es un hecho infrecuente. A menudo, estos episodios cursan con dolor torácico, lo que puede hacer pensar en una enfermedad coronaria. Se presenta el caso de un paciente de 9 años de edad, tratado en nuestro centro por un episodio de taquicardia supraventricular y dolor torácico, con posterior depresión del segmento ST que no se normalizó hasta horas después del episodio. Se realiza una revisión de las taquicardias paroxísticas supraventriculares por vía accesoria y se discute el valor diagnóstico y la etiología de las alteraciones de la repolarización durante las taquicardias supraventriculares (AU)

Repolarization abnormalities during supraventricular tachycardias are not unusual. They are frequently accompanied by chest pain, this may lead to a false diagnosis of coronary ischemia. We present a 9-year-old child with an episode of supraventricular tachycardia, chest pain and pronounced ST-segment depression treated in our hospital. A review about paroxysmal atrioventricular re-entrant tachycardia is presented. Diagnostic value and aetiology of repolarization abnormalities during supraventricular tachycardias are discussed (AU)

Regulatory role of adenosine in insulin secretion from pancreatic Beta-cells—Action via adenosine A1 receptor and beyond

Under physiological conditions, insulin secretion from pancreatic beta-cells is tightly regulated by different factors, including nutrients, nervous system, and other hormones. Pancreatic beta-cells are also influenced by paracrine and autocrine interactions. The results of rodent studies indicate that adenosine is present within pancreatic islets and is implicated in the regulation of insulin secretion; however, effects depend on adenosine and glucose concentrations. Moreover, species differences in adenosine action were found. In rat islets, low adenosine was demonstrated to decrease glucose-induced insulin secretion and this effect is mediated via adenosine A1 receptor. In the presence of high adenosine concentrations, other mechanisms are activated and glucose-induced insulin secretion is increased. It is also well established that suppression of adenosine action increases insulin-secretory response of beta-cells to glucose. In mouse islets, low adenosine concentrations do not significantly affect insulin secretion. However, in the presence of higher adenosine concentrations, potentiation of glucose-induced insulin secretion was demonstrated. It is also known that upon stimulation of insulin secretion, both rat and mouse islets release ATP. In rat islets, ATP undergoes extracellular conversion to adenosine. However, mouse islets are unable to convert extracellularly ATP to adenosine and adenosine arises from intracellular ATP degradation

El regadenosón como nuevo agente de estrés para la adquisición de imágenes SPECT de perfusión miocárdica. Experiencia inicial en Holanda / Regadenoson as a new stress agent in myocardial perfusion imaging. Initial experience in The Netherlands

Objetivo. El regadenosón es un agonista selectivo para los receptores adenosínicos-2A recién aprobado para inducir estrés farmacológico con una sola inyección en bolo para la adquisición de imágenes SPECT de perfusión miocárdica (IPM). Material y Métodos. Se incluyeron 123 pacientes sucesivos referidos para IPM por sospecha de enfermedad arterial coronaria (EAC). A 66 pacientes se les hizo una prueba de estrés con regadenosón y a 57 con adenosina, ambas seguidas por SPECT de manera estándar. A los técnicos, médicos y los pacientes mismos se les pidió que reportaran sus experiencias mediante cuestionarios. Resultados. En comparación con la adenosina, el regadenosón no produjo ningún bloqueo auriculoventricular (frente al 10% tras adenosina), pero produjo una taquicardia menor y cambios de la presión arterial pequeños. Todos los síntomas tras el regadenosón fueron más leves y de duración más corta. Hubo menos pacientes que tenían síntomas graves tras el regadenosón (17% vs. 32%, p < 0,01). El efecto secundario reportado más frecuentemente fue la disnea, seguido por rubefacción y angina, pero todos estos efectos se resolvieron rápidamente. La puntuación global de los síntomas, que incluye tanto la severidad como la duración, fue significativamente más baja después del regadenosón que después de la adenosina (6,7 ± 6,3 vs. 10,0 ± 7,9, respectivamente, p < 0,01). Las imágenes SPECT fueron similares. El procedimiento con el regadenosón fue más rápido y práctico. Conclusión. El regadenosón es un nuevo agente de estrés conveniente para IPM con un perfil muy favorable para los pacientes y los departamentos de cardiología nuclear (AU)

Objective. Regadenoson is a recently approved selective adenosine-2A receptor agonist to induce pharmacological stress in myocardial perfusion imaging (MPI) procedures using a single bolus injection. Material and Methods. We included 123 patients referred for MPI because of suspected coronary arterial disease (CAD). Of these, 66 patients underwent a regadenoson stress test and 57 patients underwent an adenosine stress test preceding standard myocardial SPECT imaging. Technicians, physicians and patients were asked to report their experience using questionnaires. Results. As compared to adenosine, regadenoson did not produce any atrio-ventricular block (0 vs. 10% with adenosine), but did produce minor tachycardia and minimal blood pressure changes while all other side effects were milder and shorter. There were fewer patients with severe complaints after taking regadenoson than adenosine (17% vs. 32%, respectively, p < 0.01). The most frequent complaint reported was dyspnea, followed by flushing and chest pain. However, when they did occur, they usually disappeared rapidly. The overall symptom score, including severity and duration of side effects, was significantly lower after regadenoson than after adenosine (6.7 ± 6.3 vs. 10.0 ± 7.9, respectively; p < 0.01.) SPECT imaging results were similar. The regadenoson procedure was faster and more practical. Conclusion. Regadenoson, the new selective adenosine-2A receptor agonist, is a stress agent for MPI with a patient- and department friendly profile (AU)

Adenosina y control homeostático del sueño. Acciones en estructuras diana de los circuitos de vigilia y sueño / Adenosine and homeostatic control of sleep. Actions in target structures of the sleep-wake circuits

La homeostasis del sueño se manifiesta ante situaciones de vigilia prolongada de forma natural o experimentalmente. En estos casos, se presenta somnolencia (o presión de sueño) y, cuando se permite dormir, hay un rebote del sueño en duración e intensidad que compensa la pérdida del mismo. Entre las moléculas que pueden intervenir en la regulación homeostática del sueño, se encuentra la adenosina, cuyos antagonistas, la cafeína y la teofilina, consume la población humana ampliamente como estimulantes. La adenosina es un factor endógeno resultante del metabolismo del ATP en neuronas y glía que se acumula en el medio extracelular y que es capaz de ejercer acciones reguladoras sobre circuitos del ciclo vigilia sueño. Actúa a través de los receptores purinérgicos A1 y A2. En este trabajo se presenta una revisión de las vías metabólicas de la adenosina cerebral y de su liberación por neuronas y glía, y se exponen las acciones de la adenosina y de sus antagonistas en regiones del sistema nervioso central de naturaleza hipnogénica y relacionadas con la vigilia. Se exponen, además, los mecanismos sinápticos involucrados en estas acciones (AU)

Sleep homeostasis occurs during prolonged wakefulness. Drowsiness and sleep pressure are its behavioral manifestations and, when sleep is allowed, there is a sleep rebound of sufficient duration and intensity to compensate for the previous deprivation. Adenosine is one of the molecules involved in sleep homeostasic regulation. Caffeine and theophylline, stimulants widely consumed by the humans, are antagonists. It is an endogenous factor, resulting from ATP metabolism in neurons and glia. Adenosine accumulates in the extracellular space, where it can exert regulatory actions on the sleep-wakefulness cycle circuits. Adenosine acts through the purinergic receptors A1 and A2. This paper reviews: 1) the metabolic pathways of cerebral adenosine, and the mechanisms of its release by neurons and glia to the extracellular space; 2) the actions of adenosine and its antagonists in regions of the central nervous system related to wakefulness, non-REM sleep, and REM sleep, and 3) the synaptic mechanisms involved in these actions (AU)