Succinic acid production by wine yeasts and the influence of GABA and glutamic acid / Producción de ácido succínico por levaduras enológicas y la influencia del GABA y el ácido glutámico

As a consequence of alcoholic fermentation (AF) in wine, several compounds are released by yeasts, and some of them are linked to the general quality and mouthfeel perceptions in wine. However, others, such as succinic acid, act as inhibitors, mainly of malolactic fermentation. Succinic acid is produced by non-Saccharomyces and Saccharomyces yeasts during the initial stages of AF, and the presence of some amino acids such as γ-aminobutyric acid (GABA) and glutamic acid can increase the concentration of succinic acid. However, the influence of these amino acids on succinic acid production has been studied very little to date. In this work, we studied the production of succinic acid by different strains of non-Saccharomyces and Saccharomyces yeasts during AF in synthetic must, and the influence of the addition of GABA or glutamic acid or a combination of both. The results showed that succinic acid can be produced by non-Saccharomyces yeasts with values in the range of 0.2–0.4 g/L. Moreover, the addition of GABA or glutamic acid can increase the concentration of succinic acid produced by some strains to almost 100 mg/L more than the control, while other strains produce less. Consequently, higher succinic acid production by non-Saccharomyces yeast in coinoculated fermentations with S. cerevisiae strains could represent a risk of inhibiting Oenococcus oeni and therefore the MLF.(AU)

Benzodiazepines related sexual dysfunctions: A critical review on pharmacology and mechanism of action / Disfunciones sexuales relacionadas con las benzodiazepinas: una revisión crítica sobre farmacología y mecanismo de acción

INTRODUCTION: Normal sexual functioning of both men and women, being a very complex process, is affected by numerous issues besides aging. Many factors affect the sexual function and lifestyle of the young population. In this article, we tried to review the literature to update the knowledge on benzodiazepine-related (BZD) sexual dysfunction (SD) and involved mechanisms of actions based on animal and human studies. METHODS: Different standard websites such as PubMed were used to review the literature and keywords including benzodiazepines, sexual dysfunction, gammaaminobutyric acid A (GABAA) receptor and erectile dysfunction were used. RESULTS: SD is one of the most common disorders in males and females which has recently been demonstrated to be associated with psychotropic medications such as antihypertensive agents, tranquilizers, antihistamines, appetite suppressants, antidepressants and anxiolytics. BZDs are among the most common psychotropic agents worldwide. SD including decreased libido, erectile dysfunction (ED) and other undesired sexual urges were observed in the patients receiving BZDs. DISCUSSION: The mechanisms of action of BZDs to induce SD mainly relate to enhanced GABAA receptor function which reduces penile erection

INTRODUCCIÓN: El funcionamiento sexual normal de los varones y las mujeres, al ser un proceso muy complejo, se ve afectado por numerosos problemas, además del envejecimiento. Muchos factores afectan a la función sexual y al estilo de vida de la población joven. En este artículo intentamos revisar la literatura para actualizar el conocimiento sobre las disfunciones sexuales (SD, por sus siglas en inglés) relacionadas con benzodiacepinas (BZD) y los mecanismos de acción involucrados en estudios con animales y humanos. MÉTODOS: Se utilizaron diferentes sitios web estándar, como PubMed, para revisar la literatura y las palabras clave que incluyen BZD, disfunciones sexuales, ácido gamma-aminobutírico A y disfunción eréctil. RESULTADOS: Las SD son uno de los trastornos más comunes en los varones y las mujeres, ya que recientemente se ha demostrado que están asociados a medicamentos psicotrópicos como agentes antihipertensivos, tranquilizantes, antihistamínicos, supresores del apetito, antidepresivos y ansiolíticos. Las BZD son uno de los agentes psicotrópicos más comunes en todo el mundo. Las SD que incluían disminución de la libido, la disfunción eréctil (DE) y otros impulsos sexuales no deseados, se observaron en los pacientes que recibieron BZD. DISCUSIÓN: Los mecanismos de acción de las BZD para inducir SD se relacionan principalmente con la función mejorada del receptor de ácido gamma-aminobutírico A (GABAA) que reduce la erección del pene

Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido gama-aminobutírico y glutamato / Time course of the effect of status epilepticus induced in the developing rat on gama-amino butyric acid and glutamate cerebellar concentration

INTRODUCCIÓN: El status epilepticus (SE) es un tipo de actividad epiléptica que causa atrofia cerebelar y pérdida de células de Purkinje en humanos y en animales de experimentación. El cerebelo es una región con alto contenido de ácido gama-aminobutírico (GABA) y glutamato, y algunos estudios refieren cambios en su concentración después de las convulsiones. Sin embargo, hasta la fecha no existen estudios que hayan analizado su efecto en diferentes regiones cerebelares en ratas en desarrollo. El objetivo del presente estudio fue realizar un curso temporal del efecto del SE inducido en ratas Wistar de 14 días de edad (P14) sobre el contenido tisular de GABA y glutamato en el vermis y los hemisferios cerebelares. MÉTODOS: El SE se indujo con el modelo de litio-pilocarpina; las ratas control se inyectaron con salina. Seis h, 24 h o 30 días después del inicio del SE o de la aplicación de solución salina, las ratas se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Las ratas de ambos grupos se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Ambas regiones se homogeneizaron (ácido perclórico 0,1 M conteniendo metabisulfito de sodio 4 mM) y centrifugaron, y el sobrenadante se empleó para cuantificar la concentración tisular de GABA y glutamato por cromatografía de líquidos de alta resolución acoplada a un detector fluorométrico. RESULTADOS: El SE no modificó la concentración de GABA y glutamato a los diferentes tiempos de análisis ni en el vermis ni en los hemisferios cerebelares. CONCLUSIONES: El cerebelo en desarrollo es resistente a los cambios neuroquímicos a corto y largo plazo producidos por el SE

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE

Uso concomitante de benzodiacepinas e hipoglucemiantes orales en pacientes diabéticos tipo 2 / Concomitant use of benzodiazepines and oral glucose-lowering drugs in patients with type-2 diabetes

Introducción: En los pacientes diabéticos en tratamiento con hipoglucemiantes orales (HGO) se observan disminuciones de las glucemias preprandiales mayores de las esperadas. Objetivo: Evaluar en pacientes diabéticos tipo 2, con hipoglucemiantes orales, la relación entre el efecto producido por el consumo de benzodiacepinas y el nivel de glucosa preprandial en el autocontrol realizado por el paciente e hipoglucemias. Métodos: Se realizó un estudio de tipo observacional, descriptivo, transversal realizado en una farmacia comunitaria de la ciudad de Córdoba (Argentina). Se utilizaron promedios de las glucemias preprandiales. Se dividen en dos grupos: con o sin prescripción conjunta de benzodiacepinas. Se compararon los grupos utilizando prueba T de Student. Resultados: Metformina fue el HGO más prescrito (n=42) como monoterapia o asociación, combinándose con más frecuencia con alprazolam (n=9) y diazepam (n=5). Las benzodiacepinas más prescritas fueron alprazolam (15 pacientes) y diazepam (13 pacientes). Diazepam ha sido la benzodiacepina que provoca mayor descenso de la glucemia (n=8) seguido de alprazolam (n=7). En el grupo que tiene prescripción de ambos medicamentos existe una disminución de los niveles de glucemias preprandiales llegando en 15 (35%) pacientes a niveles de hipoglucemia (menor a 70 mg/dl). Conclusiones: La utilización de benzodiacepinas junto con HGO en este grupo de pacientes diabéticos tipo 2 logró un mejor control de los niveles de glucemia preprandial que en aquellos que sólo emplearon monoterapia de HGO. Sin embargo, debido a las limitaciones metodológicas del estudio no se puede concluir una relación directa (AU)

Introduction: In diabetic patients undergoing treatment with oral glucose-lowering drugs (GLD), greater-than-expected decreases were observed in pre-meal blood sugar levels. Objective: In type 2 diabetic patients taking oral glucose-lowering drugs, evaluate the relationship between the effect of taking benzodiazepines and the patient’s self-monitored pre-meal glucose level in relation to hypoglycemia. Methods: A cross-sectional, descriptive, observational study was conducted in a community pharmacy in the city of Córdoba (Argentina). Averages of pre-meal blood sugar levels were used. Subjects were divided into two groups: with and without concomitant prescription of benzodiazepines. The groups were compared using Student's t-test. Results: Metformin was the most prescribed oral GLD (n=42) as a monotherapy or adjunctive therapy, most frequently combined with alprazolam (n=9) and diazepam (n=5). The most frequently prescribed benzodiazepines were alprazolam (15 patients) and diazepam (13 patients). Diazepam was the benzodiazepine that most effectively lowered the glucose level (n=8), followed by alprazolam (n=7). In the group where both drugs were prescribed, there is a decrease to hypoglycemic levels (less than 70 mg/dl) in the pre-meal blood sugar levels of 15 (35%) patients. Conclusions: The use of benzodiazepines together with oral GLD in this group of type 2 diabetic patients resulted in better control of the pre-meal glucose levels than in the group for which only GLD monotherapy was used. However, due to the methodological limitations of the study, a direct link cannot be concluded (AU)

Ligandos alfa 2-delta: pasado, presente y futuro / Alpha 2-delta ligands: past, present and future

No disponible

La esencia del temblor esencial: bases neuroquímicas / The essence of essential tremor: neurochemical bases

Introducción. El temblor esencial es el trastorno del movimiento más frecuente en el adulto. Se ha considerado una enfermedad benigna, pero puede ocasionar una importante discapacidad física y psicosocial. El tratamiento farmacológico sigue siendo poco satisfactorio. Su etiología, fisiopatología y anatomía siguen sin conocerse del todo. Objetivo. El conocimiento de las bases neuroquímicas es fundamental para el desarrollo de terapias más eficaces. Se revisan los conocimientos actuales en este campo a fin de incentivar nuevas investigaciones e ideas que permitan mejorar la comprensión de la enfermedad y que fomenten el desarrollo de nuevas terapias farmacológicas. Desarrollo. Se revisan los trabajos realizados hasta la fecha en humanos y en modelos animales de neurotransmisores (ácido gamma-aminobutírico, glutamato, noradrenalina, serotonina, adenosina), proteínas y otros fenómenos neuroquí- micos, como los canales de calcio de tipo T en el temblor esencial. Conclusiones. Se han descrito cuatro disfunciones neuroquímicas que acontecerían básicamente en el cerebelo y el núcleo olivar inferior: alteración del sistema gabérgico, aumento del rebote postinhibitorio mediante corrientes de calcio de tipo T, disminución de los mecanismos de inhibición neuronal y aumento de la actividad de los neurotransmisores excitatorios. Estas disfunciones neuroquímicas comportarían un aumento de la actividad de las neuronas profundas cerebelosas con actividad oscilatoria, que se trasladaría al núcleo del tálamo y a la corteza motora, y comportarían la aparición del temblor. Son necesarios nuevos estudios para poder confirmar estas hipótesis y seguir avanzando para conseguir tratamientos farmacológicos más eficaces para los pacientes con temblor esencial (AU)

Introduction. Essential tremor is the most frequent movement disorder in adults. It has been considered a benign disease, but can result in significant physical and psychosocial disability. Pharmacological treatment is still not very satisfactory. Its causation, pathophysiology and anatomy remain only partially understood. Aims. An understanding of its neurochemical basis is essential to be able to develop more efficient therapies. We review what is currently known in this field in order to motivate further research and ideas that allow an enhanced understanding of the disease and which foster the development of new pharmacological therapies. Development. We review the studies conducted to date in humans and in animal models of neurotransmitters (gammaaminobutyric acid, glutamate, noradrenalin, serotonin, adenosine), proteins and other neurochemical phenomena, such as T-type calcium channels, in essential tremor. Conclusions. Four neurochemical dysfunctions have been described that basically occur in the cerebellum and the inferior olivary nucleus: alteration of the GABAergic system, increased post-inhibitory rebound via T-type calcium currents, decreased neuronal inhibition mechanisms and an increase in excitatory neurotransmitter activity. These neurochemical dysfunctions would involve an increase in the activity of the deep neurons of the cerebellum with an oscillatory activity that would shift to the thalamic nucleus and the motor cortex, which in turn would lead to the appearance of tremor. Further research is needed to be able to confirm these hypotheses and to continue to advance towards achieving more efficient pharmacological treatments for patients with essential tremor (AU)

Dolor miofascial en el territorio craneocervical: Una revisión de la patología y su relación con polimorfismos genéticos del sistema GABAérgico / Myofascial Pain in the craneocervical territory: A review of the pathology and its relationship with the GABAergic system genetic polymorphisms

El dolor miofascial es una patología muscular regional no inflamatoria caracterizada por la presencia de una zona hiperirritable de tejido muscular que se encuentra en una banda tensa, denominado punto gatillo. En la región orofacial pertenece a un conglomerado de patologías denominadas trastornos temporomandibulares, correspondiendo al de mayor prevalencia. Las manifestaciones clínicas van desde dolor local, tensión muscular y disfunción estructural hasta dolor referido, fenómenos autonómicos e hiperexcitabilidad en el sistema nervioso central. Durante las últimas décadas se han asociado variantes genéticas con diferentes expresiones en patologías dolorosas, algunas de las cuales se encuentran en el sistema GABAérgico. En el presente artículo se realiza una revisión del dolor miofascial como patología y su relación con estos polimorfismos genéticos (AU)

Myofascial pain is noninflammatory regional muscular disorder characterized by the presence of a muscle tissue area hyperirritable located on a taut band, called trigger point. In the orofacial region myofascial pain belongs to a cluster of diseases called temporomandibular disorder. Within these pathologies, it is to the most prevalent of its, clinical manifestations include local pain, muscle tension, structural dysfunction, referred pain, autonomic phenomena and hyperexcitability in the central nervous system. During the last decades have been associated genetic variants to painful pathologies, some of which are in the GABAergic system. This article performs a review of myofascial pain as pathology and its relation to genetic polymorphisms in GABAergic system (AU)

El receptor postsináptico de glicina media de forma transitoria y sostenida la inhibición glicinérgica en la retina de los vertebrados / The post-synaptic glycine receptor mediates in a transitory and sustained way the glycinergic inhibition in the vertebrate retina

Introducción. La glicina y el ácido g-aminobutírico son los principales neurotransmisores inhibidores en la retina de los vertebrados. La acción inhibidora de la glicina es mediada por el receptor postsináptico de glicina, que es un canal selectivo al cloruro, constituido por tres subunidades β y dos α (α1 - α4 ) que se antagoniza por el alcaloide estricnina. En la retina se conoce que las cuatro isoformas de la subunidad α se expresan en la capa sináptica interna y que en muy raras ocasiones se localizan en la misma terminal sináptica. Los receptores de glicina formados por las isoformas α1 o α3 poseen cinéticas rápidas, mientras que los receptores α2 o α4 responden tónicamente. El empleo de ratones transgénicos que tienen eliminada (knock-out) o disminuida (knock-down) la expresión de alguno de los genes que codifican para las diferentes isoformas de la subunidad α del receptor de glicina ha permitido estudiar la participación de estas subunidades en la transmisión glicinérgica de la retina de los mamíferos. Objetivo. Describir la participación del receptor de glicina en la neurotransmisión glicinérgica, particularmente en la retina. Desarrollo. En esta revisión se describen los experimentos que han permitido localizar e identificar la participación de los diferentes subtipos del receptor de glicina en circuitos de neurotransmisión específicos en la retina de los vertebrados. Conclusiones. La localización de receptores de glicina constituidos por diferentes isoformas de la subunidad α, en tipos neuronales específicos, indica la presencia de circuitos glicinérgicos que codifican de manera distinta el paso de información en la retina (AU)

Introduction. Glycine and the g-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three β and two α subunits (α1 - α4 ), which is antagonized by the alkaloid strychnine. In the retina, it is known that all α isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either α1 or α3 shows rapid kinetics, whereas α2 or α4 receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor α subunits in the glycinegic neurotransmission of the mammalian retina. Aim. To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. Development. In this review we describe the experiments that have allowed the localization and the involvement of the α subunit isoforms in specific transmission circuits of the vertebrate retina. Conclusions. The localization of the glycine receptor conformed by different isoforms of the α subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina (AU)

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats

No disponible

The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level (AU)

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines (AU)

GABA: ¿dualidad funcional? Transición durante el neurodesarrollo / GABA: a functional duality? Transition during neurodevelopment

Introducción. El ácido gamma-aminobutírico (GABA) es el principal neurotransmisor de tipo inhibitorio y sus acciones son mediadas por receptores de tipo ionotrópico (GABAA) y metabotrópico (GABAB), ampliamente distribuidos en el tejido nervioso central. Objetivo. Revisar la estructura de los receptores GABA y su implicación en procesos fisiológicos en el sistema nervioso central. Desarrollo. Se aborda el estudio de la estructura y diversidad de los receptores GABA, especialmente durante el neurodesarrollo, y se hace referencia a la naturaleza excitatoria e inhibitoria de la transmisión gabérgica, donde la participación de los cotransportadores NKCC1 y KCC2 tiene un papel clave en dicha dualidad funcional en la transición de un estadio embrionario a uno posnatal. De igual forma, se plasma el interés por los receptores GABA como diana farmacológica de uso clínico, lo que se manifiesta por la presencia de sitios de modulación alostérica poco explorados en dicho complejo-receptor. Conclusiones. El conocimiento fisiológico y farmacológico de la gran diversidad de subunidades que conforman un determinado subtipo de receptor GABA, así como la correcta expresión en tiempo y espacio para garantizar la viabilidad de un organismo, prometen ser la respuesta a trastornos graves y añejos como la epilepsia o la drogadicción, y tan complejos como el neurodesarrollo (AU)

Introduction. Gamma-aminobutyric acid (GABA) is the most important inhibitory-type neurotransmitter and its actions are mediated by ionotropic (GABAA) and metabotropic (GABAB) type receptors, which are widely distributed throughout the tissue of the central nervous system. Aim. To review the structure of GABA receptors and their involvement in physiological processes in the central nervous system. Development. The study addresses the structure and diversity of the GABA receptors, especially during neurodevelopment, and reference is made to the excitatory and inhibitory nature of GABAergic transmission, where the participation of the cotransporters NKCC1 and KCC2 plays a key role in this functional duality in the transition from an embryonic to a postnatal state. Likewise, the interest in GABA receptors as a pharmacological target for clinical use is also discussed. This is manifested by the presence of under-explored allosteric modulation sites in the aforementioned complex-receptor. Conclusions. The physiological and pharmacological knowledge of the great diversity of subunits that make up a particular subtype of GABA receptor, as well as the correct expression in time and space in order to ensure the viability of the organism, promise to be the answer to long-time severe disorders like epilepsy or drug addiction, and such complex ones as neurodevelopment (AU)

Immunohistochemical study of the astrocytes of the adult rat cochlear nuclei

Astrocytes play crucial roles in the organization, function and maintenance of neurons and neuronal circuits. Apart from reports on reactive gliosis after auditory/vestibular injuries, few authors have focused their attention on the astroglial cytoarchytecture of the cochlear nuclei (CN). In this qualitative immunohistochemical study, we analyse the distribution of the astrocytic markers glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and S-100 protein (S-100) in the adult CN of twelve young adult male rats (AU)

No disponible

Modulación de los receptores ionotrópicos de tipo cys-loop por proteincinasas A y C / Cys-loop ligand-gated ion channels modulation by protein kinases A and C

Introducción. En el sistema nervioso, la neurotransmisión química rápida es mediada por receptores ionotrópicos que se activan por la unión de su ligando. La unión del ligando a su receptor, favorece la entrada selectiva de iones a la célula que cambia el potencial eléctrico de la membrana celular. Los receptores de tipo cys-loop pertenecen a la superfamilia de receptores ionotrópicos activados por ligando que comprende a los receptores nicotínicos de acetilcolina, del ácido gamma-aminobutírico, glicina, serotonina y zinc. En diversos estudios se demostró que la actividad de estos receptores se modifica en respuesta a la activación de las proteincinasas A y C; los diferentes resultados, aparentemente contradictorios, podrían explicarse por la participación de diversos factores como el tipo de subunidades que forman a los receptores, componentes del citoesqueleto y subtipos de cinasas y fosfatasas presentes en el tejido nervioso de estudio. Objetivo. Presentar una revisión del efecto que las proteincinasas A y C ejercen sobre la actividad de los receptores ionotrópicos de tipo cys-loop. Desarrollo. En esta revisión se describen los experimentos obtenidos en diversas regiones en las que se ha determinado el efecto que tiene la activación de estas cinasas sobre la función de los receptores de neurotransmisores mayormente distribuidos en el sistema nervioso central y que han sido objeto de estudio. Conclusiones. La regulación de los receptores de tipo cys-loop por proteincinasas ocurre por medio de la activación de otros receptores (cross-talk) que se expresan en diversas etapas del desarrollo y áreas del sistema nervioso (AU)

Introduction. In the nervous system, rapid chemical neurotransmission is mediated by ionotropic receptors that are activated by ligand binding. Ligand binding to its receptor promotes the selective flow of ions into the cell which changes the electrical potential of the cell membrane. Cys-loop type receptors belong to the ligand-gated ion channel superfamily including the nicotinic acetylcholine receptor, the gamma-aminobutyric acid, glycine, serotonin and zinc. Several studies showed that the activity of these receptors was modified in response to protein kinases A and C activation; the different results, apparently contradictory, could be explained by the involvement of several factors such as the type of subunits that make up these receptors, components of the cytoskeleton and sub-types of kinases and phosphatases present in nerve tissue studied. Aim. To review the effect of protein kinases A and C on the activity of cys-loop receptors. Development. In this review we describe experiments conducted in different regions where it was determined the effect of these kinases on the function of neurotransmitter receptors mostly distributed in the nervous system. Conclusions. The cys-loop receptors regulation by protein kinases occurs through the activation of other receptors (crosstalk) that are expressed at different stages of development and nervous system areas (AU)

Adicción a la gabapentina / Gabapentin abuse

No disponible

No disponible

Anestesia general en un paciente con síndrome de Angelman / No disponible

No disponible

Papel de las subunidades alfa del receptor GABAA en la regulación de la conducta agresiva / Role of alpha subunits of the GABAA receptor in the regulation of aggressive behavior

El ácido gamma-aminobutírico (GABA) es el principal neurotransmisor inhibidor del sistema nervioso, y realiza sus principales acciones farmacológicas mediante el receptor ionotrópico GABAA, cuya composición más frecuente es la formada por la combinación de subunidades (α1)2(β2)2γ2. Las características farmacológicas del receptor GABAA parecen depender de la subunidad alfa que se encuentre en cada subtipo de receptor. Aunque numerosos estudios han implicado al receptor de GABAA en la modulación de la conducta agresiva, aún no conocemos el papel preciso que las distintas subunidades alfa tienen en la agresión. La razón principal es la dificultad para conseguir ligandos que muestren selectividad específica por las subunidades alfa. La introducción de nuevas estrategias que incluyen el uso de modelos animales knock-out y knock-in, el empleo de ligandos con actividad agonista parcial frente a total y los nuevos compuestos con eficacia selectiva abren nuevos horizontes en el estudio del grado de participación que tienen las distintas subunidades alfa del receptor GABAA en la agresión (AU)

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and exerts its main actions via ionotropic GABAA receptors, the most abundant subunit combination being (α1)2(β2)2γ2. The pharmacological characteristics of GABAA receptor appear to depend on the alpha subunit, which is present in each receptor subtype. Although numerous studies have implicated GABAA receptors in the modulation of aggressive behavior, the precise role of the distinct alpha subunits in aggression is not well characterized. The main reason is the difficulty of obtaining ligands that exhibit specific selectivity for the α-subunits. The introduction of new strategies that include the use of "knock-out" and "knock-in" animal models, the use of ligands with partial versus total agonist activity, as well as the existence of new compounds with selective efficacy open new perspectives for studying the degree of involvement of the distinct alpha subunits in aggression (AU)

The Effects of Agonists of Ionotropic GABA A and Metabotropic GABA B Receptors on Learning

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAA and metabotropic GABAB receptors and 2) gaboxadol a selective agonist of ionotropic GABAA receptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABAB receptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAA and GABAB receptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes (AU)

Este trabajo investiga el papel de los procesos inhibitorios en la discriminación realizada por el sistema nervioso de los humanos y los animales entre sucesos familiares y no familiares y significativos y no significativos. Se comparó los efectos de dos mediadores inhibitorios del ácido gamma-aminobutírico (GABA): 1) Phenibut, un agonista no selectivo de los receptores del GABAA ionotrópico y del GABAB metabotrópico y 2) gaboxadol, un agonista selectivo de los receptores del GABAA ionotrópico, sobre el desarrollo de reflejos condicionados de defensa activa e inhibitorios en conejos en alerta y no inmovilizados. Se encontró que el phenibut, pero no el gaboxadol, acelera el desarrollo de reflejos defensivos en una etapa temprana del condicionamiento. Tanto el phenibut como el Gaboxadol facilitaron el desarrollo de la inhibición condicionada, pero el efecto del gaboxadol ocurre en etapas tardías del condicionamiento y es menos estable que el del phenibut. Los efectos más estables y más tempranos del phenibut, en comparación con el gaboxadol, sobre el almacenaje en la memoria de la significación inhibitoria de un estímulo pueden deberse a que los receptores del GABAB tienen el papel dominante en el desarrollo de la inhibición interna durante la fase inicial del condicionamiento. Por otro lado esto puede deberse a que la participación de los receptores tanto del GABAA como del GABAB son esenciales para el proceso. Comentamos la multifuncionalidad de los receptores del GABA como función de su estructura y de las posiciones de las neuronas relevantes en el cerebro, dado que este factor puede afectar la regulación de varios tipos de procesos psicológicos (AU)

Effects of gamma-hydroxybutyrate (liquid ecstasy) on the eye development of the chick embryo

Gamma-hydroxybutyrate (GHB), a precursorto gamma aminobutyric acid (GABA), wasinitially employed as an anesthetic. As a relativelynovel drug, few people are aware of itsharmful effects and few studies have beenundertaken to investigate its long-term effectsor its action on developing tissues.We performed an experimental study onthe action of GHB on the developing eye, anorgan very closely related to the developmentof the CNS. Chick embryos were treated with20% or 30% dilutions of 100 ìl GHB at 7(30-31 HH) and 11 (37 HH) days of incubation(i.e., two doses per group), and the effectswere observed at 21 days of incubation (45HH). An ophthalmologic ultrasonographydevice (Hondex A/B SCAN IS-500) was usedto measure different eye parameters (cornealthickness; posterior surface of cornea – anteriorsurface of lens; anteroposterior diameter oflens; anteroposterior diameter of eye).We observed significant differencesbetween the treated and control groups asregards the thickness of the cornea and lens,and in the anteroposterior diameter of the eye.The present results demonstrate a possibleeffect of GHB on development (AU)

No disponible

Prurito braquiorradial como síntoma de radiculopatía cervical / Brachioradial pruritus as a symptom of cervical radiculopathy

El prurito braquiorradial (PBR) se caracteriza por la presencia de prurito localizado en la cara lateralde los brazos. Se trata de una entidad enigmática con una etiología controvertida; mientras que algunos autoresconsideran el PBR como una fotodermatosis, otros atribuyen su aparición a la presencia de una radiculopatíacervical subyacente. En este artículo se presenta nuestra experiencia con esta entidad y se discute el papel de una neuropatía subyacente en la etiología de este y otros pruritos localizados como la notalgia parestésica, el prurito anogenital o el síndrome de la boca ardiente (AU)

Brachioradial pruritus is characterized by the presence of pruritus on the lateral aspect of the arms. The etiology of this enigmatic entity is the subject of some debate -some authors claim that brachioradial pruritus is a photodermatosis whereas others attribute it to the presence of underlying cervical radiculopathy. In these case reports, we present our experience with brachioradial pruritus and discuss the role of underlyingneuropathy in its etiology and that of other types of localized pruritus such as notalgia paresthetica, anogenital pruritus, and burning mouth syndrome (AU)