Síndrome alterno mesencefálico: síndrome de Weber en dos pacientes varones VIH positivos con toxoplasmosis cerebral

En este reporte se describen dos casos de pacientes varones con VIH diagnosticados por serología, que no estaban recibiendo tratamiento. Ambos pacientes desarrollaron el síndrome alterno mesencefálico y la lesión estructural, causada por la infección del sistema nervioso central por toxoplasmosis cerebral, confirmada mediante una resonancia magnética cerebral. Esta condición se constató por serología en líquido cefalorraquídeo. El síndrome de Weber es un tipo de síndrome alterno mesencefálico poco frecuente y existe poca información de su clínica y evolución. Fue descrito por sir Herman David Weber en 1863, y se caracteriza por la lesión ipsilateral del fascículo del III par craneal, con presencia de hemiparesia contralateral debida a la lesión de la vía corticoespinal y corticobulbar del pedúnculo cerebral. Las causas que lo originan incluyen tanto procesos isquémicos o hemorrágicos, que lesionan el fascículo del III par craneal y pedúnculo cerebral, como neoplasias intraencefálicas, aneurismas, hematomas extradurales y procesos infecciosos que se comportan como procesos expansivos. Los pacientes evaluados presentaron clínica de ptosis palpebral, visión doble vertical, dificultad para bipedestación, hemiparesia, hiporreflexia, sensibilidad superficial y profunda disminuidas, equilibrio y coordinación alterados, III par parético, habla incoherente, desorientación en tiempo, espacio y persona de manera intermitente y asimetría facial. Para la toxoplasmosis se aplicó un tratamiento específico con trimetropim-sulfametoxasol, clindamicina y prednisona por vía oral, lo cual permitió una mejoría del cuadro clínico. En el presente caso clínico se presenta la secuencia de los hechos, manejo y breve revisión de la literatura para su consideración como diagnóstico y su relevancia en el paciente con VIH-toxoplasmosis del sistema nervioso central.

This report describes the case of two male HIV-positive patients who were not receiving treatment and whose diagnosis was confirmed by serology testing. Both patients developed midbrain stroke syndrome and the structural injury, which was caused by a central nervous system infection due to cerebral toxoplasmosis, was verified by brain magnetic resonance imaging. This condition was confirmed by cerebrospinal fluid serology testing. Weber's syndrome is a very rare type of midbrain stroke syndrome with little information available on its symptoms and evolution. It was first described by Sir Herman David Weber in 1863 and is characterized by ipsilateral injury of the third cranial nerve fascicle with contralateral hemiparesis due to injury of the corticospinal and corticobulbar tracts of the cerebral peduncle. Its causes range from ischemic or hemorrhagic processes, which damage the third cranial nerve fascicle and cerebral peduncle, to brain tumors, aneurysms, extradural hematomas and infectious diseases that behave like spreading processes. The assessed patients showed clinical signs and symptoms such as ptosis; vertical double vision; difficulty standing up; hemiparesis; hyporeflexia; decreased superficial and deep sensation; poor balance and coordination; third cranial nerve palsy; slurred speech; intermittent disorientation in time, place and person; and facial asymmetry. Oral trimethoprim-sulfamethoxazole, clindamycin and prednisone were administered as specific treatment for toxoplasmosis, which enabled the improvement of the clinical picture. This case report presents the sequence of events, treatment and a brief review of the literature to be considered in the diagnosis and determine its importance in patients with HIV-toxoplasmosis of the central nervous system.

Early Effects of the Soluble Amyloid ß25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors.

The amyloid ß peptide (Aß) is a central player in the neuropathology of Alzheimer's disease (AD). The alteration of Aß homeostasis may impact the fine-tuning of cell signaling from the very beginning of the disease, when amyloid plaque is not deposited yet. For this reason, primary culture of rat cortical neurons was exposed to Aß25-35, a non-oligomerizable form of Aß. Cell viability, metabotropic glutamate receptors (mGluR) and adenosine receptors (AR) expression and signalling were assessed. Aß25-35 increased mGluR density and affinity, mainly due to a higher gene expression and protein presence of Group I mGluR (mGluR1 and mGluR5) in the membrane of cortical neurons. Intriguingly, the main effector of group I mGluR, the phospholipase C ß1 isoform, was less responsive. Also, the inhibitory action of group II and group III mGluR on adenylate cyclase (AC) activity was unaltered or increased, respectively. Interestingly, pre-treatment of cortical neurons with an antagonist of group I mGluR reduced the Aß25-35-induced cell death. Besides, Aß25-35 increased the density of A1R and A2AR, along with an increase in their gene expression. However, while A1R-mediated AC inhibition was increased, the A2AR-mediated stimulation of AC remained unchanged. Therefore, one of the early events that takes place after Aß25-35 exposure is the up-regulation of adenosine A1R, A2AR, and group I mGluR, and the different impacts on their corresponding signaling pathways. These results emphasize the importance of deciphering the early events and the possible involvement of metabotropic glutamate and adenosine receptors in AD physiopathology.

Efectos en la salud de los sistemas electrónicos de administración de nicotina (SEAN) / Health Effects of Electronic Nicotine Delivery Systems (SEAN)

Resumen Sin lugar a dudas, el tabaquismo continúa siendo la principal causa de enfermedad, discapacidad y muerte prematura a nivel mundial. Sin embargo, el advenimiento de los nuevos sistemas electrónicos de administración de nicotina (SEAN), entre los que destaca el cigarrillo electrónico, ha tenido un crecimiento explosivo y en algunos países ha desplazado a los cigarrillos de tabaco, especialmente entre los jóvenes que se sienten atraídos por sus llamativos sabores y por el despliegue de tecnología que se utiliza en su diseño y funcionamiento. Los SEAN surgieron inicialmente en 2003 como una supuesta ayuda para dejar de fumar, a 16 años de esta fecha no hay estudios clínicos que confirmen su superioridad sobre los medicamentos existentes para tal fin: terapias de reemplazo de nicotina, bupropión y vareniclina, ni sobre las terapias psicológicas como la racional emotiva y la cognitivo conductual. Por el contrario, se han acumulado gran cantidad de evidencias sobre el efecto deletéreo que tienen sobre la salud de los consumidores, el riesgo que representan es indudable y esto se confirma por reportes recientes de Centros de Control de Enfermedades de los Estados Unidos (CDC) que señalan 2,172 casos hospitalizados con enfermedad pulmonar aguda y 42 muertes por esta causa, siendo el 79% personas menores de 35 años. Este brote de enfermedad pulmonar ha determinado que se plantee la prohibición de los SEAN en Estados Unidos. Asimismo, la Food and Drug Administration (FDA) aprobó la venta de los cigarrillos híbridos o heets que utilizan tabaco calentado, los cuales ya están disponibles en nuestro país. No cabe duda de que como profesionales del área de la salud nuestra obligación es informar con evidencias científicas sobre los riesgos que representan los SEAN para sus consumidores, asimismo debemos aprender de la historia del tabaquismo para poder prevenir la morbimortalidad asociada con estos nuevos productos del tabaco.

Abstract Without a doubt, smoking continues to be the leading cause of disease, disability, and premature death worldwide. However, the advent of the new Electronic Administration Systems of Nicotine (SEAN), among which the electronic cigarette stands out, has had explosive growth and in some countries has depleted tobacco cigarettes, especially among young people who feel attracted by its striking flavors and the deployment of technology that is used in its design and operation. The SEANs initially emerged in 2003 as a supposed help to quit smoking, at 16 years from this date no clinical studies are confirming their superiority over existing medications for this purpose: nicotine, bupropion and varenicline replacement therapies, or over psychological therapies such as emotional and cognitive-behavioral rational. On the other side, a large amount of evidence has been accumulated on the deleterious effect they have on the health of consumers, the risk they represent is unquestionable and this is confirmed by recent reports from the Centers for Disease Control of the United States (CDC) that indicate 2142 hospitalized cases with acute lung disease and 42 deaths from this cause, 79% being people under 35 years. This outbreak of lung disease has determined that the ban on SEAN in the United States will be planted. Also, the Food and Drug Administration (FDA) approved the sale of hybrid cigarettes or "Heets" (Heat-not-burn tobacco products), which uses heated tobacco, and are now available in our country. There is no doubt that as health professionals, we must inform with scientific evidence about the risks that SEANs pose to their consumers, we must also learn from the history of smoking to prevent the morbidity and mortality associated with these new tobacco products.

On-Demand Hydrophobic Drug Release Based on Microwave-Responsive Graphene Hydrogel Scaffolds.

Electromagnetically driven drug delivery systems stand out among stimulus-responsive materials due to their ability to release cargo on demand by remote stimulation, such as light, near infrared (NIR) or microwave (MW) radiation. MW-responsive soft materials, such as hydrogels, generally operate at 2.45 GHz frequencies, which usually involves rapid overheating of the scaffold and may affect tissue surrounding the target location. In contrast, 915 MHz MW penetrate deeper tissues and are less prone to induce rapid overheating. In order to circumvent these limitations, we present here for the first time a graphene-based hydrogel that is responsive to MW irradiation of ν=915 MHz. This system is a candidate soft scaffold to deliver a model hydrophobic drug. The graphene present in the hydrogel acts as a heat-sink and avoids overheating of the scaffold upon MW irradiation. In addition, the microwave trigger stimulates the in vitro delivery of the model drug, thus suggesting a remote and deep-penetrating means to deliver a drug from a delivery reservoir. Moreover, the MW-triggered release of drug was observed to be enhanced under acidic conditions, where the swelling state is maximum due to the swelling-induced pH-responsiveness of the hydrogel. The hybrid composite described here is a harmless means to deliver remotely a hydrophobic drug on demand with a MW source of 915 MHz. Potential use in biomedical applications were evaluated by cytotoxicity tests.

Central nucleus of the amygdala as a common substrate of the incubation of drug and natural reinforcer seeking.

Relapse into drug use is a major problem faced by recovering addicts. In humans, an intensification of the desire for the drug induced by environmental cues-incubation of drug craving-has been observed. In rodents, this phenomenon has been modeled by studying drug seeking under extinction after different times of drug withdrawal (or using a natural reinforcer). Although much progress has been made, an integrated approach simultaneously studying different drug classes and natural reward and examining different brain regions is lacking. Lewis rats were used to study the effects of cocaine, heroin, and sucrose seeking incubation on six key brain regions: the nucleus accumbens shell/core, central/basolateral amygdala, and dorsomedial/ventromedial prefrontal cortex. We analyzed PSD95 and gephyrin protein levels, gene expression of glutamatergic, GABAergic and endocannabinoid elements, and amino acid transmitter levels. The relationships between the areas studied were examined by Structural Equation Modelling. Pathways from medial prefrontal cortex and basolateral complex of the amygdala to central nucleus of the amygdala, but not to the nucleus accumbens, were identified as common elements involved in the incubation phenomenon for different substances. These results suggest a key role for the central nucleus of amygdala and its cortical and amygdalar afferences in the incubation phenomenon, and we suggest that by virtue of its regulatory effects on glutamatergic and GABAergic dynamics within amygdalar circuits, the endocannabinoid system might be a potential target to develop medications that are effective in the context of relapse.

Carbohydrates and sports practice: a Twitter virtual ethnography / Hidratos de carbono y práctica deportiva: una etnografía virtual en Twitter.

Introduction: Although carbohydrates consumption is a key factor to enhance sport performance, intake levels seem questioned by some amateur athletes, leading to develop an irrational aversion to carbohydrate known as "carbophobia". On the other hand, food is the origin of virtual communities erected as a source of knowledge and a way to exchange information. Despite this, very few studies have analysed the influence of social media in eating behaviours. Objectives: To know the conceptualizations about carbohydrates intake and eating patterns related to carbophobia expressed in amateur athletes' Twitter accounts. Methods: Qualitative research designed from Hine's Virtual Ethnography. Virtual immersion was used for data collection in Twitter open accounts in a theoretical sample of tweets from amateur athletes. Discourse analysis of narrative information of tweets was carried out through open, axial and selective coding process and the constant comparison method. Results: Data analysis revealed four main categories that offered a picture of conceptualizations of carbohydrates: carbohydrates as suspects or guilty from slowing down training, carbophobia as a lifestyle, carbophobia as a religion and finally the love/hate relationship with carbohydrates. Conclusions: Low-carbohydrate diet is considered a healthy lifestyle in some amateur athletes. The results of this study show the power of virtual communication tools such as Twitter to support, promote and maintain uncommon and not necessarily healthy eating behaviours. Future studies should focus on the context in which these practices appear.

Introducción: aunque el consumo de hidratos de carbono es un factor clave para alcanzar un óptimo rendimiento deportivo, los niveles de ingesta parecen cuestionados por algunos deportistas amateurs, que llegan a desarrollar una aversión irracional por los hidratos de carbono conocida como "carbofobia". Por otro lado, la alimentación es origen de comunidades virtuales erigidas como fuente de conocimiento e intercambio de información, aunque apenas se ha analizado la influencia de estas en los comportamientos alimentarios. Objetivos: conocer las conceptualizaciones sobre el consumo de hidratos de carbono y los patrones alimentarios relacionados con la carbofobia a través de la actividad en Twitter de aficionados a la práctica deportiva. Métodos: estudio cualitativo diseñado desde la Etnografía Virtual de Hine. Realizamos una inmersión virtual en cuentas en abierto de la red social Twitter en una muestra teórica de tuits de aficionados al deporte. Se realizó un análisis del discurso de la información narrativa de tuits mediante los procesos de codificación abierta, axial y selectiva y el método de comparación constante. Resultados: del análisis emergen cuatro grandes categorías que retratan las conceptualizaciones sobre los hidratos de carbono: los hidratos de carbono como sospechosos o culpables del estancamiento en el entrenamiento y de los problemas con el peso, la carbofobia como estilo de vida, la carbofobia como religión y la relación amor/odio con los hidratos de carbono. Conclusiones: la dieta baja en hidratos de carbono, o carente de ellos, es considerada como un estilo de vida saludable en algunos aficionados a la práctica deportiva. Los resultados de este estudio ponen de manifiesto el poder de herramientas de comunicación virtual como Twitter para apoyar, fomentar y mantener conductas alimentarias no frecuentes y no siempre saludables. Futuros estudios deben seguir profundizando en el contexto en el que aparecen estas prácticas.

Hidratos de carbono y práctica deportiva: una etnografía virtual en Twitter / Carbohydrates and sports practice: a Twitter virtual ethnography

Introducción: aunque el consumo de hidratos de carbono es un factor clave para alcanzar un óptimo rendimiento deportivo, los niveles de ingesta parecen cuestionados por algunos deportistas amateurs, que llegan a desarrollar una aversión irracional por los hidratos de carbono conocida como «carbofobia». Por otro lado, la alimentación es origen de comunidades virtuales erigidas como fuente de conocimiento e intercambio de información, aunque apenas se ha analizado la influencia de estas en los comportamientos alimentarios. Objetivos: conocer las conceptualizaciones sobre el consumo de hidratos de carbono y los patrones alimentarios relacionados con la carbofobia a través de la actividad en Twitter de aficionados a la práctica deportiva. Métodos: estudio cualitativo diseñado desde la Etnografía Virtual de Hine. Realizamos una inmersión virtual en cuentas en abierto de la red social Twitter en una muestra teórica de tuits de aficionados al deporte. Se realizó un análisis del discurso de la información narrativa de tuits mediante los procesos de codificación abierta, axial y selectiva y el método de comparación constante. Resultados: del análisis emergen cuatro grandes categorías que retratan las conceptualizaciones sobre los hidratos de carbono: los hidratos de carbono como sospechosos o culpables del estancamiento en el entrenamiento y de los problemas con el peso, la carbofobia como estilo de vida, la carbofobia como religión y la relación amor/odio con los hidratos de carbono. Conclusiones: la dieta baja en hidratos de carbono, o carente de ellos, es considerada como un estilo de vida saludable en algunos aficionados a la práctica deportiva. Los resultados de este estudio ponen de manifiesto el poder de herramientas de comunicación virtual como Twitter para apoyar, fomentar y mantener conductas alimentarias no frecuentes y no siempre saludables. Futuros estudios deben seguir profundizando en el contexto en el que aparecen estas prácticas (AU)

Introduction: Although carbohydrates consumption is a key factor to enhance sport performance, intake levels seem questioned by some amateur athletes, leading to develop an irrational aversion to carbohydrate known as «carbophobia». On the other hand, food is the origin of virtual communities erected as a source of knowledge and a way to exchange information. Despite this, very few studies have analysed the influence of social media in eating behaviours. Objectives: To know the conceptualizations about carbohydrates intake and eating patterns related to carbophobia expressed in amateur athletes’ Twitter accounts. Methods: Qualitative research designed from Hine’s Virtual Ethnography. Virtual immersion was used for data collection in Twitter open accounts in a theoretical sample of tweets from amateur athletes. Discourse analysis of narrative information of tweets was carried out through open, axial and selective coding process and the constant comparison method. Results: Data analysis revealed four main categories that offered a picture of conceptualizations of carbohydrates: carbohydrates as suspects or guilty from slowing down training, carbophobia as a lifestyle, carbophobia as a religion and fi nally the love/hate relationship with carbohydrates. Conclusions: Low-carbohydrate diet is considered a healthy lifestyle in some amateur athletes. The results of this study show the power of virtual communication tools such as Twitter to support, promote and maintain uncommon and not necessarily healthy eating behaviours. Future studies should focus on the context in which these practices appear (AU)

A2a and a2b adenosine receptors affect HIF-1α signaling in activated primary microglial cells.

Microglia are central nervous system (CNS)-resident immune cells, that play a crucial role in neuroinflammation. Hypoxia-inducible factor-1 (HIF-1), the main transcription factor of hypoxia-inducible genes, is also involved in the immune response, being regulated in normoxia by inflammatory mediators. Adenosine is an ubiquitous nucleoside that has an influence on many immune properties of microglia through interaction with four receptor subtypes. The aim of this study was to investigate whether adenosine may affect microglia functions by acting on HIF-1α modulation. Primary murine microglia were activated with lipopolysaccharide (LPS) with or without adenosine, adenosine receptor agonists and antagonists and HIF-1α accumulation and downstream genes regulation were determined. Adenosine increased LPS-induced HIF-1α accumulation leading to an increase in HIF-1α target genes involved in cell metabolism [glucose transporter-1 (GLUT-1)] and pathogens killing [inducible nitric-oxide synthase (iNOS)] but did not induce HIF-1α dependent genes related to angiogenesis [vascular endothelial growth factor (VEGF)] and inflammation [tumor necrosis factor-α (TNF-α)]. The stimulatory effect of adenosine on HIF-1α and its target genes was essentially exerted by activation of A2A through p44/42 and A2B subtypes via p38 mitogen-activated protein kinases (MAPKs) and Akt phosphorylation. Furthermore the nucleoside raised VEGF and decreased TNF-α levels, by activating A2B subtypes. In conclusion adenosine increases GLUT-1 and iNOS gene expression in a HIF-1α-dependent way, through A2A and A2B receptors, suggesting their role in the regulation of microglial cells function following injury. However, inhibition of TNF-α adds an important anti-inflammatory effect only for the A2B subtype. GLIA 2015;63:1933-1952.

Differential Effect of Caffeine Consumption on Diverse Brain Areas of Pregnant Rats.

BACKGROUND: It has previously been shown that during gestation, the mother's brain has an increase in glial fibrillary acidic protein (GFAP)-immunoreactivity (-ir) and a decrease in the mRNA level of A1 adenosine receptor. Little is known about the A2A adenosine receptor in the maternal brain, and whether caffeine consumption throughout gestational period modifies GFAP and adenosine receptor density in specific brain areas. This study was undertaken to investigate the protein density of GFAP and adenosine receptors (A1 and A2A subtypes) in different regions of pregnant rat brain and the possible effect of caffeine on these proteins. METHODS: For this purpose, we examined the GFAP-, A1- and A2A-ir in the cingulate cortex (Cg2), dentate gyrus (DG), medial preoptic area (mPOA), secondary somatosensory cortex (S2), and striatum (Str) of pregnant Wistar rats (drug-free tap water or water with 1g/L diluted caffeine). RESULTS: We show a consistent and highly significant reduction of GFAP-ir in caffeine-treated pregnant rats in most of the areas analyzed. Our data demonstrate that caffeine consumption induces a significant increase of A2A-ir in Str. Concerning A1 receptor, the observed changes are dependent on the region analyzed; this receptor density is increased in Cg2, DG, and mPOA and decreased in the somatosensory cortex and Str. The results were confirmed by Western blotting. CONCLUSIONS: Our results suggest that chronic caffeine exposure could modify the physiolological situation of gestation by a reorganization of the neural circuits and the adenosine neuromodulator system.

Glutamate differently modulates excitatory and inhibitory adenosine receptors in neuronal and glial cells.

Adenosine is a neuromodulator which acts through adenosine receptors regulating functions such as inhibition of glutamate release. Adenosine A(1) and A(2A) receptor activations most often regulate opposing actions. Primary rat cortical neurons and rat C6 cells, an astrocytic derived cell line, were exposed to 100muM l-glutamate, and cell viability and transduction pathways mediated by both A(1) and A(2A) receptors were analyzed. Glutamate-induced excitotoxic damage was found only in cortical neurons, with C6 cells preserved. In C6 cells, adenosine A(1) and A(2A) receptors were increased and decreased, respectively. Consequently, A(1)-mediated adenylyl cyclase inhibition and A(2A)-mediated adenylyl cyclase stimulation were, respectively, increased and decreased after glutamate exposure. In cortical neurons, glutamate treatment increased both A(1) and A(2A) receptors. Moreover, adenylyl cyclase responsiveness to A(1) or A(2A) receptor agonists was heightened in these cells, in which pharmacological activation of AC induced cell death. Finally, activation of A(1) receptor or blockade of A(2A) receptor during glutamate treatment partially prevented the glutamate-induced cell death detected in cultured cortical neurons. Results show that adenosine receptors are regulated by glutamate, and that this regulation is dependent on the cell type, suggesting that adenosine receptors might be promising targets in the therapy against excitotoxic cell death.

Glutamate differently modulates metabotropic glutamate receptors in neuronal and glial cells.

Glutamate is an excitatory neurotransmitter implicated in learning and memory processes, but at high concentrations it acts as an excitotoxin causing degeneration and neuronal death. The aim of this work was to determine the excitotoxic effect of glutamate and the regulation of metabotropic glutamate receptors (mGluR) during excitotoxicity in neurons and C6 glioma cells. Results show that glutamate causes excitotoxic damage only in cortical neurons. Loss of cell viability in neurons was glutamate concentration- and time-dependent. Total mGluR levels were significantly reduced in these cells when exposed to glutamate. However, in C6 cells, which have been used as a model of glial cells, these receptors were regulated in a biphasic manner, decreased after 6 h, and increased after 24/48 h of treatment. Results show a cell dependent mGluR regulation by glutamate exposure which could mediate the vulnerability or not to glutamate mediated excitotoxicity.

Effect of glutamate intake during gestation on adenosine A(1) receptor/adenylyl cyclase pathway in both maternal and fetal rat brain.

Pregnant Wistar rats were orally treated with 1 g/L l-glutamate during the entire gestational period and the status of adenosine A(1) receptor (A(1)R)/adenylyl cyclase transduction pathway from maternal and fetal brain was analyzed. Glutamate consumption, estimated from the loss of water from the drinking bottles, was 110 +/- 4.6 mg/kg/day. In mother brains glutamate intake did not significantly alter the B(max) value, although the K(d) value was significantly decreased. However in fetus brain, a significant decrease in B(max) was observed, without an alteration of K(d) value. Similar results were observed by western blot assays using specific A(1)R antibody, suggesting a down-regulation of A(1)R in fetal brain. Concerning alpha subunits of inhibitory G proteins (Gi), alphaGi(3) protein was slightly but significantly decreased in maternal brain without alterations of either Gi(1) or Gi(2). In contrast, alphaGi(1) and alphaGi(2) isoforms were increased in fetal brain. On the other hand, basal, forskolin, and forskolin plus GTPgammaS-stimulated adenylyl cyclase activity was significantly decreased in both maternal and fetal brain, and this was more prominent in fetal than in maternal brain. Finally, A(1)R functionality was significantly decreased in mother brain whereas no significant differences were detected in fetus brain. These results suggest that glutamate administered to pregnant rats modulates A(1)R signaling pathways in both tissues, showing an A(1)R down-regulation in fetal brain, and desensitization in maternal brain.

Metabotropic glutamate receptor/phospholipase C system in female rat heart.

Glutamate is the main excitatory neurotransmitter in the central nervous system. This amino acid mediates learning and memory processes acting through ionotropic and metabotropic receptor binding. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that stimulate phospholipase C (PLC) or inhibit adenylyl cyclase (AC). MGluRs have been widely described in CNS. However, little is known about these receptors in peripheral system. The present work describes the mGluR/PLC pathway in membranes from pregnant and non-pregnant rat heart by radioligand binding, Western-blot assays and PLC activity determination. Furthermore, mRNA coding mGluR1, mGluR5, alphaGq/11 and PLCbeta1 was identified by RT-PCR. Binding assays indicated total mGlu receptor numbers of 4.7+/-0.2 pmol/mg protein and 4.2+/-1.0 pmol/mg protein in non-pregnant and pregnant rats respectively, and their corresponding KD values were 545.3+/-85.6 nM and 1062.8+/-393.6 nM. Western blots revealed bands corresponding to mGluR1 and mGluR5 receptors, confirming that these receptors are expressed in heart. The beta1 isoform of PLC, which mediates group I mGluRs (mGluR I) response, was also expressed in rat heart. Moreover, PLC activity was modulated by calcium in a dose-dependent manner. Finally, specific agonists for mGluRs increased the PLC activity and the increase was prevented by specific mGluR antagonists. These results demonstrate the presence of group I mGlu receptors and their functional coupling to the PLC stimulation in female rat heart, suggesting a possible role of mGluR/PLC pathway in this tissue.

Endogenous expression of adenosine A1, A2 and A3 receptors in rat C6 glioma cells.

Inhibitory and stimulatory adenosine receptors have been identified and characterized in both membranes and intact rat C6 glioma cells. In membranes, saturation experiment performed with [(3)H]DPCPX, selective A(1)R antagonist, revealed a single binding site with a K (D) = 9.4 +/- 1.4 nM and B (max) = 62.7 +/- 8.6 fmol/mg protein. Binding of [(3)H]DPCPX in intact cell revealed a K (D) = 17.7 +/- 1.3 nM and B (max )= 567.1 +/- 26.5 fmol/mg protein. On the other hand, [(3)H]ZM241385 binding experiments revealed a single binding site population of receptors with K (D) = 16.5 +/- 1.3 nM and B (max) = 358.9 +/- 52.4 fmol/mg protein in intact cells, and K (D) = 4.7 +/- 0.6 nM and B (max) = 74.3 +/- 7.9 fmol/mg protein in plasma membranes, suggesting the presence of A(2A) receptor in C6 cells. A(1), A(2A), A(2B) and A(3 )adenosine receptors were detected by Western-blotting and immunocytochemistry, and their mRNAs quantified by real time PCR assays. Gialpha and Gsalpha proteins were also detected by Western-blotting and RT-PCR assays. Furthermore, selective A(1)R agonists inhibited forskolin- and GTP-stimulated adenylyl cyclase activity and CGS 21680 and NECA stimulated this enzymatic activity in C6 cells. These results suggest that C6 glioma cells endogenously express A(1) and A(2) receptors functionally coupled to adenylyl cyclase inhibition and stimulation, respectively, and suggest these cells as a model to study the role of adenosine receptors in tumoral cells.

Utilidad diagnóstica de las pruebas cutáneas rast enzimático y determinación de eosinófilos en moco nasal en la rinitis alérgica / Diagnosis utility in skin and enzymatic tests in the nasal mucous

Antecedentes: la rinitis alérgica es la enfermedad más común mediada por inmunoglobulina E (IgE). El reto nasal es el estándar de oro para el diagnóstico de rinitis alérgica. Las pruebas cutáneas (PC) son el método diagnóstico más utilizado para detectar la presencia de la IgE específica unida a mastocitos de la piel. La exposición de la mucosa nasal al alergeno es seguida de un incremento en los eosinófilos locales; la determinación de eosinófilos en el moco nasal (DEMN) es una prueba diagnóstica de la rinitis alérgica. El RAST enzimático o prueba enzimática. Alergoabsorbente (EAST) determina el nivel de IgE específica de alergeno presente en suero. Objetivo: medir la sensibilidad, especificidad y exactitud diagnóstica de las pruebas cutáneas, la EAST y la DEMN en la rinitis alérgica. Material y método: se estudiaron 241 sujetos, 162 casos con rinitis alérgica y 79 controles. Fueron objeto de retos nasales y pruebas cutáneas intradérmicas y Dermatophagoides spp (ácaro), Fraxinus americana (fresno), Amaranthus palmeri (quelite), Cynodon dactylon (capriola) y Felis catus (gato), EAST para Dermatophagoides pteronyssinus (ácaro) y DEMN. Los resultados de las Pc, EAST y DEMN se compararon con los retos nasales correspondientes, y se determinó la prevalencia de rinitis alérgica a cada alergeno, se estimó el mejor punto de corte por medio de curvas operador receptos (ROC) y de acuerdo con el mejor punto de corte se determinó la sensibilidad, especificidad, valor predictivo positivo y negativo, coeficiente de concordancia interobservador, el área bajo la curva ROC (q), el error estándar de q (SEO) y el intervalo de confianza de 95 por ciento de q de cada prueba evaluada. Resultados. Las mejores sensibilidades y especificidades las presentaron las pruebas cutáneas y la EAST, la sensibilidad y especificidad más bajas DEMN. Conclusión. Para el diagnóstico de rinitis alérgica por Dermatophagoides spp las pruebas cutáneas para Dermatophagoides spp y la EAST para Derma-tophagoides pteronyssinus tiene la misma exactitud diagnóstica. Según los índices de exactitud diagnóstica y el coeficiente de concordancia interobservador, las pruebas cutáneas y la EAST son útiles para el diagnóstico de rinitis alérgica inducida por los alergenos evaluados y la DEMN es de poca utilidad para el diagnóstico de rinitis alérgica

Efecto en el VEF1 al administrar salbutamol con la cámara de retención, espaciador e inhalador de dosis medida / The VEF1 effect at the salbutamol administration with the retention camera, inhalator of control dosage

Se incluyeron 13 pacientes con diagnóstico de asma y que cumplían con los criterios de selección, a los cuales se les practicó espirometría antes y después de aplicar salbutamol por alguno de los dispositivos en forma aleatoria. El efecto sobre el VEF1 con el inhalador de dosis medida (MDI) fue de 22.76 por ciento, con el espaciador fue 23.35 por ciento y con la cámara de retención 23.94 por ciento. El análisis estadístico no mostró diferencia significativa entre los resultados, por lo que se refiere que los tres dispositivos tienen la misma eficacia para administrar salbutamol en aerosol

Concentración de IgE en sangre de cordón umbilical en recién nacidos sanos / Concentration of IgE in blood of the umbilical cord in newborn

Las concentraciones séricas de IgE se modifican por factores como edad, raza, condiciones ambientales y estado de salud. Se estudiaron 113 niños recién nacidos de 38 a 42 semanas de gestación, clínicamente sanos, a los que se les extrajo sangre del cordón umbilical y se les midió la concentración de IgE por el método de ELISA. Se obtuvieron los siguientes resultados: 85 por ciento de los niños recién nacidos tenían concentraciones de IgE de 0.5 UI/ml a 4.0 UI/ml. No se observaron diferencias estadísticamente significativas respecto a la edad gestacional o el sexo. Las concentraciones séricas de IgE observadas en estos pacientes fueron un poco mayores que las informadas en otros grupos estudiados. Esos resultados pueden considerarse para el diagnóstico de enfermedades alérgicas en recién nacidos e identificación de factores de riesgo