Cannabidiol Modifies the Glutamate Over-Release in Brain Tissue of Patients and Rats with Epilepsy: A Pilot Study.

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release (p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE.

Nucleoporin Nup358 Downregulation Tunes the Neuronal Excitability in Mouse Cortical Neurons.

Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophysiology of neurodegenerative diseases (NDDs). Although the downregulation of Nup358 leads to a reduction in the scaffold protein ankyrin-G at the axon initial segment (AIS) of mature neurons, the function of Nup358 in the cytoplasm of neurons remains elusive. To investigate whether Nup358 plays any role in neuronal activity, we downregulated Nup358 in non-pathological mouse cortical neurons and measured their active and passive bioelectrical properties. We identified that Nup358 downregulation is able to produce significant modifications of cell-membrane excitability via voltage-gated sodium channel kinetics. Our findings suggest that Nup358 contributes to neuronal excitability through a functional stabilization of the electrical properties of the neuronal membrane. Hypotheses will be discussed regarding the alteration of this active regulation as putatively occurring in the pathophysiology of NDDs.

GABAB Receptors Tonically Inhibit Motoneurons and Neurotransmitter Release from Descending and Primary Afferent Fibers.

Motoneurons receive thousands of excitatory and inhibitory synapses from descending tracts and primary afferent fibers. The excitability of these neurons must be precisely regulated to respond adequately to the requirements of the environment. In this context, GABAA and GABAB receptors regulate motoneuron synaptic strength. GABAA and GABAB receptors are expressed on primary afferent fibers and motoneurons, while in the descending afferent fibers, only the GABAB receptors are expressed. However, it remains to be known where the GABA that activates them comes from since the GABAergic interneurons that make axo-axonic contacts with primary afferents have yet to be identified in the descending afferent terminals. Thus, the main aim of the present report was to investigate how GABAB receptors functionally modulate synaptic strength between Ia afferent fibers, excitatory and inhibitory descending fibers of the dorsolateral funiculus, and spinal motoneurons. Using intracellular recordings from the spinal cord of the turtle, we provide evidence that the GABAB receptor antagonist, CGP55845, not only prevents baclofen-induced depression of EPSPs but also increases motoneuron excitability and enhances the synaptic strength between the afferent fibers and motoneurons. The last action of CGP55845 was similar in excitatory and inhibitory descending afferents. Interestingly, the action of baclofen was more intense in the Ia primary afferents than in the descending afferents. Even more, CGP55845 reversed the EPSP depression induced by the increased concentration of ambient GABA produced by interneuron activation and GABA transporter blockade. Immunofluorescence data corroborated the expression of GABAB receptors in the turtle's spinal cord. These findings suggest that GABAB receptors are extrasynaptic and tonically activated on descending afferent fibers and motoneurons by GABA released from astrocytes and GABAergic interneurons in the cellular microenvironment. Finally, our results also suggest that the antispastic action of baclofen may be due to reduced synaptic strength between descending fibers and motoneurons.

Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases.

Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.

Sistema de gestión TO-BE: garantizar el derecho a la salud de pacientes con ITS en Perú / TO-BE management system: guaranteeing the right to health of patients with STIs in Peru

Se realizó una investigación de campo para conocer la gestión de los procesos de solicitud y admisión de citas médicas, considerando la estigmatización y discriminación de las personas ITS, con el fin de garantizar el derecho a la salud de estos pacientes en Perú. Se ejecutó la sistematización de la información sobre los procesos y mecanismos de exigibilidad, bajo los lineamientos y manuales de los cuatro procesos estratégicos del MINSA contemplados para el otorgamiento de citas médicas, siguiendo los lineamientos de Gob.Pe, Adicionalmente, mediante verificación de los procesos se construyeron la matriz entidad-relación de la gestión por procesos del SSP, y el flujograma del proceso de solicitud y otorgamiento de citas AS-ISS. Se consideraron aspectos tecnológicos-médicos-legales con la participación de 201 pacientes independientemente del motivo o patología a consultar, identificando incidentes en la eficiencia del proceso misional. Por último, se implementó el flujograma de procesos de reserva de citas médicas a través de la aplicación ejecutable para smartphones, tabletas y otros dispositivos móviles (APP) TO-BE la cual conlleva a 10 pasos desde el registro de usuario hasta la emisión de comprobante de otorgamiento de cita médica. Se analizaron las preferencias de los usuarios sobre las causas superables en el proceso misional, mediante una encuesta estructura a 170 usuarios de SSP(AU)

A field investigation was carried out to learn about the management of the processes of request and admission of medical appointments, considering the stigmatization and discrimination of STI people, in order to guarantee the right to health of these patients in Peru. The systematization of the information on the processes and mechanisms of enforceability was carried out, under the guidelines and manuals of the four strategic processes of the MINSA contemplated for the granting of medical appointments, following the guidelines of Gov. Pe, Additionally, through verification of the processes The entity-relationship matrix of the management by processes of the SSP, and the flowchart of the process of request and granting of appointments AS-ISS were constructed. Technological-medical-legal aspects were considered with the participation of 201 patients regardless of the reason or pathology to be consulted, identifying incidents in the efficiency of the missionary process. Finally, the flowchart of medical appointment reservation processes was implemented through the executable application for smartphones, tablets and other mobile devices (APP) TO-BE, which entails 10 steps from user registration to issuance of voucher of granting a medical appointment. Users' preferences regarding causes that can be overcome in the missionary process were analyzed through a structured survey of 170 SSP users(AU)

Sars-CoV-2: impulsor del eGovernment en la administración de justicia en el distrito judicial de Junín / Sars-CoV-2: promoter of eGovernment in the administration of justice in the judicial district of Junín

El eGovernment es un sistema interconectado que interactúa con los ciudadanos y les brinda servicios aumentados a través de aplicaciones electrónicas, con la ayuda de las TIC, en este caso, con la llegada del Sars-CoV-2 se pretendió conocer el impulso en el sistema de justicia del distrito judicial de Junín, así como, las disposiciones para la contención de la propagación de este coronavirus emitidas por sistemas de justicia y salud; mediante el método Análisis- Síntesis. Se logró obtener que el 60.55% de los encuestados han manifestado que la implementación del Gobierno Electrónico coadyuva en la garantía en la impartición de justicia; coadyuva al cumplimiento del debido proceso y el 49.54% indicó estar de acuerdo en que la aplicación del eGovernment incide efectivizando la función jurisdiccional en el Distrito Judicial de Junín. A nivel nacional, se encuentra en pleno proceso de transformación digital a través de la identificación y adopción de soluciones digitales tales como la historia clínica electrónica, la telesalud y todas sus formas, y la Agenda Digital del Sector Salud 2020-2025, constituye un valioso instrumento para la articulación y conducción del sector, promoción de la transformación digital en salud con el uso de tecnologías de información para la mejora de calidad de la atención en salud y, la necesidad de acelerar dicha transformación, a fin de contribuir en mitigar los efectos de la emergencia sanitaria por la actual pandemia Covid-19 y, de otras que se presenten(AU)

The eGovernment is an interconnected system that interacts with citizens and provides them increased services through electronic applications, with the help of ICT, in this case, with the arrival of Sars-CoV-2, it was intended to know the momentum in the system of justice of the judicial district of Junín, as well as, the provisions for the containment of the spread of this coronavirus issued by justice and health systems; using the Analysis-Synthesis method. It was possible to obtain that 60.55% of the respondents have stated that the implementation of the Electronic Government contributes to the guarantee in the administration of justice; It contributes to compliance with due process and 49.54% indicated they agree that the application of the eGovernment affects the judicial function in the Junín Judicial District. At the national level, it is in the process of digital transformation through the identification and adoption of digital solutions such as electronic medical records, telehealth and all its forms, and the Digital Agenda of the Health Sector 2020-2025, constitutes a valuable instrument for the articulation and management of the sector, promotion of digital transformation in health with the use of information technologies to improve the quality of health care and, the need to accelerate said transformation, in order to contribute to mitigating the effects of the health emergency due to the current Covid-19 pandemic and, of others that arise(AU)

Asistencia sanitaria y servicios sociales: enseñanza y aprendizaje significativo en talleres técnicos por el método de proyecto / Healthcare and social services: meaningful teaching and learning in technical workshops by the project method

Los derechos humanos, incluyendo la concreción del derecho a la salud, en Perú, contempla el mandato dirigido a los poderes públicos para que organicen la asistencia sanitaria, como elemento causal, específico y adopten el conjunto de medidas necesarias para lograr la prevención de las enfermedades o la mejora de las condiciones sanitarias generales, mediante el método de proyecto en el proceso enseñanza-aprendizaje se abordan los principios rectores de la política social y económica, contenidos del Estado social, y los mecanismos de justiciabilidad y exigibilidad. Se estudió el proceso enseñanza y aprendizaje significativo sobre asistencia sanitaria y servicios sociales en los talleres técnicos, en la Facultad de Derecho y Ciencias Políticas, de la Universidad Peruana Los Andes, durante el periodo lectivo 2019-II. En el egresado conlleva la interacción entre los conocimientos y la información nueva que recibe, en este proceso se construye un nuevo conocimiento o profundiza en los ya existentes. Este conocimiento es organizado y sistemático con conexiones interdisciplinarias entre ideas, se promueve desde el trabajo en equipo y colaborativo, capaz de vencer ambigüedades, complejidades y a lo impredecible; y aprovecha los recursos o herramientas de la vida real, por lo que el método de proyecto es una herramienta pedagógica aplicable a la formación del abogado(AU)

Human rights, including the realization of the right to health, in Peru, contemplates the mandate directed to the public powers to organize health care, as a causal, specific element and adopt the set of measures necessary to achieve the prevention of diseases or the improvement of general sanitary conditions, through the project method in the teaching-learning process, the guiding principles of social and economic policy, contents of the social State, and the mechanisms of justiciability and enforceability are addressed. The teaching and meaningful learning process on health care and social services was studied in technical workshops at the Faculty of Law and Political Sciences, Universidad Peruana Los Andes, during the 2019-II school period. In the graduate, it involves the interaction between knowledge and the new information received, in this process a new knowledge is built or deepens existing ones. This knowledge is organized and systematic with interdisciplinary connections between ideas, it is promoted from team and collaborative work, capable of overcoming ambiguities, complexities and the unpredictable; and it takes advantage of the resources or tools of the real life, reason why the project method is a pedagogical tool applicable to the training of the lawyer(AU)

TREK-1 potassium channels participate in acute and long-lasting nociceptive hypersensitivity induced by formalin in rats.

TREK-1 channels are expressed in small nociceptive dorsal root ganglion (DRG) neurons where they participate in acute inflammatory and neuropathic pain. However, the role of TREK-1 in persistent pain is not well understood. The aim of this study was to investigate the local peripheral and spinal participation of TREK-1 in formalin-induced acute and long-lasting nociceptive hypersensitivity. Local peripheral or intrathecal pre-treatment with spadin, selective blocker of TREK-1, increased acute flinching behavior and secondary mechanical allodynia and hyperalgesia behavior observed 6 days after formalin injection. Local peripheral or intrathecal pre-treatment with BL-1249, selective opener of TREK-1, decreased long-lasting secondary mechanical allodynia and hyperalgesia induced by formalin. Pre-treatment with BL-1249 prevented the pro-nociceptive effect of spadin on acute nociception and long-lasting mechanical allodynia and hyperalgesia in rats. Pre-treatment with two recombinant channels that produce a high TREK-1 current, S300A and S333A (non-phosphorylated state of TREK-1), reduced formalin-induced acute pain and long-lasting mechanical allodynia and hyperalgesia. Besides, post-treatment with S300A, S333A or BL-1249 reversed long-lasting mechanical allodynia and hyperalgesia induced by formalin. Formalin increased TREK-1 expression at 1 and 6 days in DRG and dorsal spinal cord in rats, whereas that it increased c-fos expression at the DRG. Intrathecal repeated transfection of rats with S300A and S333A or injection with BL-1249 reduced formalin-induced enhanced c-fos expression. Data suggest that TREK-1 activity at peripheral and spinal sites reduces neuronal excitability in the process of acute and long-lasting nociception induced by formalin in rats.

A Monolayer System for the Efficient Generation of Motor Neuron Progenitors and Functional Motor Neurons from Human Pluripotent Stem Cells.

Methods for the conversion of human induced pluripotent stem cells (hiPSCs) into motor neurons (MNs) have opened to the generation of patient-derived in vitro systems that can be exploited for MN disease modelling. However, the lack of simplified and consistent protocols and the fact that hiPSC-derived MNs are often functionally immature yet limit the opportunity to fully take advantage of this technology, especially in research aimed at revealing the disease phenotypes that are manifested in functionally mature cells. In this study, we present a robust, optimized monolayer procedure to rapidly convert hiPSCs into enriched populations of motor neuron progenitor cells (MNPCs) that can be further amplified to produce a large number of cells to cover many experimental needs. These MNPCs can be efficiently differentiated towards mature MNs exhibiting functional electrical and pharmacological neuronal properties. Finally, we report that MN cultures can be long-term maintained, thus offering the opportunity to study degenerative phenomena associated with pathologies involving MNs and their functional, networked activity. These results indicate that our optimized procedure enables the efficient and robust generation of large quantities of MNPCs and functional MNs, providing a valid tool for MNs disease modelling and for drug discovery applications.

Interaction of NHE1 and TRPA1 Activity in DRG Neurons Isolated from Adult Rats and its Role in Inflammatory Nociception.

Transient receptor potential ankyrin 1 (TRPA1) channel is expressed in a subset of nociceptive neurons. This channel integrates several nociceptive signals. Particularly, it is modulated by intracellular pH (pHi). Na+/H+ exchanger 1 (NHE1) contributes to the maintenance of pHi in nociceptors. However, it is currently unknown whether the interaction between TRPA1 and NHE1 contributes to the nociceptive processing. Thus, the purpose of this study was to assess the functional interaction between NHE1 and TRPA1 in small dorsal root ganglion (DRG) neurons from primary culture obtained from adult rats. Moreover, we also evaluated their possible interaction in acute and inflammatory pain. Zoniporide (selective NHE1 inhibitor) reduced pHi and increased intracellular calcium in a concentration-dependent fashion in DRG neurons. Zoniporide and allyl isothiocyanate (AITC, TRPA1 agonist) increased calcium transients in the same DRG neuron, whereas that A-967079 (TRPA1 antagonist) prevented the effect of zoniporide in DRG neurons. Repeated AITC induced TRPA1 desensitization and this effect was prevented by zoniporide. Both NHE1 and TRPA1 were localized at the membrane surface of DRG neurons in culture. Local peripheral zoniporide enhanced AITC-induced pronociception and this effect was prevented by A-967079. Likewise, zoniporide potentiated Complete Freund's Adjuvant (CFA)-induced hypersensitivity, effect which was prevented by A-967079 in vivo. CFA paw injection increased TRPA1 and decresed NHE1 protein expression in DRG. These results suggest a functional interaction between NHE1 and TRPA1 in DRG neurons in vitro. Moreover, data suggest that this interaction participates in acute and inflamatory pain conditions in vivo.

Clenbuterol-sensitive delayed outward potassium currents in a cell model of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. SBMA is characterized by selective dysfunction and degeneration of motor neurons in the brainstem and spinal cord through still unclear mechanisms in which ion channel modulation might play a central role as for other neurodegenerative diseases. The beta2-adrenergic agonist clenbuterol was observed to ameliorate the SBMA phenotype in mice and patient-derived myotubes. However, the underlying molecular mechanism has yet to be clarified. Here, we unveil that ionic current alterations induced by the expression of polyQ-expanded AR in motor neuron-derived MN-1 cells are attenuated by the administration of clenbuterol. Our combined electrophysiological and pharmacological approach allowed us to reveal that clenbuterol modifies delayed outward potassium currents. Overall, we demonstrated that the protection provided by clenbuterol restores the normal function through the modulation of KV2-type outward potassium currents, possibly contributing to the protective effect on motor neuron toxicity in SBMA.

ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by expansions of a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is associated with the progressive loss of lower motor neurons, together with muscle weakness and atrophy. PolyQ-AR is converted to a toxic species upon binding to its natural ligands, testosterone, and dihydrotestosterone (DHT). Our previous patch-clamp studies on a motor neuron-derived cell model of SBMA showed alterations in voltage-gated ion currents. Here, we identified and characterized chloride currents most likely belonging to the chloride channel-2 (ClC-2) subfamily, which showed significantly increased amplitudes in the SBMA cells. The treatment with the pituitary adenylyl cyclase-activating polypeptide (PACAP), a neuropeptide with a proven protective effect in a mouse model of SBMA, recovered chloride channel current alterations in SBMA cells. These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease.

Spinal TASK-1 and TASK-3 modulate inflammatory and neuropathic pain.

This study assessed the participation of spinal TWIK-related acid-sensitive K+ channels 1 and 3 (TASK-1 and TASK-3) in inflammatory (formalin test) and neuropathic (spinal nerve ligation, SNL) pain in rats. Intrathecal pre-treatment (-10 min) with the TASK-1 blocker ML365 or TASK-3 blocker PK-THPP, but not vehicle, enhanced in a dose-dependent manner 1% formalin-induced acute and long-lasting secondary mechanical allodynia and mechanical hyperalgesia in rats. In contrast, intrathecal pre-treatment with terbinafine, an activator of TASK-3, reduced formalin-induced flinching and allodynia/hyperalgesia. Both blockers and terbinafine had similar effects on female and male rats. In addition, intrathecal injection of ML365 or PK-THPP blocked the terbinafine-induced antiallodynic effect in neuropathic rats, but they did not modify baseline withdrawal threshold in naïve or sham-operated rats. TASK-1 and TASK-3 mRNA and protein were expressed in L4 and L5 dorsal root ganglia (DRG) and dorsal and ventral spinal cord of naïve animals. Interestingly, formalin injection increased TASK-1 expression in ipsilateral L5 DRG, but not in the spinal cord. Moreover, formalin injection transiently enhanced TASK-3 expression in ipsilateral L5 DRG and dorsal spinal cord. In contrast, SNL down-regulated TASK-3 expression in the ipsilateral L4 and L5 DRG but not in dorsal or ventral spinal cord, while SNL did not modify TASK-1 expression at any tissue. The pharmacological and molecular results suggest that TASK-1 and TASK-3 have a relevant antinociceptive role in inflammatory and neuropathic pain.

Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain.

The aim of this study was to determine the participation of anoctamin-1 in 2 models of neuropathic pain in rats (L5/L6 spinal nerve ligation [SNL] and L5 spinal nerve transection [SNT]). SNL and SNT diminished withdrawal threshold in rats. Moreover, SNL up-regulated anoctamin-1 protein expression in injured L5 and uninjured L4 DRG whereas that it enhanced activating transcription factor 3 (ATF-3) and caspase-3 expression only in injured L5 DRG. In marked contrast, SNT enhanced ATF-3 and caspase-3, but not anoctamin-1, expression in injured L5 DRG but it did not modify anoctamin-1, ATF-3 nor caspase-3 expression in uninjured L4 DRG. Accordingly, repeated (3 times) intrathecal injection of the anoctamin-1 blocker T16Ainh-A01 (0.1-1 µg) or MONNA (1-10 µg) partially reverted SNL-induced mechanical allodynia in a dose-dependent manner. In contrast, anoctamin-1 blockers only produced a modest effect in SNT-induced mechanical allodynia. Interestingly, intrathecal injection of T16Ainh-A01 (1 µg) or MONNA (10 µg) prevented SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 in injured L5 DRG. Repeated intrathecal injection of T16Ainh-A01 or MONNA also reduced SNT-induced up-regulation of ATF-3 in injured L5 DRG. In contrast, T16Ainh-A01 and MONNA did not affect SNT-induced up-regulation of caspase-3 expression in L5 DRG. Likewise, gabapentin (100 µg) diminished SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 expression in injured L5 DRG. These data suggest that spinal anoctamin-1 in injured and uninjured DRG participates in the maintenance of neuropathic pain in rats. Our data also indicate that expression of anoctamin-1 in DRG is differentially regulated depending on the neuropathic pain model.

Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity. MATERIALS AND METHODS: Formalin (1%)-induced chronic hypersensitivity was determined by the application of von Frey filaments to ipsilateral and contralateral paws and through pharmacological testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting. RESULTS: Formalin (1%) injection produced acute flinching behavior (1 h) as well as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment (10 min before) or posttreatment (6 days later) with A-967079 (1-100 µM) partially prevented and reversed, respectively, in a dose-dependent manner, long-lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin. Likewise, intrathecal pretreatment or posttreatment with A-967079 partially prevented and reversed, respectively, formalin-induced long-lasting hypersensitivity. A-967079 (100 µM) completely abolished the pro-nociceptive effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased TRPA1 protein expression in the DRG and spinal cord. CONCLUSION: Results indicate that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin-induced long-lasting secondary nociceptive hypersensitivity.

Resumen Reunión Nacional de la Red de Vivienda Saludable Proyecciones, logros y retos al culminar el 2014 / Report on the National Meeting of the Healthy Housing Network. Perspectives, achievements and challenges at the end of 2014

Se realiza una relatoría de lo acontecido en la Reunión Nacional de Vivienda Saludable 2014, para informar a los interesados en el tema de los logros y los retos del trabajo de la Red Cubana durante el año 2014 y las proyecciones a futuro, cuyos miembros trazan para el próximo año(AU)

A report is provided on the National Meeting of the Healthy Housing Network 2014, with the purpose of informing those interested in the topic about the achievements and challenges of the Cuban Network in 2014, as well as the actions planned by its members for next year(AU)

Resumen Reunión Nacional de la Red de Vivienda Saludable Proyecciones, logros y retos al culminar el 2014 / Report on the National Meeting of the Healthy Housing Network. Perspectives, achievements and challenges at the end of 2014

Se realiza una relatoría de lo acontecido en la Reunión Nacional de Vivienda Saludable 2014, para informar a los interesados en el tema de los logros y los retos del trabajo de la Red Cubana durante el año 2014 ylas proyecciones a futuro, cuyos miembros trazan para el próximo año(AU)

A report is provided on the National Meeting of the Healthy Housing Network 2014, with the purpose of informing those interested in the topic about the achievements and challenges of the Cuban Network in 2014, as well as the actions planned by its members for next year(AU)

Role of TRPV1 and ASIC3 in formalin-induced secondary allodynia and hyperalgesia.

BACKGROUND: In the present study we determined the role of transient receptor potential V1 channel (TRPV1) and acid-sensing ion channel 3 (ASIC3) in chronic nociception. METHODS: 1% formalin was used to produce long-lasting secondary allodynia and hyperalgesia in rats. Western blot was used to determine TRPV1 and ASIC3 expression in dorsal root ganglia. RESULTS: Peripheral ipsilateral, but not contralateral, pre-treatment (-10min) with the TRPV1 receptor antagonists capsazepine (0.03-0.3µM/paw) and A-784168 (0.01-1µM/paw) prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in the ipsilateral and contralateral paws. Likewise, peripheral ipsilateral, but not contralateral, pre-treatment with the non-selective and selective ASIC3 blocker benzamil (0.1-10µM/paw) and APETx2 (0.02-2µM/paw), respectively, prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Peripheral ipsilateral post-treatment (day 6 after formalin injection) with capsazepine (0.03-0.3µM/paw) and A-784168 (0.01-1µM/paw) reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. In addition, peripheral ipsilateral post-treatment with benzamil (0.1-10µM/paw) and APETx2 (0.02-2µM/paw), respectively, reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. TRPV1 and ASIC3 proteins were expressed in dorsal root ganglion in normal conditions, and 1% formalin injection increased expression of both proteins in this location at 1 and 6 days compared to naive rats. CONCLUSIONS: Data suggest that TRPV1 and ASIC3 participate in the development and maintenance of long-lasting secondary allodynia and hyperalgesia induced by formalin in rats. The use of TRPV1 and ASIC3 antagonists by peripheral administration could prove useful to treat chronic pain.

Experiencias exitosas con escolares en programas de vigilancia entomológica no convencional en una comunidad del estado Cojedes, Venezuela / Successful Experience with students in programmes of non-conventional entomological surveillance in a rural community from Cojedes State, Venezuela

Motivated the resurgence of dengue and the emergence of chikungunya fever active entomological surveillance of triatomines in Cojedes state decreased dramatically. In this situation there is a need to incorporate communities unconventional entomological surveillance. To this end, conducting a pilot study in school Peasant Village Settlement Fundo Zamorano Paraima, Aroita sector in the municipality of San Juan Bautista Pao Cojedes state in Venezuela, to provide skills and abilities in the considered chipos capture and thus avoid the paralysis of entomological surveillance. The test results showed that predict good omens in the incorporation of the community in the work of entomological surveillance.

Motivado al recrudecimiento del dengue y a la emergencia de la fiebre de Chikungunya la vigilancia entomológica activa de los triatominos en el estado Cojedes disminuyó drásticamente. Ante esta situación se planteó la necesidad de incorporar a las comunidades a la vigilancia entomológica no convencional. A tal efecto, se consideró la realización de un estudio piloto en escolares del Asentamiento campesino Fundo Zamorano Pueblo Paraima, sector Aroita, ubicado en el municipio Pao de San Juan Bautista del estado Cojedes en Venezuela, con el fin de proporcionarles habilidades y destrezas en la captura de chipos y, de esta forma, evitar la paralización de la vigilancia entomológica. El ensayo arrojó resultados que permiten predecir buenos augurios en la incorporación de la comunidad en las labores de vigilancia entomológica.

Evidence for the participation of Ca(2+)-activated chloride channels in formalin-induced acute and chronic nociception.

In this study we determined the role of Ca(2+)-activated chloride channels (CaCC) in acute and chronic nociceptive responses elicited by 1% formalin. Formalin injection produced a typical pattern of flinching behavior for about 1h. Moreover, it produced secondary allodynia and hyperalgesia in the ipsilateral and contralateral paws for at least 6 days. Local peripheral and intrathecal pre-treatment (-10 min) with the non-selective and selective CaCC blockers niflumic acid and CaCCinh-A01, respectively, prevented formalin-induced flinching behavior mainly during phase 2 of the formalin test. Furthermore, niflumic acid and CaCCinh-A01 also prevented in a dose-dependent manner the long-lasting evoked secondary mechanical allodynia and hyperalgesia in the ipsilateral and contralateral paws. Moreover, local peripheral and intrathecal post-treatment (on day 6) with both CaCC blockers decreased the established formalin-induced secondary mechanical allodynia and hyperalgesia behavior in both paws. CaCC anoctamin-1 and bestrophin-1 were detected in the dorsal root ganglia. Formalin injection increased anoctamin-1, but not bestrophin-1 protein levels at 6 days. Intrathecal injection of the CaCC inhibitor CaCCinh-A01 prevented formalin-induced anoctamin-1 increase. Data suggest that peripheral and spinal CaCC, and particularly anoctamin-1, participates in the acute nociception induced by formalin as well as in the development and maintenance of secondary mechanical allodynia and hyperalgesia. Thus, CaCC activity contributes to neuronal excitability in the process of nociception induced by formalin.