Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory Axons / 神经科学通报·英文版

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.

A utilização da imitação facial em tarefas de reconhecimento de expressões emocionais / The use of facial mimicry in emotional expressions recognition tasks / El uso de la imitación facial en tareas de reconocimiento de expresiones emocionales

A imitação facial é um comportamento involuntário capaz de facilitar a transmissão de informações não verbais relevantes em diferentes contextos sociais. Este estudo teve por objetivo analisar a capacidade de reconhecimento de expressões emocionais enquanto o observador tensiona a própria face ou imita a face-alvo. A hipótese utilizada foi a de que indivíduos que tensionam a própria face terão menor probabilidade de acertos na execução das tarefas de reconhecimento de expressões emocionais e aqueles que imitam a expressão terão uma maior probabilidade de acertos na execução das mesmas tarefas. A amostra foi composta por 30 participantes, divididos em dois grupos experimentais: o Grupo Imitação (GI) e o Grupo Ruído (GR), ambos com 18 participantes do sexo feminino e 12 do sexo masculino. O experimento consistiu em apresentar fotos de atores expressando facialmente uma emoção básica por 10 segundos. Neste período, os participantes deveriam, então, observar ou intervir facialmente, imitando ou tensionando a própria face (de acordo com o grupo alocado, Imitação ou Ruído). Após os 10 segundos executando a instrução (observar, imitar ou interferir), o participante deveria responder - entre as opções alegria, tristeza, nojo, raiva, surpresa e medo - a emoção correspondente à imagem. Os resultados apresentaram diferenças significativas quando comparadas as tarefas de tensionar ou imitar a face-alvo, sugerindo que a alteração da própria face do observador pode influenciar durante o desempenho de uma tarefa de reconhecimento de emoções em faces.(AU)

Facial mimicry is an involuntary behavior capable of facilitating the transmission of relevant non-verbal information in different social contexts. The present study aimed to analyze the ability to recognize emotional expressions while the observer tenses their own face or imitates the target face. The hypothesis used was that individuals who tension their own face or imitate the expression of facial emotion have less or greater probability of success in performing tasks to recognize emotional expressions on faces, respectively. The sample consisted of 30 participants, divided into two experimental groups: the Imitation Group - GI (18 female participants and 12 male participants) and the Noise Group - GR (18 female participants and 12 male participants). The experiment consisted of presenting pictures of actors facially expressing a basic emotion for 10 seconds; the participants should then observe or intervene facially, imitating or tensing their own face (according to the allocated group, Imitation or Noise). After 10 seconds of executing the instruction (observing, imitating or interfering), the participant should respond - among the options joy, sadness, disgust, anger, surprise and fear - the emotion corresponding to the image. The results showed significant differences when comparing the tasks of tensioning or imitating the target face, suggesting that the alteration of the observer's own face may influence during the performance of a facial emotion recognition task.(AU)

La imitación facial es un comportamiento involuntario capaz de facilitar la transmisión de información no verbal relevante en diferentes contextos sociales. Esto estudio tuvo como objetivo analizar la capacidad de reconocer expresiones emocionales mientras el observador tensa su propio rostro o imita el rostro objetivo. Se utilizó la hipótesis de que los individuos que tensan su propio rostro tendrán menor probabilidad de éxito en la realización de tareas de reconocimiento de expresiones emocionales y los individuos que imitan la expresión tendrán una mayor probabilidad de éxito en la realización de las mismas tareas. La muestra estuvo formada por 30 participantes divididos en dos grupos experimentales: el Grupo de Imitación - GI (18 mujeres y 12 hombres) y el Grupo de Ruido - GR (18 mujeres y 12 hombres). El experimento consistió en presentar imágenes de actores expresando facialmente una emoción básica durante 10 segundos; los participantes deberían entonces observar o intervenir facialmente, imitando o tensando su propio rostro (según el grupo asignado, Imitación o Ruido). Después de 10 segundos de ejecutar la instrucción (observar, imitar o interferir), el participante debería responder - entre las opciones de alegría, tristeza, asco, ira, sorpresa y miedo - la emoción correspondiente a la imagen. Los resultados mostraron diferencias significativas al comparar las tareas de tensar o imitar el rostro objetivo, sugiriendo que la alteración del propio rostro del observador puede influir durante la realización de una tarea de reconocimiento de emociones en rostros.(AU)

Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons / 神经科学通报·英文版

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.

The Mechanistic Basis for Photobiomodulation Therapy of Neuropathic Pain by Near Infrared Laser Light

Background and Objective Various irradiances have been reported to be beneficial for the treatment of neuropathic pain with near infrared light. However, the mechanistic basis for the beneficial outcomes may vary based on the level of irradiance or fluence rate used. Using in vivo and in vitro experimentalmodels, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance. Study Design/Materials and Methods ln vitro experiments: Cultured, rat DRG were randomly assigned to control or laser treatment (L T) groups with different irradiation times (2, 5, 30, 60 or 120s). The laser parameters were: output power » 960 mW, irradiance » 300mW/cm2, 808 nm wavelength and spot size » 3cm diameter/ area » 7.07cm2, with different fluences according to irradiation times. Mitochondrial metabolic activity was measured with the MTS assay. The DRG neurons were immunostained using a primary antibody to ß-Tubulin III. ln vivo experiments: spared nerve injury surgery (SNI), an animal model of persistent peripheral neuropathic pain, was used. The injured rats were randomly divided into three groups (n » 5). 1) Control: SNI without LT, 2) Short term: SNI with LT on day 7 and euthanized on day 7, 3) Long term: SNI with LT on day 7 and euthanized on day 22. An 808 nm wavelength laser was used for all treatment groups. Treatment was performed once on Day 7 post-surgery. The transcutaneous treatment parameters were: output power: 10 W, fluence rate: 270 mW/cm2, treatment time: 120s. The laser probe was moved along the course of the sciatic/sural nerve during the treatment. Within 1 hour of irradiation, behavior tests were performed to assess its immediate effect on sensory allodynia and hyperalgesia caused by SNI. Results ln vitro experiments: Mitochondrial metabolism was significantly lower compared with controls for all LT groups. Varicosities and undulations formed in neurites of DRG neurons with a cell body diameter 30µm or less. ln neurites of DRG neurons with a cell body diameter of greater than 30µm, varicosities formed only in the 120s group. ln vivo experiments: For heat hyperalgesia, there was a statistically significant reduction in sensitivity to the heat stimulus compared with the measurements done on day 7 prior to LT. A decrease in the sensitivity to the heat stimulus was found in the LT groups compared with the control group on day 15 and 21. For cold allodynia and mechanical hyperalgesia, a significant decrease in sensitivity to cold and pin prick was found within 1 hour after L T. Sensitivity to these stimuli returned to the control levels after 5 days post-L T. No significant difference was found in mechanical allodynia between control and L T groups for all time points examined. Conclusion These in vitro and in vivo studies indicate that treatment with an irradiance/fluence rate at 270 m W/cm2 or higher at the level of the nerve can rapidly block pain transmission. A combination therapy is proposed to treat neuropathic pain with initial high irradiance/fluence rates for fast pain relief, followed by low irradiance/ fluence rates for prolonged pain relief by altering chronic inflammation.

Percepción del gusto como factor de riesgo para obesidad infantil / Taste perception as a risk factor for childhood obesity

Resumen Objetivo Describir el papel de la percepción del gusto como factor de riesgo para el desarrollo de obesidad en niños. Material y métodos Se realizó una búsqueda inicial de artículos científicos publicados en PubMed entre el 1 de enero de 2011 y el 20 de marzo de 2016 para el tema sobrepeso y obesidad en niños de entre 0 y 12 años. Los algoritmos utilizados fueron (Obesity OR Overweight) AND Taste perception, Satiation, Satiety response, Appetite, Appetite regulation, Habituation, Taste receptors [MeSH] y PROP phenotype. En búsquedas subsecuentes se incluyeron artículos previos y posteriores a la fecha de la búsqueda general (hasta mayo 2018). Resultados Las preferencias por los sabores inician desde la gestación, por lo que los niños que son expuestos a sabores dulces en etapas tempranas de la infancia aumentan su riesgo de habituación a éstos. Asimismo, las experiencias hedónicas dadas por la ingestión de alimentos y bebidas dulces refuerzan el consumo de estos alimentos, lo que propicia la selección de productos o bebidas de sabor dulce en etapas posteriores. Estas preferencias se han asociado con el desarrollo de obesidad en los niños. Las variantes genéticas relacionadas con la percepción del gusto también pueden contribuir a la selección de cierto tipo de alimentos. Sin embargo, su relación con una mayor ingestión de energía, así como con un mayor peso corporal, ha sido poco explorada y ha mostrado resultados inconsistentes. Conclusiones Se requiere más evidencia para entender las interacciones ambientales y genéticas de la percepción del gusto, a fin de considerarlo un factor más en las intervenciones de política pública.

Abstract Objective To describe the role of taste perception in the development of sweet taste habituation as well as its relationship to the development of obesity in children. Materials and methods An initial search of scientific articles published in PubMed between January 1st, 2011 and March 20th, 2016 was performed in children between 0 and 12 years old. The algorithms used were (Obesity OR Overweight) AND (Taste perception, Satiation, Satiety response, Appetite, Appetite regulation Habituation, Taste receptors [MeSH]) and PROP phenotype. Subsequent searches included papers published before and after date of initial search (until May 2018). Results Flavor preferences start as early as taste system development during pregnancy. Therefore, children who are exposed to sweet flavors in early childhood, increase their risk of habituation to them. Likewise, the hedonic experiences given by the ingestion of sweet foods and beverages, reinforce the consumption of these foods, perpetuating their selection in later stages. Preference for sweet taste has been associated with the development of obesity in children. Functional genetic variants related to taste perception can also contribute to the selection of certain types of foods and there is enough evidence that supports this idea. However, its contribution to a higher energy intake as well as a higher body weight has been poorly explored with inconsistent results. Conclusions More evidence is required to understand the environmental and genetic interactions of taste perception, so in turn, it can be consider as a key factor for preventing child obesity.

La fisiología vista desde un sistema nervioso autónomo ampliado y circadianamente organizado Bases para un enfoque Bio-Psico-Social-Ecológico de la salud y la enfermedad / THE PHYSIOLOGY OBSERVED SINCE AN AMPLIED AND CIRCADIANILLY ORGANIZED AUTONOMIC NERVOUS SYSTEM. BASIS FOR A BIO-PSICHO-SOCIAL-ECOLOGICAL APPROACH DURING HEALTH AND DISEASE

El sistema nervioso autónomo (SNA) es un componente fundamental del sistema nervioso cuya función es mantener la homeostasis y reaccionar de forma adaptativa a los cambios en el medio externo e interno. Participa en la regulación de la respiración, la circulación, la digestión, el metabolismo y el medio interno, la secreción exocrina y endocrina, las respuestas inmunes, la temperatura corporal y la reproducción. En este trabajo se analizará cómo la organización del SNA se construye en 4 niveles jerárquicos, a partir de un periodo de diferenciación crítico neonatal en el cual el medio ambiente y el vínculo afectivo con la madre juega un rol predominante. A continuación, se discutirá cómo la función del SNA cambia en las tres configuraciones corporales (vigilia, sueño de ondas lentas, sueño de movimientos oculares rápidos, REM) que se suceden durante un ciclo de 24 horas. Por último, se discutirá la aplicación de estos conceptos en la Unidad Neurofisiología del Curso de Fisiología para alumnos de 2º año de la Facultad de Ciencias Médicas, UCA, enfatizando los aspectos instrumentales destinados a aumentar la participación de los alumnos en el proceso de enseñanza

The autonomic nervous system (ANS) is a fundamental component of the nervous system whose function is to maintain homeostasis and react adaptively to changes in the external and internal environment. It participates in the regulation of respiration, circulation, digestion, metabolism and internal environment, exocrine and endocrine secretion, immune response, body temperature and reproduction. In this review article I will analyze how the organization of the ANS is built on 4 hierarchical levels, starting from a period of critical neonatal differentiation in which the environment and the affective bond with the mother plays a predominant role. Next, I will discuss how the ANS function changes in the three body configurations (wakefulness, slow wave sleep, fast eye movement, REM) that occur during a 24 hour cycle. Finally, the application of these concepts to teaching Neurophysiology at the Physiology Course for 2nd year medical students of the Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, emphasizing the instrumental aspects intended to increase the participation of students in the teaching process is discussed.

KAAACI Evidence-Based Clinical Practice Guidelines for Chronic Cough in Adults and Children in Korea

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.

Glande Peneano ­ Teoría Integral y su Relación con la Triada Disfuncional (Glande Frío, Blando o Doloroso) / Penis Glans ­ Integral Theory and its Relationship with Dysfunctional Triad (Cold, Soft and Painful Glans)

El glande peneano forma parte de un ingenioso diseño evolutivo que convirtió el pene en una compleja maquina hidráulica bicameral para la intromisión exitosa en la vagina. El objetivo del glande es tener un extremo blando, recubierto con una piel de terminales altamente sensitivas que forma parte de un tercer cuerpo cilíndrico, que debe colaborar en la tumescencia peneana sin interferir ni en la eyección del semen, ni en la evacuación de la orina, al estar las funciones reproductivas y urinarias compartidas por el mismo órgano. Los cuerpos cavernosos y el esponjoso, incluyendo el glande, comparten anatomía y fisiología en lo referente a trabéculas, túnica albugínea y llenado de sangre, pero no son idénticos en función, por lo que conceptos como rigidez axial, distribución de receptores o venoclusión varían de una a otra cámara. Adicionalmente a su discreta colaboración en la erección, el glande es el origen del llamado reflejo eyaculatorio, que es básico en el proceso sexual humano. La disfunción de esa porción terminal, incluye tres situaciones patológicas que son el glande frío, blando o doloroso, con etiología común, relacionada con factores como trauma, disfunción eréctil o cirugías tales como prostatectomía radical o cirugía uretral, con muy pocos tratamientos específicos disponibles en la actualidad y que sin embargo deberán ir mejorando por la inusitada frecuencia de esos padecimientos

The glans arises from a clever evolving design through which that the penis was transformed into a complex bicameral hydraulic machine for successful intervention in the vagina; aiming to maintain a highly sensitive at soft end, being part of a third cylindrical body and functioning as an aid in the tumescence with no interference with the evacuation of urine or semen, as the reproductive and urinary functions are shared by the same body. The previous asseveration implies that corpora cavernosa and spongiosum, including glans, share anatomy and physiology, trabeculation, tunica albuginea and blood filled, although not identical in function yet concepts as axial rigidity, sensory receptors distribution or venoclussion, they are different from each other and dysfunction in this terminal portion, includes three pathological situations: cold, soft or painful glans, with common etiology related to factors such as trauma, erectile dysfunction and surgeries such as radical prostatectomy or urethral surgery, with few specific treatments currently available, yet they should be improving by the unusual frequency of these conditions.

Spinal Mechanisms of Itch Transmission / 神经科学通报·英文版

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.

Modulation of Pain and Itch by Spinal Glia / 神经科学通报·英文版

Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.

Somatosensory Neuron Typing with High-Coverage Single-Cell RNA Sequencing and Functional Analysis / 神经科学通报·英文版

Different physical and chemical stimuli are detected by the peripheral sensory receptors of dorsal root ganglion (DRG) neurons, and the generated inputs are transmitted via afferent fibers into the central nervous system. The gene expression profiles of DRG neurons contribute to the generation, transmission, and regulation of various somatosensory signals. Recently, the single-cell transcriptomes, cell types, and functional annotations of somatosensory neurons have been studied. In this review, we introduce our classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and discuss the technical approaches. Moreover, studies on the molecular and cellular mechanisms underlying somatic sensations are discussed.

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies / 神经科学通报·英文版

The voltage-gated Na channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

Avaliação da interferência da irradiação por feixe de elétrons nas características sensoriais de filés de corvina (Micropogonias furnieri) refrigerados / Evaluaiton of irradiation interference by electron beam on the sensory characteristics of chilled croaker (Micropogonias furnieri) fillets / Evaluación de la interferencia de irradiación por rayos de electrones en las características sensoriales de filetes de corvina (Micropogonias furnieri) refrigerados

O processo de deterioração do pescado é facilitado por suas características intrínsecas, como a proximidade da neutralidade que se encontra o pH; ação das enzimas autolíticas; elevada atividade de água e presença de nutrientes; além da elevada quantidade de gorduras insaturadas que auxiliam agilizando o processo de formação do ranço. Por isso, o emprego dos métodos de conservação deve ser realizado o mais prontamente possível, retardando a instalação da deterioração e mantendo o produto fresco por um período maior. Entre as tecnologias disponíveis para a conservação estão as radiações ionizantes. A irradiação de alimentos já é utilizada em vários países, sendo eficaz na extensão da validade comercial e até mesmo na melhora de alguns atributos sensoriais. Objetivou-se no presente trabalho contribuir para a avaliação da interferência da irradiação por feixe de elétrons nas características sensoriais de filés de corvina (M. furnieri) refrigerados, desembarcados no município de Niterói - RJ, Brasil. As amostras foram divididas em três grupos: controle; irradiado a 0,7 kGy; e irradiado a 1,0 kGy, os quais foram comparados sensorialmente entre si através de testes triangulares realizados com 30 provadores cada. Foram avaliados aroma, sabor, odor, textura e "outros". Os peixes inteiros foram adquiridos no cais de Itaipú, filetados no mercado, embalados a vácuo e mantidos à ±4°C. Foi encontrada diferença estatisticamente significativa (p<0,05) entre as amostras, quando confrontado o grupo irradiado a 1,0 kGy com os outros dois grupos. Concluiu-se portanto, que a dose de 1,0 kGy alterou as características sensoriais dos filés de corvina irradiados.(AU)

The process of spoilage of fish is facilitated by its intrinsic features, such as the proximity of neutrality of its pH; action of autolytic enzymes; high presence of water and nutrients; as well as a high amount of unsaturated fats that helps accelerate the process of rancidity. Therefore, preservation methods should be used as promptly as possible, delaying the installation of deterioration and keeping the product fresh for a longer period. Ionizing radiation is one of the technologies available for conservation. Food irradiation is already used in several countries, being effective for the improvement of some sensory attributes and even to extent the commercial validity. The objective of the present work is to contribute to the evaluation of the interference of electron beam irradiation on the sensory characteristics of chilled croaker (M. furnieri) fillets, unloaded in Niterói - RJ, Brazil. The samples were divided into three groups: control; irradiated at 0.7 KGy; and irradiated at 1.0 kGy, which were compared with each other through sensory tests with 30 triangular panelists each. They evaluated aroma, flavor, odor, texture and "other". Whole fish were purchased at Itaipú pier, were fillet in the market, vacuum packed and kept at ± 4 °C. Statistically significant differences were found (p<0,05) between samples when comparing the 1.0-kGy irradiated group with the other groups. It is therefore concluded that a 1.0-kGy dose alters the sensory characteristics of irradiated croaker fillets.(AU)

El proceso de deterioro de peces se facilita por sus características intrínsecas, tales como la proximidad de la neutralidad que se encuentra el PH; acción de las enzimas autolíticas; alta actividad de agua y presencia de nutrientes; además de la alta cantidad de grasas insaturadas que ayudan a acelerar el proceso de formación de rancidez. El uso de métodos de conservación debe realizarse lo más temprano posible, retardando la instalación de deterioro y manteniendo el producto fresco durante un largo espacio de tiempo. Entre las tecnologías disponibles para la conservación están las radiaciones ionizantes. Esta tecnología ya se utiliza en varios países y es muy eficaz en la ampliación de la validad comercial e incluso la mejora de algunos atributos sensoriales. El objetivo del presente trabajo ha sido evaluar el impacto de la irradiación por rayos de electrones en las características sensoriales de filetes de corvina (M. furnieri) refrigerados, desembarcados en el municipio de Niterói - RJ, Brasil. Las muestras se dividieron en tres grupos: control; irradiados a 0.7 kGy; e irradiados a 1,0 kGy, los cuales fueron comparados sensorialmente entre sí a través de pruebas triangulares realizadas con 30 panelistas. También, se evaluaron el aroma, sabor, olor, textura y "otros". Los pescados enteros fueron comprados en el muelle de Itaipú, fileteados en el mercado, envasados al vacío y mantenidos a ± 4°C. Se encontraron diferencias estadísticamente significativas (p<0,05) entre las muestras, cuando se compara el grupo irradiado a 1,0 kGy con los demás. Se concluye que una dosis de 1,0 kGy altera las características sensoriales de filetes de corvina irradiados.(AU)

Effects of analgesics and antidepressants on TREK-2 and TRESK currents

TWIK-related K+ channel-2 (TREK-2) and TWIK-related spinal cord K+ (TRESK) channel are members of two-pore domain K+ channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specifi c activators of TREK-2 and TRESK may be benefi cial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently.

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.

Nav1.7 and Nav1.8: Diabetes-induced Changes in Primary Sensory Neurons in Rats

No abstract available.

Vanilloid Receptor 1 Agonists, Capsaicin and Resiniferatoxin, Enhance MHC Class I-restricted Viral Antigen Presentation in Virus-infected Dendritic Cells

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-Kb complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.

Percepção sensorial tátil perturbada em pacientes oncológicos sob quimioterapia: análise da literatura e validação clínica / Tactile sensory perception disturbed in cancer patients undergoing chemotherapy: literature's analysis and clinical validation

Pacientes com câncer estão sujeitos a diversos efeitos tóxicos decorrentes do tratamento quimioterápico, incluindo a toxicidade neuro sensorial. A percepção sensorial tátil perturbada (PSTP) é considerada uma resposta do paciente ao tratamento antineoplásico o que torna este fenômeno relevante para a praticado enfermeiro. Apesar do impacto que esta questão traz às atividades de vida diária e qualidade de vida do paciente oncológico, a sua representatividade na NANDA-I ainda é inexistente, dificultando a assistência de enfermagem para esta população. Trata-se de estudo realizado em duas etapas: revisão integrativa da literatura e coorte não concorrente para atender o objetivo de validar o diagnóstico de enfermagem PSTP em pacientes adultos oncológicos sob quimioterapia. Dos artigos analisados 46 foram selecionados, a maioria(34,8%) estudos de coorte (Nível de Evidência III), realizados nos EUA (32,6%)e publicados na língua inglesa (98%). Os fatores relacionados (uso de quimioterapia neurotóxica, acúmulo de dose ao longo do tratamento) e as características definidoras (formigamento e dormência, especialmente em extremidades como mãos e pés) mais relevantes foram identificados e compuseram o instrumento utilizado na coorte. Foram incluídos no estudo 127pacientes entre junho de 2006 até dezembro de 2013, que revelou incidência global de PSTP de 57%. O modelo de predição para o desenvolvimento da PSTP foi obtido pela regressão de Cox encontrando-se ao final as variáveis que se mostraram significativas como alcoolismo, presença de metástases,radioterapia prévia, uso de anti-helmínticos, quimioterapia paliativa e desconforto nos membros inferiores. Os resultados revelam que a PSTP é um achado comum em pacientes oncológicos durante a quimioterapia antineoplásica.

Cancer patients may develop many chemotherapy toxic effects, including neurosensory toxicity. The disturbed tactile perception (PSTP) is considered apatient's response to anticancer treatment making this phenomenon relevant for the nursing practice. Despite the influence of this problem in patient's daily activities and quality of life, their representativeness in NANDA-I is still lacking,hampering for nursing care in this population. This is an integrative literature review studyand non-concurrent cohort that aimed validate the diagnosis of nursing diagnoses PSTP in adult cancer patients undergoing chemotherapy. Articles were analyzed and 46 were selected, most (34.8%) cohort studies (LoEIII), conducted in the US (32.6%) and published in English (98%). The most relevant related factors (use of neurotoxic chemotherapy, dose accumulation during treatment) and defining characteristics (tingling and numbness, especially on extremities like hands and feet) were identified and composed the cohort instrument. A total of 127 patients were included in the study from June2006 until December 2013, which revealed 57% overall incidence of PSTP. The prediction model of PSTP development was obtained by Cox regression, andthe significant variables identified were alcoholism, presence of metastases, radiotherapy, anthelmintic use, palliative chemotherapy and discomfort in the lower limbs. The results show that PSTP is a common finding in cancer patients during cancer chemotherapy.