The role of protein convertases in bigdynorphin and dynorphin A metabolic pathway

Les dynorphines sont des neuropeptides importants avec un rôle central dans la nociception et l’atténuation de la douleur. De nombreux mécanismes régulent les concentrations de dynorphine endogènes, y compris la protéolyse. Les Proprotéines convertases (PC) sont largement exprimées dans le système nerveux central et clivent spécifiquement le C-terminale de couple acides aminés basiques, ou un résidu basique unique. Le contrôle protéolytique des concentrations endogènes de Big Dynorphine (BDyn) et dynorphine A (Dyn A) a un effet important sur la perception de la douleur et le rôle de PC reste à être déterminée. L'objectif de cette étude était de décrypter le rôle de PC1 et PC2 dans le contrôle protéolytique de BDyn et Dyn A avec l'aide de fractions cellulaires de la moelle épinière de type sauvage (WT), PC1 -/+ et PC2 -/+ de souris et par la spectrométrie de masse. Nos résultats démontrent clairement que PC1 et PC2 sont impliquées dans la protéolyse de BDyn et Dyn A avec un rôle plus significatif pour PC1. Le traitement en C-terminal de BDyn génère des fragments peptidiques spécifiques incluant dynorphine 1-19, dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7 et Dyn A génère les fragments dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7. Ils sont tous des fragments de peptides associés à PC1 ou PC2. En plus, la protéolyse de BDyn conduit à la formation de Dyn A et Leu-Enk, deux peptides opioïdes importants. La vitesse de formation des deux est réduite de manière significative dans les fractions cellulaires de la moelle épinière de souris mutantes. En conséquence, l'inhibition même partielle de PC1 ou PC2 peut altérer le système opioïde endogène.

La experiencia de los receptores en el trasplante de órganos y tejidos

El trasplante de órganos y/o tejidos es considerado como una opción terapéutica viable para el tratamiento tanto de enfermedades crónicas o en estadios terminales, como de afectaciones no vitales, pero que generen una disminución en la calidad de vida percibida por el paciente. Este procedimiento, de carácter multidimensional, está compuesto por 3 actores principales: el donante, el órgano/tejido, y el receptor. Si bien un porcentaje significativo de investigaciones y planes de intervención han girado en torno a la dimensión biológica del trasplante, y a la promoción de la donación; el interés por la experiencia psicosocial y la calidad de vida de los receptores en este proceso ha aumentado durante la última década. En relación con esto, la presente monografía se plantea como objetivo general la exploración de la experiencia y los significados construidos por los pacientes trasplantados, a través de una revisión sistemática de la literatura sobre esta temática. Para ello, se plantearon unos objetivos específicos derivados del general, se seleccionaron términos o palabras claves por cada uno de estos, y se realizó una búsqueda en 5 bases de datos para revistas indexadas: Ebsco Host (Academic Search; y Psychology and Behavioral Sciences Collection); Proquest; Pubmed; y Science Direct. A partir de los resultados, se establece que si bien la vivencia de los receptores ha comenzado a ser investigada, aún es necesaria una mayor exploración sobre la experiencia de estos pacientes; exploración que carecería de objetivo si no se hiciera a través de las narrativas o testimonios de los mismos receptores

Análisis del gen adra2a receptor alfa 2a adrenergico en pacientes con trastorno de hiperactividad y déficit de atención

El trastorno de hiperactividad y déficit de atención (THDA), es definido clínicamente como una alteración en el comportamiento, caracterizada por inatención, hiperactividad e impulsividad. Estos aspectos son clasificados en tres subtipos, que son: Inatento, hiperactivo impulsivo y mixto. Clínicamente se describe un espectro amplio que incluye desordenes académicos, trastornos de aprendizaje, déficit cognitivo, trastornos de conducta, personalidad antisocial, pobres relaciones interpersonales y aumento de la ansiedad, que pueden continuar hasta la adultez. A nivel global se ha estimado una prevalencia entre el 1% y el 22%, con amplias variaciones, dadas por la edad, procedencia y características sociales. En Colombia, se han realizado estudios en Bogotá y Antioquia, que han permitido establecer una prevalencia del 5% y 15%, respectivamente. La causa específica no ha sido totalmente esclarecida, sin embargo se ha calculado una heredabilidad cercana al 80% en algunas poblaciones, demostrando el papel fundamental de la genética en la etiología de la enfermedad. Los factores genéticos involucrados se relacionan con cambios neuroquímicos de los sistemas dopaminérgicos, serotoninérgicos y noradrenérgicos, particularmente en los sistemas frontales subcorticales, corteza cerebral prefrontal, en las regiones ventral, medial, dorsolateral y la porción anterior del cíngulo. Basados en los datos de estudios previos que sugieren una herencia poligénica multifactorial, se han realizado esfuerzos continuos en la búsqueda de genes candidatos, a través de diferentes estrategias. Particularmente los receptores Alfa 2 adrenérgicos, se encuentran en la corteza cerebral, cumpliendo funciones de asociación, memoria y es el sitio de acción de fármacos utilizados comúnmente en el tratamiento de este trastorno, siendo esta la principal evidencia de la asociación de este receptor con el desarrollo del THDA. Hasta la fecha se han descrito más de 80 polimorfismos en el gen (ADRA2A), algunos de los cuales se han asociado con la entidad. Sin embargo, los resultados son controversiales y varían según la metodología diagnóstica empleada y la población estudiada, antecedentes y comorbilidades. Este trabajo pretende establecer si las variaciones en la secuencia codificante del gen ADRA2A, podrían relacionarse con el fenotipo del Trastorno de Hiperactividad y el Déficit de Atención.

Neurokinin-B transcription in erythroid cells - Direct activation by the hematopoietic transcription factor GATA-1

The GATA family of transcription factors establishes genetic networks that control developmental processes including hematopoiesis, vasculogenesis, and cardiogenesis. We found that GATA-1 strongly activates transcription of the Tac-2 gene, which encodes proneurokinin-B, a precursor of neurokinin-B (NK-B). Neurokinins function through G protein-coupled transmembrane receptors to mediate diverse physiological responses including pain perception and the control of vascular tone. Whereas an elevated level of NK-B was implicated in pregnancy-associated pre-eclampsia ( Page, N. M., Woods, R. J., Gardiner, S. M., Lomthaisong, K., Gladwell, R. T., Butlin, D. J., Manyonda, I. T., and Lowry, P. J. ( 2000) Nature 405, 797 - 800), the regulation of NK-B synthesis and function are poorly understood. Tac-2 was expressed in normal murine erythroid cells and was induced upon ex vivo erythropoiesis. An estrogen receptor fusion to GATA-1 (ER-GATA-1) and endogenous GATA-1 both occupied a region of Tac-2 intron-7, which contains two conserved GATA motifs. Genetic complementation analysis in GATA-1-null G1E cells revealed that endogenous GATA-2 occupied the same region of intron-7, and expression of ER-GATA-1 displaced GATA-2 and activated Tac-2 transcription. Erythroid cells did not express neurokinin receptors, whereas aortic and yolk sac endothelial cells differentially expressed neurokinin receptor subtypes. Since NK-B induced cAMP accumulation in yolk sac endothelial cells, these results suggest a new mode of vascular regulation in which GATA-1 controls NK-B synthesis in erythroid cells.

Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca2+ channel peptides

Abstract: Modulation of presynaptic voltage-dependent Ca+ channels is a major means of controlling neurotransmitter release. The CaV 2.2 Ca2+ channel subunit contains several inhibitory interaction sites for Gβγ subunits, including the amino terminal (NT) and I–II loop. The NT and I–II loop have also been proposed to undergo a G protein-gated inhibitory interaction, whilst the NT itself has also been proposed to suppress CaV 2 channel activity. Here, we investigate the effects of an amino terminal (CaV 2.2[45–55]) ‘NT peptide’ and a I–II loop alpha interaction domain (CaV 2.2[377–393]) ‘AID peptide’ on synaptic transmission, Ca2+ channel activity and G protein modulation in superior cervical ganglion neurones (SCGNs). Presynaptic injection of NT or AID peptide into SCGN synapses inhibited synaptic transmission and also attenuated noradrenaline-induced G protein modulation. In isolated SCGNs, NT and AID peptides reduced whole-cell Ca2+ current amplitude, modified voltage dependence of Ca2+ channel activation and attenuated noradrenaline-induced G protein modulation. Co-application of NT and AID peptide negated inhibitory actions. Together, these data favour direct peptide interaction with presynaptic Ca2+ channels, with effects on current amplitude and gating representing likely mechanisms responsible for inhibition of synaptic transmission. Mutations to residues reported as determinants of Ca2+ channel function within the NT peptide negated inhibitory effects on synaptic transmission, Ca2+ current amplitude and gating and G protein modulation. A mutation within the proposed QXXER motif for G protein modulation did not abolish inhibitory effects of the AID peptide. This study suggests that the CaV 2.2 amino terminal and I–II loop contribute molecular determinants for Ca2+ channel function; the data favour a direct interaction of peptides with Ca2+ channels to inhibit synaptic transmission and attenuate G protein modulation. Non-technical summary: Nerve cells (neurones) in the body communicate with each other by releasing chemicals (neurotransmitters) which act on proteins called receptors. An important group of receptors (called G protein coupled receptors, GPCRs) regulate the release of neurotransmitters by an action on the ion channels that let calcium into the cell. Here, we show for the first time that small peptides based on specific regions of calcium ion channels involved in GPCR signalling can themselves inhibit nerve cell communication. We show that these peptides act directly on calcium channels to make them more difficult to open and thus reduce calcium influx into native neurones. These peptides also reduce GPCR-mediated signalling. This work is important in increasing our knowledge about modulation of the calcium ion channel protein; such knowledge may help in the development of drugs to prevent signalling in pathways such as those involved in pain perception.

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49oC) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid- cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Modulação pela progesterona da sensibilidade dolorosa a estímulos mecânicos e isquêmicos em mulheres saudáveis e jovens

BRUNO, S. S. ; SOUSA, M. B. C. . Modulação pela progesterona da sensibilidade dolorosa a estímulos mecânicos e isquêmicos em mulheres saudáveis e jovens. RBGO. Revista Brasileira de Ginecologia e Obstetrícia , v. 30, p. 306-311, 2008

Interações físicas e psicossociais em mulheres com fibromialgia

Fibromyalgia (FM) is a non-inflammatory rheumatic syndrome of unknown etiology, with symptoms of diffuse musculoskeletal pain and presence of specific anatomic sites called tender points. The symptoms are often associated with fatigue, sleep disturbances, morning stiffness, alterations in pain perception, anxiety and depression. Fibromyalgia exhibits a correlation between physical and behavioral symptoms, which have a negative influence on the quality of life of patients. Emotional skills are important factors since they are related to subjective well-being, personal productivity, social interaction and interpersonal relationships. We aim to describe the physical and psychosocial interactions in women with FM, showing the association between perceived social support and affect with symptoms of pain, functionality and mood. We will also describe a body representation of pain in women with FM. Data were collected over 3 years and the sample size ranged between studies. This is an exploratory cross-sectional study conducted with a convenience sample of 63 women with FM and 42 healthy women as a control group (CT), aged 20-76 years, recruited through spontaneous demand at Onofre Lopes University Hospital (HUOL) and the Clinical School of Physiotherapy of Universidade Potiguar (UNP). The Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), Social Support Scale (MOS), Hamilton Anxiety Scale and Scale of Positive and Negative Affect Schedule (PANAS), in addition to pressure algometry were used. For data analysis, we used parametric and non-parametric tests and a general linear model with adjustment variables and analysis of variance. A significant difference was found between pain threshold and tolerance, functionality, depression, anxiety, social support, and positive and negative affect between the groups. Affective states and social support were associated with anxiety, depression and functionality. A body was drawn representing pain with higher incidences in trapeze, supraspinatus and second ribs. The reason for studying sensory aspects, affective behavior and social support in FM patients opens perspectives for scientific and clinical research of this syndrome. Women with chronic pain such as FM appear to have altered mood states, less social support and affective dysfunctions, influencing the other symptoms of the syndrome

Evaluating quality of life in mercury intoxicated people in urban-industrial environments through short-form 36 application

Context and objective: Records of contact with mercury (Hg) exist for more than 3500 years and several problems related to the use of this element can be noticed. Considering inexistence of current reports about it, quality of life perception evaluation was studied in people chronically intoxicated by mercury in an industrial environment. Design and setting: This is a cross-sectional descriptive observational study. Information from 47 urban-industrial workers from lamps manufacturing in São Paulo, clinically diagnosed as intoxicated by mercury and currently followed by the Occupational Health Service of Faculdade de Medicine da Universidade de São Paulo, with average age of 41.7 years old, was considered. Methods: SF36 questionnaire application was performed, with inferences tested by χ-square proof, by Spearman linear correlation and Mann-Whitney non-parametric test, adopting p < 0.05 as significant level. Results: In the eight domains, observed medians are 40% for physical functioning; 0 for physical function; 30% for body pain; 30% for general health; 22.2% for vitality; 50% for social functioning; 0 for emotional role and 36% for mental health. Correlation between age and SF36 domains does not reveal statistical significance, except for physical functioning, indicating that lower scores presented by older people in this domain are not followed by changes on other ones. Conclusions: Values obtained in people chronically intoxicated by mercury are actually lower, in the motor and mental scope components. Some instruments domains are higher for men than for women. Older ages are inversely associated to good performance in physical function domain. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Avaliação da efetividade do laser terapêutico no controle de índice de dor de pacientes em tratamento ortodôntico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Instrução como estratégia de enfrentamento para a realização de curativo sem sedação em enfermaria com crianças vítimas de queimadura

A queimadura corresponde ao quadro resultante da ação direta ou indireta do calor do fogo, de substâncias químicas ou da eletricidade sobre o organismo humano. Alguns estudos apontam as crianças como as maiores vítimas. Procedimentos inerentes ao processo de recuperação são reconhecidos como particularmente dolorosos. A frequência de procedimentos médicos invasivos, situação constante ao paciente vítima de queimadura, favorece a emissão de comportamentos concorrentes pela criança, bem como pode ocasionar a generalização do caráter aversivo do procedimento invasivo para estímulos presentes no ambiente, justificando estudos sobre a eficácia de intervenções neste contexto. A pesquisa foi dividida em dois estudos com objetivos específicos. Estudo 1 (n=5): caracterizar comportamentos de crianças vítimas de queimadura emitidos durante procedimento de curativo sem sedação em enfermaria e comparar a frequência de comportamentos concorrentes e não concorrentes emitidos por estas crianças em duas sessões consecutivas deste procedimento. Estudo 2 (n=2): analisar os efeitos do uso de instrução sobre a frequência de comportamentos concorrentes e não concorrentes em crianças vítimas de queimadura durante procedimento de curativo sem sedação em enfermaria. Participaram sete crianças (4 meninos e 3 meninas; 7 a 12 anos) vítimas de queimadura em área corporal inferior a 70% e seus acompanhantes, selecionados em um Centro de Tratamento de Queimados (CTQ). Como instrumentos, foram utilizados: (a) Protocolo de consulta à equipe de saúde; (b) Lista de Verificação Comportamental para crianças/adolescentes (CBCL 6-18anos); (c) Roteiro de entrevista com a criança; (d) Escala de observação comportamental OSBD (Observation Scale of Behavioral Distress); (e) Escala facial para avaliar a percepção de dor da criança (FACES); e (f) Manual de instrução sobre o procedimento de curativo. No Estudo 1, observou-se maior frequência de comportamentos concorrentes sobre os não concorrentes nas duas sessões de curativo. No Estudo 2, após o uso do Manual de instrução, observou-se redução estatisticamente significante na frequência do comportamento concorrente Choramingar (= 0,0447) e aumento significativo (= 0,0324) na frequência do comportamento não concorrente Auxiliar na execução do procedimento. Houve correlação significativa (p-valor = 0,0066) entre a frequência de comportamentos não concorrentes entre as crianças do Estudo 1 e as que participaram do Estudo 2, sugerindo que a intervenção, por meio de instruções, foi eficaz para aumentar a frequência de comportamentos não concorrentes nas crianças participantes do Estudo 2.

Avaliação dos níveis de ruído e das soluções arquitetônicas adotadas em ambientes das unidades de urgência e emergência no município de Belém-PA

Nos grandes centros urbanos pode-se constatar que o nível de ruído é tão elevado que ameaça a integridade psicológica e física dos habitantes. Entretanto, observa-se que muito do ruído no ambiente hospitalar origina-se de dentro do hospital, tendo como uma das principais fontes geradoras de ruído nas unidades os equipamentos e a conversação entre a equipe hospitalar. A perda auditiva induzida pelo ruído (PAIR) é uma das consequências que o ruído elevado pode acarretar à saúde, entre outros danos. Assim, o ambiente hospitalar que deveria ser sereno e silencioso transforma-se em um espaço ruidoso e estressante, aumentando a ansiedade e a percepção dolorosa do paciente, reduzindo o sono e estendendo a convalescença. Objetivo: Avaliar as condições acústicas dos principais ambientes nas unidades de urgência e emergência no município de Belém, Estado do Pará, Brasil. Verificar a adequação às normas sanitárias e técnicas vigentes, com a simulação de um ambiente piloto validado com a utilização do software ODEON e apresentar soluções virtuais de condicionamento acústico. Material e Métodos: foi utilizado o equipamento Medidor de Nível Sonoro com certificado de calibração da Rede Brasileira de Calibração (RBC) para aferição dos NPS nos períodos diurno e noturno, de acordo com o estabelecido pela NBR 10.151 (2000), além da observação e identificação das fontes de ruído dos ambientes. Resultados: Os valores obtidos durante as aferições dos NPS nos ambientes do Hospital A foram de 58 dB(A) a 70 dB(A) e do Hospital B foram de 62 dB(A) a 70 dB(A). O ambiente piloto foi selecionado de acordo com os resultados e com o tempo de permanência da equipe de saúde e dos pacientes. Conclusão: foi desenvolvido o modelo computacional validado do ambiente piloto, gerando um modelo proposto com intervenções arquitetônicas visando o conforto acústico da equipe de saúde e dos pacientes. Os ambientes pesquisados não apresentaram níveis de ruído superiores a 85 dB(A), comprovando que não há risco ocupacional para as equipes de saúde. Entretanto, níveis de ruídos elevados, por mais que não causem PAIR nos trabalhadores, são responsáveis por estimular ou até mesmo por desencadear diversos sintomas que prejudicam a capacidade laborativa da equipe de saúde, além de aumentar a convalescença e prejudicar a recuperação dos pacientes.

Influência de abordagens biopsicossociais e autocuidados no controle das disfunções temporomandibulares crônicas

BACKGROUND AND OBJECTIVES: Temporomandibular joint disorder (TMD), which is a musculoskeletal condition of the masticatory system, may become chronic and further worsen quality of life (QL) of patients. Due to the inter-relationship between physical and emotional symptoms, there is an increasing search for the integrative model, which includes psychosocial approaches for the treatment of painful conditions. This study aimed at reviewing in the literature the impact of education and simple self-care modalities on pain and disorders related to chronic painful TMD. CONTENTS: Psychosocial factors are often involved with pain chronicity, making bio-behavioral approaches increasingly more indicated to change pain perception and to decrease distress and psychosocial changes which go along with persistent pain. CONCLUSION: Current literature, although not extensive, indicates positive results of education and self-care methods for chronic painful TMD. Further studies are needed to reinforce such findings and spread the application of such approaches to control chronic and TMD pain.

Relação entre postura, queixa dolorosa e lesão em bailarinas clássicas

Introduction: Due to the high recurrence of pain complaints and the increasing incidence of musculoskeletal injuries and postural changes in dance practice, researches related to this issue gained greater importance in scientific community. Objective: This study aimed to evaluate complaints and pain threshold, postural misalignments and the incidence of injuries in dancers noting if there is a relationship between these variables. Method: Participants were 15 ballet dancers in Marília - SP. We used photogrammetry for postural analysis, the McGill Pain Questionnaire for pain location of the volunteer, algometry pressure for measuring the threshold of pain perception and Referred Morbidity to verify and characterize the incidence of injuries this population. In the data analysis we use to percentage to quantify the data from questionnaires and Pearson correlation test angles of photogrammetry correlating with the values of the threshold of pain perception. Results: 73.33% of dancers reported to have suffered some kind of injury in the last year. The area of greatest pain complaint checked at McGill, was the region of the foot (73.30%). Conclusion: There was an agreement between regions of injury and pain, however, there wasn’t a correlation between the threshold of pain tolerance and postural angles.

Functional neurologic recovery in two dogs diagnosed with severe luxation of the vertebral column

Traumatic injuries to the vertebral column, spinal cord, and cauda equina nerve roots occur frequently in human and veterinary medicine and lead to devastating consequences. Complications include partial or complete loss of motor, sensory, and visceral functions, which are among the main causes of euthanasia in dogs. The present case report describes neurological functional recovery in two dogs that were treated surgically for severe spinal fracture and vertebral luxation. In the first case, a stray, mixed breed puppy was diagnosed with thoracolumbar syndrome and Schiff-Scherrington posture, as well as a T13 caudal epiphyseal fracture with 100% luxation between vertebrae T13 and L1; despite these injuries, the animal did show deep pain sensation in the pelvic limbs. Decompression through hemilaminectomy and spinal stabilization with vertebral body pins and bone cement were performed, and the treatment was supplemented with physiotherapy and acupuncture. In the second case, a mixed breed dog was diagnosed with a vertebral fracture and severe luxation between L6 and L7 after a vehicular trauma, but maintained nociception and perineal reflex. Surgical stabilization of the spine was performed using a modified dorsal segmental fixation technique Both patients showed significant recovery of neurological function. Complete luxation of the spinal canal observed radiographically does not mean a poor prognosis, and in some cases, motor, sensory, and visceral functions all have the potential for recovery. In the first case the determining factor for good prognosis was the presence of deep pain perception, and in the second case the prognosis was determined by the presence of sensitivity and anal sphincter tone during the initial neurological examination.