Lidocaine-derivative JMF2-1 prevents ovalbumin-induced airway inflammation by regulating the function and survival of T cells.

BACKGROUND: Inhalation of the local anaesthetic lidocaine has been suggested to be beneficial for asthmatics, but airway anaesthesia is unpleasant and may exacerbate bronchoconstriction. Our previous study showed that inhalation of the lidocaine analogue JMF2-1 can elicit the anti-inflammatory properties of lidocaine without anaesthesia. This prompted further research on the mechanism of action and putative therapeutic application of JMF2-1. OBJECTIVE: We tested the hypothesis that JMF2-1 would prevent allergen-induced lung inflammation and airway hyperresponsiveness (AHR) by modulating T cell function in vivo and in vitro. Methods Local and systemic changes in leucocyte levels, cytokine production and lung mechanics were examined in a murine model of lung inflammation. JMF2-1 (0.05-2%) or saline was aerosolized twice a day during the ovalbumin (OVA)-provocation period (19-21 days post-sensitization). Analyses were performed 24 h after the final challenge. Primary cultured lymph node cells were used to assess the effects of JMF2-1 (100-600 µm) at the cellular level. RESULTS: OVA challenge resulted in lung recruitment of CD4(+) T cells and eosinophils, increased generation of inflammatory cytokines and AHR to inhaled methacholine within 24 h. These changes were prevented by JMF2-1 nebulization, and occurred in parallel with an increase in the number of apoptotic cells in the lung. JMF2-1 treatment did not alter levels of CD4(+) or CD8(+) T cells in the thymus or lymph nodes of naïve mice, although it inhibited OVA-induced IL-13 production and the lymphocyte proliferative response in vitro. It also induced apoptosis of OVA-activated lymphocytes in a mechanism sensitive to z-VAD, indicating that JMF2-1 mediates caspase-dependent apoptosis. CONCLUSION: Inhalation of JMF2-1 prevents the cardinal features of asthma by reducing T(H) 2 cytokine generation and lung eosinophilic inflammatory infiltrates via local inhibition of T cell function and survival. JMF2-1 may represent a novel therapeutic alternative for asthma control with distinct advantages over local anaesthetics.

Descriptive electromyography signals analysis of equine longissimus dorsi, rectus abdominis and gluteus medius muscles during maneuvers used to activate the core / [Análise descritiva do sinal eletromiográfico dos músculos longuíssimo dorsal, reto abdominal e glúteo médio de equinos durante a realização de manobras utilizadas para ativação do core]

Maneuvers to activate the equine's core can make a difference in their physical and psychic health. Although these activities are recommended and practiced, there is little research proving their effectiveness. This article aims to describe, through surface electromyography, the occurrences, durations and sequences activity of longissimus dorsi, rectus abdominis and gluteus medius during thoracolumbar flexion (TLF), lumbar and lumbosacral flexion (LLSF), global flexion (GF), which is the combination of TLF and LLSF, and tail traction (TT). Seven healthy adult horses of three different breeds performed five repetitions of these movements for five seconds (sec). Electromyographic activity was captured with non-invasive superficial sensors positioned in the skin regions covering these muscles. The sequence was performed once per animal, muscle activity captured by surface electromyography, data from two replicates of each animal were selected, analyzed on matLab software and data tabulation were described during each maneuver. These maneuvers provoked punctual and transient activation of muscles mentioned above, confirming the ability to activate equine core muscles. However, responses were not standardized, which means there were variations of occurrence, duration and sequence, suggesting that for practical application of those maneuvers it is necessary to perform more repetitions with longer durations to activate more muscles.(AU)

Manobras para ativação da musculatura do core equino podem ser diferenciais para saúde física e psíquica dos animais, sendo recomendadas e praticadas, mas existem poucas pesquisas comprovando a eficácia delas. Este artigo tem como objetivo descrever, por meio da eletromiografia de superfície, as ocorrências, as durações e as sequências temporais da atividade muscular do longuíssimo dorsal, do reto abdominal e do glúteo médio durante a realização das manobras de flexão toracolombar, flexão lombar e lombossacra, flexão global (toracolombar e lombossacra) e tração de cauda. Para isso, sete equinos adultos e hígidos de três raças realizaram esses quatro movimentos clássicos para ativar o core equino, com cinco repetições e manutenção do estímulo reflexivo por cinco segundos. Durante a realização, a atividade eletromiográfica foi capturada com a utilização de sensores superficiais posicionados de forma não invasiva em regiões cutâneas referentes a cada músculo. O protocolo completo de manobras foi realizado uma vez por cada animal enquanto a atividade muscular era capturada. Posteriormente, duas repetições de cada animal foram triadas e submetidas ao software matLab para análise. Com base na tabulação dos dados, foram descritas as variáveis eletromiográficas de presença ou ausência de ativação muscular, a duração média dos picos eletromiográficos superiores ao RMS (root mean square) e a sequência da atividade muscular observada durante cada manobra. Essas manobras provocaram ativações pontuais e transitórias nos três músculos, o que confirma a capacidade de excitar músculos do core equino. Contudo, as respostas não foram padronizadas, sugerindo que, na prática dessa atividade, devem-se realizar mais repetições com durações superiores a cinco segundos, a fim de se buscarem maiores ativações.(AU)

NFAT transcription factors: from cell cycle to tumor development.

The nuclear factor of activated T cells (NFAT) family of transcription factors has been primarily identified in immune cells; however, these proteins have been recently found to be functionally active in several other non-immune cell types. NFAT proteins are activated upon different stimuli that lead to increased intracellular calcium levels. Regardless of their widely known cytokine gene expression properties, NFATs have been shown to regulate other genes related to cell cycle progression, cell differentiation and apoptosis, revealing a broader role for these proteins in normal cell physiology. Several reports have addressed the participation of NFATs in many aspects of malignant cell transformation and tumorigenic processes. In this review, we will discuss the involvement of the different NFAT family members in the regulation of cell cycling, differentiation and tumor formation, and also its implications on oncogenesis. Better understanding the mechanisms by which NFATs regulate cell cycle and tumor-related events should be relevant for the development of rational anti-cancer therapies.

Thermographic assessment of saddles used in Mangalarga Marchador horses / Avaliação termográfica de selas utilizadas em cavalos da raça Mangalarga Marchador

Poor saddle-fitting is one of the main causes of back pain in horses. Mangalarga Marchador is a popular breed in Brazil, being used mainly for pleasure riding and sports. This study aimed to thermographically assess saddles used in horses of this breed. Thermographic images were obtained from 18 saddles of animals from different categories during a Mangalarga Marchador National Exposition. The evaluation was based on three parameters: contact area symmetry, dorsal midline interaction and total skin contact area (25%, 50%, 75% or 100%). Contact area asymmetry was observed in 83.3% of saddles. Dorsal midline interaction was observed with the same frequency. Only 22.2% of saddles assessed in the present study had panels with contact areas greater than 50%. Based on the results of this essay it can be concluded that thermography is a useful tool for the evaluation of saddle contact area with the back of horses and that there is a high frequency of fitting unconformities in saddles used in Mangalarga Marchador horses.(AU)

O ajuste inadequado da sela é um dos principais causadores de lombalgias em equinos. A raça Mangalarga Marchador está entre as mais populares do Brasil, sendo muito utilizada para cavalgadas e prática de esportes. O presente estudo teve como objetivo avaliar termograficamente as selas utilizadas em cavalos dessa raça. Para tal, foram realizadas imagens termográficas de 18 selas de animais de diversas categorias durante uma Exposição Nacional do Cavalo Mangalarga Marchador. A avaliação foi realizada baseando-se em três parâmetros: simetria da área de contato, interação com a linha média dorsal e área total de contato com a pele (25%, 50%, 75% ou 100%). Em 83,3% das selas avaliadas foi observada assimetria da área de contato. A interação com a linha média dorsal foi observada com a mesma frequência. Apenas 22,2% das selas avaliadas no presente estudo tinham suadouros com área de contato maior que 50%. Com base nos resultados obtidos neste trabalho, conclui-se que a termografia é uma ferramenta útil na avaliação do contato das selas com o dorso dos cavalos e que existe alta frequência de inconformidades no ajuste de selas utilizadas na raça Mangalarga Marchador.(AU)

Fratura de fíbula e lesões de ligamento colateral e menisco lateral em muar: relato de caso / Fibula fracture and injuries to the collateral ligament and lateral meniscus in mules: case report

Relata-se a ocorrência de fratura de fíbula e lesões de ligamento colateral e menisco lateral em um muar, fêmea, de dois anos de idade, provavelmente produzida por um coice na região da articulação femorotibiopatelar do membro pélvico esquerdo. O animal apresentava claudicação de grau 5 desse membro e obteve melhora após bloqueio dos nervos fibular, tibial e safena e da articulação afetada. O exame radiográfico da região acometida revelou fratura do terço proximal da fíbula e, ao exame ultrassonográfico, observaram-se pontos anecoicos no ligamento colateral lateral e menisco.

This is a report of the occurrence of fibula fracture and injuries of the collateral ligament and lateral meniscus in a two year old mule, probably due to a kick in the joint area of the femurtibiopatellar left pelvic limb. The animal presented degree 5 lameness which improved after a nerve block of the affected joint. Radiographic examination of the affected area revealed a fracture on the proximal third of the fibula, and the ultrasound examination showed anechoic points observed in the lateral collateral ligament and meniscus.

NFAT transcription factors: from cell cycle to tumor development

The nuclear factor of activated T cells (NFAT) family of transcription factors has been primarily identified in immune cells; however, these proteins have been recently found to be functionally active in several other non-immune cell types. NFAT proteins are activated upon different stimuli that lead to increased intracellular calcium levels. Regardless of their widely known cytokine gene expression properties, NFATs have been shown to regulate other genes related to cell cycle progression, cell differentiation and apoptosis, revealing a broader role for these proteins in normal cell physiology. Several reports have addressed the participation of NFATs in many aspects of malignant cell transformation and tumorigenic processes. In this review, we will discuss the involvement of the different NFAT family members in the regulation of cell cycling, differentiation and tumor formation, and also its implications on oncogenesis. Better understanding the mechanisms by which NFATs regulate cell cycle and tumor-related events should be relevant for the development of rational anti-cancer therapies.