Importância dos mastócitos na patogênese da distrofia muscular de Duchenne em cães Golden Retriever

Golden Retriever Muscular Dystrophy (GRMD) is the best natural model of Duchenne muscular dystrophy (DMD) with genotypic and phenotypic manifestations similar the human disease. As in to DMD patients, the progressive proliferation of connective tissue in the endomysium of the muscle fibers is parallel to the clinical course of disease in GRMD animals. Studies indicate the relationship of mast cells with the deposition of fibrous tissue due to the release of mediators that activate fibroblasts. The aim of this study was to evaluate the expression of mast cells and its possible relation with muscle injury and fibrosis in GRMD dogs at different ages. It was used fragments of four skeletal muscle groups (masseter, diaphragm, triceps brachial and biceps femoris) of ten dogs between two and eight months age, six affected and four controls. Samples were processed by usual techniques of histology, stained with hematoxylin-eosin and toluidine blue, to verify the expression of mast cells, and Azan trichrome for evaluation and quantification of fibrous. In all muscle groups of dogs GRMD the infiltration of mast cells increased significantly compared to control group. The average number of mast cells decreased with the age of GRMD dogs. All muscle groups showed a significant increase in the amount of collagenous tissue in the control group. The deposition of fibrous tissue decreased with the age of the animals. Possibly, the increase of mast cell degranulation and mediator release would occur in younger GRMD dogs (2 months), fact that potentiated the increase deposition of fibrous tissue in muscle fibers which was gradually decreasing over time and age of the animals. Other studies are needed to clarify the role of mast cells in the pathogenesis of fibrosis in order to contribute to the development of new therapeutic approaches and improve the life expectancy of humans and dogs affected by muscular dystrophyO cão Golden Retriever Muscular Dystrophy (GRMD) é o melhor modelo natural da distrofia muscular de Duchenne (DMD) com manifestações genotípicas e fenotípicas semelhantes à doença humana. Como nos afetados pela DMD, a proliferação progressiva de tecido conectivo no endomísio das fibras musculares ocorre em paralelo ao curso clínico da doença nos animais GRMD. Estudos indicam a relação dos mastócitos com a deposição de tecido fibroso devido a liberação de seus mediadores que ativam os fibroblastos. O objetivo desse trabalho foi o de avaliar a expressão dos mastócitos e sua possível relação com as lesões musculares e fibrose em cães GRMD de diferentes idades. Foram utilizados fragmentos de quatro grupos musculares esqueléticos (masseter, diafragma, tríceps braquial e bíceps femoral) de dez cães entre dois a oito meses de idade sendo seis afetados e quatro controles. As amostras foram processadas por técnicas usuais de histologia, coradas com hematoxilina e eosina, azul de toluidina para verificar a expressão dos mastócitos e tricrômio de Azan para a evidenciação e quantificação da fibrose. Em todos os grupos musculares dos cães GRMD o infiltrado de mastócitos apresentou aumento significativo comparado ao grupo controle. O número médio de mastócitos diminuiu com a idade dos cães GRMD. Todos os grupos musculares apresentaram aumento significativo na quantidade de tecido colagenoso em relação ao grupo controle. A deposição de tecido fibroso diminuiu de acordo com a idade dos animais. Dos resultados afere-se que o aumento da degranulação dos mastócitos ocorreu em cães GRMD mais jovens (2 meses) fato que potencializou o aumento na deposição de tecido fibroso nas fibras musculares que foi diminuindo gradativamente com o tempo e a idade dos animais. Outros estudos são necessários para esclarecer o papel dos mastócitos na patogênese da fibrose, a fim de contribuir no desenvolvimento de novas..

Relevant aspects of golden retriever muscular dystrophy for the study of Duchenne muscular dystrophy in humans

ABSTRACT: Golden Retriever muscular dystrophy (GRMD) is the most representative model for studying Duchenne muscular dystrophy (DMD) in humans, owing its phenotypic expression. DMD is a recessive disorder linked to the X chromosome in which the loss of dystrophin induces progressive weakness and degeneration of the skeletal and cardiac muscles, which lead to replacement by connective and adipose tissues. Onset of clinical signs occurs between 2 and 5 years of age, and many patients die from heart or respiratory failure. The main studies concerning dystrophic Golden Retrievers (DGR) sought to elucidate the pathophysiology of the disease and its clinical implications to develop therapies and alternative treatments to improve the quality of life and increase longevity of DMD patients. This review presents an overview of relevant contributions of the DGR model for elucidating DMD in humans

Accuracy of anemia diagnosis by physical examination

CONTEXT AND OBJECTIVES: Quantification of clinical signs such as the presence or absence of pallor at clinical examination is a key step for making diagnoses. The aim was, firstly, to evaluate two methods for anemia diagnosis by physical examination: four-level evaluation (crosses method: +/++/+++/++++) and estimated hemoglobin values, both performed by medical students and staff physicians; and secondly, to investigate whether there was any improvement in assessment accuracy according to the number of years in clinical practice. DESIGN AND SETTING: Forty-four randomly selected physicians and medical students in a tertiary care teaching hospital completed a physical examination on five patients with mild to severe anemia. METHODS: The observers used four-level evaluation and also predicted the hemoglobin level. Both methods were compared with the real hemoglobin value as the gold standard. RESULTS: The mean estimated hemoglobin value correlated better with the real hemoglobin values than did the four-level evaluation method, for attending physicians, residents and students (Spearman's correlation coefficients, respectively: 1.0, 1.0 and 0.9 for guessed hemoglobin and -0.8, -0.8 and -0.7 for the four-level evaluation method). There were no differences in the mean "guessed" hemoglobin values from attending physicians, residents and students. However, the correlation between guessed hemoglobin value and the four-level method was positive for attending physicians, thus suggesting some kind of improvement with time (p = 0.04). CONCLUSIONS: This study showed that estimated hemoglobin was more accurate than evaluation by the four-level method. The number of years in clinical practice did not improve the accuracy of clinical examination for anemia