Relationship between objective and subjective assessment of limb function in normal dogs with an experimentally induced lameness.

OBJECTIVE: To evaluate the relationship between previously used subjective and objective measures of limb function in normal dogs that had an induced lameness. STUDY DESIGN: Prospective, blinded, and induced animal model trial. ANIMALS: Normal, adult, and mixed-breed dogs (n=24) weighing 25-35 kg. METHODS: Force platform gait analysis was collected in all dogs before and after induction of lameness. All gait trials were videotaped; 60 video trials were evaluated by 3 surgeons with practice limited to small animal orthopedics and 3 first year veterinary students in an effort to establish the relationship between subjective and objective measures of lameness. Evaluators were unaware of the force platform data. RESULTS: Concordance coefficients were low for all observers and were similar between students and surgeons. These values were further decreased when normal and non-weight bearing trials were removed. Agreement with the force platform data was low even when observers only had to be within +/-10% of the ground reaction forces. When repeat trials were evaluated surgeons had a much higher repeatability compared with students. CONCLUSIONS: Subjective evaluation of the lameness in this study varied greatly between observers and agreed poorly with objective measures of limb function. CLINICAL RELEVANCE: Subjective evaluation of gait should be interpreted cautiously as an outcome measure whether performed from a single or from multiple observers.

Correction: Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets.

[This corrects the article DOI: 10.1371/journal.pone.0209112.].

Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets.

INTRODUCTION: Golden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation. OBJECTIVE: To describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers. ANIMALS: Twenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers. METHODS: In this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated. RESULTS: Twenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%. CONCLUSIONS: Certain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.

Interactions between TGFß1 and cyclic strain in modulation of myofibroblastic differentiation of canine mitral valve interstitial cells in 3D culture.

OBJECTIVES: The mechanisms of myxomatous valve degeneration (MVD) are poorly understood. Transforming growth factor-beta1 (TGFß1) induces myofibroblastic activation in mitral valve interstitial cells (MVIC) in static 2D culture, but the roles of more physiological 3D matrix and cyclic mechanical strain are unclear. In this paper, we test the hypothesis that cyclic strain and TGFß1 interact to modify MVIC phenotype in 3D culture. ANIMALS, MATERIALS AND METHODS: MVIC were isolated from dogs with and without MVD and cultured for 7 days in type 1 collagen hydrogels with and without 5 ng/ml TGFß1. MVIC with MVD were subjected to 15% cyclic equibiaxial strain with static cultures serving as controls. Myofibroblastic phenotype was assessed via 3D matrix compaction, cell morphology, and expression of myofibroblastic (TGFß3, alpha-smooth muscle actin - αSMA) and fibroblastic (vimentin) markers. RESULTS: Exogenous TGFß1 increased matrix compaction by canine MVIC with and without MVD, which correlated with increased cell spreading and elongation. TGFß1 increased αSMA and TGFß3 gene expression, but not vimentin expression, in 15% cyclically stretched MVIC. Conversely, 15% cyclic strain significantly increased vimentin protein and gene expression, but not αSMA or TGFß3. 15% cyclic strain however was unable to counteract the effects of TGFß1 stimulation on MVIC. CONCLUSIONS: These results suggest that TGFß1 induces myofibroblastic differentiation (MVD phenotype) of canine MVIC in 3D culture, while 15% cyclic strain promotes a more fibroblastic phenotype. Mechanical and biochemical interactions likely regulate MVIC phenotype with dose dependence. 3D culture systems can systematically investigate these phenomena and identify their underlying molecular mechanisms.