Background: Untreated rotator cuff tears lead to irreversible tendon degeneration, resulting in unacceptable repair prognosis. The inability of current animal models of degenerated rotator cuff tendons to more fully emulate the manifestation and degree of pathology seen in humans with a previously torn rotator cuff tendon (s) significantly impairs the development of novel therapeutics. Therefore, the objective of this study was to develop a large-animal translational model of enthesis damage to the rotator cuff tendons to mimic the chronic degenerative changes that occur in patients that demonstrate clinical manifestations of tendinopathy.Methods: A partial enthesis tear model (i.e., sharp transection) in adult sheep was created by cutting the tendon fibers perpendicularly through the enthesis midpoint, while leaving the other portion of the tendon in-tact. To assess tendon integrity, non-destructive biomechanical tests were performed, followed by histopathological, histomorphological, and gene expression analysis. Samples of degenerated human rotator cuff tendons obtained from patients undergoing reverse total shoulder arthroplasty to use for comparative pathological analysis.Results: In the sheep model, transected tendons at all timepoints had significantly decreased mechanical properties. Histopathologic evaluation and Bonar scoring revealed that the tendons in sheep underwent degenerative changes similar in magnitude and manifestation as the degenerated human tendon samples. Furthermore, similar levels of collagen disorganization were noted between the 6 and 12-week ovine samples and the degenerated human samples. Conclusions: These findings indicate that the new sheep model of rotator cuff injury reliably recapitulates the structural and cellular changes that occur clinically in humans with chronic rotator cuff tendon injuries and suggest that this new model is well suited to evaluation of new therapeutic interventions.
This study examined the relationships between hair cortisol concentrations (HCC) and sex, age, nutritional status (as determined by body condition scores, or BCS), and body mass (geometric mean calculated from morphometric measurements), as well as the potential influence of hair pigmentation (light, dark, or agouti/mixed) on HCC in dogs of the Bosawas Biosphere Reserve, Nicaragua. The dogs examined in this study live in a marginal environment where disease, malnutrition, and mortality rates are high. For fur color, HCC was significantly higher in light fur than in than dark and mixed fur (p < 0.001). In addition, BCS scores were found to have a negative effect on HCC (p < 0.001). Measures of sex and body size exhibited inconclusive effects on HCC, and when compared to adult dogs, juvenile dogs did not exhibit significantly different HCC. Repeated measures of dogs over time reveal a moderate intra-class correlation, suggesting that there are unmeasured sources of individual-level heterogeneity. These findings imply a need to account for fur color in studies of HCC in dogs, and the study suggests an overlooked relationship between cortisol and body condition scores in undernourished dogs in diverse settings.
Background: Chronic degeneration of rotator cuff tendons is a major contributing factor to the unacceptably high prevalence of rotator cuff repair surgery failures. The etiology of chronic rotator cuff degeneration is not well understood, and current therapies are not effective, necessitating preclinical research to fill this knowledge gap. Unfortunately, current large animal models rely on enthesis disruption as a means of model generation, which is not representative of human patients with chronic rotator cuff degeneration prior to full-thickness tears. Following, the goal of this study was to develop and characterize a translational large-animal model of chronic rotator cuff degeneration without enthesis release.Methods: A midsubstance damage model [i.e., "combed fenestration" (CF)] in adult sheep was generated by creating 16 longitudinal cuts within the top third of the infraspinatus tendon thickness. Tendon integrity was characterized through exhaustive non-destructive biomechanical stress relaxation testing [peak stress, peak load, percent relaxation, and cross-sectional area (CSA)], followed by histopathological degeneration scoring and analysis (Bonar score), histomorphological analysis of collagen organization and fatty atrophy (percent adipose area), and gene expression analyses.Results: The CF model tendons exhibited significantly decreased mechanical properties as evidenced by decreased peak stress (P<0.025) and increased percent relaxation (18-week vs. Control, P<0.035) at multiple strain magnitudes and across all timepoints. At all timepoints, the CF tendons exhibited pathological changes aligned with tendon degeneration, as evidenced by increased Bonar scoring (P<0.001) and decreased collagen organization (6-week vs. Control, p=0.013). Increases in intramuscular adipose content were also documented through histomorphology analysis (6-week and 18-week vs. Control, P<0.077). Significant changes in gene expression were noted at all timepoints.Conclusions: These data reveal that this new ovine CF model of chronic rotator cuff degeneration results in tendons with decreased mechanical properties, degenerative pathology characteristics, and gene expression profiles that aligned with the degenerative changes that have been noted in humans with tendinopathy. For these reasons, we believe this novel large animal model of chronic rotator cuff degeneration is a translational platform in which to test devices, therapies, and/or technologies aimed at repairing damage to the shoulder.
Positron emission tomography (PET) imaging utilizing fluorine-18 labeled fluorodeoxyglucose is a relatively new imaging modality in veterinary medicine that is becoming more common for oncological staging and for musculoskeletal imaging. Thus, it is important to identify the normal variations on PET imaging that may be mistaken for pathology. Variation in standardized uptake values (SUVmax) have been anecdotally identified in the spinal cord of dogs undergoing fluorodeoxyglucose (FDG) PET-CT examinations for oncological staging, with notable increase in SUVmax values identified in the region of the cervical and lumbar spinal intumescences. The aim of this retrospective, analytical study was to compare the SUVmax values at four different locations throughout the spinal cord (C3, C5-T1, T13, and L3-S1) of a group of dogs with no evidence of neurologic disease and compare those findings to histologic specimens from dogs euthanized for unrelated disease. SUVmax values were significantly higher at the cervical and lumbar intumescences in comparison to the control regions (P < .0001 and P < .0001, respectively). Neuronal count and spinal cord gray matter area were also significantly greater at the cervical and lumbar intumescences (neuronal count P = .0025 and P = .0001; area P = .0004 and P = .0009, respectively) while overall neuronal density was lower (P = .003 and P = .028, respectively). We presume the increased SUVmax values at the spinal cord intumescences are the result of overall increased neuron count, increased proportion of gray matter, and increased spinal cord gray matter area. These findings will aid in the interpretation of future PET-CT studies and hopefully prevent the misdiagnosis of spinal cord disease in normal canines.
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