RESUMEN
OBJECTIVE: To measure the nerve fiber density in synovial membranes from healthy and OA equine joints and to investigate the relationship between synovial innervation and OA severity, synovial vascularity and synovitis. DESIGN: Twenty-five equine metacarpophalangeal joints were collected post-mortem. The joints were dissected and the macroscopic lesions of the articular cartilage were scored. Synovial membrane specimens (n = 50) were harvested, fixed, sectioned and scored histologically. Immunohistochemical staining and immunofluorescence with S-100 protein, that identifies nerve fibers, and âº-actin, that stains vascular smooth muscle, were also performed on site-matched specimens and the relationships between these tissues was interrogated. RESULTS: The nerve fiber density was higher in the superficial layer (≤200 µm) of the synovium when compared to the deeper layer in control equine joints (mean difference (95% C.I.): 0.054% (0.018%, 0.11%)). In osteoarthritic joints, synovial innervation decreased in the superficial layer with increasing macroscopic OA score (ß (SEM), 95% C.I.: -0.0061 (0.00021), -0.0011, -0.00017). The blood vessel density was also higher in the superficial layer of the synovium compared to the deep layer in the control (mean difference (95% C.I.): 1.1% (0.36%, 2.3%)) and OA (mean difference (95% C.I.): 0.60% (0.22%, 1.2%)) equine joints. Moreover, considering all synovial specimens, higher nerve fiber density in the deep layer positively correlated with blood vessel density (ß (SEM), 95% C.I.: 0.11 (0.036), 0.035, 0.18). CONCLUSION: The reduction in nerve fiber density with advanced cartilage degeneration suggests that peripheral neuropathy is associated with equine OA. Whether this link is associated with neuropathic pain, requires further investigation.
Asunto(s)
Enfermedades de los Caballos/patología , Articulación Metacarpofalángica , Fibras Nerviosas/patología , Osteoartritis/patología , Membrana Sinovial/inervación , Animales , Progresión de la Enfermedad , Femenino , Caballos , Masculino , Osteoartritis/veterinariaRESUMEN
AIM: The primary goal of this body of work is to suggest a standardized system for histopathological assessment of experimental surgical instability models of osteoarthritis (OA) in rabbits, building on past experience, to achieve comparability of studies from different centres. An additional objective is to review methodologies that have been employed in the past for assessing OA in rabbits with particular reference to the surgical anterior cruciate ligament transection (ACLT) model. METHODS: A panel of scientists and clinician-scientists with recognized expertise in assessing rabbit models of OA reviewed the literature to provide a critical appraisal of the methods that have been employed to assess both macroscopic and microscopic changes occurring in rabbit joint tissues in experimental OA. In addition, a validation of the proposed histologic histochemical grading system was performed. RESULTS: The ACLT variant of the surgical instability model in skeletally mature rabbits is the variation most capable of reproducing the entire range of cartilage, synovial and bone lesions recognized to be associated with OA. These lesions can be semiquantitatively graded using macroscopic and microscopic techniques. Further, as well as cartilage lesions, this ACLT model can produce synovial and bone lesions similar to that of human OA. CONCLUSIONS: The ACLT variant of the surgical instability model in rabbits is a reproducible and effective model of OA. The cartilage lesions in this model and their response to therapy can be graded according to an adapted histological and histochemical grading system, though also this system is to some extent subjective and, thus, neither objective nor entirely reproducible.
Asunto(s)
Artritis Experimental/patología , Osteoartritis/patología , Animales , Lesiones del Ligamento Cruzado Anterior , Artritis Experimental/etiología , Cartílago Articular/patología , Modelos Animales de Enfermedad , Femenino , Articulaciones/patología , Masculino , Meniscos Tibiales/patología , Osteoartritis/etiología , Conejos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate in vivo the evolution of osteoarthritis (OA) lesions temporally in a rabbit model of OA with clinically available imaging modalities: computed radiography (CR), helical single-slice computed tomography (CT), and 1.5 tesla (T) magnetic resonance imaging (MRI). METHODS: Imaging was performed on knees of anesthetized rabbits [10 anterior cruciate ligament transection (ACLT) and contralateral sham joints and six control rabbits] at baseline and at intervals up to 12 weeks post-surgery. Osteophytosis, subchondral bone sclerosis, bone marrow lesions (BMLs), femoropatellar effusion and articular cartilage were assessed. RESULTS: CT had the highest sensitivity (90%) and specificity (91%) to detect osteophytes. A significant increase in total joint osteophyte score occurred at all time-points post-operatively in the ACLT group alone. BMLs were identified and occurred most commonly in the lateral femoral condyle of the ACLT joints and were not identified in the tibia. A significant increase in joint effusion was present in the ACLT joints until 8 weeks after surgery. Bone sclerosis or cartilage defects were not reliably assessed with the selected imaging modalities. CONCLUSION: Combined, clinically available CT and 1.5 T MRI allowed the assessment of most of the characteristic lesions of OA and at early time-points in the development of the disease. However, the selected 1.5 T MRI sequences and acquisition times did not permit the detection of cartilage lesions in this rabbit OA model.
Asunto(s)
Artritis Experimental/diagnóstico , Animales , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/patología , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Progresión de la Enfermedad , Exudados y Transudados/diagnóstico por imagen , Exudados y Transudados/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Osteofito/diagnóstico , Osteofito/diagnóstico por imagen , Osteosclerosis/diagnóstico , Osteosclerosis/diagnóstico por imagen , Conejos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
REASONS FOR PERFORMING STUDY: The earliest osteochondrosis (OC) microscopic lesion reported in the literature was present in the femorotibial joint of a 2-day-old foal suggesting that OC lesions and factors initiating them may arise prior to birth. OBJECTIVE: To examine the developing equine epiphysis to detect histological changes that could be precursors to OC lesions. METHODS: Osteochondral samples from 21 equine fetuses and 13 foals were harvested from selected sites in the scapulohumeral, humeroradial, metacarpophalangeal, femoropatellar, femorotibial, tarsocrural and metatarsophalangeal joints. Sections were stained with safranin O and picrosiruis red to assess cartilage changes and structural arrangement of the collagen matrix. RESULTS: Extracellular matrix changes observed included perivascular areas of paleness of the proteoglycan matrix associated with hypocellularity and, sometimes, necrotic chondrocytes. These changes were most abundant in the youngest fetuses and in the femoropatellar/femorotibial (FP/FT) joints. Indentations of the ossification front were also observed in most specimens, but, most frequently, in scapulohumeral and FP/FT joints. A cartilage canal was almost always present in these indentations. The vascular density of the cartilage was higher in the youngest fetuses. In these fetuses, the most vascularised joints were the metacarpo- and metatarsophalangeal joints but their cartilage canals regressed quickly. After birth, the most vascularised cartilage was present in the FP/FT joint. Articular cartilage differentiated into 4 zones early in fetal life and the epiphyseal cartilage also had a distinct zonal cartilage structure. A striking difference was observed in the collagen structure at the junction of the proliferative and hypertrophic zones where OCD lesions occur. CONCLUSION: Matrix and ossification front changes were frequently observed and significantly associated with cartilage canals suggesting that they may be physiological changes associated with matrix remodelling and development. The collagen structure was variable through the growing epiphysis and a differential in biomechanical properties at focal sites may predispose them to injury.
Asunto(s)
Cartílago Articular/embriología , Placa de Crecimiento/embriología , Enfermedades de los Caballos/embriología , Caballos/embriología , Articulaciones , Osteocondritis/veterinaria , Envejecimiento , Animales , Animales Recién Nacidos , Cartílago Articular/irrigación sanguínea , Cartílago Articular/patología , Femenino , Placa de Crecimiento/irrigación sanguínea , Placa de Crecimiento/patología , Enfermedades de los Caballos/patología , Caballos/crecimiento & desarrollo , Articulaciones/irrigación sanguínea , Articulaciones/embriología , Articulaciones/patología , Masculino , Osteocondritis/embriología , Osteocondritis/patología , Flujo Sanguíneo Regional , Tarso Animal/irrigación sanguínea , Tarso Animal/embriología , Tarso Animal/patología , Tibia/irrigación sanguínea , Tibia/embriología , Tibia/patologíaRESUMEN
Heterozygous activating mutations in Kir6.2 (KCNJ11), the pore-forming subunit of the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel, are a common cause of neonatal diabetes (ND). We assessed the functional effects of two Kir6.2 mutations associated with ND: K170T and E322K. K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)). Both mutations reduced the sensitivity of the K(ATP) channel to inhibition by MgATP and enhanced whole-cell K(ATP) currents. In pancreatic beta cells, such an increase in the K(ATP) current is expected to reduce insulin secretion and thereby cause diabetes. The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1. This is consistent with its predicted location on the outer surface of the tetrameric Kir6.2 pore. The kinetics of K170T channel opening and closing were altered by the mutation, which may contribute to the lower ATP sensitivity. Neither mutation affected the sensitivity of the channel to inhibition by the sulphonylurea tolbutamide, suggesting that patients carrying these mutations may respond to these drugs.
Asunto(s)
Diabetes Mellitus/genética , Mutación/genética , Canales de Potasio de Rectificación Interna/genética , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/fisiología , Adenosina Trifosfato/fisiología , Animales , Diabetes Mellitus/fisiopatología , Conductividad Eléctrica , Heterocigoto , Humanos , Recién Nacido , Canales de Potasio de Rectificación Interna/metabolismo , Canales de Potasio de Rectificación Interna/fisiología , RatasAsunto(s)
Neoplasias Abdominales/veterinaria , Enfermedades de los Bovinos/patología , Mesotelioma/veterinaria , Neoplasias Abdominales/patología , Animales , Bovinos , Femenino , Técnicas para Inmunoenzimas , Queratinas/análisis , Ganglios Linfáticos/química , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Mesotelioma/patología , Vimentina/análisisRESUMEN
Twenty post-stroke patients were assigned to one of three treatment conditions or to a control group to test whether exercises, determined in a previous study to recruit maximal extensor digitorum participation, would improve finger extension function over time. The exercises were resisted grasp, resisted extension, and ballistic extension. Improved function was defined as increased active range of motion, speed of reversal of movement, and ability to grasp and release cylinders. Significantly more subjects assigned to ballistic or resisted extension conditions improved in their ability to rapidly reverse movement over the course of treatment as opposed to those assigned to resisted grasp or control conditions. However, Kruskal-Wallis nonparametric analyses of variance indicated that no exercise improved all three components of function significantly more than another or the control condition. Since no clear difference was found between the control and treatment conditions, it was concluded that motor unit recruitment as an attribute of activity is insufficient to improve function in post-stroke patients. The strength of this conclusion is limited by a chance imbalance of patient assignment in which significantly more patients assigned to resisted and ballistic extension conditions were at a higher level of recovery of motor control.