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2.
Vet Clin Pathol ; 50(3): 376-383, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34435372

RESUMO

BACKGROUND: Hyperproteinorrachia (raised cerebrospinal fluid total protein [CSF-TP]) without pleocytosis (HP) (also known as albuminocytologic dissociation) is identified in dogs with different neurologic diseases. However, the association between survival and increased CSF-TP is unknown. OBJECTIVES: (a) Identify conditions commonly associated with HP in dogs and (b) investigate whether higher CSF-TP concentrations or other relevant factors are associated with 1-year survival. METHODS: This is a retrospective study that identified dogs with HP (Cisternal CSF-TP >0.30 g/L, Lumbar CSF-TP >0.45 g/L with total nucleated cell concentrations [TNCCs] and RBC counts within RIs) from 2008 to 2019: recording signalment, weight, vital parameters, inflammation, neuroanatomic localization, CSF-TP, sampling site, final diagnosis, etiologic classification, and 1-year survival. Corrected CSF-TP was calculated as CSF-TP minus 0.3 (cisternal) or 0.45 (lumbar or unknown). Descriptive statistics were produced, CSF-TP differences between groups (eg, neuroanatomic localizations) were evaluated using the Mann-Whitney U test or Kruskal-Wallis test (post-hoc testing). The Cox proportional hazards model was used for survival data. Statistical significance was set at a P < 0.05. RESULTS: In all, 39 dogs had HP, associated with 17 conditions, including neoplasia (n = 6), meningoencephalitis of unknown origin (n = 4) (MUO), and intervertebral disc disease (n = 4) (IVDD) as the most common conditions. There was no significant difference between the CSF-TP/corrected CSF-TP between 1-year survivors and non-survivors, nor was there a difference between different neuroanatomic localizations or etiologic classifications (P > 0.05). Neoplasia, after adjustment for age, was the only variable associated with a worse survival (P = 0.01 HR: 2.08 (95% CI: 1.65-39.2). CSF-TP was not associated with age (P > 0.05). CONCLUSIONS: HP in dogs is associated with a wide range of conditions; the most common conditions are neoplasia, MUO, and IVDD. Higher CSF-TP levels do not correlate with a worse 1-year survival; however, they do correlate with neoplastic lesions.


Assuntos
Doenças do Cão , Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Animais , Cães , Degeneração do Disco Intervertebral/veterinária , Deslocamento do Disco Intervertebral/veterinária , Leucocitose/veterinária , Estudos Retrospectivos
3.
FASEB J ; 34(1): 458-473, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914665

RESUMO

A glutamic acid to lysine (E40K) residue substitution in superoxide dismutase 1 (SOD1) is associated with canine degenerative myelopathy: the only naturally occurring large animal model of amyotrophic lateral sclerosis (ALS). The E40 residue is highly conserved across mammals, except the horse, which naturally carries the (dog mutant) K40 residue. Here we hypothesized that in vitro expression of mutant dog SOD1 would recapitulate features of human ALS (ie, SOD1 protein aggregation, reduced cell viability, perturbations in mitochondrial morphology and membrane potential, reduced ATP production, and increased superoxide ion levels); further, we hypothesized that an equivalent equine SOD1 variant would share similar perturbations in vitro, thereby explain horses' susceptibility to certain neurodegenerative diseases. As in human ALS, expression of mutant dog SOD1 was associated with statistically significant increased aggregate formation, raised superoxide levels (ROS), and altered mitochondrial morphology (increased branching (form factor)), when compared to wild-type dog SOD1-expressing cells. Similar deficits were not detected in cells expressing the equivalent horse SOD1 variant. Our data helps explain the ALS-associated cellular phenotype of dogs expressing the mutant SOD1 protein and reveals that species-specific sequence conservation does not necessarily predict pathogenicity. The work improves understanding of the etiopathogenesis of canine degenerative myelopathy.


Assuntos
Trifosfato de Adenosina/metabolismo , Esclerose Lateral Amiotrófica/patologia , Mitocôndrias/metabolismo , Mutação de Sentido Incorreto , Superóxido Dismutase-1/genética , Transgenes/fisiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Cães , Cavalos , Humanos , Mitocôndrias/patologia , Filogenia , Especificidade da Espécie
4.
Muscle Nerve ; 60(6): 762-768, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31498901

RESUMO

INTRODUCTION: Equine recurrent laryngeal neuropathy (RLN) is a naturally occurring model of length-dependent axonopathy characterized by asymmetrical degeneration of recurrent laryngeal nerve axons (RLn). Distal RLn degeneration is marked, but it is unclear whether degeneration extends to include cell bodies (consistent with a neuronopathy). METHODS: With examiners blinded to RLN severity, brainstem location, and side, we examined correlations between RLN severity (assessed using left distal RLn myelinated axon count) and histopathological features (including chromatolysis and glial responses) in the nucleus ambiguus cell bodies, and myelinated axon count of the right distal RLn of 16 horses. RESULTS: RLN severity was not associated with RLn cell body number (P > .05), or degeneration. A positive correlation between the left and right distal RLn myelinated axon counts was identified (R2 = 0.57, P < .05). DISCUSSION: We confirm that RLN, a length-dependent distal axonopathy, occurs in the absence of detectable neuronopathy.


Assuntos
Corpo Celular/patologia , Bulbo/patologia , Fibras Nervosas Mielinizadas/patologia , Neurônios/patologia , Nervo Laríngeo Recorrente/patologia , Paralisia das Pregas Vocais/patologia , Animais , Atrofia , Contagem de Células , Cavalos , Nervo Laríngeo Recorrente/fisiopatologia , Paralisia das Pregas Vocais/fisiopatologia
5.
J Vet Intern Med ; 32(4): 1397-1409, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29691904

RESUMO

Recurrent Laryngeal Neuropathy (RLN) is a highly prevalent and predominantly left-sided, degenerative disorder of the recurrent laryngeal nerves (RLn) of tall horses, that causes inspiratory stridor at exercise because of intrinsic laryngeal muscle paresis. The associated laryngeal dysfunction and exercise intolerance in athletic horses commonly leads to surgical intervention, retirement or euthanasia with associated financial and welfare implications. Despite speculation, there is a lack of consensus and conflicting evidence supporting the primary classification of RLN, as either a distal ("dying back") axonopathy or as a primary myelinopathy and as either a (bilateral) mononeuropathy or a polyneuropathy; this uncertainty hinders etiological and pathophysiological research. In this review, we discuss the neuropathological changes and electrophysiological deficits reported in the RLn of affected horses, and the evidence for correct classification of the disorder. In so doing, we summarize and reveal the limitations of much historical research on RLN and propose future directions that might best help identify the etiology and pathophysiology of this enigmatic disorder.


Assuntos
Doenças dos Nervos Cranianos/veterinária , Doenças dos Cavalos/classificação , Nervo Laríngeo Recorrente/patologia , Animais , Doenças dos Nervos Cranianos/classificação , Doenças dos Nervos Cranianos/patologia , Doenças dos Cavalos/patologia , Cavalos
6.
Vet Radiol Ultrasound ; 53(3): 336-41, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22168823

RESUMO

The aims of this study were to establish a normal reference range (mean ± 2 SD) and assess reliability of renal dimensions obtained using transabdominal ultrasonography in Thoroughbred horses (n = 7). A minimum of three ultrasonographic cineloops were obtained from each intercostal space and the left paralumbar fossa by two observers daily for three consecutive days. Renal length, width, and thickness and cortex, medulla, and pelvic dimensions were obtained. Measurements were undertaken by both observers, who were unaware of prior measurements, to assess reproducibility and measured on three separate occasions to evaluate short-term measurement repeatability. Measurements from images obtained by both operators were compared to evaluate image repeatability. The left kidney was consistently identified in the left 15th-17th intercostal space and the paralumbar fossa with maximal length in the 16th intercostal space (12.7 ± 2.0 cm) and maximal width in the paralumbar fossa (7.9 ± 1.1 cm). The right kidney was consistently identified in the right 15th-17th intercostal space with maximal length and maximal width in the 15th intercostal space (16.0 ± 0.7 cm and 7.9 ± 1.0 cm). Reproducibility, image repeatability, measurement repeatability were good to excellent, although were less good for the smaller structures. There were no differences in renal dimensions between horses. Overall renal ultrasonography was reliable and a normal reference range for Thoroughbred horses was established. Renal dimensions vary between rib spaces. As repeatability and reproducibility were excellent for renal length and width, it may be prudent to use those measurements in rib spaces where parameters were maximal.


Assuntos
Cavalos/anatomia & histologia , Rim/diagnóstico por imagem , Animais , Feminino , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Ultrassonografia/métodos
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