Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears.

Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. We also used bear gluteal adipocyte cultures to test insulin and beta-adrenergic sensitivity in vitro. Bears were insulin resistant during hibernation but were sensitive during the spring and fall active periods. Hibernating bears remained euglycemic, possibly due to hyperinsulinemia and hyperglucagonemia. Adipokine concentrations were relatively low throughout the active season but peaked in mid-October prior to hibernation when fat content was greatest. Serum glycerol was highest during hibernation, indicating ongoing lipolysis. Centrally administered leptin reduced food intake in October, but not in August, revealing seasonal variation in the brain's sensitivity to its anorectic effects. This was supported by strong phosphorylated signal transducer and activator of transcription 3 labeling within the hypothalamus of hibernating bears; labeling virtually disappeared in active bears. Adipocytes collected during hibernation were insulin resistant when cultured with hibernation serum but became sensitive when cultured with active season serum. Heat treatment of active serum blocked much of this action. Clarifying the cellular mechanisms responsible for the physiology of hibernating bears may inform new treatments for metabolic disorders.

Prospectively recorded versus medical record-derived spinal cord injury scores in dogs with intervertebral disk herniation.

BACKGROUND: Validated spinal cord injury (SCI) scores have been established for veterinary species but are not uniformly used in practice. HYPOTHESIS/OBJECTIVES: To determine the level of agreement of SCI scores at the time of admission versus those assigned from reconstructed medical records in a population of dogs with intervertebral disk herniation (IVDH). ANIMALS: Eighty-six client-owned dogs with confirmed IVDH. METHODS: Retrospective study. Medical records were reviewed for history, physical examination, neurologic examination, and recorded Modified Frankel score (MFS) and Texas spinal cord injury score (TSCIS) at the time of admission. Three raters, all board-certified neurologists, assigned MFS and TSCIS based on digitized abstracted medical records to each patient. These scores were then compared to the recorded score at the time of admission. RESULTS: Actual agreement for MFS and TSCIS derived from medical records by the 3 raters compared to prospectively derived MFS and TSCIS was 77.9 and 51.2%, respectively. A kappa value of 0.572 (95% CI 0.450, 0.694; P < .001) and an ICC of 0.533 (95% CI 0.410, 0.646; P < .001) were calculated for MFS scores. A kappa value of 0.100 (95% CI 0.000, 0.222; P = .107), and an ICC of 0.503 (95% CI 0.377, 0.620; P < .001) were calculated for TSCIS scores. CONCLUSIONS AND CLINICAL IMPORTANCE: Results showed that SCI scores recorded at the time of admission often do not agree with those retrospectively abstracted from medical records. Agreement was less when using the more complex TSCIS scale and therefore the MFS scale might be more appropriate for use in retrospective studies.

Magnetic resonance imaging for the differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs.

BACKGROUND: The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown. OBJECTIVES: To estimate sensitivity, specificity, and inter-rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs. ANIMALS: One hundred and twenty-one client-owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44). METHODS: Retrospective, multi-institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter-rater agreement were calculated to estimate diagnostic performance. RESULTS: MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter-rater agreement was very good for overall detection of structural brain lesions (κ = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (κ = 0.299, 95% CI = 0, 0.761, P = .21). CONCLUSIONS AND CLINICAL IMPORTANCE: MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.

Pharmacokinetics of oral rufinamide in dogs.

The objective of this study was to determine the pharmacokinetic properties and short-term adverse effect profile of single-dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6-20.8 mg/kg). Plasma rufinamide concentrations were determined using high-performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half-life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 µg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 µg · h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half-life sufficient to achieve the therapeutic level extrapolated from humans without short-term adverse effects. Further investigation into the efficacy and long-term safety of rufinamide in the treatment of canine epilepsy is warranted.

Magnetic resonance imaging in dogs with neurologic impairment due to acute thoracic and lumbar intervertebral disk herniation.

BACKGROUND: Magnetic resonance imaging (MRI) is a correlate to physical examination in various myelopathies and a predictor of functional outcome. OBJECTIVES: To describe associations among MRI features, neurological dysfunction before MRI, and functional outcome in dogs with disk herniation. ANIMALS: One hundred and fifty-nine dogs with acute thoracolumbar disk herniation. METHODS: Retrospective case series. Signalment, initial neurological function as assessed by a modified Frankel score (MFS), and ambulatory outcome at hospital discharge and >3 months (long-term) follow-up were recorded from medical records and telephone interview of owners. Associations were estimated between these parameters and MRI signal and morphometric data. RESULTS: Dogs with intramedullary T2W hyperintensity had more severe pre-MRI MFS (median 2, range 0-4) and lower ambulatory proportion at long-term follow-up (0.76) than those dogs lacking hyperintensity (median MFS 3, range 0-5; ambulatory proportion, 0.93) (P=.001 and .013, respectively). Each unit of T2W length ratio was associated with a 1.9 times lower odds of long-term ambulation when adjusted for pre-MRI MFS (95% confidence interval 1.0-3.52, P=.05). Dogs with a compressive length ratio >1.31 (which was the median ratio within this population) had more severe pre-MRI MFS (median 3, range 0-5) compared with those with ratios < or =1.31 (median MFS 3, range 0-4; P=.006). CONCLUSIONS AND CLINICAL IMPORTANCE: MRI features were associated with initial injury severity in dogs with thoracolumbar disk herniation. Based on results of this study, the T2W length ratio and presence of T2W intramedullary hyperintensity appear to be predictive of long-term ambulatory status.