Studies on the clinical course of familial ALS suggest that the duration of illness is relatively consistent for each mutation but variable among the different mutations. The authors analyzed the relative amount of mutant compared with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22 different mutations. Turnover of mutant SOD1 correlated with a shorter disease survival time.
ABSTRACT. Immunohistochemistry was performed to assess whether oxidative stress and/or denatured proteins play roles in the pathogenesis of canine degenerative myelopathy (DM). Two Pembroke Welsh Corgi (PWC) dogs with a homozygous mutation (c.118G>A) in the canine superoxide dismutase 1 (SOD1) gene were examined. The pathological features of the dogs were consistent with those of previous cases of DM in PWC. In the spinal lesions, diffuse SOD1 expression was observed in the neurons while no inclusion-like aggregates had formed, which disagreed with the findings of a previous study. A unique inducible nitric oxide synthase (iNOS) staining pattern in reactive astrocytes and a significant increase in ubiquitin immunoreactivity in the spinal lesions were also observed. These findings indicate the involvement of oxidative stress and the accumulation of ubiquitinated proteins in the pathogenesis of canine DM, whereas the role of SOD1 remains unclear.KEY WORDS: canine, degenerative myelopathy, oxidative stress, Pembroke Welsh Corgi.
Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease that is frequently found in Pembroke Welsh Corgi (PWC) dogs. Canine DM is potentially a spontaneous animal model for human amyotrophic lateral sclerosis (ALS) because of similar lesions and the involvement of superoxide dismutase 1 (SOD1) mutation. However, the ventral horn lesion in DM has not been characterized in detail. Glutamate excitotoxicity due to deficiency of the glutamine-glutamate cycle has been implicated in neuron death in ALS. Thus, we examined 5 PWC dogs with an SOD1 mutation that were affected by DM, 5 non-DM PWC dogs, and 5 Beagle dogs without neurologic signs to assess the neuronal changes and the expression levels of 2 glial excitatory amino acid transporters (glutamate transporter 1 [GLT-1] and glutamate/aspartate transporter [GLAST]). The number of neurons in the spinal ventral horns of the DM dogs was significantly decreased, whereas no change was found in the cell size. Chromatolysis, lipofuscin-laden neurons, and marked synapse loss were also observed. GLT-1 expression was strikingly decreased in DM dogs, whereas GLAST expression showed no significant change. The results indicate that excitotoxicity related to the reduced expression of GLT-1, but not GLAST, may be involved in neuron loss in DM, as in human ALS, whereas intraneuronal events may differ between the 2 diseases.
Objectives
To examine the relationship between fibroblast growth factor‐23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs.
Materials and Methods
Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor‐23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor‐23.
Results
Serum fibroblast growth factor‐23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor‐23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5 ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor‐23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor‐23.
Clinical Significance
This preliminary study suggests that canine fibroblast growth factor‐23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.
We examined early morphological changes in pancreatic endocrine cells within 12 h of intravenous streptozotocin (STZ) administration (60 mg/kg). Thirty rats were allocated either to a control group (vehicle alone) or to one of four experimental groups tested after 3, 6, 9 and 12 h. Karyopyknosis and cytoplasmic vacuoles were first observed in beta-cell cytoplasm 3 h after STZ administration (STZ-3 h), and the most severe damage was found in beta cells at STZ-12 h. Insulin-positive non-islet cells were observed near the intercalated duct (ICD) and/or centroacinar (CA) cells at STZ-6 h and their numbers peaked at STZ-6 h. The distribution patterns of the insulin-positive cells and those of nestin and insulin-like growth factor-1 were similar and their nuclei were positive for proliferating cell nuclear antigen. Thus, ICD cells and/or CA cells reacted immediately to transform into insulin-secreting cells to replace injured beta cells (or to compensate for the lack of beta cells) within 12 h of STZ administration.
Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with
progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre,
prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide
(NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their
characteristics and discriminatory ability to detect cardiac dilatation and congestive
heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical
variables were obtained via physical examination, thoracic radiography, and
echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine
the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated
using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP
concentrations showed a significant association with the left atrium/aorta ratio
(
P
<0.01). The area under the curve of plasma NT-proANP and NT-proBNP
concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively
in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and
80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00
pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2
(cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD,
plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement.
Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful
in the discriminatory ability to detect cardiac dilatation and CHF.
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