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  • Author or Editor: Gaylen L. Edwards x
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Abstract

Objective—To determine and compare the ratio of uracil (U) to dihydrouracil (UH2) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency.

Animals—101 client-and shelter-owned dogs.

Procedures—Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency. For each dog, a blood sample was collected into an EDTA-containing tube; plasma U and UH2 concentrations were determined via UV high-performance liquid chromatography, and the U:UH2 concentration ratio was calculated. Data were compared among dogs grouped on the basis of sex, clinical group assignment, reproductive status (sexually intact, spayed, or castrated), and age.

Results—Mean ± SEM U:UH2 concentration ratio for all dogs was 1.55 ± 0.08 (median, 1.38; range, 0.4 to 7.14). In 14 (13.9%) dogs, the U:UH2 concentration ratio was considered abnormal (ie, > 2). Overall, mean ratio for sexually intact dogs was significantly higher than that for neutered dogs; a similar difference was apparent among males but not females. Dogs with ratios > 2 and dogs with ratios ≤ 2 did not differ significantly with regard to sex, clinical group, reproductive status, or age.

Conclusions and Clinical Relevance—Determination of the U:UH2 concentration ratio was easy to perform. Ratios were variable among dogs, possibly suggesting differences in dihydropyrimidine dehydrogenase activity. However, studies correlating U:UH2 concentration ratio and fluoropyrimidine antimetabolite drug tolerability are required to further evaluate the test's validity and its appropriate use in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To measure concentrations of glutamate, aspartate, γ-aminobutyric acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these concentrations.

Sample—CSF samples from 13 dogs.

Procedures—In a previous study, SAH was induced in dogs via 2 injections of autologous blood into the cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5) or received simvastatin alone (4) or simvastatin in combination with cyclosporine (4). Samples of CSF were collected before the first blood injection (baseline; time 0), before the second blood injection, and on days 3, 7, and 10. For the study reported here, neurotransmitter concentrations in CSF were analyzed via high-performance liquid chromatography. Data were analyzed with a repeated-measures model with adjustments for multiple comparisons by use of the Tukey method.

Results—In control dogs, the glutamate concentration peaked on day 3 and there was a significant increase in GABA and glutamate concentrations. Glutamate concentrations were significantly lower and glycine concentrations significantly higher on day 3 after administration of simvastatin alone or simvastatin in combination with cyclosporine, compared with concentrations for the control group. No significant differences in GABA and aspartate concentrations were detected among treatment groups at any time point.

Conclusions and Clinical Relevance—Glutamate concentrations were increased in the CSF of dogs with SAH. Simvastatin administration attenuated high glutamate concentrations. A combination of immunosuppression and upregulation of nitric oxide synthase may be useful in lowering high glutamate concentrations in ischemic CNS conditions.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate differences in CSF concentrations of excitatory and inhibitory neurotransmitters in dogs with and without T2-weighted (T2W) MRI hyperintense areas in the limbic system.

Sample—Archived CSF samples and stored brain MRI images of 5 healthy research dogs (group 1), 8 dogs with idiopathic epilepsy (IE) with no abnormal MRI findings (group 2), and 4 dogs with IE with hyperintense areas in the limbic system detected by means of T2W MRI (group 3).

Procedures—Archived CSF samples and stored MRI images obtained from all dogs were evaluated. Dogs in groups 2 and 3 were matched on the basis of age and breed. High-performance liquid chromatography was used to evaluate glutamate and γ-aminobutyric acid (GABA) concentrations in CSF samples.

Results—Glutamate concentrations were higher in CSF of both groups of dogs with IE than in healthy dogs. However, glutamate concentrations in CSF were not significantly higher in dogs with IE and with hyperintense areas than in dogs with IE but no abnormal MRI findings. Concentrations of GABA in CSF were higher in group 3 than in group 2 and in group 2 than in group 1.

Conclusions and Clinical Relevance—No significant difference was evident between glutamate concentrations in CSF of dogs with IE and with and without hyperintense areas detected by means of T2W MRI. However, glutamate concentrations typically were higher in CSF of dogs with IE and MRI hyperintense areas. Future studies with larger sample sizes should be conducted to confirm this finding and to determine the clinical importance of high glutamate concentrations in CSF of dogs with IE.

Full access
in American Journal of Veterinary Research