Objective—To compare characteristics and enzymatic products of leukocytes detected in the skin and laminar tissues of horses administered black walnut heartwood extract (BWHE) and horses administered purified lipopolysaccharide (LPS).
Animals—25 healthy 5- to 15-year-old horses.
Procedures—Horses were randomly assigned to receive LPS (20 ng of O55:B5 Escherichia coli endotoxin/kg; n = 5) IV or 6 L of BWHE (10) or water (control group; 10) via nasogastric intubation. Horses were euthanatized 12 hours after treatment or at onset of Obel grade 1 lameness. Laminar tissue samples and skin samples from the middle region of the neck were harvested at the time of euthanasia. Leukocyte emigration (determined via CD13 immunohistochemical analysis) and matrix metalloproteinase (MMP)-2 and MMP-9 gene expressions and activities (determined via reverse transcription PCR assay and gelatin zymography, respectively) were measured in skin and laminar tissue samples.
Results—Tissues of horses receiving BWHE contained significantly higher numbers of CD13-positive cells and increased MMP-9 gene expression and activity, compared with findings in the other 2 groups. Values for laminar tissue and skin from LPS-treated horses were not increased, compared with findings in the control group, in any experiment.
Conclusions and Clinical Relevance—Results indicated that BWHE administration causes increases in CD13-positive leukocyte numbers and MMP-9 expression and activity in laminar tissue and skin in horses; similar effects were not detected following LPS administration. Leukocyte emigration in horses with experimentally induced endotoxemia and in horses administered BWHE differed markedly, thereby providing additional evidence that the development of laminitis involves more complex mechanisms than endotoxemia-induced leukocyte activation alone.
Objective—To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors.
Sample—CSF from 55 dogs with intracranial tumors and 37 control dogs.
Procedures—Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated.
Results—Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration.
Conclusions and Clinical Relevance—Latent MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.
Objective—To assess serum 17-α-hydroxyprogesterone
(17OHP) and corticosterone concentrations in
dogs with nonadrenal neoplasia and dogs being
screened for hyperadrenocorticism.
Animals—16 clinically normal dogs, 35 dogs with
nonadrenal neoplasia, and 127 dogs with suspected
Procedure—ACTH stimulation tests were performed
in all dogs. Baseline serum cortisol and corticosterone
concentrations were measured in the healthy dogs;
baseline serum cortisol concentration and ACTH-stimulated
cortisol, corticosterone, and 17OHP concentrations
were measured in all dogs. Endogenous plasma
ACTH concentration was also measured before
administration of ACTH in dogs with neoplasia.
Results—In 35 dogs with neoplasia, 31.4% had high
serum 17OHP concentration and 22.9% had high
serum corticosterone concentration. Of the 127 dogs
with suspected hyperadrenocorticism, 59 (46.5%) had
high ACTH-stimulated cortisol concentrations; of those,
42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum
17OHP and corticosterone concentrations, respectively.
Of dogs with serum cortisol concentration within reference
range after ACTH administration, 9 of 68 (13.2%)
and 7 of 67 (10.4%) had high serum 17OHP and corticosterone
concentrations, respectively. In the dogs
with neoplasia and dogs suspected of having hyperadrenocorticism,
post-ACTH serum hormone concentrations
were significantly correlated.
Conclusions and Clinical Relevance—Serum concentrations
of 17OHP or corticosterone after administration
of ACTH may be high in dogs with nonadrenal neoplasia
and no evidence of hyperadrenocorticism. Changes in
serum 17OHP or corticosterone concentrations after
administration of ACTH are proportionate with changes
in cortisol concentration. (J Am Vet Med Assoc 2005;227:1762–1767)
Objective—To determine complications and neurologic outcomes associated with dexamethasone administration to dogs with surgically treated thoracolumbar intervertebral disk herniation, compared with dogs not receiving dexamethasone.
Design—Retrospective case series.
Animals—161 dogs with surgically confirmed thoracolumbar disk herniation.
Procedures—Medical records from 2 hospitals were used to identify dogs that had received dexamethasone < 48 hours prior to admission (dexamethasone group dogs), dogs that received glucocorticoids other than dexamethasone < 48 hours prior to admission (other-glucocorticoid group dogs), and dogs that received no glucocorticoids (nontreatment group dogs). Signalment, neurologic injury grade, laboratory data, and complications were extracted from medical records.
Results—Dexamethasone group dogs were 3.4 times as likely to have a complication, compared with other-glucocorticoid or nontreatment group dogs. Dexamethasone group dogs were 11.4 times as likely to have a urinary tract infection and 3.5 times as likely to have diarrhea, compared with other-glucocorticoid or nontreatment group dogs. No differences in neurologic function at discharge or recheck evaluation were detected among groups.
Conclusions and Clinical Relevance—Results indicated that treatment with dexamethasone before surgery is associated with more adverse effects, compared with treatment with glucocorticoids other than dexamethasone or no treatment with glucocorticoids, in dogs with thoracolumbar intervertebral disk herniation. In this study population, no difference in outcome was found among groups. These findings suggest that the value of dexamethasone administration before surgery in dogs with thoracolumbar disk herniation should be reconsidered.
OBJECTIVE To compare the pharmacokinetics of various formulations of levetiracetam after oral administration of a single dose to healthy dogs.
ANIMALS 6 neurologically normal mixed-breed dogs.
PROCEDURES A crossover study design was used. Blood samples for serum harvest were collected from each dog before and at various points after oral administration of one 500-mg tablet of each of 2 generic extended-release (ER) formulations, 1 brand-name ER formulation, or 1 brand-name immediate-release (IR) formulation of levetiracetam. Serum samples were analyzed to determine pharmacokinetic properties of each formulation by means of ultra–high-performance liquid chromatography with tandem mass spectrometry.
RESULTS No dogs had clinically important adverse effects for any formulation of levetiracetam. All ER formulations had a significantly lower maximum serum drug concentration and longer time to achieve that concentration than did the IR formulation. Half-lives and elimination rate constants did not differ significantly among formulations. Values for area under the drug concentration-versus-time curve did not differ significantly between ER formulations and the IR formulation; however, 1 generic ER formulation had a significantly lower area under the curve than did other ER formulations.
CONCLUSIONS AND CLINICAL RELEVANCE All ER formulations of levetiracetam had similar pharmacokinetic properties in healthy dogs, with some exceptions. Studies will be needed to evaluate the clinical efficacy of the various formulations; however, findings suggested that twice-daily administration of ER formulations may be efficacious in the treatment of seizures in dogs.