Objective—To determine essential fatty acid concentrations
in plasma and tissue before and after supplementation
with n-3 fatty acids in dogs with atopic dermatitis.
Animals—30 dogs with atopic dermatitis.
Procedure—Dogs received supplemental flaxseed oil
(200 mg/kg/d), eicosapentaenoic acid (EPA;
50 mg/kg/d)-docosahexaenoic acid (DHA;
35 mg/kg/d), or mineral oil as a placebo in a doubleblind,
placebo-controlled, randomized trial. Clinical
scores and plasma and cutaneous concentrations of
linoleic acid, arachidonic acid, α-linolenic acid (α-LLA),
EPA, DHA, prostaglandin E2, and leukotriene B4 were
Results—Total plasma concentrations of α-LLA and
EPA increased and those of arachidonic acid
decreased significantly with administration of EPADHA,
and concentrations of α-LLA increased with
flaxseed oil supplementation; nevertheless, there
was no significant change in the concentrations of
these fatty acids or eicosanoids in the skin. There was
no correlation between clinical scores and plasma or
cutaneous concentrations for any of the measured
fatty acids or eicosanoids.
Conclusion and Clinical Relevance—Results indicated
that at the dose used, neither the concentrations
of fatty acids in skin or plasma nor a decrease in
the production of inflammatory eicosanoids was a
major factor involved in the mechanism of action in
dogs with atopy that responded to fatty acid supplementation.
(Am J Vet Res 2005;66:868–873)
Objective—To identify matrix metalloproteinases
(MMP) 2 and 9 in canine tumor tissue and to compare
the amount of activity to that in unaffected stromal
Animals—30 dogs with spontaneously developing,
Procedure—Tumor and nearby stromal tissue (muscle)
were obtained at the time of surgery. Specimens were
homogenized, and supernatants were assayed, using
gelatin zymography. Human derived standards were
run concurrently. Densitometry was done to obtain a
semiquantitative arbitrary unit value for each specimen.
The amount of activity in tumor tissue was compared
with the amount in stromal tissue.
Results—Gelatinolytic bands were observed from
the analysis of all tumor tissues and in most stromal
tissues. These bands migrated in the same molecular
weight area as the human MMP 2 and 9 standards.
Gelatinolytic activity could be quenched by the addition
of 50 mM EDTA and 1 µg of synthetic tissue
inhibitor of metalloproteinase (TIMP) 2 per 100 ml.
There was significantly more gelatinolytic activity in
tumor tissue than in stromal tissue.
Conclusions and Clinical Relevance—MMP 2 and 9
are detectable in canine neoplastic tissue. matrix metalloproteinases
activity in tumor tissue is higher than in
unaffected stromal tissue, indicating that canine MMP
may be involved in the pathogenesis of tumor growth
and metastasis. (Am J Vet Res 2000;61:111–114)
Objective—To determine toxic effects of streptozocin
given in combination with a diuresis protocol in dogs
and establish whether streptozocin is efficacious in
treatment of pancreatic islet cell tumors in dogs.
Procedure—Medical records were reviewed to
obtain information regarding signalment, tumor stage
and staging tests performed, number of streptozocin
treatments, adverse effects, results of biochemical
and hematologic monitoring during streptozocin treatment,
tumor dimensions, duration of normoglycemia,
and date of death, when applicable. Dogs were compared
with a historical control group of 15 dogs treated
surgically and medically.
Results—58 treatments were administered to the 17
dogs. Only 1 dog developed azotemia. Serum alanine
aminotransferase activity increased in some dogs but
decreased when treatment was discontinued.
Hematologic toxicoses were rare. Vomiting during
administration was uncommon but occasionally
severe. Two dogs developed diabetes mellitus after
receiving 5 doses. Median duration of normoglycemia
for 14 dogs with stage-II or -III insulinoma treated with
streptozocin was 163 days (95% confidence interval,
16 to 309 days), which was not significantly different
from that for the control dogs (90 days; 95% confidence
interval, 0 to 426 days). Two dogs had rapid resolution
of paraneoplastic peripheral neuropathy, and 2
others had measurable reductions in tumor size.
Conclusions and Clinical Relevance—Results
suggest that streptozocin can be administered safely
to dogs at a dosage of 500 mg/m2, IV, every 3
weeks when combined with a protocol for induction
of diuresis and may be efficacious in the treatment
of dogs with metastatic pancreatic islet cell tumors.
(J Am Vet Med Assoc 2002;221:811–818)
Objective—To evaluate changes in resting energy
expenditure (REE) as well as protein and carbohydrate
metabolism in dogs with osteosarcoma (OSA).
Animals—15 weight-stable dogs with OSA that did
not have other concurrent metabolic or endocrine illness
and twelve 1-year-old sexually intact female
Beagles (control dogs).
Procedures—Indirect calorimetry was performed on
all dogs to determine REE and respiratory quotient
(RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of
body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV
as a bolus, followed by continuous-rate infusion at 1.5
mg/kg/h for 3 hours) were used to determine rate of
protein synthesis and glucose flux in all dogs. Dualenergy
x-ray absorptiometry (DEXA) scans were performed
to determine total body composition.
Results—Accounting for metabolic body size, REE in
dogs with OSA was significantly higher before and
after surgery, compared with REE of healthy control
dogs. The RQ values did not differ significantly
between groups. Dogs with OSA also had decreased
rates of protein synthesis, increased urinary nitrogen
loss, and increased glucose flux during the postoperative
Conclusions and Clinical Relevance—Alterations in
energy expenditure, protein synthesis, urinary nitrogen
loss, and carbohydrate flux were evident in dogs
with OSA, similar to results documented in humans
with neoplasia. Changes were documented in REE as
well as protein and carbohydrate metabolism in dogs
with OSA. These changes were evident even in dogs
that did not have clinical signs of cachexia. (Am J Vet
Procedure—Pharmacokinetic studies of phenobarbital
were performed before and 2 months after dogs
were fed 1 of 3 diets (group 1, maintenance diet;
group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital
(approx 3 mg/kg [1.4 mg/lb] of body weight, PO, q 12
h). Pharmacokinetic studies involved administering
phenobarbital (15 mg/kg [6.8 mg/lb], IV) and collecting
blood samples at specific intervals for 240 hours.
Effects of diet and time were determined by repeated-measures ANOVA.
Results—Volume of distribution, mean residence
time, and half-life (t1/2) of phenobarbital significantly
decreased, whereas clearance rate and elimination
rate significantly increased with time in all groups.
Dietary protein or fat restriction induced significantly
greater changes: t1/2 (hours) was lower in groups 2
(mean ± SD; 25.9 ± 6.10 hours) and 3 (24.0 ± 4.70)
than in group 1 (32.9 ± 5.20). Phenobarbital clearance
rate (ml/kg/min) was significantly higher in group 3
(0.22 ± 0.05 ml/kg/min) than in groups 1 (0.17 ± 0.03)
or 2 (0.18 ± 0.03). Induction of serum alkaline phosphatase
activity (U/L) was greater in groups 2 (192.4
± 47.5 U/L) and 3 (202.0 ± 98.2) than in group 1 (125.0
Conclusions and Clinical Relevance—Clinically
important differences between diet groups were
observed regarding pharmacokinetics of phenobarbital,
changes in CBC and serum biochemical variables,
and body composition. Drug dosage must be reevaluated
if a dog's diet, body weight, or body composition
changes during treatment. Changes in blood variables
that may indicate liver toxicosis caused by phenobarbital
may be amplified by diet-drug interactions. (J Am
Vet Med Assoc 2000;217:847–852)
Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.
Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.
Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.
Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.
Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.
Objective—To determine outcome for dogs with
grade-II mast cell tumors treated with surgery alone.
Procedures—Medical records were examined, and
signalment; location and size of tumor; staging status;
dates of local recurrence, metastasis, death, or last
follow-up examination; status of surgical margins; previous
surgery; postoperative complications; and
cause of death were recorded. Follow-up information
was obtained via reexamination or telephone conversations
with owners or referring veterinarians.
Univariate analysis was performed to identify prognostic
Results—60 tumors in 55 dogs were included.
Median follow-up time was 540 days. Three (5%)
mast cell tumors recurred locally; median time to local
recurrence was 62 days. Six (11%) dogs developed
another mast cell tumor at a different cutaneous location;
median time to a different location was 240 days.
Three (5%) dogs developed metastases; median time
to metastasis was 158 days. Fourteen dogs died; 3
deaths were related to mast cell tumor, and 7 were
unrelated. The relationship with mast cell tumor was
not known for 4. Median survival times were 151,
841, and 827 days, respectively, for these 3 groups.
Forty-six (84%) dogs were free of mast cell tumors
during the study period. A reliable prognostic factor
could not be identified.
Conclusions and Clinical Relevance—Results suggest
that additional local treatment may not be required
after complete excision of grade-II mast cell tumors
and that most dogs do not require systemic treatment.
(J Am Vet Med Assoc 2001;218:1120–1123)
Objective—To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment.
Animals—132 dogs with nonresectable grade 2 or 3 MCTs.
Procedures—Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time.
Results—In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib.
Conclusions and Clinical Relevance—Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.