Objective—To investigate the activities of
hyaluronidases in equine sera and synovial fluid samples
and sera from fetal and adult bovids and evaluate
the extent to which the degradation of hyaluronan is
influenced by chondrocytes.
Sample Population—Commercial and noncommercial
samples of equine (n = 6) and bovine (6) sera and
16 synovial fluid samples from horses.
Procedure—Hyaluronidase activities in sera and synovial
fluid samples were assessed via enzyme
zymography (performed at pH 4, 5, 6, or 7).
Chondrocytes were isolated from equine cartilage
and cultured with or without hyaluronan (1 mg/mL);
the degradation of hyaluronan was assessed via
agarose gel electrophoresis.
Results—Hyaluronidase activity was detected in
equine sera and synovial fluid samples at pH 4, but not
at pH 7, and in bovine sera at both pH values. In all
samples at pH 4, a major band of activity (molecular
weight, approx 60 kd) and some additional higher molecular
weight bands were detected; high- and low-molecular-weight activities were detected in bovine
sera at pH 7. Hyaluronan in tissue culture medium with
or without fetal calf serum was degraded in the presence,
but not the absence, of equine chondrocytes.
Conclusions and Clinical Relevance—Hyaluronidase
activity was detected in equine sera and synovial fluid
at pH 4 and in bovine sera at pH 4 and 7. Primary chondrocytes
in monolayer culture can degrade exogenous
hyaluronan. Modulating native hyaluronidase activity
may offer a new approach to improve the quantity and
quality of hyaluronan in articular joints. ( Am J Vet Res 2005;66:984–990)
OBJECTIVE To evaluate the pharmacokinetics of zonisamide following rectal administration of 20 or 30 mg/kg suspended in sterile water or polyethylene glycol (PEG) to healthy dogs and determine whether either dose resulted in plasma zonisamide concentrations within the recommended therapeutic target range (10 to 40 μg/mL).
ANIMALS 8 healthy mixed-breed dogs.
PROCEDURES Each dog received each of 2 doses (20 or 30 mg/kg) of zonisamide suspended in each of 2 delivery substrates (sterile water or PEG) in a randomized crossover study with a 7-day washout period between phases. A blood sample was collected from each dog immediately before and at predetermined times for 48 hours after zonisamide administration. Plasma zonisamide concentrations were determined by high-performance liquid chromatography, and data were analyzed with a noncompartmental model.
RESULTS Mean maximum plasma concentration, time to maximum plasma concentration, mean residence time, and elimination half-life did not differ significantly among the 4 treatments. The mean maximum plasma concentration for all 4 treatments was less than the therapeutic target range. The mean ± SD area under the concentration-time curve for the 30 mg/kg-in-water treatment (391.94 ± 237.00 h•μg/mL) was significantly greater than that for the 20 mg/kg-in-water (146.19 ± 66.27 h•μg/mL) and 20 mg/kg-in-PEG (87.09 ± 96.87 h•μg/mL) treatments.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that rectal administration of zonisamide at doses of 20 and 30 mg/kg failed to achieve plasma zonisamide concentrations within the recommended therapeutic target range. Therefore, rectal administration of zonisamide cannot be recommended as a suitable alternative to oral administration.
Objective—To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs).
Design—Retrospective case series.
Animals—38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage ≥ 50 mg/m2.
Procedures—Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration.
Results—26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m2 in 22 cats and 60 mg/m2 in 16 cats. Median administered dosage of lomustine was 56 mg/m2 (range, 48 to 65 mg/m2), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia.
Conclusions and Clinical Relevance—Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.
To characterize osteolytic lesions in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) hospitalized for rehabilitation and describe methods used for the management of such lesions.
25 stranded, cold-stunned Kemp's ridley sea turtles hospitalized between 2008 and 2018.
Medical records of sea turtles with a diagnosis of osteolytic lesions were reviewed retrospectively to obtain the date of diagnosis, clinical signs, radiographic findings, microbial culture results, hematologic and plasma biochemical data, cytologic and histologic findings, antimicrobial history, time to first negative culture result, treatment duration, and outcome.
Lesions were identified radiographically a median of 50 days after admission and were located within epiphyses or metaphyses of various appendicular joints. Lesions were associated with periarticular swelling (n = 24), lameness (16), lethargy (2), and hyporexia (2). Bacterial culture yielded growth of single organisms (n = 16), multiple organisms (2), or no growth (6). Significant differences in hematologic and biochemical data were detected between the times of diagnosis and convalescence. Cytologic and histologic findings characterized the lesions as osteomyelitis leading to septic arthritis. Sixteen sea turtles were managed medically, and 8 were managed medically and surgically. Surgery resulted in rapid improvement in joint mobility and overall clinical status. Most (22/25 [88%]) sea turtles survived and were released after long-term management.
CONCLUSIONS AND CLINICAL RELEVANCE
During rehabilitation, cold-stunned Kemp's ridley sea turtles may be affected by osteomyelitis. Medical management based on antimicrobial susceptibility testing was effective for most turtles. Long term management efforts in turtles are justified by high survival rate.
Objective—To determine whether the active metabolite of leflunomide, A77 1726 (A77), inhibits replication of feline herpesvirus-1 (FHV-1) in cell culture.
Study Population—Crandell Rees feline kidney (CRFK) cell cultures.
Procedures—Cell cultures were inoculated with FHV-1 and treated simultaneously with concentrations of A77 ranging from 0 to 200μM. The antiviral effect of A77 was determined by use of conventional plaque reduction assays. The effect of A77 on viral load was determined via real-time PCR analysis, and transmission electron microscopy was used to evaluate the effect of A77 on viral morphology. To determine whether the antiviral effect was attributable to alterations in CRFK cell viability and number, CRFK cells were treated with various concentrations of A77 and stained with Annexin V and propidium iodide to assess apoptosis and a mitochondrial function assay was used to determine cell viability.
Results—Concentrations of A77 ≥ 20μM were associated with substantial reduction in plaque number and viral load. Concentrations ≥ 100μM were associated with complete suppression of plaque formation. At low concentrations of A77, clusters of intracytoplasmic virus particles that appeared to lack tegument and an external membrane were detected. Treatment of uninfected CRFK cell monolayers with A77 was associated with reduction in mitochondrial function with minimal evidence of apoptosis.
Conclusions and Clinical Relevance—Leflunomide may be an alternative to current calcineurin-based immunosuppressive protocols used in feline organ transplantation because of its antiherpesviral activity.