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Abstract

Objective—To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between sheep and cattle and elucidate the protective mechanism of sheep.

Sample Population—Liver microsomes and cytosol from 8 sheep and 8 cattle.

Procedure—The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7-hydroxy- 1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in microsomal incubations. The kcat (turnover number) was determined for DHP and N-oxide formation. Chemical and immunochemical inhibitors were used to assess the role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO concentrations and activities were determined, in addition to the role of glutathione (GSH) in senecionine metabolism.

Results—DHP concentration did not differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and metabolized senecionine faster than cattle. The P450 concentrations and isoforms had a large influence on DHP formation, whereas FMOs had a large influence on N-oxide formation. In cattle, CYP3A played a larger role in DHP formation than in sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in vitro microsomal incubations decreased DHP formation; addition of cytosol decreased N-oxide formation.

Conclusions and Clinical Relevance—Hepatic metabolism differences alone do not account for the variation in susceptibility seen between these species. Rather, increased ruminal metabolism in sheep appears to be an important protective mechanism, with hepatic enzymes providing a secondary means to degrade any PAs that are absorbed from the rumen. (Am J Vet Res 2004;65:1563–1572)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the prevalence of selected intestinal parasites in pet dogs and recently apprehended free-roaming (AFR) shelter dogs in the Phoenix metropolitan area and compare those prevalences between the 2 groups.

DESIGN Cross-sectional study.

SAMPLE Convenience samples of fecal specimens from owned pet dogs from the Phoenix metropolitan area (n = 175) and free-roaming dogs apprehended and admitted to Maricopa County Animal Care and Control and Arizona Humane Society facilities from November 2014 through March 2015 (188).

PROCEDURES Fresh fecal specimens were collected from all dogs; for AFR shelter dogs, specimens were collected within 72 hours after facility admission. Standard centrifugal flotation tests and an ELISA were performed to detect 5 common intestinal parasites (roundworms, hookworms, whipworms, Giardia spp, and Cystoisospora spp). Group comparisons were performed by means of the χ2 test and Rogan-Gladen prevalence estimate.

RESULTS At least 1 of the 5 evaluated parasites was detected in 85 (45.2%) fecal specimens from AFR shelter dogs and 24 (13.7%) specimens from owned pet dogs. This prevalence differed significantly between the groups. Notably, the prevalence of Giardia spp in AFR shelter dogs (n = 76 [40.4%]) was higher than previously reported in the United States.

CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of the evaluated intestinal parasites, particularly of Giardia spp, in AFR shelter dogs was higher than expected. This information is important for veterinarians, animal shelter personnel, pet owners, human health-care providers, and public health officials to consider when devising effective interventions and risk communication efforts against potential zoonotic threats, particularly those relevant to the Phoenix metropolitan area.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the insulin response curve during IV glucose tolerance testing of mature Holstein bulls.

Animals—8 Holstein bulls between 5 and 8 years old and weighing between 911.5 and 1035.5 kg.

Procedure—A 50% glucose solution was rapidly administered IV so that each bull received a mean dose of 258 mg of glucose/kg of body weight. Serum glucose and insulin concentrations were determined before and 30, 60, 120, and 240 minutes after glucose infusion.

Results—Serum glucose concentrations 30 and 60 minutes after infusion were significantly greater than baseline concentration. Concentrations returned to baseline values 120 minutes after infusion. Serum insulin concentration was significantly greater 30 minutes after glucose administration, compared with baseline and 240-minute concentrations.

Conclusions and Clinical Relevance—Intravenous glucose tolerance testing of mature Holstein bulls resulted in a characteristic insulin response curve. Baseline and peak insulin concentrations were higher in these bulls, compared with values reported for mature Norwegian Red cows. (Am J Vet Res 2000; 61:61–63)

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in American Journal of Veterinary Research

Abstract

Objective—To correlate serum concentrations of fibrinogen (Fib), haptoglobin (Hap), serum amyloid-A (SAA), and α-1 acid glycoprotein (AGP) with clinical respiratory tract disease and response to treatment in transport-stressed feedlot cattle fed vitamin E-supplemented diets.

Animals—387 heifer calves (mean initial weight, 197 kg).

Procedure—Calves purchased from an order buyer were delivered to a feedlot to study the effects of dietary supplementation with 2,000 IU of vitamin E for 0, 7, 14, or 28 days after arrival. Serum or plasma Fib, Hap, SAA, and AGP concentrations were measured on days 0, 7, and 28 after arrival as well as at the time of treatment for respiratory tract disease with antimicrobial drugs and after completion of treatment.

Results—Vitamin E supplementation was associated with decreased treatment costs. In cattle that were not recognized as sick or responded positively to 1 antimicrobial treatment, serum Hap concentrations were significantly lower on days 0 and 7 than concentrations for cattle that required > 1 treatment. Serum Hap concentrations and ratios of Hap to SAA on day 0 significantly correlated with the number of antimicrobial treatments required. Serum Hap concentrations at the time of initial treatment were significantly lower for cattle that required only 1 treatment, compared with those that required > 1 treatment.

Conclusions and Clinical Relevance—Serum Hap concentrations are of potential value for use in assessing feedlot cattle that may become ill as a result of respiratory tract disease and for use in monitoring treatment efficacy. (Am J Vet Res 2002; 63:1111–1117)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs.

Animals—21 healthy male and female mixed-breed dogs and 24 healthy male Beagles.

Procedure—Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after IV (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis.

Results—Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1µM and 0.31µM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (7.7 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis.

Conclusions and Clinical Relevance—ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other nonsteroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective nonsteroidal anti-inflammatory drugs. (Am J Vet Res 2004;65:503–512)

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objectives—To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin.

Animals—18 young adult domestic shorthair cats of both sexes.

Procedures—Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis. Beginning 26 days after inoculation, 11 cats were administered azithromycin (15 mg/kg of body weight, PO, q 12 h, for 7 days).

Results—Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR. Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats. Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation. Administration of azithromycin had little effect on clinical variables, including anemia. All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period.

Conclusions and Clinical Relevance—In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected. Results of the PCR were superior to results of CBC for detecting infection with H felis. Azithromycin administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis. ( Am J Vet Res 2000;62:687–691)

Full access
in American Journal of Veterinary Research

Abstract

Case Description—A 2.5-month-old female alpaca that had been born prematurely was examined because of moderate mucopurulent nasal discharge and high rectal temperature.

Clinical Findings—In addition to pyrexia and clinical signs of disease of the upper portion of the respiratory tract, the cria had inappetence and was in an unthrifty condition. Hematologic abnormalities included low WBC count, low hemoglobin concentration, and low PCV. Samples of blood were submitted for bovine viral diarrhea virus (BVDV) isolation and serologic evaluation. Other adults and newborn crias in the herd were similarly examined. Bovine viral diarrhea virus was detected in the cria, and a diagnosis of persistent infection with BVDV was made at 5.5 months of age. Persistent BVDV infection was suspected in another cria born into the herd but was not identified in any of the adult alpacas.

Treatment and Outcome—Despite several treatments with antimicrobials, no permanent improvement of the cria's condition was achieved. Because of the poor prognosis, the owners requested euthanasia of the cria; BVDV was isolated from specimens of multiple organs collected at necropsy.

Clinical Relevance—To date, BVDV infection in New World camelids has not been regarded as a major disease entity. Findings in the cria of this report illustrate that some strains of BVDV readily infect alpacas. Clinical description of the disease plus clinicopathologic findings suggest that persistent BVDV infection may be greatly overlooked as a cause of chronic anemia and failure to thrive in alpacas.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine whether a single contusive impact injury to the palmar aspect of the metacarpus would progress to post-traumatic osteoarthritis or palmar osteochondral disease in horses.

Animals—12 horses.

Procedures—In each horse, an impact injury was created on the palmar aspect of the medial metacarpal condyle of 1 randomly chosen limb with an impactor device under arthroscopic and fluoroscopic guidance. The opposite limb was sham operated as a control. A low to moderate amount of forced exercise was instituted, and horses were evaluated clinically via lameness examinations weekly for 5 months, then biweekly until endpoint, with synovial fluid analysis performed at 0, 1, 2, 3, 4, 6, 8, and 10 months and radiography at baseline and endpoint. Macroscopic examination, micro-CT, and sample collection for cartilage viability and sulfated glycosaminoglycan content, histologic evaluation, immunohistochemical analysis, and fluorochrome analysis were performed following euthanasia at 1 (3 horses), 4 (4), and 8 to 10 (5) months after surgery.

Results—There was variability in impact lesion location, depth, and area on macroscopic inspection, but on histologic evaluation, cartilage defects were less variable. Mean sulfated glycosaminoglycan concentration from cartilage at the impact site was significantly lower than that at a similar site in control limbs. Higher concentrations of cartilage oligomeric matrix protein were observed in synovial fluid from impact-injured joints.

Conclusions and Clinical Relevance—The impact injury method caused mild focal osteoarthritic lesions in the metacarpophalangeal joint, but did not progress to palmar osteochondral disease at this site. Repeated injury is probably required for the development of palmar osteochondral disease.

Full access
in American Journal of Veterinary Research