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Abstract

Objective—To investigate the effect of therapeutic dosages of meloxicam on the plasma clearance of iohexol in healthy, euvolemic, conscious cats fed a sodium-replete diet.

Animals—6 healthy adult neutered male cats.

Procedures—For each treatment period in a masked, randomized, crossover study, cats were administered either no treatment or meloxicam. Iohexol clearance studies were performed before the treatment period began (baseline) and on the final day of the treatment period. Iohexol concentrations were determined by use of a high-performance liquid chromatography assay, and plasma iohexol clearance as a marker of glomerular filtration rate was calculated by use of a 1-compartment model.

Results—No significant treatment effect was detected. Mean ± SE iohexol clearance for cats administered meloxicam (3.31 ± 0.27 mL/min/kg) was not significantly different from mean baseline value for the meloxicam treatment period (3.07 ± 0.32 mL/min/kg).

Conclusions and Clinical Relevance—In this study, short-term meloxicam administration did not measurably alter the glomerular filtration rate as assessed via plasma clearance of iohexol. This suggests that renal prostaglandins in cats did not have a measurable effect on glomerular filtration rates in healthy, euvolemic, conscious states as determined on the basis of methods used in this study.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare the results of regulatory screening and confirmation assays with those of highperformance liquid chromatography (HPLC) in the detection of ceftiofur metabolites in the tissues of culled dairy cattle.

Animals—17 lactating Holstein dairy cows.

Procedure—Daily IM injections of ceftiofur sodium were administered at a dose of 2.2 mg of ceftiofur equivalents/kg (n = 6) or 1.0 mg of ceftiofur equivalents/kg (10) for 5 days. Following withdrawal times of 12 hours (high-dose ceftiofur) and either 5 or 10 days (low-dose ceftiofur), cows were slaughtered and liver, kidney, and diaphragmatic muscle specimens were harvested and analyzed by HPLC and standard regulatory methods that included the following assays: the swab test on premises, the fast antimicrobial screen test, the calf antibiotic and sulfa test, and the 7-plate bioassay confirmation test.

Results—In all tissue specimens, residues of ceftiofur and desfuroylceftiofur-related metabolites, as measured by HPLC, were less than regulatory tolerance, as defined by the FDA. False-positive screening assay results were more likely for tissue specimens that had been frozen for shipment to a federal laboratory, compared with fresh tissue specimens that were assayed at the slaughter establishment (23% vs 3% false-positive results, respectively).

Conclusions and Clinical Relevance—The observation that fresh tissues had negative results on screening assays, whereas subsets of the same tissue specimens had false-positive results on screening assays following freezing, suggests that freezing and thawing interferes with microbial inhibition-based regulatory screening assays. (Am J Vet Res 2004;65:1730–1733)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate angiotensin I and angiotensin II rapid pressor response tests in healthy cats.

Animals—6 purpose-bred sexually intact male cats.

Procedures—Telemetric blood pressure (BP) implants were placed in all cats. After 2 weeks, cats were anesthetized for challenge with exogenous angiotensin I or angiotensin II. Continuous direct arterial BP was recorded during and immediately after IV administration of boluses of angiotensin I or angiotensin II at increasing doses. Blood pressure responses were evaluated for change in systolic BP (SBP), change in diastolic BP (DBP), and rate of increase of SBP by 4 observers.

Results—Following IV angiotensin I and angiotensin II administration, transient, dose-dependent increases in BP (mean ± SEM change in SBP, 25.7 ± 5.2 and 45.0 ± 9.1; change in DBP, 23.4 ± 4.7 mm Hg and 36.4 ± 7.8 mm Hg; for 100 ng of angiotensin I/kg and angiotensin II/kg, respectively) and rate of increase of SBP were detected. At angiotensin I and II doses < 2.0 ng/kg, minimal responses were detected, with greater responses at doses ranging from 20 to 1,000 ng/kg. A significant effect of observer was not found. No adverse effects were observed.

Conclusions and Clinical Relevance—The rapid pressor response test elicited dose-dependent, transient increases in SBP and DBP. The test has potential as a means of objectively evaluating the efficacy of various modifiers of the renin-angiotensin-aldosterone system in cats. Ranges of response values are provided for reference in future studies.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether a single intranasal dose of modified-live bovine respiratory syncytial virus (BRSV) vaccine protects calves from BRSV challenge and characterize cell-mediated immune response in calves following BRSV challenge.

Animals—13 conventionally reared 4- to 6-week-old Holstein calves.

Procedure—Calves received intranasal vaccination with modified live BRSV vaccine (VC-group calves; n = 4) or mock vaccine (MC-group calves; 6) 1 month before BRSV challenge; unvaccinated control-group calves (n = 3) underwent mock challenge. Serum virus neutralizing (VN) antibodies were measured on days –30, -14, 0, and 7 relative to BRSV challenge; nasal swab specimens were collected for virus isolation on days 0 to 7. At necropsy examination on day 7, tissue specimens were collected for measurement of BRSV-specific interferon gamma (IFN-γ) production. Tissue distribution of CD3+ T and BLA.36+ B cells was evaluated by use of immunohistochemistry.

Results—The MC-group calves had significantly higher rectal temperatures, respiratory rates, and clinical scores on days 5 to 7 after BRSV challenge than VCgroup calves. No difference was seen between distributions of BRSV in lung tissue of VC- and MC-group calves. Production of BRSV-specific IFN-γ was increased in tissue specimens from VC-group calves, compared with MC- and control-group calves. Virusspecific IFN-γ production was highest in the mediastinal lymph node of VC-group calves. Increased numbers of T cells were found in expanded bronchialassociated lymphoid tissue and airway epithelium of VC-group calves.

Conclusions and Clinical Relevance—An intranasal dose of modified-live BRSV vaccine can protect calves against virulent BRSV challenge 1 month later. ( Am J Vet Res 2004;65:363–372)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize cytokine messenger RNA (mRNA) expression in intranasally vaccinated calves after bovine respiratory syncytial virus (BRSV) challenge.

Animals—Twelve 8- to 12-week-old calves.

Procedures—Calves received modified-live BRSV vaccine (vaccinated) or spent tissue culture medium (mock-vaccinated) intranasally, followed by challenge 30 days later with BRSV, or mock challenge with spent tissue culture medium (mock-challenge controls). Interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA was measured in lungs, bronchoalveolar lavage (BAL) fluid cells, pharyngeal tonsils, and tracheobronchial lymph nodes, and tumor necrosis factor-α (TNF-α) mRNA was measured in lungs and BAL fluid cells by reverse transcriptase-competitive polymerase chain reaction assay.

Results—Resistance to clinical signs of disease was conferred in vaccinated calves. Expression of TNF-α mRNA in lungs and BAL fluid cells was higher in mock-vaccinated calves than control or vaccinated calves. In the lung, IL-4 mRNA expression was higher in vaccinated calves than control or mock-vaccinated calves. In pharyngeal tonsils, expression of mRNA for IL-4 and IFN-γ was higher in mock-vaccinated calves than control calves. In tracheobronchial lymph nodes, IFN-γ mRNA expression was higher in mock-vaccinated calves than vaccinated calves.

Conclusions and Clinical Relevance—Although vaccinated calves had decreased clinical signs of disease after BRSV challenge, compared with mock-vaccinated calves, this difference was not related to a T helper type 1 bias, as determined by increased expression of interferon-γ mRNA relative to interleukin-4 mRNA in lungs, BAL fluid cells, or tracheobronchial lymph nodes of vaccinated calves. Pulmonary inflammation was decreased in vaccinated calves as determined by decreased expression of TNF-α mRNA. (Am J Vet Res 2004;65:725–733)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To establish a reference interval for glomerular filtration rate (GFR) determined by measuring serum clearance of a single IV dose of inulin in clinically normal cheetahs (Acinonyx jubatus) and compare serum symmetric dimethylarginine (SDMA) concentration in cheetahs with GFR.

ANIMALS

33 cheetahs housed at 3 institutions.

PROCEDURES

A single bolus of inulin (3,000 mg/m2) was administered IV, and 5 serial blood samples were collected and analyzed for serum inulin concentration with the anthrone technique. The GFR was estimated with a modified slope-intercept method for the slow component of the serum concentration-versus-time curve. Blood urea nitrogen and serum creatinine concentrations were measured in samples obtained immediately prior to inulin administration, and serum SDMA concentration was measured in stored samples.

RESULTS

Mean ± SD measured GFR was 1.58 ± 0.39 mL/min/kg, and the calculated reference interval was 0.84 to 2.37 mL/min/kg. There were significant negative correlations between GFR and serum creatinine concentration (r = −0.499), BUN concentration (r = −0.592), and age (r = −0.463). Serum SDMA concentration was not significantly correlated with GFR (r = 0.385), BUN concentration (r = −0.281), or serum creatinine concentration (r = 0.165).

CONCLUSIONS AND CLINICAL RELEVANCE

A reference interval for GFR in clinically normal cheetahs was obtained. Further evaluation of animals with renal disease is needed to determine whether measuring serum clearance of a single IV dose of inulin is a reliable diagnostic test for early detection of renal disease in cheetahs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether amlodipine besylate decreases systemic arterial blood pressure (BP) and reduces the prevalence of complications in cats with induced hypertensive renal insufficiency.

Animals—20 cats with partial nephrectomy.

Procedure—Following reduction in renal mass, 10 cats were administered 0.25 mg of amlodipine/kg, PO, q 24 h (group A). Ten cats served as a control group (group C). Systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP), physical activity, and pulse rate were measured continuously for 36 days by use of radiotelemetric devices.

Results—Compared with values for clinically normal cats, SBP, DBP, and MBP were significantly increased in cats of group C. Cats in group A had significant reductions in SBP, DBP, and MBP, compared with values for cats in group C. Albuminuria but not urine protein- to-creatinine ratio was significantly correlated ( R2 = 0.317) with SBP in hypertensive cats. Prevalence of ocular lesions attributable to systemic hypertension in group C (7 cats) was greater than that observed in group A (2). Two cats in group C were euthanatized on day 16 because of nuerologic complications attributed to systemic hypertension. One normotensive cat in group A was euthanatized because of purulent enteritis of unknown cause on day 27.

Conclusion and Clinical Relevance—Amlodipine had an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high BP. (Am J Vet Res 2002;63:833–839)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To use RNA sequencing (RNAseq) to characterize renal transcriptional activities of genes associated with proinflammatory and profibrotic pathways in ischemia-induced chronic kidney disease (CKD) in cats.

SAMPLES

Banked renal tissues from 6 cats with experimentally induced CKD (renal ischemia [RI] group) and 9 healthy cats (control group).

PROCEDURES

Transcriptome analysis with RNAseq, followed by gene ontology and cluster analyses, were performed on banked tissue samples of the right kidneys (control kidneys) from cats in the control group and of both kidneys from cats in the RI group, in which unilateral (right) RI had been induced 6 months before the cats were euthanized and the ischemic kidneys (IKs) and contralateral nonischemic kidneys (CNIKs) were harvested. Results for the IKs, CNIKs, and control kidneys were compared to identify potential differentially expressed genes and overrepresented proinflammatory and profibrotic pathways.

RESULTS

Genes from the gene ontology pathways of collagen binding (eg, transforming growth factor-β1), metalloendopeptidase activity (eg, metalloproteinase [MMP]-7, MMP-9, MMP-11, MMP-13, MMP-16, MMP-23B, and MMP-28), chemokine activity, and T-cell migration were overrepresented as upregulated in tissue samples of the IKs versus control kidneys. Genes associated with the extracellular matrix (eg, TIMP-1, fibulin-1, secreted phosphoprotein-1, matrix Gla protein, and connective tissue growth factor) were upregulated in tissue samples from both the IKs and CNIKs, compared with tissues from the control kidneys.

CONCLUSIONS AND CLINICAL RELEVANCE

Unilateral ischemic injury differentially altered gene expression in both kidneys, compared with control kidneys. Fibulin-1, secreted phosphoprotein-1, and matrix Gla protein may be candidate biomarkers of active kidney injury in cats.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD).

SAMPLE

Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats.

PROCEDURES

For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys.

RESULTS

Ischemic kidneys had greater transcript levels of MMP-7, MMP-9, and transforming growth factor-β1 relative to control kidneys and of MMP-2 relative to contralateral kidneys. Transcription of TIMP-1 was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of HIF-1α did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of HIF-1α, MMP-2, MMP-7, and TIMP-1 and severity of fibrosis.

CONCLUSIONS AND CLINICAL RELEVANCE

Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.

Full access
in American Journal of Veterinary Research