OBJECTIVE To determine effects of 2 tiludronate administration protocols on measures of lameness in horses with navicular syndrome (NS). ANIMALS 12 horses with bilateral forelimb NS. PROCEDURES Horses were randomly assigned to receive tiludronate (1 mg/kg), diluted in 5 L of isotonic electrolyte solution and delivered through a jugular vein catheter (systemic treatment group; n = 6), or tiludronate (0.1 mg/kg), diluted with saline (0.9% NaCl) solution to a total volume of 35 mL and delivered into the lateral digital vein of each forelimb with an IV regional limb perfusion (IVRLP) technique (IVRLP group; 6). Mean peak vertical ground reaction force (pVGRF) measured with a stationary force plate and subjective lameness scores (SLSs) were recorded before (day −1) and at predetermined time points after tiludronate administration on day 0. Mean pVGRFs (standardized as percentage body weight of force) and mean SLSs for the most lame forelimb and for both forelimbs of horses in each group were compared with day −1 values to determine treatment effect. RESULTS Mean pVGRF for both forelimbs and for the most lame forelimbs of systemically treated horses were significantly increased on days 120 and 200, compared with day −1 results. No significant difference in mean pVGRF was observed for IVRLP-treated horses. The SLSs were not improved at any time point following systemic treatment and were improved only on day 120 following IVRLP. CONCLUSIONS AND CLINICAL RELEVANCE Tiludronate (1 mg/kg, IV) as a single systemic treatment appeared to be beneficial for horses with NS, but no horses were judged as sound during the study period. Additional research on IVRLP with tiludronate is needed before this method can be recommended.

OBJECTIVE To investigate the role of the major equine acute phase protein serum amyloid A (SAA) in inflammation of equine intraarticular tissues. SAMPLE Articular chondrocytes and fibroblast-like synoviocytes (FLSs) from 8 horses (4 horses/cell type). PROCEDURES Chondrocytes and FLSs were stimulated in vitro for various periods up to 48 hours with cytokines (recombinant interleukin [IL]-1β, IL-6, tumor necrosis factor-α, or a combination of all 3 [IIT]) or with recombinant SAA. Gene expression of SAA, IL-6, matrix metalloproteinases (MMP)-1 and −3, and cartilage-derived retinoic acid-sensitive protein were assessed by quantitative real-time PCR assay; SAA protein was evaluated by immunoturbidimetry and denaturing isoelectric focusing and western blotting. RESULTS All cytokine stimulation protocols increased expression of SAA mRNA and resulted in detectable SAA protein production in chondrocytes and FLSs. Isoforms of SAA in lysed chondrocytes and their culture medium corresponded to those previously detected in synovial fluid from horses with joint disease. When exposed to SAA, chondrocytes and FLSs had increased expression of IL-6, SAA, and MMP3, and chondrocytes had increased expression of MMP-1. Chondrocytes had decreased expression of cartilage-derived retinoic acid-sensitive protein. CONCLUSIONS AND CLINICAL RELEVANCE Upregulation of SAA in chondrocytes and FLSs stimulated with proinflammatory cytokines and the proinflammatory effects of SAA suggested that SAA may be involved in key aspects of pathogenesis of the joint inflammation in horses.

OBJECTIVE To compare regional proportions and spatial distributions of volumetric bone mineral density (BMDv) of the palmar aspect of the distal epiphysis of the third metacarpal bone (McIII) in limbs with or without a condylar fracture from Thoroughbred racehorses. SAMPLE McIIIs from cadavers of Thoroughbred racehorses with (n = 6 bones) and without (8) a condylar fracture. PROCEDURES BMDv and spatial distributions of BMDv in peripheral quantitative CT images of the distal epiphysis of McIIIs were quantitatively assessed with spatial analysis software. Relative proportions of voxels within 9 threshold categories of BMDv and spatial statistics for BMDv distribution were compared between fractured and nonfractured limbs. RESULTS No significant differences in BMDv characteristics were identified between fractured and nonfractured limbs, although fractured limbs had a lower proportion of voxels in the BMDv thresholds 700 to < 800 mg/cm3 and 800 to < 900 mg/cm3 but a higher proportion of voxels in the BMDv threshold 1,000 to < 1,100 mg/cm3 for the central condylar region of the medial condyle. Results of spatial analysis reflected the response of bone to race training rather than differences between fractured and nonfractured limbs. In both limb groups, uniform clusters of low BMDv with areas of high BMDv were identified. CONCLUSIONS AND CLINICAL RELEVANCE BMDv characteristics of the distal epiphysis of McIII reflected training load, and fracture characteristics were subtle. Serial imaging techniques in conjunction with detailed training data are required to elucidate the onset of the pathological response to load in horses.

The objective of this study was to assess the minimum dose, antigen content, and immunization duration of a trivalent vaccine containing inactivated Haemophilus parasuis serovars 4, 5, and 12 and the Montanide GEL 01 PR adjuvant in piglets and pregnant sows. Our results demonstrated that the minimum vaccine dose was 2 mL per pig and the optimal antigen content 2.0 × 10(9), 1.0 × 10(9), and 1.0 × 10(9) colony-forming units/mL of serovars 4, 5, and 12, respectively. The vaccine provided effective protection 14 d after the 2nd vaccination, and the period of immune protection was 180 d (6 mo) after the 2nd vaccination. Maternal antibodies provided early protection for the piglets, and vaccinating the sows before farrowing helped to control disease and protected the piglets during lactation; the piglets were protected during the finishing period by being vaccinated during lactation. Our findings provide a basis for developing a commercial trivalent vaccine of inactivated H. parasuis serovars 4, 5, and 12 against Glässer’s disease.

Abnormal body temperature is a major indicator of disease; infrared thermography (IRT) can assess changes in body surface temperature quickly and remotely. This technology can be applied to a myriad of diseases of various etiologies across a wide range of host species in veterinary medicine. It is used to monitor the physiologic status of individual animals, such as measuring feed efficiency or diagnosing pregnancy. Infrared thermography has applications in the assessment of animal welfare, and has been used to detect soring in horses and monitor stress responses. This review addresses the variety of uses for IRT in veterinary medicine, including disease detection, physiologic monitoring, welfare assessment, and potential future applications.

OBJECTIVE To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. ANIMALS 5 healthy purpose-bred hounds. PROCEDURES The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography–tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. RESULTS Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

OBJECTIVE To evaluate the usefulness of autologous bone marrow–derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 106 cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days −7 and 2; BM-MSC tracking by MRI was performed on BM-MSC–treated dogs on days −14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays. RESULTS Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs.

OBJECTIVE To assess the expression of inflammatory cytokines and enzymes in venous whole blood of dogs with impaired renal function attributable to various causes. ANIMALS 46 dogs with acute kidney injury (AKI), 8 dogs with chronic kidney disease (CKD), and 10 healthy dogs. PROCEDURES Dogs with AKI and CKD were prospectively enrolled during 2010 if they met inclusion criteria. Demographic and laboratory characteristics were evaluated for each dog, and expression of inflammatory cytokines (interleukin [IL]-1α, IL-1β, IL-8, tumor necrosis factor [TNF]-α, IL-10, and transforming growth factor [TGF]-β) and enzymes (inducible nitric oxide synthase [iNOS] and 5-lipoxygenase [5-LO]) was measured in venous whole blood obtained at initial evaluation. RESULTS Dogs with impaired renal function had markedly higher expression of the cytokines IL-1α, IL-1β, and TGF-β and the enzyme 5-LO, compared with expression in healthy dogs. Additionally, 17 of 46 AKI dogs (but none of the CKD dogs) had higher IL-8 mRNA expression and 3 of 8 CKD dogs (but only 2/46 AKI dogs) had higher TNF-α expression, compared with results for healthy dogs. No significant difference between renal disease groups was detected for inflammatory markers and laboratory variables, degree of azotemia, or cause of impaired renal function. CONCLUSIONS AND CLINICAL RELEVANCE In this study, expression of the cytokines IL-1α, IL-1β, and TGF-β and the enzyme 5-LO was clearly increased in dogs with renal disease, which suggested that these markers were part of an inflammatory response in animals with AKI or CKD.

OBJECTIVE To compare results obtained with a handheld reference point indentation instrument for bone material strength index (BMSi) measurements in the equine third metacarpal bone for various testing conditions. SAMPLE 24 third metacarpal bones. PROCEDURES Third metacarpal bones from both forelimbs of 12 horses were obtained. The dorsal surface of each bone was divided into 6 testing regions. In vivo and ex vivo measurements of BMSi were obtained through the skin and on exposed bone, respectively, to determine effects of each testing condition. Difference plots were used to assess agreement between BMSi obtained for various conditions. Linear regression analysis was used to assess effects of age, sex, and body weight on BMSi. A mixed-model ANOVA was used to assess effects of age, sex, limb, bone region, and testing condition on BMSi values. RESULTS Indentation measurements were performed on standing sedated and recumbent anesthetized horses and on cadaveric bone. Regional differences in BMSi values were detected in adult horses. A significant linear relationship (r2 = 0.71) was found between body weight and BMSi values. There was no difference between in vivo and ex vivo BMSi values. A small constant bias was detected between BMSi obtained through the skin, compared with values obtained directly on bone. CONCLUSIONS AND CLINICAL RELEVANCE Reference point indentation can be used for in vivo assessment of the resistance of bone tissue to microfracture in horses. Testing through the skin should account for a small constant bias, compared with results for testing directly on exposed bone.

OBJECTIVE To evaluate plasma interleukin 6 (IL-6) concentration in Standardbred racehorses by means of a novel ELISA following validation of the assay for use with equine plasma samples. SAMPLE Plasma samples obtained from 25 Thoroughbreds for use in assay validation and from 319 Standardbred racehorses at rest 2 to 2.5 hours prior to warm-up and racing. PROCEDURES A sandwich ELISA was developed with equine anti–IL-6 polyclonal antibody and the biotin-streptavidin chemical interaction to enhance sensitivity. The assay was validated for specificity, sensitivity, precision, and accuracy by use of both recombinant and endogenous proteins. RESULTS For the assay, cross-reactivity with other human and equine cytokines was very low or absent. Serial dilution of plasma samples resulted in proportional decreases in reactivity, indicating high specificity of the method. Partial replacement of detection antibody with capture antibody or pretreatment of samples with capture antibody caused assay signals to significantly decrease by 55%. The inter- and intra-assay precisions were ≤ 13.6% and ≤ 9.3%, respectively; inter- and intra-assay accuracies were within ranges of ± 14.1% and ± 8.6%, respectively, at concentrations from 78 to 5,000 pg/mL, and the sensitivity was 18 pg/mL. Plasma IL-6 concentration varied widely among the 319 Standardbreds at rest (range, 0 to 193,630 pg/mL; mean, 6,153 pg/mL; median, 376 pg/mL). CONCLUSIONS AND CLINICAL RELEVANCE This ELISA method proved suitable for quantification of IL-6 concentration in equine plasma samples. Plasma IL-6 concentration was high (> 10,000 pg/mL) in 9.1% of the Standardbred racehorses, which warrants further investigation.