Objective: To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration. Animals: 6 healthy cats. Procedures: In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis. Results: Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%. Conclusions and Clinical Relevance: The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Objective—To determine the association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association. Animals—60 dogs evaluated by an internal medicine service. Procedures—From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at −80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis. Results—The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality. Conclusions and Clinical Relevance—Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.

Objective: To compare acoustic startle reflexes (ASRs) of healthy cats and cats with interstitial cystitis (IC). Animals: 28 healthy cats (11 males and 17 females) and 20 cats with IC (13 males and 7 females). Procedures: To evaluate the effect of neutering on ASRs, ASRs in neutered and unneutered healthy cats were measured. To evaluate the effect of housing facility acclimation on ASRs in cats with IC, ASRs were measured in cats with IC within 1 month after arrival at the housing facility and again 2 to 3 months after arrival. To evaluate the effect of the environment on ASRs, ASRs were evaluated in all cats with and without IC after acclimation but before and then after environmental enrichment. Results: Neutering led to a significant decrease in overall ASR in the healthy cats. Habituation to the housing facility resulted in a significant decrease in overall ASR of female but not male cats with IC. Environmental enrichment led to a significant decrease in ASR in cats with IC but not in healthy cats. Conclusions and Clinical Relevance: The magnitude of the ASR appeared to be sensitive to environmental conditions and affected by sex, both in healthy cats and cats with IC. It was also higher in cats with IC versus healthy cats, except when cats were housed in a highly enriched environment. Impact for Human Medicine: Treatment approaches that include reduction of a patient's perception of environmental unpredictability may benefit humans with IC.

Objective-To characterize and quantitatively assess the typical pulmonary anatomy of healthy adult alpacas with multidetector row CT. Animals-10 clinically normal adult female alpacas. Procedures-CT examination of the thorax was performed before and after IV administration of iodinated contrast medium in sedated alpacas in sternal recumbency. Measurements of the trachea, bronchi and related blood vessels, and selected vertebrae as well as the extent and density of lung parenchyma were performed with a Digital Imaging and Communications in Medicine (DICOM) viewer. Morphometric and quantitative data were summarized. Results-Separation of individual lung lobes could not be identified, except for the accessory lung lobe. In all alpacas, both lungs extended farther caudally at the medial aspect than at the lateral aspect. The right lung extended farther in both cranial and caudal directions than did the left lung. The branching pattern of the bronchial tree varied only slightly among alpacas and consisted of 1 cranial bronchus and 3 caudal bronchi bilaterally, with a right accessory bronchus. Luminal diameters of first-generation bronchi ranged from 3 to 9 mm. Mean +/- SD parenchymal lung density was −869 +/- 40 Hounsfield units (HU) before contrast injection and −825 +/- 51 HU after contrast injection. Mean difference in diameter between bronchi and associated arteries or veins was 0.8 +/- 0.9 mm. Conclusions and Clinical Relevance-Knowledge of the typical anatomy of the lungs and bronchial tree in healthy alpacas as determined via CT will aid veterinarians in clinical assessment and bronchoscopic evaluation of alpacas.

Objective: To characterize equine muscle tissue– and periosteal tissue–derived cells as mesenchymal stem cells (MSCs) and assess their proliferation capacity and osteogenic potential in comparison with bone marrow– and adipose tissue–derived MSCs. Sample: Tissues from 10 equine cadavers. Procedures: Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and adipose tissue from the left subcutaneous region. Mesenchymal stem cells were characterized on the basis of morphology, adherence to plastic, trilineage differentiation, and detection of stem cell surface markers via immunofluorescence and flow cytometry. Mesenchymal stem cells were tested for osteogenic potential with osteocalcin gene expression via real-time PCR assay. Mesenchymal stem cell cultures were counted at 24, 48, 72, and 96 hours to determine tissue-specific MSC proliferative capacity. Results: Equine muscle tissue– and periosteal tissue–derived cells were characterized as MSCs on the basis of spindle-shaped morphology, adherence to plastic, trilineage differentiation, presence of CD44 and CD90 cell surface markers, and nearly complete absence of CD45 and CD34 cell surface markers. Muscle tissue–, periosteal tissue–, and adipose tissue–derived MSCs proliferated significantly faster than did bone marrow–derived MSCs at 72 and 96 hours. Conclusions and Clinical Relevance: Equine muscle and periosteum are sources of MSCs. Equine muscle- and periosteal-derived MSCs have osteogenic potential comparable to that of equine adipose- and bone marrow–derived MSCs, which could make them useful for tissue engineering applications in equine medicine.

Objective: To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals: 27 athymic nude mice. Procedures: To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results: Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance: Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine: Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.