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Objective—To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis.
Animals—8 dogs with chronic unilateral osteoarthritis of the stifle joint.
Procedure—Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood.
Results—Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10.
Conclusions and Clinical Relevance—Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1–sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations. (Am J Vet Res 2005;66:812–817)
Objective—To evaluate in vivo effects of tepoxalin, an inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), on prostaglandin (PG) and leukotriene production in osteoarthritic dogs.
Animals—7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint.
Procedure—Dogs were treated in accordance with a randomized 3-way crossover design. Each dog received an inert substance, meloxicam, or tepoxalin for 10 days. On day 0 (baseline), 3, and 10, dogs were anesthetized and samples of blood, stifle joint synovial fluid, and gastric mucosa were collected. Concentrations of PGE2 were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE1 and PGE2 synthesis was measured in gastric mucosa. Thromboxane B2 (TxB2) concentration was measured in whole blood. Leukotriene B4 (LTB4) concentration was determined in gastric mucosa and in whole blood after ex vivo stimulation with a calcium ionophore.
Results—Tepoxalin significantly decreased LTB4 concentrations in the blood and gastric mucosa at day 10 and TxB2 concentrations in the blood and PGE2 in the gastric mucosa and synovial fluid at days 3 and 10, compared with baseline values. Meloxicam significantly decreased PGE2 concentrations in the blood at days 3 and 10 and synovial fluid at day 3. Meloxicam also decreased PGE1 and PGE2 synthesis in the gastric mucosa at day 3. Meloxicam did not affect LTB4 synthesis in the blood or LTB4 concentrations in the gastric mucosa.
Conclusions and Clinical Relevance—Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage. (Am J Vet Res 2005;66:966–972)
Objective—To evaluate the effects of firocoxib, meloxicam, and tepoxalin administration in healthy cats by measuring the ability of stimulated tissues to synthesize eicosanoids ex vivo.
Animals—8 healthy adult male cats.
Procedures—In a blinded, randomized, crossover study design, cats were treated with firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2) concentrations were measured in serum, and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1 (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in mucosal biopsy specimens. A 21-day minimum washout period was observed between treatments. Repeated-measures analyses were performed.
Results—Firocoxib and meloxicam administration resulted in a lower plasma PGE2 concentration than at baseline on days 3 and 8 of administration, whereas tepoxalin administration did not. Tepoxalin administration resulted in a lower serum TXB2 concentration and pyloric and duodenal PGE1 synthesis on both days, compared with baseline and placebo administration. Neither firocoxib nor meloxicam administration altered pyloric or duodenal PGE1 synthesis on either day, compared with placebo administration. Tepoxalin administration also resulted in lower pyloric mucosal LTB4 concentrations on both days, compared with baseline values.
Conclusions and Clinical Relevance—Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase. (Am J Vet Res 2010;71:1067–1073)
Objective—To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).
Animals—8 dogs with chronic, unilateral OA of the stifle joint.
Procedures—In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.
Results—Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.
Conclusions and Clinical Relevance—PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1–sparing effect in vivo.
Objective—To examine the ability of preemptive administration of a proprietary neurokinin-1 (NK1) receptor antagonist to attenuate limb dysfunction associated with monosodium urate–induced synovitis in the stifle joints of dogs.
Animals—16 clinically normal adult mixed-breed dogs (8 males and 8 females).
Procedures—A crossover study was conducted in 2 phases. Dogs were assigned to 2 groups (8 dogs/group) and orally administered an NK1 receptor antagonist (3 mg/kg) or a control substance once daily for 4 days. Synovitis was then induced in the left stifle joint by intra-articular injection of monosodium urate. Investigators were not aware of treatment group assignments. Dogs were evaluated by use of subjective lameness scores during standing, walking, and trotting and by use of ground reaction force data 3, 6, 9, 12, and 24 hours after urate injection. After a 21-day washout period, the experiment was repeated with each dog administered the other treatment and injected with monosodium urate in the contralateral stifle joint.
Results—No significant differences were detected between the NK1 receptor antagonist and control treatments with regard to peak vertical force, vertical impulse area, or subjective evaluations of lameness during standing, walking, or trotting, except during walking 24 hours after monosodium urate injection.
Conclusions and Clinical Relevance—Preemptive administration of an NK1 receptor antagonist failed to significantly improve subjective or objective outcome measures in dogs with monosodium urate–induced synovitis.
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.
Objective—To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis.
Animals—8 purpose-bred mixed-breed dogs.
Procedures—In a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward.
Results—Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments.
Conclusions and Clinical Relevance—HDA had no apparent effect on sodium urate–induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.
Objective—To compare overground and treadmill-based gaits of dogs.
Animals —5 clinically normal adult mixed-breed dogs.
Procedures—To obtain dynamic gait data, 30 retroreflective markers were affixed bilaterally to specific regions of the hind limbs and pelvis of each dog. For each dog, 3-D joint motion data (sagittal [flexion and extension], transverse [internal and external rotation], and frontal [abduction and adduction] planes of motion) for the hip, femorotibial, and tarsal joints were acquired during walking and trotting through a calibrated testing space overground or on a treadmill. Comparison of data was performed via generalized indicator function analysis and Fourier analysis.
Results—Both overground and treadmill-based gaits produced similar waveforms in all planes of motion. Fourier analysis revealed no difference between overground and treadmill-based gaits in the sagittal plane of motion; however, small differences were detected between overground and treadmill-based gaits in the other 2 planes of motion. Additionally, femorotibial joint motion during walking did not differ among planes of motion. Generalized indicator function analysis was able to detect differences between overground and treadmill-based gait waveforms in all planes of motion for all joints during walking and trotting.
Conclusions and Clinical Relevance—In dogs, overground and treadmill-based gaits produced similar waveform shapes. Of the 3 planes of motion evaluated, only sagittal plane kinematic gait data were unaffected by mode of ambulation as determined via Fourier analysis. Sagittal kinematic gait data collected from dogs during overground or treadmill-based ambulation were comparable. However, analysis methods may affect data comparisons.
Objective—To determine the effect of treatment approach on outcome and the appropriateness of initial empirical antimicrobial treatment in dogs with pyothorax.
Design—Retrospective case series.
Animals—46 dogs with pyothorax confirmed by either (n = 15) or both (31) of the following: intracellular bacteria in pleural fluid or tissue (41) and bacteria recovered via culture of pleural fluid (36).
Procedures—Medical records of dogs treated for pyothorax from 1983 through 2001 were reviewed. Data on signalment, history, clinical signs, and treatment and results of diagnostic imaging and cytologic and microbiological evaluations were obtained. Follow-up was performed via reexamination (n = 15) and contact with referring veterinarians (26) and owners (24).
Results—46 dogs were treated with at least 1 antimicrobial and thoracocentesis (n = 7; noninvasive group), a thoracostomy tube (26; invasive group) with or without pleural lavage and heparin, or a thoracotomy (13; surgical group) and thoracostomy tube with or without pleural lavage and heparin. Pyothorax recurred in 7 dogs, and 5 of the 7 died or were euthanatized. In the respective groups, the short-term survival rate was 29%, 77%, and 92% and the long-term survival rate was 29%, 71%, and 70%. Pleural lavage and heparin treatment increased the likelihood of short- and long-term survival. Results of antimicrobial susceptibility testing suggested empirical antimicrobial selection was associated with a 35% risk of inefficacy.
Conclusions and Clinical Relevance—In the dogs with pyothorax in this study, favorable treatment effects were achieved with surgery (for short-term survival) and pleural lavage and heparin treatment (for short- and long-term survival). Findings failed to support the hypothesis that invasive (surgical) versus noninvasive treatment of pyothorax in dogs leads to a better long-term outcome.
Objective—To compare methicillin-resistant Staphylococcus pseudintermedius (MRSP) and methicillin-susceptible S pseudintermedius (MSSP) infections in dogs.
Design—Multicenter case-control study.
Animals—Dogs with MRSP infections were matched, by hospital, with 2 MSSP controls, with the infections occurring immediately before and after the case infection.
Procedures—Signalment, historical, clinical, treatment, and outcome data were documented. Conditional logistic regression was performed. A manual stepwise backward elimination procedure was used to build the multivariable model.
Results—56 case and 112 control dogs were enrolled. Pyoderma was the most common infection type in both groups. In the final multivariable model, systemic administration of antimicrobials within 30 days prior to infection was significantly associated with an MRSP versus an MSSP infection (OR, 9.9; 95% confidence interval, 3.59 to 27.53).
Conclusions and Clinical Relevance—The association of prior antimicrobial administration and MRSP infection indicated the potential impact of routine antimicrobial use in veterinary medicine on antimicrobial resistance and the need for prudent use of these important drugs. Mortality rate was not significantly different between MRSP and MSSP infections; the lack of a significant difference suggested that MRSP was inherently no more virulent than MSSP, provided the infection was properly diagnosed and appropriate treatment was started. Basic concepts such as prudent antimicrobial use and early diagnosis through timely submission of appropriate culture specimens therefore can be important measures to try to reduce the impact of this pathogen.