A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

OBJECTIVE: To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. DESIGN: Randomized, controlled, multisite clinical trial. ANIMALS: 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. PROCEDURES: In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. RESULTS: Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.

Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs.

OBJECTIVE: To assess the effect of food containing high concentrations of fish oil omega-3 fatty acids and a low omega-6-omega-3 fatty acid ratio on clinical signs of osteoarthritis in dogs. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. PROCEDURES: Dogs were randomly assigned to be fed for 6 months with a typical commercial food or a test food containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold decrease in omega-6-omega-3 ratio, compared with the control food. Dog owners completed a questionnaire about their dog's arthritic condition, and investigators performed a physical examination and collected samples for a CBC and serum biochemical analyses (including measurement of fatty acids concentration) at the onset of the study and at 6, 12, and 24 weeks afterward. RESULTS: Dogs fed the test food had a significantly higher serum concentration of total omega-3 fatty acids and a significantly lower serum concentration of arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test food had a significantly improved ability to rise from a resting position and play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis.

Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis.

OBJECTIVE: To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. PROCEDURES: Dogs were randomly assigned to receive a typical commercial food (n = 16) or a test food (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial began) and days 45 and 90 after the trial began, investigators conducted orthopedic evaluations and force-plate analyses of the most severely affected limb of each dog, and owners completed questionnaires to characterize their dogs' arthritis signs. RESULTS: The change in mean peak vertical force between days 90 and 0 was significant for the test-food group (5.6%) but not for the control-food group (0.4%). Improvement in peak vertical force values was evident in 82% of the dogs in the test-food group, compared with 38% of the dogs in the control-food group. In addition, according to investigators' subjective evaluations, dogs fed the test food had significant improvements in lameness and weight bearing on day 90, compared with measurements obtained on day 0. CONCLUSIONS AND CLINICAL RELEVANCE: At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis.

Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT.

BACKGROUND: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. METHODOLOGY/PRINCIPAL FINDINGS: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC(50)) of 200+/-40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC(50) of 150+/-80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. CONCLUSIONS: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity.