Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia.

BACKGROUND: The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs. HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4-week time period. ANIMALS: Fourteen dogs with cachexia of any underlying cause, except cancer of the oral cavity or gastrointestinal tract, were eligible for enrollment with informed client consent. METHODS: This study was a prospective, 1-armed open-label trial. Physical examination, complete blood count, chemistry panel, and owner-assessed quality of life surveys were checked at weeks 1, 2, and 4. Due to potential for bradycardia and hypotension, Holter monitoring and blood pressure evaluations were scheduled at pre-enrollment and week 4. RESULTS: Fourteen dogs completed the trial. Significant changes detected included increased mean body weight (18.6-19.5 kg, P < .02), increased body condition score (median Tufts 5-point thin dog scale score P < .004 and WSAVA muscle condition score P < .02) and increased mean blood urea nitrogen (21.79-30.43 mg dL-1 , P < .004). On quality of life surveys, pet owners perceived their dog appeared to be panting less (P < .002) and that the general health improved (P < .03). Four dogs had a change in coat pigmentation. The peak plasma concentration of TCMCB07 in cachectic dogs was similar to that in healthy beagle dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: TCMCB07 was safe and has potential efficacy in pet dogs with cachexia.

Evaluation of the relationship between clinical variables and thromboelastographic findings in dogs with protein-losing nephropathy.

OBJECTIVE: To determine whether hypercoagulability in proteinuric dogs, defined by thromboelastography (TEG), is related to the degree of proteinuria, presence of systemic arterial hypertension, presence of hypoalbuminemia, or reduced antithrombin activity. DESIGN: Prospective study of client-owned dogs. Data collected from each patient included signalment, body weight, urine protein-to-creatinine ratio (UPC), serum albumin concentration, TEG values, noninvasive arterial blood pressure, and AT activity. Hypercoagulability was diagnosed by TEG and odds ratios for other measurements were assessed by univariate logistic regression. SETTING: Urban referral center and teaching hospital. ANIMALS: Seventy-six dogs with protein-losing nephropathy (PLN) based on UPC, diagnosed between Oct 2009 and Oct 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of hypercoagulability was 89%. No statistically significant associations were detected between hypercoagulability and UPC, serum albumin, noninvasive blood pressure, or AT activity (all P > 0.05). The prevalence of thromboembolism was 6.6%. CONCLUSIONS: Hypercoagulability was prevalent in dogs with PLN but could not be predicted based upon the presence or degree of proteinuria, systemic arterial hypertension, hypoalbuminemia, or low AT activity. The prevalance of thromboembolism was low in this population with PLN.

Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster.

Certain breeds are known to be overrepresented among mast cell tumor (MCT) patients, but other risk factors have not been evaluated. This study presents results from a case-control study of 252 dogs with grade 2 or grade 3 cutaneous MCT. Increased risk for MCT development was found in spayed females (adjusted odds ratio [OR], 4.11), boxers (adjusted OR, 6.09), Labrador retrievers (adjusted OR, 3.95), pugs (adjusted OR, 3.17), golden retrievers (adjusted OR, 2.12), the mastiff and terrier phylogenetic cluster (adjusted OR, 3.19), and breeds classified as large (adjusted OR, 2.10) or giant (adjusted OR, 5.44). Additional studies are needed to evaluate the role of these and other potential risk factors in MCT development.