Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers

The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B involved 72 dogs randomized to nine treatments: placebo (24 weeks); dirlotapide (24 weeks) followed by placebo (28 weeks); or dirlotapide (52 weeks); on diets containing 5%, 10% or 15% fat. Dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly during 24-week weight-loss and subsequent 28-week weight-stabilization phases. Food was offered above maintenance energy requirements (MER× 1.1–1.2) based on initial BW. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy X-ray absorptiometry. After treatment, dogs that had received dirlotapide for 52 weeks were fed 90% of quantity consumed at week 52. In study A, BW and food intake decreased asymptotically with dose: mean weekly weight loss exceeded 1% at 0.1–0.4 mg/kg. In study B, dirlotapide resulted in significant mean weekly weight loss (>0.8%) and decreased food intake over 24 weeks compared with placebo ( P  = 0.0001) for all diets. Food restriction minimized post-treatment weight rebound. Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction.     

Disseminated Aspergillus flavus infection in broiler breeder pullets

Increased morbidity and mortality occurred in a 5-wk-old broiler breeder replacement pullet flock. The affected broiler pullet flock was housed on the first floor of a two-story confinement building. Mortality increased to 0.1%/day compared to the flock on the second floor, which had mortality levels of less than 0.01%/day. Clinical signs in the affected chickens included inactivity, decreased response to stimuli, and anorexia. No respiratory or neurologic signs were observed. On necropsy, affected pullets were dehydrated and emaciated and had disseminated variably sized single or multiple heterophilic granulomas that contained intralesional septate and branching fungal hyphae. Lesions were extensive around the base of the heart in the thoracic inlet and in the kidneys. Other affected organs included eyelid, muscle, proventriculus, ventriculus, intestine, liver, spleen, lung, and heart. Aspergillus flavus was cultured from the visceral granulomas. The source of flock exposure to the organism was not determined.     

ULTRASONOGRAPHIC, GROSS, AND HISTOLOGIC EVALUATION OF A TENDINITIS DISEASE MODEL IN THE HORSE

Collagenase-induced lesions of the superficial digital flexor tendon were monitored using diagnostic ultrasound and subsequently compared with gross and microscopic findings. The postinjury sonograms demonstrated hypoechoic or anechoic areas corresponding to areas of hemorrhage and necrosis. The size of the lesion increased and the echogenicity decreased with increasing units of collagenase injected into the tendon. As postinjury time increased, echogenicity increased, which corresponded to fibrous-tissue invasion and collagen deposition. The extent of tendon injury produced correlated with the amount of collagenase injected into the tendon. Diagnostic ultrasound is useful in evaluating injury and healing in collagenase— induced tendinitis.     

Outcome of 19 dogs with parathyroid carcinoma after surgical excision

Parathyroid carcinoma (PTC) is rare in dogs and there is little information documenting its treatment and prognosis. The objective of this study was to describe the outcome of dogs with PTC treated with surgical excision. Medical records of 19 dogs undergoing surgical excision of PTC between 1990 and 2010 were reviewed retrospectively. Dogs were presented for clinical hypercalcaemia or incidental hypercalcaemia noted by referring veterinarians on routine serum chemistry profiles. A parathyroid nodule was identified with cervical ultrasound in 17/17 dogs. Hypercalcaemia resolved in 18/19 dogs within 4 days postoperatively. Nine developed hypocalcaemia. None were confirmed to develop recurrent or metastatic PTC. The only death associated with PTC was a dog that was euthanized for intractable hypocalcaemia 9 days after surgery. Estimated 1-, 2- and 3-year survival rates were 72, 37 and 30%, respectively. Excision of PTC results in resolution of hypercalcaemia and excellent tumour control.     

The effect of a single intramammary infusion of a biological response modifier in cows at drying off

Biological response modifiers (BRM) are compounds that interact with the immune system to regulate specific aspects of host response. The objective of this study was to describe clinical and morphological changes during involution of bovine mammary gland following a single-dose infusion of a BRM containing lipopolysaccharide and cellular fractions of Escherichia coli incorporated into liposomes. A massive leukocyte response and increased subepithelial stroma infiltration of mononuclear cells, eosinophils and mast cells was observed in BRM-treated quarters compared with untreated controls; however, morphologic parameters assessed at 11 days post infusion were indicative of only slightly accelerated involution compared with untreated controls. In addition, BRM infusion at the end of lactation did not interfere with mammary epithelial cell proliferation and caused only mild systemic effects.     

Oral glucose leads to a differential response in glucose,insulin, and GLP-1 in lean versus obese cats

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2 g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated.     

Expression of receptors for luteinizing hormone,gastric-inhibitory polypeptide,and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs

Hypercortisolism caused by an adrenocortical tumor (AT) results from adrenocorticotropic hormone (ACTH)-independent hypersecretion of glucocorticoids. Studies in humans demonstrate that steroidogenesis in ATs may be stimulated by ectopic or overexpressed eutopic G protein-coupled receptors. We report on a screening of 23 surgically removed, cortisol-secreting ATs for the expression of receptors for luteinizing hormone (LH), gastric-inhibitory polypeptide (GIP), and vasopressin (V_1a, V_1b, and V₂). Normal adrenal glands served as control tissues. Abundance of mRNA for these receptors was quantified using quantitative polymerase chain reaction (QPCR), and the presence and localization of these receptors were determined by immunohistochemistry. In both normal adrenal glands and ATs, mRNA encoding for all receptors was present, although the expression abundance of the V_1b receptor was very low. The mRNA expression abundance for GIP and V₂ receptors in ATs were significantly lower (0.03 and 0.01, respectively) than in normal adrenal glands. The zona fasciculata of normal adrenal glands stained immunonegative for the GIP receptor. In contrast, islands of GIP receptor-immunopositive cells were detected in about half of the ATs. The zona fasciculata of both normal adrenal glands and AT tissue were immunopositive for LH receptor; in ATs in a homogenous or heterogenous pattern. In normal adrenal glands, no immunolabeling for V_1bR and V₂ receptor was present, but in ATs, V₂ receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V_1a, V_1b, or V₂ receptors in the ATs. However, the ectopic expression of GIP and V₂ receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.