Comparison of body condition score and urinalysis variables between dogs with and without calcium oxalate uroliths.

OBJECTIVE To compare body condition score (BCS) and urinalysis variables between dogs with and without calcium oxalate (CaOx) uroliths. DESIGN Case-control study. ANIMALS 46 Miniature Schnauzers, 16 Bichons Frises, and 6 Shih Tzus. PROCEDURES Medical records were reviewed for Miniature Schnauzers, Bichons Frises, and Shih Tzus that were examined between January 2001 and November 2014 for another urolithiasis study or for a urolith removal procedure. Dogs with CaOx uroliths were classified as cases. Dogs without a history of urinary tract disease and with no evidence of radiopaque uroliths on abdominal radiographs were classified as controls. Each case was matched with 1 control on the basis of age (± 2 years), sex, and breed. Body condition score and urinalysis results were compared between cases and controls, and the relationship between BCS and urine pH was analyzed. RESULTS Median BCS was significantly greater for cases than controls, although the proportion of overweight dogs did not differ significantly between the 2 groups. Urine pH was negatively associated with age, but was not associated with BCS or the presence of CaOx uroliths. Cases infrequently had acidic urine or CaOx crystalluria but frequently had hematuria and proteinuria. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with CaOx uroliths had a greater median BCS than control dogs, but the clinical importance of that finding was unclear. Acidic urine and CaOx crystalluria were uncommon and not adequate predictors of CaOx urolith status. Hematuria and proteinuria were commonly observed in dogs with CaOx urolithiasis, but they are not pathognomonic for that condition.

Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.

Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.

Stimulation with Concanavalin-A Induces IL-17 Production by Canine Peripheral T Cells.

The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; however, no associations have been found between IL-17 gene expression and disease phenotype in these conditions. Robust assessment of the role of IL-17-producing cells in dogs will require measuring the frequency of these cells in health and disease in balance with other lymphocyte subsets. The aim of this study was to confirm that the T-cell IL-17 response in dogs is evolutionarily conserved. Canine peripheral blood mononuclear cells were stimulated with Concanavalin A with or without polarizing cytokines. We used a canine specific IL-17 ELISA and flow cytometry to identify IL-17-producing T cells. Accumulation of intracellular IL-17 was observed in stimulated CD4 and CD8 T cells. The addition of pro-inflammatory cytokines appeared to enhance polarization of canine CD4 T cells to the Th17 phenotype. Conversely, the addition of IL-2 in the presence of TGF-ß resulted in expansion of Treg cells. We conclude that canine IL-17-producing cells behave similarly to those from humans and mice when stimulated with mitogens and polarized with pro-inflammatory or immune regulatory cytokines.

Renal secondary hyperparathyroidism in dogs.

The parathyroid glands secrete parathyroid hormone (PTH), which is important for maintaining calcium homeostasis. Parathyroid gland hyperplasia and subsequent hyperparathyroidism can occur secondary to chronic renal failure in dogs, resulting in significant alterations in calcium metabolism. Renal secondary hyperparathyroidism is a complex, multifactorial syndrome that involves changes in circulating levels of calcium, PTH, phosphorus, and 1,25-dihydroxycholecalciferol (calcitriol). An increased PTH level can have deleterious effects, including soft tissue mineralization, fibrous osteodystrophy, bone marrow suppression, urolithiasis, and neuropathy. Dietary phosphorus restriction, intestinal phosphate binders, and calcitriol supplementation may slow the progression of renal disease and decrease PTH concentrations in animals with secondary hyperparathyroidism; however, the prognosis for these animals is guarded to poor.

Enhancing antimelanoma immune responses through apoptosis.

We examined the feasibility of using tumor apoptosis at accessible sites to enhance antimelanoma immune responses in a model of spontaneous canine melanoma. We show that priming peripheral blood mononuclear cells with apoptotic melanoma cells significantly enhanced autologous and allogeneic lymphokine-activated killing of tumor cells. Since various pathways required for intrinsic apoptosis are often inactivated in melanoma, we used Fas ligand (FasL) overexpression to promote extrinsic apoptosis. FasL induced apoptosis in five of six cell lines. Each of the susceptible lines, but not the resistant one, expressed Fas mRNA. In addition, direct intratumoral administration of FasL DNA to tumor-bearing dogs was safe, with no adverse events reported over 7 days of observation. A reduction of tumor burden was seen in three of five dogs treated. The reduction of tumor volume was correlated with Fas expression by the tumors, although one dog with a Fas-negative tumor survived for 82 weeks after treatment. Our data show that overexpression of FasL is suitable to promote apoptosis of Fas(+) melanomas, and support the notion that priming immune responder cells with apoptotic tumor cells may enhance antitumor responses. The results also suggest that intratumoral administration of FasL offers a safe route for therapeutic gene delivery.