Canine inflammatory mammary cancer (IMC) is highly malignant, invasive and a therapeutic challenge, because effective medical treatment is still unavailable. This retrospective study compares the efficacy of an oral cyclooxygenase‐2 (COX‐2) inhibitor combined with toceranib phosphate and oral cyclophosphamide (multi‐drug therapy [MT]) with COX‐2 inhibitor therapy alone (single‐drug therapy [ST]) in dogs diagnosed with secondary IMC. Clinical response, adverse events, overall survival time (OST), disease‐free survival (DFS) and time to progression (TTP) were evaluated. Sixteen patients were included, eight received MT and eight receiving ST. Median OST was significantly higher in patients receiving MT (96.0 vs. 37.5 days; p = .046) and in patients with post‐surgical rather than non‐surgical IMC (86.5 vs. 41.5 days; p = .038). Additionally, median TTP was significantly higher in patients treated with MT (p = .010). In patients with non‐surgical IMC, the clinical benefit (CB) was reached in 100% (n = 3) of patients receiving MT and in 33% (n = 1) of those receiving ST; the response duration was significantly longer in MT cases (p = .026). The absence of disease progression at day 30 of treatment was significantly associated with longer OST, DFS and TTP (p = .018, p = .002 and p < .001, respectively). Adverse events occurred more frequently in patients treated with MT compared with ST (p = .026). The MT protocol produced primarily mild to moderate toxicities, which were resolved with supportive care; therefore, the combination of drugs was adequately tolerated by most of the patients. The combination of toceranib, a COX‐2 inhibitor and oral cyclophosphamide may be a protocol with potential therapeutic efficacy for dogs with IMC.

The aim of this work was to establish the possible involvement of mitochondria in the apoptotic event triggered by nitric oxide (NO) in chromaffin cells. Using bovine chromaffin cells in primary culture and several NO donors (SNP, SNAP, and GSNO) at apoptotic concentrations (50 microM-1 mM), we have shown that NO induces a time-dependent decrease in the mitochondrial transmembrane potential (DeltaPsi(m)), which correlates with the appearance of hypodiploid cells. Disruption in DeltaPsi(m) is followed by cytochrome c release to the cytosol, which in turn precedes caspase 3 activation. In this mechanism participates the Bcl-2 protein family, because NO donors downregulate the expression of anti-apoptotic members of the family such as Bcl-2 and Bcl-XL, and increase the expression of pro-apoptotic members, Bax and Bcl-Xs, inductors of cytochrome c release to cytosol. Different cell signaling pathways seem to regulate Bax induction and Bcl-2 inhibition because decreased Bcl-2 levels are detected later than enhanced Bax expression. The tumour suppressor protein p53 is also upregulated in a very early phase (30 min) of the NO-induced apoptosis and may be responsible for the further induction of Bax expression. Finally, the translocation of NF-kappaB to the nucleus seems to be another early event in NO-induced apoptosis and it may be involved in the regulation of p53 expression. These results support strongly the participation of mitochondrial mechanisms in NO-induced apoptosis in chromaffin cells and suggest that these cells may be good models for the investigation of molecular basis of neurodegeneration and neuroprotection.

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Background Twice daily low trilostane doses have proven to be effective to manage canine Cushing's syndrome. However, survival and prognostic factors in dogs treated with this protocol have not been evaluated. The aim of the study was to evaluate survival and prognostic factors, including systolic blood pressure (SBP) at diagnosis, in dogs with pituitary‐dependent hypercortisolism (PDH) treated with low trilostane doses. Methods Medical records of 91 dogs newly diagnosed with PDH initially treated with 0.2–1.1 mg/kg of trilostane twice daily were retrospectively included. Survival times were calculated using the Kaplan–Meier estimator. Univariable and multivariable analysis were performed using the Cox proportional hazard regression analysis. Results Overall, median survival was 998 days (range 26–1832 days, 95% confidence interval = 755–1241 days). In the multivariable analysis, age (hazard ratio [HR] = 1.337, p < 0.001), presence of calcinosis cutis (HR = 5.271, p < 0.001), body condition score (BCS) ≤3/9 (HR = 8.100, p < 0.001) and higher platelet count (HR = 1.002, p = 0.022) were negatively correlated with survival. SBP was not associated with survival. Conclusions Low‐dose trilostane treatment twice daily provides slightly longer survival than previously reported for dogs with PDH treated once or twice daily at higher doses. Older age, presence of calcinosis cutis, low BCS and higher platelet count, but not systemic hypertension, are predictive of poorer prognosis in dogs with PDH.

Objectives Thelaziosis caused by the nematode Thelazia callipaeda (Spirurida, Thelaziidae) affects the eyes of domestic and wild carnivores, lagomorphs and even humans. The role of cats in spreading thelaziosis remains unclear. The present study assesses the current status of feline T callipaeda infection in Spain and presents the results of the first prophylactic trial conducted in this species. Methods We retrospectively analysed the occurrence of feline thelaziosis (study 1), examined its prevalence based on cross-sectional sampling of endemic areas (study 2), and assessed the therapeutic/prophylactic benefits of a spot-on (moxidectin) and therapeutic efficacy of an eye drop (ivermectin) formulation (study 3). Results In study 1, 69 Thelazia-infected cats were examined. Autochthonous cases were detected in 18/26 municipalities surveyed in Spain, which corresponds to 88.4% (n = 61/69) of the total number of cases. In study 2, 74 cats (20 from La Vera region and 54 from Orense province) were examined from 2011 to 2013. Ten of these cats (13.5%) were infected with T callipaeda. The infection prevalence was 40% (n = 8/20) in La Vera and 3.7% (n = 2/54) in Orense. The therapeutic efficacy of ivermectin was assessed over a summer (2011) in 12 cats, while that of moxidectin was examined over a 17-month period in seven cats. Four of these seven cats were subsequently included in an all-year-round prophylaxis trial. Treatment efficacy ranged from 91.7% (ivermectin) on day 28 after treatment to 100% (moxidectin) on day 14. Moxidectin prevented reinfections in cats. Conclusions and relevance Our data confirm the endemic status of T callipaeda infection in Spain, revealing its high prevalence in cats living in known endemic areas. Moxidectin was effective in treating and preventing infection. We strongly recommend the inclusion of thelaziosis in the differential diagnosis of pets and humans presenting with ocular manifestations, along with adequate preventive measures.

The main hypothesis for the aetiology of meningoencephalitis of unknown origin (MUO) in dogs is an autoimmune or genetic cause that is associated with a triggering event (environmental factors/infectious agents). The aim of this ambispective cohort study was to test for Leishmania infantum infection in the blood and cerebrospinal fluid (CSF) of dogs with MUO in an endemic area of canine leishmaniosis. Dogs with MUO were selected amongst all dogs undergoing blood anti-L. infantum antibody testing (control group). The blood plasma or serum samples from all dogs were analysed for anti- L. infantum antibodies by a quantitative indirect fluorescent assay (IFAT). In dogs with MUO, CSF samples were obtained for analysed by PCR detection of L. infantum DNA. Forty-four percent and 22% of the dogs in the MUO group featured magnetic resonance imaging (MRI) findings and CSF cytology respectively, consistent with L. infantum infection. IFAT, PCR, and histological findings were negative for L. infantum. A significant difference in L. infantum infection prevalence was found between the control and MUO group (p = 0.0022). While it seems unlikely that L. infantum plays a role in the aetiology of MUO, in endemic areas, this pathogen should be included in the differential diagnosis of this neurological disorder.