EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID‐TO‐SALIVARY RATIO AND THYROID‐TO‐BACKGROUND RATIOS

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid‐to‐salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid‐to‐background ratios (T/B) or percent thyroidal uptake of ^99mTcO^?₄ (TcTU) has only been reported in a few studies. The purpose of this prospective, cross‐sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T₄), triiodothyronine (T₃), free T₄ (fT₄), and thyroid‐stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T₄ (r = 0.76 vs. 0.64), T₃ (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.     

The 5‐lipoxygenase inhibitor tepoxalin induces oxidative damage and altered PTEN status prior to apoptosis in canine osteosarcoma cell lines

The 5‐lipoxygenase (5‐LOX) inhibitor tepoxalin has been shown to slow canine osteosarcoma (OSA) tumour xenografts growth, yet the mechanisms are poorly elucidated. Further examination of tepoxalin in canine OSA cell lines shows that tepoxalin treated cells undergo apoptosis through caspase‐3 activation and annexin staining. Interestingly, apoptosis is superseded by an increase in reactive oxygen species (ROS), as measured by activation of dihydrorhodamine 123 and mitosox. This increase in ROS appears to be related to the 5‐LOX inhibitor regardless of cellular 5‐LOX status, and was not observed after treatment with the tepoxalin metabolite RWJ20142. Additionally, 5‐LOX inhibition by tepoxalin appears to increase phosphatase and tensin (PTEN) homolog activity by preventing its alkylation or oxidation. PTEN modification or inhibition allows phosphoinositide‐3 (PI3) kinase activity thereby heightening activation of protein kinase B (AKT) phosphorylation. Our data suggest that off target oxidation and LOX inhibition play roles in the apoptotic response.     

Of mice and men: olfactory neuroblastoma among animals and humans

Olfactory neuroblastoma (ONB) is a rare tumour of nasal cavity and paranasal sinuses that arises from the olfactory neuroepithelium and has unpredictable clinical course. As the sense of smell is phylogenetically one of the first senses and olfactory neuroepithelium is evolutionary conserved with striking similarities among different species, we performed an extensive analysis of the literature in order to evaluate the similarities and differences between animals and humans on the clinical, morphological, immunohistochemical, ultrastructural and molecular level. Our analysis revealed that ONB was reported mainly in mammals and showed striking similarities to human ONB. These observations provide rationale for introduction of therapy modalities used in humans into the veterinary medicine. Animal models of neuroblastoma should be considered for the preclinical studies evaluating novel therapies for ONB.     

Plasma biomarkers profile of female dogs with mammary carcinoma and its association with clinical and pathological features

The immunological biomarkers profiles were evaluated using Luminex as putative measures to monitor canine mammary carcinomas (MCs). Forty female dogs were categorized into benign mixed tumour (MC‐BMT = 28) and mammary carcinoma (MC=12). The ascendant biomarker signatures were used to compare the groups. For example, a higher frequency of MC‐BMT animals producing IL‐6, CXCL‐8 and CXCL‐10 was observed, whereas for the MC group IL‐2 and CXCL‐8 were detected. MC‐BMT animals without metastasis had an increase in the levels of IL‐2, CXCL‐8, CXCL‐10, IL‐6, TNF‐α, IL‐15 and a decrease in IL‐10 and CXCL‐8. MC‐BMT animals with metastasis showed only an increase in CXCL‐10 and a decrease in IL‐18. After comparing the ascendant signatures following the presence of metastasis in both groups, a higher frequency of dogs exhibiting IL‐10 production was observed. Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC) curve analysis revealed that this pattern was associated with worse outcome and lower survival rates in MC animals.     

Evaluation of tizanidine as a marker of canine CYP1A2 activity

The dog CYP1A2 enzyme is likely an important contributor to the metabolism of veterinary drugs. Dog CYP1A2 is expressed in liver, plus it is inducible and polymorphic, creating the potential for intersubject differences in pharmacokinetics. Hence, the ability to probe dog CYP1A2 activity and inhibition is relevant toward veterinary drug development and drug–drug interaction assessment. Previous studies have relied on human probes with questionable specificity for CYP1A2, so it was hypothesized that recombinant CYP1A2 could be used to find a specific CYP1A2 substrate. Intrinsic clearance experiments demonstrated that tizanidine was a substrate of CYP1A2. Profiling of tizanidine metabolites generated by CYP1A2 identified the imidazole metabolite that was detectable in dog plasma. The imidazole metabolite was subsequently used to evaluate tizanidine as a CYP1A2 probe. Co‐administration of the CYP1A inhibitor enrofloxacin with tizanidine significantly decreased (30%; n = 3) the formation of the imidazole metabolite vs. control experiments. As enrofloxacin is a weak inhibitor, further studies are required to confirm the sensitivity of tizanidine as an in vivo probe. However, tizanidine may be a more selective CYP1A2 probe than phenacetin when conducting in vitro studies due to the presence of other phenacetin‐metabolizing enzymes in dog liver microsomes.