Haematological and biochemical investigations of diseased koalas (Phascolarctos cinereus)

Haematological and biochemical investigations were performed on 14 koalas with uncomplicated cystitis, 8 with complicated cystitis, 8 with conjunctivitis, 8 with lymphosarcoma, and 14 with miscellaneous diseases. Changes were limited and inconsistent in individual koalas with uncomplicated cystitis and conjunctivitis. In contrast, individual koalas with complicated cystitis were more likely to have anaemia, leukocytosis due to neutrophilia, hypoproteinaemia due to hypoalbuminaemia, and azotaemia due to elevated urea concentration. Although these changes were non-specific they did allow assessment of prognosis for survival and response to treatment. Koalas with lymphosarcoma were invariably anaemic, leukaemic, azotaemic and hypoalbuminaemic. Elevated enzymes (aspartate transaminase [AST]. lactate dehydrogenase [LD] and gamma glutamyl transferase [GGT]) were more common in koalas with lymphosarcoma. Koalas affected by miscellaneous conditions showed variable changes but once again anaemia, leukocytosis, azotaemia, elevated AST and LD, and hypoalbuminaemia were not uncommon. On the basis of these findings a minimal profile is suggested for the investigation of sick koalas and would include haematocrit, total and differential leukocyte counts, urea, total protein and albumin concentrations and AST, GGT and LD activities.     

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 Interestingly, apoptosis is superseded by an increase in reactive oxygen species (ROS), as measured by activation of dihydrorhodamine 123 and mitosox.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.     

Comparison of the properties of hyaluronate products used in treatment of joint dysfunction in horses

A standardized investigation was conducted to compare the biophysical properties of hyaluronate products used in the treatment of joint dysfunction in horses. Results showed that two of the five products, Hyvisc® and Hylartin®V, contained higher-weight molecular hyaluronate (greater than 1.5×10⁶). Other investigations have shown that higher molecular weight hyaluronate is effective in providing physical resistance to shear, in stimulating endogenous hyaluronate synthesis, and in inhibiting excess cell proliferation which may be associated with synovial pannus formation. It is suggested that the therapeutic benefits of hyaluronate products may be dependent on the molecular size of the hyaluronate molecules. Higher molecular weight hyaluronate products would be expected to be more effective than lower molecular hyaluronate products in providing therapeutic benefits.     

Cloning and antibody recognition analysis of the canine 5-lipoxygenase gene

5-Lipoxygenase cDNA was prepared from canine white blood cells revealing the full-length message using an oligonucleotide capping method. The sequenced 5-Lipoxygenase open reading frame revealed a 2031 base pair message encoding a 676 amino acid protein. The amino acid sequence showed mild variation with the presumed canine sequence, as well as differences in important residues of known phosphorylation observed in other species. The sequence had between 86 and 92% homology with other species, revealing a highly conserved sequence. Confirmation of gene product identity was achieved through transient transfection of the gene in a V5-Histidine tagged pcDNA 3.1 vector into a known canine cell line. Both V5 antibody and 5-lipoxygenase antibody confirmed the gene product using Western blotting and immunoflourescence.     

IMAGING DIAGNOSIS—MENINGOENCEPHALITIS SECONDARY TO SUPPURATIVE RHINITIS AND MENINGOENCEPHALOCELE INFECTION IN A DOG

Nasal encephaloceles (meningoceles or meningoencephaloceles) are rare and not reported to be infected or coupled with a facial deformity in dogs. This report describes an older dog with acute worsening of seizures due to suppurative meningoencephalitis with coexisting suppurative rhinitis and infection of a meningoencephalocele. Additionally, the dog had a facial deformity for at least 5 years. The results of necropsy, computed tomography, and postmortem magnetic resonance imaging are compared. The development of nasal encephaloceles is discussed, including the potential role of early trauma, and whether separation of neural ectoderm from the surface ectoderm is part of the pathogenesis.     

Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors

With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important link in feeding regulation and may be a potential therapeutic target.