Comparison of lente insulin and NPH insulin therapy for the treatment of newly diagnosed diabetic dogs: a randomised study.

Clinical studies that compare lente insulin and neutral protamine Hagedorn (NPH) insulin in diabetic dogs are lacking. This is a prospective, randomised, controlled clinical study aimed to compare the efficacy and safety of lente insulin and NPH insulin in diabetic dogs. Thirty client-owned, newly diagnosed diabetic dogs were included. Animals were randomised into two groups and received lente insulin or NPH insulin administered every 12 hours. Follow-up re-evaluations were done at 1, 2, 4, 6, 8 and 12 weeks. At each re-evaluation, a physical exam, blood glucose curve, and serum fructosamine concentrations were performed. At the end of the study, the median insulin dose per injection was 0.61 U/kg (range, 0.34-0.92 U/kg) and 0.49 U/kg (range, 0.23-0.68 U/kg) in the lente and NPH groups, respectively. There was a significant improvement of polyuria and polydipsia and glucose concentrations in both groups. At the end of the study, the glycaemic control was considered good in 9/15 (60 per cent) and 11/15 (73 per cent) in the lente and NPH groups, respectively. These differences were not significant. Lente insulin and NPH insulin were similarly effective in the treatment of dogs with diabetes mellitus.

Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone.

Inhibition of proteasome activity promotes the correct localization of disease-causing alpha-sarcoglycan mutants in HEK-293 cells constitutively expressing beta-, gamma-, and delta-sarcoglycan.

Sarcoglycanopathies are progressive muscle-wasting disorders caused by genetic defects of four proteins, alpha-, beta-, gamma-, and delta-sarcoglycan, which are elements of a key transmembrane complex of striated muscle. The proper assembly of the sarcoglycan complex represents a critical issue of sarcoglycanopathies, as several mutations severely perturb tetramer formation. Misfolded proteins are generally degraded through the cell's quality-control system; however, this can also lead to the removal of some functional polypeptides. To explore whether it is possible to rescue sarcoglycan mutants by preventing their degradation, we generated a heterologous cell system, based on human embryonic kidney (HEK) 293 cells, constitutively expressing three (beta, gamma, and delta) of the four sarcoglycans. In these betagammadelta-HEK cells, the lack of alpha-sarcoglycan prevented complex formation and cell surface localization, wheras the presence of alpha-sarcoglycan allowed maturation and targeting of the tetramer. As in muscles of sarcoglycanopathy patients, transfection of betagammadelta-HEK cells with disease-causing alpha-sarcoglycan mutants led to dramatic reduction of the mutated proteins and the absence of the complex from the cell surface. Proteasomal inhibition reduced the degradation of mutants and facilitated the assembly and targeting of the sarcoglycan complex to the plasma membrane. These data provide important insights for the potential development of pharmacological therapies for sarcoglycanopathies.