Ursolic Acid Induces Beneficial Changes in Skeletal Muscle mRNA Expression and Increases Exercise Participation and Performance in Dogs with Age-Related Muscle Atrophy.

Muscle atrophy and weakness are prevalent and debilitating conditions in dogs that cannot be reliably prevented or treated by current approaches. In non-canine species, the natural dietary compound ursolic acid inhibits molecular mechanisms of muscle atrophy, leading to improvements in muscle health. To begin to translate ursolic acid to canine health, we developed a novel ursolic acid dietary supplement for dogs and confirmed its safety and tolerability in dogs. We then conducted a randomized, placebo-controlled, proof-of-concept efficacy study in older beagles with age-related muscle atrophy, also known as sarcopenia. Animals received placebo or ursolic acid dietary supplements once a day for 60 days. To assess the study's primary outcome, we biopsied the quadriceps muscle and quantified atrophy-associated mRNA expression. Additionally, to determine whether the molecular effects of ursolic acid might have functional correlates consistent with improvements in muscle health, we assessed secondary outcomes of exercise participation and T-maze performance. Importantly, in canine skeletal muscle, ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. Furthermore, ursolic acid significantly improved exercise participation and T-maze performance. These findings identify ursolic acid as a natural dietary compound that inhibits molecular mechanisms of muscle atrophy and improves functional performance in dogs.

Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study.

BACKGROUND: Long-term remission between flares of canine atopic dermatitis (CAD) can be difficult to achieve. Therefore, additional strategic forms of treatment are needed in order to target flare prevention. The concept of proactive therapy is recommended in the European guidelines for the treatment of human atopic eczema. OBJECTIVES: To evaluate the efficacy of a proactive treatment regimen with a 0.0584% hydrocortisone aceponate (HCA) spray for CAD. ANIMALS: Client-owned dogs with spontaneous atopic dermatitis (AD) (n = 41). METHODS: This pilot study was conducted as a randomised, placebo-controlled, double-blinded clinical trial with an end-point of treatment failure. Dogs were treated once daily to remission, then randomly assigned to receive either the HCA spray (n = 21) or a placebo (n = 20) spray on two consecutive days each week. All dogs were on appropriate flea control. No topical or systemic anti-inflammatory or antimicrobial agents were permitted. Intention-to-treat analysis was used. RESULTS: At Day 0, all the dogs were in remission or had mild AD based on their Canine Atopic Dermatitis Extent and Severity Index, version 3 (CADESI-03) scores. The time to relapse was significantly higher in the HCA group (median 115 d; range 31-260 d) compared to the placebo group (median 33 d; range 15-61 d) (P < 0.0001). No adverse events were attributable to the HCA spray. Four dogs were lost to follow-up and four were withdrawn after receiving prohibited medication. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that proactive long-term therapy of CAD with an HCA spray administered on two consecutive days each week is effective and well-tolerated.

Comparable efficacy of a topical 0.0584% hydrocortisone aceponate spray and oral ciclosporin in treating canine atopic dermatitis.

This study compared the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance(®); Virbac SA) and ciclosporin (Atopica(®); Novartis Animal Health) in canine atopic dermatitis in a single-blind randomized controlled trial. Dogs received HCA (two sprays/100 cm(2); n=24) or ciclosporin (5 mg/kg; n=21). Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03, pruritus (visual analog scale with grade descriptors) and owner scores (5-point scales) were recorded every 28 days for 84 days. Intention-to-treat data were analysed. CADESI-03 and pruritus significantly decreased over time (P<0.0001), but there was no difference between the treatment groups (P=0.91 and P=0.52, respectively). Similar proportions of HCA- and ciclosporin-treated dogs achieved ≥50% reductions in CADESI-03 and pruritus scores at 28 days (CADESI-03 58.3 and 57.1%, P=0.76; pruritus 33.3 and 38.1%, P=1.0), 56 days (CADESI-03 70.8 and 81.0%, P=1.0; pruritus 62.5 and 57.1%, P=1.0) and 84 days (CADESI-03 75 and 85.7%, P=0.72; pruritus 65.2 and 57.1%, P=0.76). The CADESI-03 and pruritus scores were close to equivalence (0.47 and 0.51, respectively). By 84 days, every-other-day or twice-weekly therapy was achieved in 13 of 24 HCA- and 12 of 21 ciclosporin-treated dogs (P=0.85). There were no significant differences in scores for efficacy (P=0.82), tolerance (P=0.62) and ease of administration (P=0.25). Scores for tolerance (0.49) and administration (0.46) were close to equivalence. The score for efficacy favoured HCA (0.68). Mild adverse events were noted in six of 21 ciclosporin and none of 24 HCA dogs (P=0.008). Five HCA-treated dogs and three ciclosporin-treated dogs were prematurely withdrawn (P=0.7). In conclusion, HCA and ciclosporin proved equally effective in treating canine atopic dermatitis for up to 84 days.

Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study.

This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance(®); Virbac SA) in 10 cats with presumed allergic dermatitis. The cats initially received two sprays/100 cm(2) of skin once daily. Clinical lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm visual analog scale with grade descriptors) and owner assessments of efficacy, tolerance and ease of use (from 1=very poor to 5=excellent) were assessed every 14 days. The frequency of treatment was reduced after day 28 in cats with a >50% reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28 and two at day 42. Intention-to-treat data were analysed. The FeDESI [mean (SD): day 0, 42.2 (15.7) and day 56, 9.9 (11.7); P<0.0001] and pruritus scores [day 0, 61.2 mm (20.1) and day 56, 14.6 mm (16.1); P<0.0001] significantly decreased throughout the trial. The owner scores for tolerance [median (range): day 14, 4 (1-5) and day 56, 4 (3-5); P=0.003] and ease of administration [day 14, 3 (2-5) and day 56, 4 (2-5); P=0.02] significantly increased during the trial, but there was no significant change in efficacy scores [day 14, 4 (3-5) and day 56, 4 (2-5); P=0.5]. There were no adverse effects attributable to the HCA spray, no significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg (1.6); P=0.51] and no significant changes in haematology, biochemistry or urinalysis (n=4). Six cats required every-other-day treatment and four required daily treatment. In conclusion, HCA spray appeared to be effective and safe in these cats, although it is not licensed for use in this species.

The use of recombinant omega interferon therapy in canine atopic dermatitis: a double-blind controlled study.

This double-blind controlled study assessed whether reduced doses of omega interferon (rFeIFN-omega) (Virbagen Omega) could improve the clinical signs of canine atopic dermatitis (CAD) over a 6-month period, in comparison with cyclosporin. Thirty-one dogs diagnosed with CAD were entered in the study. Complicating infections were treated prior to entry. Dogs received 10 injections of rFeIFN-omega (1-5 million units according to bodyweight) or placebo over 6 months, and placebo capsules or cyclosporin (5 mg/kg) once daily for 2 months and then twice weekly for 4 months in groups 1 and 2 respectively. Flea control, non-medicated shampooing and ear cleansing were performed regularly. If a bacterial infection or Malassezia overgrowth developed, it was treated with oral cephalexin or with 3% chlorhexidine shampoo respectively. Oral prednisolone was used before day 90 to relieve pruritus when required for humane reasons (1 mg/kg once daily for 7 days). The CADESI-03 and a pruritus index were evaluated on day (D) 0, D14, D35, D56, D90, D120 and D180. No significant difference was detected between the groups for the time courses of lesions or pruritus over 6 months. On D90, the proportions of dogs with > or =50% improvement of pruritus and lesion scores were 56% and 72% respectively with interferon, 75% and 75% respectively with cyclosporin. Five dogs from group 1 and two dogs from group 2 were withdrawn from the study for treatment failure. Both products were well tolerated. Treatment with rfeIFN-omega at low doses may help for the long-term management of CAD.

Monosaccharide inhibition of adherence by Pseudomonas aeruginosa to canine corneocytes.

The effect of D-galactose, D-mannose, L-rhamnose and dextrose on the adhesion to canine corneocytes by three strains of Pseudomonas aeruginosa was studied in six healthy dogs. Canine corneocytes were collected from the inner aspect of the pinna using adhesive discs (D-Squame). Half millimetre of bacterial suspension in phosphate-buffered saline (PBS) with or without the addition of a monosaccharide was placed over the corneocyte layer and incubated in moist chambers. Image analysis was used to quantify bacterial adherence to corneocytes. The three strains of Pseudomonas adhered well to canine corneocytes. All monosaccharides tested inhibited the adherence of Pseudomonas to canine corneocytes. The mean reduction in adhesion for individual sugars at a concentration of 0.1% was 40.2% (dextrose), 30.8% (L-rhamnose), 25.6% (D-galactose) and 19.4% (D-mannose). When D-galactose, D-mannose and L-rhamnose were used in combination at 0.1% concentration, the mean reduction in adherence was 52.9%. The monosaccharides studied may have a potential role in the management of Pseudomonas infections in dogs.

Role of sugars in surface microbe-host interactions and immune reaction modulation.

Sugars in the form of monosaccharides, oligosaccharides, polysaccharides and glycoconjugates (glycoproteins, glycolipids) are vital components of infecting microbes and host cells, and are involved in cell signalling associated with modulation of inflammation in all integumental structures. Indeed, sugars are the molecules most commonly involved in cell recognition and communication. In skin, they are essential to epidermal development and homeostasis. They play important roles in microbial adherence, colonization and biofilm formation, and in virulence. Two groups of pathogen recognition receptors, C-type lectins (CTL) and their receptors (CTLR), and the Toll-like receptors enable the host to recognize pathogen-associated molecular patterns (PAMPs), which are mainly glycolipids. The CTLs can recognize a wide variety of bacteria, fungi and parasites and are important in phagocytosis and endocytosis. TLRs are expressed on the surfaces of a variety of cells, including keratinocytes, dendritic cells, monocytes and macrophages; they play a major role in innate immunity. Interaction of TLRs with PAMPs initiates a cascade of events leading to production of reactive oxygen intermediates, cytokines and chemokines, and promotes inflammation. Exogenous sugars can block carbohydrate receptors and competitively displace bacteria from attachment to cells, including keratinocytes. Thus sugars may provide valuable adjunctive anti-inflammatory and/or antimicrobial treatment. A promising approach is the use of a panel of carbohydrate derivatives with anti-adhesive efficacy against bacteria frequently involved in diseases affecting skin and other epithelia. More complete characterization of sugar receptors and their ligands will provide further keys to use of carbohydrates in immunomodulation and infection control in skin.