Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors.

Cancer Osaka thyroid (COT) kinase is an important regulator of pro-inflammatory cytokines in macrophages. Thus, pharmacologic inhibition of COT should be a valid approach to therapeutically intervene in the pathogenesis of macrophage-driven inflammatory diseases such as rheumatoid arthritis. We report the discovery and chemical optimization of a novel series of COT kinase inhibitors, with unprecedented nanomolar potency for the inhibition of TNFα.

Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study.

Canine atopic dermatitis (cAD) is a common disease with a multifactorial aetiology associated with impaired immunoregulation. The immunopathogenesis has similarities to that of human atopic dermatitis. Clinical signs of allergic disease in humans and mice are reduced by administration of saprophytic mycobacteria that amplify regulatory cytokines and hence the effect of Mycobacterium vaccae on the clinical severity of cAD was investigated.

Penetration of ASM 981 in canine skin: a comparative study.

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin.

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis.

Objective: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy.

Animals: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses.

Procedure: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution.

Evaluation of the usefulness of sensitization to aeroallergens as a model for canine atopic dermatitis in genetically predisposed Beagles.

Objective: To evaluate a model for atopic dermatitis (AD) and to measure the effect of sensitization in Beagles genetically predisposed to produce high serum concentrations of allergen specific IgE.

Animals: 22 laboratory Beagles.

Procedure: Seventeen dogs were sensitized from birth to 3 allergens (recombinant birch pollen, Dermatophagoides pteronyssinus, and D farinae).