Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.

The classi®cation of autoimmune blistering skin diseases is based on the skin antigen(s) targeted by pathogenic autoantibodies. In humans and dogs, there is increasing evidence that autoimmune subepidermal bullous diseases represent dierent nosological entities. This study establishes the existence of the canine equivalent of epidermolysis bullosa acquisita (EBA) in humans. Canine EBA, like the in¯ammatory variant of its human counterpart, is characterized by spontaneous vesicles arising from an in¯ammatory eruption. Dermo-epidermal separation occurs in association with neutrophilic in®ltration in the super®cial dermis. Tissue-®xed and circulating IgA and IgG autoantibodies speci®c for the lower basement membrane zone can be detected by immuno¯uorescence methods. Using immunoelectron microscopy, autoantibodies are shown to target the distal end of anchoring ®brils in the sublamina densa. ELISA and immunoblotting utilizing eukaryotically expressed recombinant collagen VII subdomains con®rm that the circulating autoantibodies are speci®c for the aminoterminal globular non-collagenous NC1 domain of type VII collagen.

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, were characterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hereditary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lameness affected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinical phenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG antibodies were demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease usually responds poorly to immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatory therapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This study demonstrates the existence of a cellular and humoral immune response directed against the epidermal basement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to further characterize the immunological pathogenesis of this disease.

Abstract. The barrier function of mammalian skin is maintained by intercellular stratum corneum lipids. In human patients with atopic dermatitis, an abnormal lipid barrier results in dry skin and increased transepidermal water loss. At this time, it is not known if a defective lipid barrier is present in atopic dogs. Normal and atopic canine skin were postfixed in ruthenium tetroxide and studied using transmission electron microscopy to determine structural differences within stratum corneum lipids. Intercellular lipid lamellae were graded on a semiquantitative scale. The deposition of stratum corneum lipid lamellae in atopic canine skin appeared markedly heterogeneous compared with that seen in normal canine skin. When present, the lamellae often exhibited an abnormal structure. The continuity and thickness of the intercellular lipid lamellae were significantly less in nonlesional atopic than in normal canine skin. These preliminary observations suggest that the epidermal lipid barrier is defective in atopic canine skin. Additional studies are needed to further characterize the biochemical defect and to possibly correct it with nutritional and/or pharmacologic intervention.Key words: Barrier defect; canine atopic dermatitis; dogs; lipid lamellae; ruthenium tetroxide.The barrier function of mammalian skin is maintained by epidermal lipids, especially those interspersed between the layers of the stratum corneum. In mammalian stratum corneum, epidermal lipids consist of ceramides, cholesterol,

In canine and human atopic patients, the intracutaneous injection of offending allergens is followed by the development of both immediate and late-phase reactions. The present study was performed to expand on the characterization and dynamics of inflammatory cell subsets during IgE-mediated late-phase reactions in canine skin. Three normal dogs and three Dermatophagoides farinae-allergic dogs were selected for this experiment. All dogs were challenged intradermally with mite allergen, purified anticanine IgE antibodies (positive control) or phosphate-buffered saline (negative control). Skin biopsies were obtained before and 6, 12 and 24 h post-injection. Sections were stained with metachromatic and eosinophil-specific histological stains. Additionally, we used an immunohistochemical method with antibodies specific for canine leukocyte antigens. This study confirmed the occurrence of a late-phase reaction in atopic skin following allergen challenge, and in normal and atopic canine skin after intradermal injection of IgE-specific antibodies. Whereas early emigrating dermal cells were composed chiefly of neutrophil and activated eosinophil granulocytes, there was an influx of alpha beta T-lymphocytes and dermal dendritic cells in later stages of the late-phase reactions. Because IgE-mediated late-phase reactions resemble spontaneous atopic canine skin lesions, both at macroscopic and microscopic levels, we propose the use of similar challenges to study the anti-inflammatory effects of anti-allergic drugs in a pre-clinical setting.

These findings are very similar to those reported for human AA patients; therefore, they support the consideration of dogs with AA as a useful homologue for the study of the pathogenesis of this common autoimmune disease of humans.

This study demonstrated that epicutaneous application of HDM slurry to MAB dogs results in elevations of HDM-specific IgE, localized and generalized pruritic dermatitis resembling spontaneous canine AD, and histologic changes typical of IgE-driven inflammation. We feel that these results suggest that epicutaneous exposure to allergen may play an important role during both the sensitization and the perpetuation of AD, and provide support for the use of a canine model in the investigation of the pathogenesis of AD.

In this blinded randomized placebo-controlled trial, 20 dogs with atopic dermatitis (AD) were given placebo (8 dogs) or misoprostol (12 dogs) at 5 micro g kg-1, orally, three times daily for 3 weeks. Administration of the active drug, but not of placebo, led to a significant decrease in lesional and pruritus scores. The median reduction from baseline of both scores was approximately 30%. Misoprostol therapy did not lead to decreases of dermal cell counts or skin tumour necrosis factor (TNF)alpha mRNA copy numbers that were significantly different from those of placebo. Skin TNFalpha protein production, assessed using indirect immunofluorescence, decreased or remained unchanged in dogs receiving misoprostol. In contrast, post treatment TNFalpha fluorescence scores were higher in all but two dogs given placebo. The changes from baseline of TNFalpha fluorescence scores did not correlate significantly with those of lesional or pruritus indices. These observations confirm the modest efficacy of misoprostol for treatment of canine AD and suggest that its mild anti-allergic effects are not associated with either inhibition of inflammatory cell emigration or TNFalpha production.