Longitudinal evaluation of immunological responses to allergen-specific immunotherapy in horses with IgE associated dermatological disease, a pilot study.

BACKGROUND: The long-term effects of allergen specific immunotherapy (ASIT) on concentrations of circulating immunoglobulin E (IgE) and immunoglobulin G (IgG) in horses have not been reported. OBJECTIVES: To document changes in clinical severity of horses with atopic dermatitis (AD) and to monitor allergen-specific IgE and IgG concentrations during a two-year course of ASIT. ANIMALS: Nineteen client-owned horses with a conditional diagnosis of AD. METHODS AND MATERIALS: Three ASIT groups were randomly assigned based upon results obtained by either intradermal testing (IDT) for regional allergens (n = 7); enzyme-linked immunosorbent assay (ELISA) for specific IgE (n = 6); or a composite of results from both tests (n = 6). Serum concentrations of IgE and IgG specific for allergens included in ASIT were measured at time zero and at four-month intervals. A visual analog scale (VAS) was used to record severity of clinical signs at times zero, 12 and 24 months. RESULTS: Positive correlations were documented between IgE and both immediate and delayed IDT results (P < 0.00001), and between immediate IDT and IgG results (P = 0.003). Specific IgE in sera decreased significantly (P < 0.05) for allergens that were included in ASIT, whereas IgG increased. Across all horses, the mean VAS score decreased by 1.2 units [95% CI: 1.28, 1.14; (P < 0.0001)] during each 12-month period of ASIT therapy. Improvement in clinical signs was noted in 76.5% of the horses following 12 months of ASIT and in 82% after 24 months on ASIT. CONCLUSIONS AND CLINICAL IMPORTANCE: In this pilot study, ASIT in horses with AD provided significant clinical benefit associated with a concomitant reduction of allergen-specific IgE and elevation of IgG.

Soy isoflavone metabolism in cats compared with other species: urinary metabolite concentrations and glucuronidation by liver microsomes.

1. Soybean is a common source of protein in many pet foods. Slow glucuronidation of soy-derived isoflavones in cats has been hypothesized to result in accumulation with adverse health consequences. Here, we evaluated species' differences in soy isoflavone glucuronidation using urine samples from cats and dogs fed a soy-based diet and liver microsomes from cats compared with microsomes from 12 other species. 2. Significant concentrations of conjugated (but not unconjugated) genistein, daidzein and glycitein, and the gut microbiome metabolites, dihydrogenistein and dihydrodaidzein, were found in cat and dog urine samples. Substantial amounts of conjugated equol were also found in cat urine but not in dog urine. 3. ß-Glucuronidase treatment showed that all these compounds were significantly glucuronidated in dog urine while only daidzein (11%) and glycitein (37%) showed any glucuronidation in cat urine suggesting that alternate metabolic pathways including sulfation predominate in cats. 4. Glucuronidation rates of genistein, daidzein and equol by cat livers were consistently ranked within the lowest 3 out of 13 species' livers evaluated. Ferret and mongoose livers were also ranked in the lowest four species. 5. Our results demonstrate that glucuronidation is a minor pathway for soy isoflavone metabolism in cats compared with most other species.

Effects of dietary soy isoflavones on health, steroidogenesis, and thyroid gland function in dogs.

OBJECTIVE: To evaluate the effect of a soy-based diet on general health and adrenocortical and thyroid gland function in dogs. Animals-20 healthy privately owned adult dogs. PROCEDURES: In a randomized controlled clinical trial, dogs were fed a soy-based diet with high (HID; n = 10) or low (LID; 10) isoflavones content. General health of dogs, clinicopathologic variables, and serum concentrations of adrenal gland and thyroid gland hormones were assessed before treatment was initiated and up to 1 year later. Differences between groups with respect to changes in the values of variables after treatment were assessed by means of a Student t test (2 time points) and repeated-measures ANOVA (3 time points). RESULTS: No differences were detected between the 2 groups with respect to body condition and results of hematologic, serum biochemical, and urine analyses. Most serum concentrations of hormones did not change significantly after treatment, nor were they affected by diet. However, the mean change in serum concentration of total thyroxine was higher in the HID group (15.7 pmol/L) than that in the LID group (-1.9 pmol/L). The mean change in estradiol concentration after ACTH stimulation at 1 year after diets began was also higher in the HID group (19.0 pg/mL) than that in the LID group (-5.6 pg/mL). CONCLUSIONS AND CLINICAL RELEVANCE: Phytoestrogens may influence endocrine function in dogs. Feeding soy to dogs on a long-term basis may influence results of studies in which endocrine function is evaluated, although larger studies are needed to confirm this supposition.

Incidence of anti-Der f 2 and anti-Zen 1-specific immunoglobulin E antibodies in atopic dogs from South-East England.

Recent studies from North America and continental Europe have reported Zen 1 as a major allergen in atopic dogs, and Der f 2 as a minor allergen. In contrast, Der f 2 is considered a major allergen in Japan. In this study, allergen-specific IgE against Der f 2, Zen 1 and crude Dermatophagoides farinae (DF) was determined using ELISA assays in English atopic dogs. Serum samples were obtained from 59 dogs with non-seasonal atopic dermatitis. ELISA assays using horseradish peroxidase-labelled anti-dog IgE monoclonal antibody (Bethyl; A40-125P) and recombinant Der f 2 (Zenoaq), natural Zen 1 (Zenoaq) and DF extract (Greer Laboratories; North Carolina) were performed by Zenoaq, Fukushima, Japan. The mean optical density (OD) of each sample was determined and the cut-off value was calculated from OD readings obtained from four healthy control dogs. Der f 2, Zen 1 and DF-specific IgE antibodies were found in the serum samples taken from 57 (97 per cent), 45 (76 per cent) and 47 (80 per cent) atopic dogs, respectively, suggesting that both Zen 1 and Der f 2 are 'major allergens' in the South-East England.

Identification and concentration of soy phytoestrogens in commercial dog foods.

OBJECTIVE: To identify and determine the concentrations of phytoestrogens in commercial dog foods. SAMPLE POPULATION: 24 commercial dog foods, including 12 moist or dry extruded commercial dog foods that contained soybeans or soybean fractions and 12 foods without any soybean-related ingredients listed on the label. PROCEDURE: Foods were analyzed for phytoestrogen content, including 4 isoflavones (genistein, glycitein, daidzein, and biochanin A), 1 coumestan (coumestrol), and 2 lignans (secoisolariciresinol and matairesinol) by use of acid-methanol hydrolysis and high-pressure liquid chromatography with UV-absorbance detection. Phytoestrogens were identified and quantified by reference to authentic standards. RESULTS: Isoflavones, coumestans, and lignans were undetectable in diets that did not list soybean-related ingredients on the label. Only 1 of the 12 diets that included soybean or soybean fractions had undetectable concentrations of phytoestrogens and that product contained soy fiber. The major phytoestrogens were the isoflavones daidzein (24 to 615 microg/g of dry matter) and genistein (4 to 238 microg/g of dry matter). CONCLUSIONS AND CLINICAL RELEVANCE: Soybean and soybean fractions are commonly used ingredients in commercial dog foods. Dietary intake of phytoestrogens may have both beneficial and deleterious health effects. Our results indicated that certain commercial dog foods contain phytoestrogens in amounts that could have biological effects when ingested long-term.

An analysis of factors underlying hypotrichosis and alopecia in Irish Water Spaniels in the United Kingdom.

A survey on the occurrence of dermatoses in the Irish Water spaniel (IWS) was carried out in the United Kingdom. A group of 20 dogs was selected and examined clinically. All dogs had a nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in males and females, although an initial cyclical pattern associated with the oestrus cycle was identified. Hormonal investigations showed features suggestive of an abnormality of steroidogenesis. Histopathology revealed features similar to canine recurrent flank alopecia (CRFA) and follicular dysplasia associated with abnormal melanization, as in colour dilution alopecia, although the clinical features did not correlate with those conditions. Dietary changes improved coat and skin quality in most of the cases in this series but the role of the diet was not investigated further. This study suggests that hair loss in IWS is influenced by dietary factors and sexual hormones. Abnormalities of the steroidogenic pathways may contribute to the severity of the condition.

Colour Dilution Alopecia (CDA) in Ten yorkshire Terriers.

Abstract- Clinical laboratory investigations as well as light, electron microscopic and X-ray microanalytical studies on skin biopsy specimens and hair from 10 yorkshire terriers suffering from Colour Dilution Alopecia (CDA) were carried out. Biochemical data detected a marked melanin reduction in hair from affected areas. Histologically, melanin clumps were mainly evident in the epidermal basal layer cells as well as inside the bulb and hair shaft. Ultrastructurally, basal keratinocytes were overloaded by fully melanized melanosomes disrupting cytoplasmic structures. Intracytoplasmic and free melanosomes were also evident in all cutaneous layers. Scanning electron microscopy showed holes and bulges scattered in the hair shaft. X-Ray microanalysis demonstrated silicate particles in the more superficial cuticular holes and calcium in the deeper fractured layers. Based on these observations a new hypothesis on the pathogenetic mechanism(s) of alopecia is proposed. Résumé- Diverses investigations, microscopie optique, microscopie électronique, études microanalytiques aux rayons X ont été réalisées sur des biopsies cutanées et des poils provenant de dix yorkshire Terriers présentant une Alopécie des Robes Diluées. Les examens biochemiques montrent une diminution nette de la mélanine dans les poils provenant des régions malades. Des aggrégate de mélanine sont observés dans les cellules de l'assise basale épidermique ainsi qu'à l'intérieur des bulbes pileux et des tiges pilaires. Sur le plan ultrastructural, les kératinocytes basaux montrent une surcharge en mélanosomes détruisant ainsi les structures cytoplasmiques. Des mélanosomes libres et intra-cytoplasmiques sont également observés dans toutes les couches épidermiques. La microscopie électronique à balayage montrent des trous et des bosses dispersés dans la gaine folliculaine. Des analyses en rayons X démontrent la présence de particules de silicate dans les trous les plus superficiels de la cuticule et du calcium dans les couches plus profondes. A partir de ces observations, une nouvelle hypothèse sur la pathogénie de dette alopécie est proposée. [Roperto F., Cerundolo, R., Restucci, B., Vincensi, M. R., De Caprariis, D., De Vico, G., Maiolino, P. Colour dilution alopecia (CDA) in ten yorkshire Terriers (Alopécie des robes diluées (ARD) chez dix yorkshire Terriers). Resumen- Se llevaron a cabo análisis clinicos asi como estudios microanaliticos con rayos X y microscopia electrónica sobre biopsias cutáneas tomadas a diez yorkshire Terriers que padecian de Alopecia de Color Diluido (CDA). Los estudios bioquimicos detectaron una fuerte reducción en melanina en el pelo de las zonas afectadas. A nivel histológico, los agregados de melanina se localizaban principalmente en la capa basal de la epidermis asi como en el bulbo piloso y en en pelo. A nivel ultraestructural, los queratinocitos basales estaban sobrecargados de melanosomas totalmente melanizados, alterando su estructura citoplasmática. También se identificaron melanosomas en forma libre o a nivel intracitoplasmático en todas las capas cutáneas. La microscopia electrónica de escáner mostró cavidades y prominencias diseminadas a lo largo del pelo. Mediante microanalisis por rayos X se detectaron partículas de silicato en las cavidades cuticulares más superficiales y calcio en las capas més profundas. Teniendo en cuenta estos hallazgos, se propone una nueva hipótesis sobre el/los mecanismo/s patogénico/s de la alopecia. [Roperto F., Cerundolo, R., Restucci, B., Vincensi, M. R., De Caprariis, D., De Vico, G., Maiolino, P. Colour dilution alopecia (CDA) in ten yorkshire Terriers (Alopecia de color diluido (CDA) en diez yorkshire Terriers).

Effects of powdered whole grapefruit and metoclopramide on the pharmacokinetics of cyclosporine in dogs.

OBJECTIVE: To determine whether oral administration of metoclopramide or a commercially available powdered whole grapefruit (PWG) nutraceutical in combination with cyclosporine enhances systemic availability of cyclosporine in dogs. SAMPLE: 8 healthy mixed-breed dogs in part 1 and 6 of these 8 dogs in part 2. PROCEDURES: Cyclosporine pharmacokinetics were determined over the course of 24 hours after oral administration of cyclosporine (5 mg/kg) alone, cyclosporine with metoclopramide (0.3 to 0.5 mg/kg), cyclosporine with 2 g of PWG, or cyclosporine combined with both metoclopramide and 2 g of PWG by use of a Latin square crossover study with a 14-day washout period between treatments. Sixty days later, 6 of the 8 dogs were given 10 g of PWG followed by cyclosporine, and pharmacokinetic parameters were compared with those previously obtained after administration of cyclosporine alone. RESULTS: Although metoclopramide or coadministration of metoclopramide and 2 g of PWG had no effect on the pharmacokinetic parameters of cyclosporine, compared with results for cyclosporine alone, the higher (10-g) dose of PWG resulted in 29% faster mean time to maximal plasma cyclosporine concentration, 54% larger area under the curve, and 38% lower apparent oral clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Adjustment of the cyclosporine dose may not be needed when metoclopramide is coadministered orally to prevent common adverse effects of cyclosporine. Powdered whole grapefruit has the potential to reduce the required orally administered dose of cyclosporine but only when PWG is used in an amount (at least 10 g) that is currently not cost-effective.

Generalized Microsporum canis dermatophytosis in six Yorkshire terrier dogs.

Six Yorkshire terrier dogs with generalized, chronic dermatophytosis caused by Microsporum canis were seen over a 3-year period. Specific tests showed that they also had concurrent leishmaniosis (four cases), leishmaniosis and ehrlichiosis (one case) or diabetes mellitus (one case). Although specific therapy for these infectious diseases was instituted and the dogs were treated systemically and topically with appropriate antifungal drugs, only partial clinical resolution of the dermatophytosis was achieved. M. canis infection resolved in the dog with diabetes mellitus after stabilizing the diabetes mellitus. Although immunological studies were not performed in these cases, it is theorized that the immune disregulation caused by leishmaniosis, ehrlichiosis or diabetes mellitus may have favoured generalization of the infection and prevented favourable responses to appropriate treatment of the M. canis infection.

Review cutaneous lesions of the canine scrotum.

Scrotal lesions are uncommon and often present a diagnostic challenge. In the veterinary literature there are no texts devoted to this subject. This study reviews and illustrates canine scrotal lesions following an aetiological layout with the aim of facilitating clinical identification and diagnosis. Infectious, immune-mediated, endocrinological and neoplastic conditions are the most commonly reported causes of scrotal lesions in the dog. They may affect the scrotum only or other parts of the body as well. The clinical presentation of the lesions, the presence of primary or secondary lesions and the presence of clinical signs of systemic disease may help in obtaining a diagnosis. In some cases further investigations are necessary to reach a definitive diagnosis. Histopathology aids in understanding pathological reactions of the scrotal skin but unfortunately this is not commonly carried out and few reports in the literature include histopathology. The list of conditions given in this review is not exhaustive and other, more rare, diseases may be encountered.

Treatment of canine Alopecia X with trilostane.

Sixteen Pomeranians and eight miniature poodles presenting with clinical signs of alopecia X, elevated blood concentrations of 17-hydroxyprogesterone post stimulation with adrenocorticotropic hormone and increased urinary cortisol/creatinine ratios were treated with trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Trilostane was given once or twice daily at a mean dose of 10.85 mg kg(-1) day(-1). Adrenal function was evaluated with a follow-up of 28 months in the Pomeranians and 33 months in the miniature poodles. Treatment with trilostane led to complete hair re-growth in 85% of the Pomeranians and in all of the miniature poodles within 4 to 8 weeks. No adverse events attributed to treatment with trilostane were recognized. The hair re-growth might have been the result of a down-regulation of adrenal steroids and/or of the noncompetitive inhibition of the oestrogen receptors at the hair follicle level.