Retrospective evaluation of hypersensitivity reactions and anaphylaxis in dogs (2003-2014): 86 cases.

OBJECTIVE: To characterize anaphylactic reactions in dogs, including clinical signs, severity, treatments, prognosis, and estimated incidence. To determine whether glucocorticoids influence clinical recovery and survival. DESIGN: Retrospective study between January 1, 2003 and April 28, 2014. SETTING: University teaching hospital. ANIMALS: Eighty-six dogs treated for a type I hypersensitivity reaction. Nineteen dogs fulfilled the criteria for anaphylaxis, and 67 dogs had mild cutaneous reactions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The estimated incidence was 0.04% for anaphylaxis and 0.15% for mild hypersensitivity reactions. The female:male ratio (2.3:1) was significantly higher (P = 0.032) compared to our source population (ratio of 1:1.158). Vaccines were the most frequent trigger for anaphylaxis (57.9%) and mild hypersensitivity reactions (28.4%). Seventy-four (86%) dogs had cutaneous signs, and 11 (57.9%) dogs with anaphylaxis had no cutaneous signs reported. Forty-two (48.8%) dogs received both an H1 antagonist and a glucocorticoid, 34 (39.5%) dogs received an H1 antagonist only, and 6 (6.9%) dogs received a glucocorticoid only. The majority of the dogs survived, and 1 was euthanized due to complications. Clinical signs associated with nonsurvival included respiratory signs (P = 0.006), particularly respiratory distress (P < 0.00001) and cyanosis (P < 0.00001), and circulatory shock (P = 0.005). The analysis of the interaction between etiology, clinical signs, treatment, and outcome did not show any association between pairs of variables. CONCLUSIONS: In the current study, anaphylaxis had a relatively good prognosis, and cutaneous signs were not always present. Based on the present data, the use of glucocorticoids to treat mild type I hypersensitivity reactions and anaphylaxis in dogs was not associated with clinical improvement or survival.

The effect of 'allergenic' and 'nonallergenic' antibiotics on dog keratinocyte viability in vitro.

BACKGROUND: Immune-mediated adverse drug reactions (drug hypersensitivity) are relatively common in veterinary medicine, but their pathogenesis is not well understood. For an unknown reason, delayed drug hypersensitivity often targets the skin. Antibiotics, especially ß-lactams and sulfonamides, are commonly associated with these adverse events. The 'danger theory' hypothesizes that 'danger' signals, such as drug-induced cell death, might be part of the pathogenesis of drug hypersensitivity reactions. HYPOTHESIS/OBJECTIVES: The goal of this study was to determine whether antibiotics that are commonly associated with cutaneous drug hypersensitivity (allergenic) decrease canine keratinocyte viability in vitro more than antibiotics that rarely cause such reactions (nonallergenic). METHODS: Immortalized canine keratinocytes (CPEK cells) were exposed to a therapeutic range of drug concentrations of four 'allergenic' antibiotics (two ß-lactams, i.e. amoxicillin and cefalexin, and two sulfonamides, i.e. sulfamethoxazole and sulfadimethoxine) or two 'nonallergenic' antibiotics (enrofloxacin and amikacin) over 48 h (2, 4, 8, 24 and 48 h). The reactive nitroso metabolite of sulfamethoxazole was also tested. RESULTS: Cefalexin (2 mmol/L) significantly decreased cell viability after 48 h (28 ± 7%; P = 0.035). The nitroso metabolite of sulfamethoxazole (100 µmol/L) decreased cell viability after 2 h (21 ± 7%; P = 0.049), but cell numbers were increased after 8 h (22 ± 6%; P = 0.018). In addition, enrofloxacin (500 µmol/L) also significantly decreased cell viability by 37% (±6%; P = 0.0035) at 24 h and by 70% (±8%; P < 0.001) at 48 h. CONCLUSION: It appears that the effect of drugs on the in vitro viability of dog keratinocytes is not a good predictor of the 'allergenic' potential of an antibiotic. Further work is required to investigate other drug-induced 'danger' signals in dog keratinocytes exposed to 'allergenic' antibiotics in vitro.

Mono-(2-ethylhexyl)-phthalate (MEHP) affects ERK-dependent GDNF signalling in mouse stem-progenitor spermatogonia.

Many commercial and household products such as lubricants, cosmetics, plastics, and paint contain phthalates, in particular bis-(2-ethyhexyl)-phthalate (DEHP). As a consequence, phthalates have been found in a number of locations and foods (streambeds, household dust, bottled water and dairy products). Epidemiological and animal studies analysing phthalate exposure in males provide evidence of degradation in sperm quality, associated to an increase in the incidence of genital birth defects and testicular cancers. In the testis, spermatogenesis is maintained throughout life by a small number of spermatogonial stem cells (SSCs) that self-renew or differentiate to produce adequate numbers of spermatozoa. Disruption or alteration of SSC self-renewal induce decreased sperm count and sperm quality, or may potentially lead to testicular cancer. GDNF, or glial cell-line-derived neurotrophic factor, is a growth factor that is essential for the self-renewal of SSCs and continuous spermatogenesis. In the present study, the SSC-derived cell line C18-4 was used as a model for preliminary assessment of the effects of mono-(2-ethylhexyl)-phthalate (MEHP, main metabolite of DEHP) on spermatogonial stem cells. Our data demonstrate that MEHP disrupts one of the known GDNF signalling pathways in these cells. MEHP induced a decrease of C18-4 cell viability in a time- and dose-dependent manner, as well as a disruption of ERK1/2 activation but not of SRC signalling. As a result, we observed a decrease of expression of the transcription factor FOS, which is downstream of the GDNF/ERK1/2 axis in these cells. Taken together, our data suggest that MEHP exposure affects SSC proliferation through inhibition of specific signalling molecules.