Case report: First isolation of Exophiala dermatitidis from subcutaneous phaeohyphomycosis in a cat.

Phaeohyphomycosis, which is caused by the opportunistic black yeast-like fungus Exophiala dermatitidis, has been reported in humans and dogs. However, no previous studies describing E. dermatitidis infections in cats have been published. Herein, we report a case of subcutaneous phaeohyphomycosis caused by E. dermatitidis. A 12-year-old, castrated male Japanese domestic short-haired cat presented with a solitary subcutaneous abscess on the left side of the neck, where an esophageal tube for force-feeding had been placed previously. The cat was diagnosed with hepatitis and was treated with prednisolone. The subcutaneous abscess was incised using a scalpel blade and the pus was excreted. The cytology of the pus revealed hyphae with neutrophil and macrophage infiltration. Although the cat was treated with oral itraconazole or an infusion of topical ketoconazole cream applied to the lesion, it died. The fungal culture of the pus specimen developed dark-green, waxy, smooth, yeast-like colonies. Sequencing of the internal transcribed spacer 1-4 regions of the ribosomal DNA of the pus specimen showed 100% identity with that of the standard strains of E. dermatitidis. Based on these results, the cat was diagnosed with subcutaneous phaeohyphomycosis caused by E. dermatitidis. The antifungal susceptibility test revealed that the fungus showed low or moderate susceptibility to the antifungal drugs examined, except for amphotericin B, which exhibited high in vitro antifungal activity. This is the first case report to provide definitive evidence of E. dermatitidis infection in cats and antifungal susceptibility test results against clinically isolated E. dermatitidis.

Toceranib phosphate and firocoxib-mediated partial response in a dog with advanced intranasal sarcoma.

A nine-year-old, castrated male mixed-breed dog presented with a three-month history of sneezing and stertorous breathing. Computed tomography revealed a soft tissue mass in the left nasal cavity with lysis of the cribriform plate. The mass was diagnosed as intranasal sarcoma based on histopathological analysis. The tumor cells were immunohistochemically positive for KIT and platelet-derived growth factor receptor α/ß and negative for vascular endothelial growth factor receptor 2 and cyclooxygenase-2. Treatment with toceranib phosphate (TOC) and firocoxib reduced the tumor size, which was defined as partial response (PR). After PR induction, TOC alone mediated survival for 205 days. This case report suggests that the combination of TOC and possibly firocoxib may be a therapeutic option for canine intranasal sarcoma.

Expression of genes encoding interleukin 15 and its receptor subunits in the duodenal and colonic mucosae of dogs with chronic enteropathy.

A pro-inflammatory role of interleukin (IL)-15 and IL-15 receptor (R) in chronic intestinal inflammation, such as inflammatory bowel disease, has been reported in humans. However, the contribution of IL-15 signaling in the pathogenesis of canine chronic enteropathy (CE) remains unclear. Therefore, as a first step in elucidating the importance of IL-15 signaling in canine CE, we measured the mRNA expression of IL-15 and IL-15R subunits, including IL-15Rα, IL-15Rß, and IL-15Rγ, in the duodenal and colonic mucosae of healthy dogs and those with CE, including food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE). Real-time PCR analysis revealed significantly lower IL-15Rα mRNA expression levels in the duodenal mucosa of dogs with IRE compared to healthy dogs. In contrast, the mRNA expression levels of IL-15, IL-15Rß, and IL-15Rγ in the duodenal mucosa and IL-15, IL-15Rα, IL-15Rß, and IL-15Rγ in the colonic mucosa did not differ among healthy dogs and those with FRE, ARE, or IRE. These findings suggest that decreased mRNA expression of IL-15Rα might be involved in the pathogenesis of duodenitis in dogs with IRE. Moreover, even in canine CE, IL-15 signaling appears to play different roles in duodenitis and colitis in dogs with FRE, ARE, and IRE. However, there were no correlations between the gene expression levels of IL-15Rα and clinical severity or histopathological scores in the duodenum of dogs with IRE. Further studies are necessary to investigate the IL-15Rα protein localization and to determine how impaired IL-15Rα expression contributes to the development of duodenitis in dogs with IRE.

Clinical characteristics of dogs presenting with vomiting as a gastrointestinal sign of chronic enteropathy.

Vomiting is a major gastrointestinal (GI) sign of chronic enteropathy (CE) in dogs. Previous studies have reported clinical characteristics of dogs with CE, who developed diarrhea with or without vomiting as GI signs. However, to characterize clinical features of dogs with CE appropriately, dogs presenting with vomiting without diarrhea should be included in the analysis. Thus, this study aimed to characterize clinical features and outcomes of dogs that presented with vomiting without diarrhea. Based on their presenting GI signs, we retrospectively classified 66 dogs with CE into "Vomiting", "Diarrhea", or "Vomiting and diarrhea" groups and compared clinical and histological characteristics of each group. We found that 18 of the 66 dogs with CE (27%) presented with vomiting without diarrhea as a GI sign. Compared to the other 2 groups, the Vomiting group was significantly associated with food-responsive enteropathy (FRE), Beagle, lower clinical severity scores, higher plasma albumin levels, and higher histological scores for eosinophils in the duodenal lamina propria according to the univariate analysis. The multivariate analysis revealed that FRE and higher histological scores for eosinophils in the duodenal lamina propria were significant variables in the Vomiting group. Moreover, the survival time was the longest in the Vomiting group among dogs with CE. These findings are of clinical significance as they indicate that presenting with vomiting without diarrhea may not only be helpful in differentiating FRE from the other types of CE, but also in predicting the prognosis.

Presence of the house dust mite allergen in the gastrointestinal tract of dogs with chronic enteropathy: A potential inducer of interleukin-1ß.

House dust mite (HDM) is an environmental allergen ubiquitously present indoors, causing allergic inflammation in dogs. However, it is unclear whether HDM allergens can be detected in the gastrointestinal (GI) tract of dogs. In addition, although expression of interleukin (IL)-1ß is increased in the intestinal mucosa of dogs with chronic enteropathy (CE), the role of HDM allergens in the production of IL-1ß has not been evaluated. The objectives of this study were to determine the presence of HDM allergens in the GI tract of dogs and to elucidate the effect of HDM on IL-1ß expression in canine macrophages. HDM allergen, Dermatophagoides pteronyssinus (Der p) 1, was quantified in the gastric and duodenal fluids and the duodenal and colonic mucosae of dogs with CE and healthy laboratory dogs, and faeces of dogs with CE, healthy laboratory dogs and healthy client-owned dogs. Gene expression and protein levels of IL-1ß were measured in HDM-stimulated canine peripheral macrophages from healthy laboratory dogs. Der p 1 was detected in the gastric and duodenal fluids of dogs with CE and healthy laboratory dogs, and faeces of all dogs examined. Der p 1 levels in the duodenal and colonic mucosae were significantly higher in dogs with CE than in healthy laboratory dogs. HDM increased both gene expression and protein levels of IL-1ß in canine macrophages. These findings demonstrate the presence of HDM allergens in the GI tract of dogs and the possible involvement of HDM allergens in the pathogenesis of CE by promoting IL-1ß expression in macrophages.

Effect of interleukin-1ß on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease.

BACKGROUND: Mucosal imbalance of interleukin (IL)-1ß and IL-1 receptor antagonist (Ra) has been reported in the duodenal mucosa of dogs with inflammatory bowel disease (IBD). However, the imbalance in the colonic mucosa and its role in duodenitis and colitis in IBD of dogs remain unclear. OBJECTIVES: To measure the expression of IL-1ß and IL-1Ra proteins in the colonic mucosa of dogs with IBD, and to determine the effect of IL-1ß on expression of occludin (ocln) mRNA, a tight junction component, in the duodenal and colonic mucosa of dogs with IBD. ANIMALS: Twelve dogs with IBD and 6 healthy dogs. METHODS: IL-1ß and IL-1 Ra proteins in the colonic mucosa were quantified by ELISA in 7 of the 12 dogs with IBD. Expression of ocln mRNA in the duodenal and colonic mucosa was examined in the 12 dogs by real-time PCR. RESULTS: The ratio of IL-1ß to IL-1Ra in the colonic mucosa was significantly higher in dogs with IBD than in healthy dogs. The ex vivo experiment determined that IL-1ß suppressed expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, of healthy dogs. Expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, was significantly lower in dogs with IBD than in healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A relative increase in IL-1ß may attenuate ocln expression, leading to intestinal barrier dysfunction and promotion of intestinal inflammation in the colonic mucosa, but not in the duodenal mucosa, of dogs with IBD.

Influence of glucocorticoids on time-of-day-dependent variations in IgE-, histamine-, and platelet-activating factor-mediated systemic anaphylaxis in different mouse strains.

A time-of-day-dependent variation in IgE-mediated passive systemic anaphylaxis was previously reported in ICR mice. In the present study, we investigated time-of-day-dependent variations in IgE-, histamine-, and platelet-activating factor (PAF)-mediated systemic anaphylaxis in C57BL/6, BALB/c, and NC/Nga mice at 9:00 h and 21:00 h, and evaluated the potential influence of glucocorticoids (GCs) on these variations. We found significant time-of-day-dependent variations in IgE-mediated systemic anaphylaxis in C57BL/6 mice, and in histamine- and PAF-mediated systemic anaphylaxis in BALB/c mice. Significant daily variations in IgE-, histamine-, and PAF-mediated systemic anaphylaxis were not observed in NC/Nga mice. Pretreatment with dexamethasone and adrenalectomy abolished the daily variations in IgE-mediated systemic anaphylaxis in C57BL/6 mice and in PAF-mediated systemic anaphylaxis in BALB/c mice, suggesting that GCs from adrenal glands are pivotal in regulating these variations. In contrast, pretreatment with dexamethasone and adrenalectomy did not abolish the daily variation in histamine-mediated systemic anaphylaxis in BALB/c mice, suggesting that GC-independent and adrenal gland-independent mechanisms are important for the variation. The present study demonstrated that time-of-day-dependent variations in systemic anaphylaxis differed among inbred mouse strains and with anaphylaxis-inducing substances. Thus, mouse strains, time of experiment, and anaphylaxis-inducing substances used must be considered to obtain appropriate experimental results.

Clinical and pathological features and outcome of bilateral incidental adrenocortical carcinomas in a dog.

A 9-year-old, spayed female Chihuahua was presented with a 1-week history of lethargy and anorexia. Abdominal ultrasonography and computed tomography found bilateral adrenal masses without metastasis. Serum cortisol levels that were sampled before and after an adrenocorticotropic hormone stimulation test were within reference ranges. Lethargy and anorexia completely resolved after short-term fluid therapy; the clinical signs did not occur for approximately 8 months until her sudden death. A postmortem examination revealed bilateral adrenocortical carcinomas and liver metastasis. Primary adrenocortical carcinomas developed in the dog met the definition of bilateral incidental adrenal gland masses (IAGMs). This is the first case report to demonstrate based on histological identification that adrenocortical carcinomas cause bilateral IAGMs in dogs.

Expression of epithelial cell-derived cytokine genes in the duodenal and colonic mucosae of dogs with chronic enteropathy.

It remains unclear whether epithelial cell-derived cytokines, including interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), contribute to development of canine chronic enteropathy (CE), which includes antibiotic-responsive enteropathy (ARE), food-responsive enteropathy (FRE) and inflammatory bowel disease (IBD). In the present study, we examined mRNA expression of il-25, il-33 and tslp in the duodenal and colonic mucosae of dogs with ARE, FRE and IBD. Real-time PCR analysis revealed that mRNA expression of il-33 was significantly lower in the duodenum in dogs with FRE than in healthy dogs. The results suggest that epithelial cell-derived cytokines may not be an inducer of Th2-type immunity in the gut of dogs with CE, and decreased expression of IL-33 may be involved in induction of FRE. Further studies are required to clarify roles of epithelial cell-derived cytokines, especially IL-33, in the pathogenesis of canine CE.

Characterization of platelet-activating factor-induced cutaneous edema and erythema in dogs.

OBJECTIVE To characterize platelet-activating factor (PAF)-induced edema and erythema in the skin of dogs and compare those reactions with histamine-induced cutaneous reactions. ANIMALS 6 healthy Beagles. PROCEDURES Experiments were performed at ≥ 2-week intervals. Each dog received ID injections (5 µg/site) of PAF C16, PAF C18, lyso-PAF, and histamine. Edema (mean diameter) and erythema scores (none, mild, moderate, or severe) were assessed 30 minutes after the injections. Dogs received ID injections of PAF and histamine each with various concentrations of WEB 2086 (PAF receptor antagonist) or underwent ID testing with PAF and histamine before and 3 hours after oral administration of cetirizine hydrochloride or prednisolone (at 2 doses each). RESULTS ID injections of PAF C16 and PAF C18, but not lyso-PAF, induced comparable levels of edema and erythema. The PAF-induced edema and erythema peaked at 30 minutes and lasted for 6 hours after the injection; histamine-induced edema and erythema peaked at 30 minutes and lasted for 3 hours after the injection. Edema sizes and erythema scores were significantly smaller and lower, respectively, for PAF than for histamine. The WEB 2086 inhibited PAF-induced but not histamine-induced edema and erythema. Cetirizine slightly, but significantly, repressed PAF-induced edema and erythema as well as histamine-induced cutaneous reactions. Prednisolone suppressed both PAF-induced and histamine-induced edema and erythema. CONCLUSIONS AND CLINICAL RELEVANCE In canine skin, the duration of PAF-induced inflammation was longer than that of histamine-induced inflammation. The PAF- and histamine-induced cutaneous reactions were effectively suppressed by oral administration of prednisolone. The importance of PAF in dogs with anaphylaxis and allergic disorders warrants further investigation.

Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs.

The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of-day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs.