Oral administration of voriconazole with surgical fungal plaque debridement for the treatment of sinonasal aspergillosis with cribriform plate lysis in three dogs.

CASE DESCRIPTION: 3 dogs with chronic sinonasal signs (sneezing, nasal discharge, or epistaxis [or a combination of signs]) were examined. CLINICAL FINDINGS: For all 3 dogs, CT revealed variable degrees of nasal turbinate destruction and frontal sinus involvement with cribriform plate lysis. Fungal plaques were detected during rhinoscopy or sinusoscopy. Results of fungal culture (2 dogs) or cytologic examination of a plaque specimen (1 dog) supported a diagnosis of sinonasal aspergillosis. TREATMENT AND OUTCOME: All dogs underwent surgical rhinotomy or sinusotomy (or both) for fungal plaque debridement followed by oral treatment with voriconazole and periodic physical examinations, clinicopathologic analyses, and assessments of serum drug concentrations for a period ≥ 22 weeks. All dogs had considerable to complete reduction of their clinical signs and tolerated voriconazole treatment with minimal adverse effects. Adverse effects included development of reversible neurotoxicosis (associated with high serum voriconazole concentration) and mildly high serum liver enzyme activities. The dosage of voriconazole administered to achieve therapeutic serum concentrations (2.5 to 3.3 mg/kg [1.1 to 1.5 mg/lb], PO, q 12 h) was substantially lower than dosages suggested by previously published studies in dogs. The 3 dogs remained clinically normal or had mild clinical signs after voriconazole discontinuation for follow-up times of 6 to 15 months. CLINICAL RELEVANCE: Findings in these 3 dogs indicated that surgical fungal plaque debridement followed by oral treatment with voriconazole may be an effective treatment option for dogs with sinonasal aspergillosis and cribriform plate lysis. Further evaluation of this treatment regimen with repeated CT examinations and longer follow-up times is warranted.

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

BACKGROUND: Oxidative stress is associated with a diverse group of liver disorders across species. OBJECTIVES: Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8-isoprostanes/creatinine (F2 -IsoPs/Cr) concentrations, correlate with liver GSH. ANIMALS: Thirty-four client-owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs. METHODS: Prospective, observational cross-sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2 -IsoPs/Cr was measured by gas chromatography/mass spectrometry. RESULTS: All dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2 -IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2 -IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.