Idiosyncratic adverse drug reactions (IADRs) occur in a small subset of patients, are unrelated to the pharmacological action of the drug, and occur without an obvious relationship to dose or duration of drug exposure. The liver is often the target of these reactions. Why they occur is unknown. One possibility is that episodic inflammatory stress interacts with the drug to precipitate a toxic response. We set out to determine if lipopolysaccharide (LPS) renders mice sensitive to trovafloxacin (TVX), a fluoroquinolone antibiotic linked to idiosyncratic hepatotoxicity in humans and if the cytokine tumor necrosis factor-alpha (TNFalpha) is involved in the development of liver injury. Male mice were treated with a nontoxic dose of TVX followed 3 h later by a nonhepatotoxic dose of LPS. Coexposure to TVX and LPS led to a significant increase in liver injury as determined by plasma alanine aminotransferase activity and histopathological examination. In contrast, coexposure of mice to LPS and levofloxacin (LVX), a fluoroquinolone without liability for causing IADRs in humans, was not hepatotoxic. Measurements of TNFalpha concentration in the plasma revealed a significant, selective increase in TVX/LPS-treated mice at times prior to and at the onset of liver injury. Treatment with either pentoxifylline to inhibit TNFalpha transcription or etanercept to inhibit TNFalpha activity significantly reduced TVX/LPS-induced liver injury. The results suggest that the model in mice is able to distinguish between drugs with and without the propensity to cause idiosyncratic liver injury and that the hepatotoxicity is dependent on TNFalpha.

Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

BackgroundUrinary disorders in cats often require subjective caregiver quantification of clinical signs to establish a diagnosis and monitor therapeutic outcomes.ObjectiveTo investigate use of a video recording system (VRS) to better assess and quantify urination behaviors in cats.AnimalsEleven healthy cats and 8 cats with disorders potentially associated with abnormal urination patterns.MethodsProspective study design. Litter box urination behaviors were quantified with a VRS for 14 days and compared to daily caregiver observations. Video recordings were analyzed by a behavior analysis software program.ResultsThe mean number of urinations per day detected by VRS (2.5 ± 0.7) was significantly higher compared with caregiver observations (0.6 ± 0.6; P < .0001). Five cats were never observed in the litter box by their caregivers. The mean number of urinations per day detected by VRS was significantly higher for abnormal cats (2.9 ± 0.7) compared with healthy cats (2.1 ± 0.7; P = .02); there were no apparent differences in frequency between these groups reported by caregivers (0.7 ± 1.0 and 0.5 ± 1.0, respectively). There were no differences in mean urination time between healthy and abnormal cats as determined by VRS or caregivers. Mean cover‐up time determined by VRS was significantly longer in healthy cats (22.7 ± 12.9 seconds/urination) compared with abnormal cats (8.7 ± 12.9 seconds/urination; P = .03); differences in cover‐up time were not detected by caregivers.Conclusions and Clinical ImportanceCaregivers commonly underestimate urination frequency in cats when compared to video‐based observations. Video recording appears to facilitate objective assessment of urination behaviors and could be of value in future clinical studies of urinary disorders in cats.

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