OBJCTIVE To investigate the effects of dietary lipid overload on bile acid metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES In a crossover study, dogs were fed a high-fat–high-cholesterol diet (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout period, dogs were fed the other diet for 2 weeks. Before and at the end of each feeding period, the concentrations of each of the gallbladder bile acids, cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism–related hepatic gene expression were examined in all dogs. RESULTS The HFCD significantly increased plasma total cholesterol concentrations. The HFCD also increased the concentration of taurochenodeoxycholic acid and decreased the concentration of taurocholic acid in bile and reduced gallbladder contractility, whereas the LFD significantly decreased the concentration of taurodeoxycholic acid in bile. Gene expression analysis revealed significant elevation of cholesterol 7α-hydroxylase mRNA expression after feeding the HFCD for 2 weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder bile acid composition and gallbladder motility in dogs. In particular, feeding the HFCD caused an increase in plasma total cholesterol concentration, an increase of hydrophobic bile acid concentration in bile, and a decrease in gallbladder sensitivity to CCK. These results suggested that similar bile acid compositional changes and gallbladder hypomotility might be evident in dogs with hyperlipidemia.

Objective-To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. Animals-6 adult horses. Procedures-Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. Results-Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microgram/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. Conclusions and Clinical Relevance-Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration less than or equal to 1 microgram/mL. Because of the possible nonlinearity of this drug as well as the potential for accumulation, chronic dosing studies and clinical trials are needed to determine the appropriate dosing regimen for voriconazole in horses.

Cell surface hydrophobicity of Mycoplasma hyopneumoniae was evaluated by phase partitioning in a hydro-carbon-aqueous mixture, by hydrophobic interaction chromatography, and by salting out with ammonium sulfate. Results obtained by use of these techniques gave evidence that the cell surface of M hyopneumoniae is weakly hydrophobic, compared with strongly hydrophobic Staphylococcus aureus Cowan I and hydrophilic Klebsiella pneumoniae. After treatment of the organisms with trypsin, M hyopneumoniae became less hydrophobic as measured by hydrophobic interaction chromatography. Significant changes in hydrophobicity were not seen after periodate treatment. Electron microscopy of M hyopneumoniae treated with polycationic ferritin revealed an intermediate, compact, unlabeled layer between the cytoplasmic membrane and an external, heavily labeled layer. Electron microscopy of ferritin-labeled M hyopneumoniae after treatment with trypsin or periodate revealed the intermediate layer to be composed of a trypsin-sensitive protein(s). The outer layer was made of periodate-sensitive carbohydrate(s). Therefore, it appears that proteins in the intermediate layer confer at least part of the total hydrophobicity of the mycoplasmal cell and may contribute to adherence of M hyopneumoniae to target respiratory cells by hydrophobic interactions.

Objective—To investigate the effects of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs. Animals—6 placebo-treated control dogs and 6 hydrocortisone-treated dogs. Procedures—Dogs received hydrocortisone (median dose, 8.5 mg/kg) or a gelatin capsule (control group) orally every 12 hours for 84 days. Gallbladder bile samples were obtained via percutaneous ultrasound-guided cholecystocentesis from each dog before (day 0 [baseline]), during (days 28, 56, and 84), and after (days 28p, 56p, and 84p) treatment for differentiated quantification of unconjugated bile acids and taurine-conjugated and glycine-conjugated bile acids via high-performance liquid chromatography–tandem mass spectrometry. Results—Treatment with hydrocortisone for 84 days resulted in significant and reversible increases in the concentrations of unconjugated bile acids (ie, cholic, chenodeoxycholic, and deoxycholic acids) and a significant and reversible decrease in the concentration of total taurine-conjugated bile acids, compared with baseline or control group values. Treatment with hydrocortisone had no effect on bile concentrations of glycine-conjugated bile acids. Conclusions and Clinical Relevance—In dogs, hydrocortisone administration caused reversible shifts toward higher concentrations of the more hydrophobic unconjugated bile acids (chenodeoxycholic acid and deoxycholic acid) and toward lower concentrations of the amphipathic taurine-conjugated bile acids in gallbladder bile. These data suggest that similar bile acids changes could cause major alterations in gallbladder structure or function over time in hypercortisolemic dogs.