Consistency and efficacy of two methods of intranasal oxytocin application in dogs.

Over the last few years, oxytocin (OT) administration to investigate the role of the oxytocinergic system in the social behavior of dogs has become of more and more interest. To date, the most common OT administration method for dogs is the intranasal spray commonly used for humans. Due to the different nasal conformation of dogs and the unpleasantness of the procedure, most dogs need to be restrained to allow administration. This has 2 main drawbacks-it may hinder reliable administration, which might lead to tremendous variance in the uptake of OT across individuals and it is likely to be stressful for the dogs. Alternatively, a vaporizer mask can be used to administer aerolized OT and dogs can be trained to voluntarily enter the mask, which might enable a more reliable administration without having to restrain the dogs. The aim of this study was to compare the efficacy of these 2 methods to identify a reliable non-invasive method for exogenous OT administration, thereby assisting future research on the role of OT in canines. We administered OT to pet dogs using either an intranasal spray bottle or a vaporizer mask and assessed urinary OT concentrations as a measure of OT uptake. We found that only when administered using a vaporizer mask, OT significantly increased in all subjects, while using a spray bottle led to considerable variance in OT uptake and an inconsistent increase in urinary OT concentrations across individuals. These results suggest that using a vaporizer mask should be preferred over using an intranasal spray bottle for OT administration in dogs. If not available, experimenters should at least monitor OT uptake after administration using spray bottles, to evaluate the success of the method.

Vitamin E supplementation decreases basal levels of F(2)-isoprostanes and prostaglandin f(2alpha) in rats.

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. We investigated the effects of supplementation with vitamin E on lipid peroxidation in rats. Both free radical-induced nonenzymatic- and cyclooxygenase-catalyzed enzymatic lipid peroxidation were investigated by measuring the levels of F(2)-isoprostanes (8-iso-PGF(2alpha)) and PGF(2alpha)-metabolite (15-K-DH-PGF(2alpha)), respectively, in blood, urine and liver. Samples were collected from control rats (n = 6) and from rats supplemented with vitamin E in the diet for 3 wk (n = 8, 20 g/kg diet of DL-alpha-tocopherol hydrogen succinate). Plasma alpha-tocopherol concentration and antioxidative capacity were greater in the vitamin E-supplemented rats than in the control rats (17.9 +/- 1.7 vs. 50.4 +/- 10.4 micromol/L, P < 0.001 and 181 +/- 6 vs. 275 +/- 27 micromol/L trolox equivalents, P < 0.001). Urine 8-iso-PGF(2alpha) tended to be lower in the vitamin E-supplemented rats (0.72 +/- 0.40 vs. 0.34 +/- 0.19 nmol/mmol creatinine, P = 0.056). Urine 15-K-DH-PGF(2alpha) was lower due to vitamin E supplementation (0.97 +/- 0.38 vs. 0.56 +/- 0. 21 nmol/mmol creatinine, P < 0.05), as was liver-free 8-iso-PGF(2alpha) concentration (0.47 +/- 0.11 vs. 0.18 +/- 0.04 nmol/g, P < 0.001). Supplementation with vitamin E did not affect plasma 8-iso-PGF(2alpha) or 15-K-DH-PGF(2alpha) concentrations, liver total 8-iso-PGF(2alpha) or plasma malondialdehyde levels. Thus, vitamin E supplementation reduced urine basal levels of biomarkers of both nonenzymatic and enzymatic lipid peroxidation. In liver, vitamin E reduced the basal level of free 8-iso-PGF(2alpha) but not total 8-iso-PGF(2alpha).

Assessment of individual CYP2D6 activity in extensive metabolizers with renal failure: comparison of sparteine and dextromethorphan.

OBJECTIVES: To examine whether the variability of CYP2D6 activity in patients with chronic renal failure can be assessed, particularly among subjects with the extensive metabolizer phenotype, by use of standard in vivo indexes of CYP2D6 activity derived from oral administration of dextromethorphan and sparteine. METHODS: A single 100 mg oral dose of sparteine and a single 40 mg oral dose of dextromethorphan were administered on two occasions to 12 patients with chronic renal failure (creatinine clearance ranging from 20 to 70 ml/min) and 12 age- and sex-matched healthy subjects. Sparteine clearances, sparteine metabolic ratio, and urinary recovery of dextrorphan were calculated. Patients and healthy control subjects were not selected on the basis of their CYP2D6 phenotypes. RESULTS: Chronic renal failure was associated with a decrease in sparteine partial metabolic clearance to dehydrosparteine (median of 322 ml/min and range of 62 to 670 ml/min in patients with renal failure versus median of 635 ml/min and range of 77 to 1276 ml/min in normal subjects; p < 0.02). Sparteine apparent oral clearance (p < 0.03) and renal clearance (p < 0.001) decreased in patients with renal failure. However, sparteine metabolic ratio was not significantly altered in patients with renal failure and showed that all patients were extensive metabolizers of sparteine. Although fractional urinary excretion of dextrorphan decreased in patients with renal failure (median, 24.4%; range, 9.7% to 55.9%) compared with control (median, 47.5%; range, 24.1% to 72.1%) (p = 0.02), it also showed that all subjects were extensive metabolizers of dextromethorphan. The amount of dextromethorphan excreted in urine correlated with creatinine clearance independently from CYP2D6 activity measured as sparteine partial metabolic clearance. However, it did not correlate with sparteine metabolic ratio or with fractional urinary excretion of dehydrosparteine. CONCLUSION: Assessment of CYP2D6 activity by use of dextromethorphan and sparteine is possible in extensive metabolizer patients with chronic renal failure. However, in these subjects, dextromethorphan and sparteine do not reflect CYP2D6 activity in the same way.

Oxidative phenotype polymorphism (P450 2D6) and metabolism of toluene.

Oxidative phenotype P-450 2D6 was examined using sparteine test in 3 groups of persons to determine if there is a coincidence in the defect of the oxidative biotransformation of sparteine and impaired oxidation of toluene, which could explain interindividual differences in the amounts of hippuric acid in the urine in exposed persons. The following groups of persons were examined: 30 rotogravure printers exposed to toluene vapors at concentrations of 8-307 ppm; 20 workers, 2 months after the cessation of the long-term exposure to toluene at concentrations of 104-1,170 ppm; 48 healthy volunteers with no exposure to toluene. Among the 98 persons 5 poor metabolizers (PMs) of sparteine were found, none in the group of printers exposed to toluene. In the experimental exposure chamber 5 PMs and 6 extensive metabolizers (EMs) were exposed to toluene concentration of 245 ppm for 5 hours. Hippuric acid and o-cresol in the urine, and toluene both in blood and in alveolar air were measured. However, no significant differences were found in either of these parameters between the PM and EM groups. Thus, the sparteine test does not appear to be applicable in the identification of persons with higher risk arising from toluene exposure.