Effect of repeated oral administration of hypertonic electrolyte solution on equine gastric mucosa.

REASONS FOR PERFORMING STUDY: Electrolyte supplementation is common in horses during endurance competitions, but the effect on the gastric mucosa is unknown. HYPOTHESIS: Repeated oral administration of hypertonic electrolyte solution is associated with exacerbation of gastric ulcers in mature horses. METHODS: The study design was a randomised, blinded, crossover trial. Fourteen horses were divided randomly into equal groups and administered either 60 ml water (placebo) or 56.7 g commercial electrolyte supplement mixed with 60 ml water by dose syringe orally once an hour for 8 h. The minimum concentration of individual constituent electrolytes/28.35 g dry commercial product used was: sodium (5528 mg); chloride (11,886 mg); potassium (3657 mg); calcium (754 mg); and magnesium (153 mg). Gastric lesions were scored prior to and after oral treatments, and analysis of variance procedures were then performed. RESULTS: Administration of hypertonic electrolytes resulted in a significant increase in mean ulcer number (P = 0.0174) and severity (P = 0.0006) scores in the nonglandular stomach. Mean ulcer number score was 3.6 and mean ulcer severity score 2.7 after hypertonic electrolyte treatment. CONCLUSIONS: Oral hypertonic electrolyte administration to horses in this model was associated with exacerbation of gastric ulcers. POTENTIAL RELEVANCE: Our findings suggest that one schedule of electrolyte supplementation used commonly in endurance horses may be harmful to the gastric mucosa.

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals.

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.

Prenatal diazepam exposure in rats: long-lasting functional changes in the offspring.

Adult (90-100 day-old) rats exposed prenatally (13-20 days of gestation) to diazepam (DZ) at 1.0, 2.5, or 10 mg/kg/day, were examined for functional deficits. Tests were designed to (1) correlate with known neural alterations induced by the prenatal exposure, or (2) to address the problem of developing tests of functional teratology in animals which have relevance to complex human functions. The careful selection of functional tests has disclosed several effects of prenatal DZ exposure on adult rat progeny. The dose-effect relationship was found to vary with the different tests, indicating that a thorough evaluation of the consequences of prenatal drug exposure necessitates utilization of several functional approaches. The results of these studies on the effects of prenatal exposure to DZ support the hypothesis that in utero exposure to drugs targeted for action on the central nervous system can induce long-lasting alterations on the neural substrates of behavior on the offspring with resulting functional consequences.

Prenatal exposure to diazepam alters central and peripheral responses to stress in adult rat offspring.

Central and peripheral responses to restraint stress were evaluated in 90-day-old rats exposed prenatally to diazepam (1.0, 2.5, or 10.0 mg/kg/day) over gestational days 13-20. As a measure of a central response to stress, the utilization of norepinephrine (NE) by hypothalamic NE neurons was assessed by determining the effect of stress on the loss of NE after synthesis inhibition. The stress-induced changes in plasma corticosterone and prolactin levels were evaluated as a physiologic index of stress. While stress increased the loss of NE after synthesis inhibition in the non-exposed control animals, it totally prevented any loss of NE after synthesis inhibition in offspring prenatally exposed to DZ. Additionally, the stress-induced change in plasma corticosterone was attenuated in a dose-related manner by prenatal exposure to DZ. The stress-induced change in plasma prolactin was also altered in a dose-related manner by the prenatal exposure. Both the altered response to stress within hypothalamic NE neurons and the attenuated change in plasma corticosterone induced by prenatal exposure to DZ (2.5 mg/kg) were prevented by concurrent administration of the centrally acting benzodiazepine antagonist Ro15-1788 to the pregnant dam, indicating that the effects of DZ were mediated via binding of the drug to central sites during gestation. These results indicate that activation of specific binding sites during early development can induce neural alterations in the adult offspring which can be reflected in functional changes which may compromise the organism.

Prenatal diazepam exposure in rats: long-lasting, receptor-mediated effects on hypothalamic norepinephrine-containing neurons.

The concentration and turnover of catecholamines (CAs) were measured in the cortex, hippocampus, and hypothalamus of rats exposed in utero to diazepam (DZ, 1.0, 2.5, or 10.0 mg/kg/day) over gestational days 13-20. Prenatal DZ induced a regionally specific, dose-related decrease in the level of norepinephrine (NE) (maximum decrease, 65%) and turnover rate of NE (maximum decrease, 85%) in the hypothalamus of 90-day-old adult rats. Dopamine levels were not altered in this region and neither of the CAs were altered in the other regions. Dividing the prenatal exposure period into two shorter periods revealed that late gestation (days 17-20) was the period when factors influencing NE function in the hypothalamus were most sensitive to DZ. Analysis of the development of the CA in the hypothalamus demonstrated that the effect of the prenatal exposure on NE levels did not become apparent until after 28 days of age. However, at 28 days, there was a dose-related increase in turnover rate of NE (maximum increase, 52%). Concurrent administration of the specific benzodiazepine (BZ) antagonist RO15-1788 with DZ (2.5 mg/kg) to pregnant rats effectively reversed the effects of DZ in the hypothalamus of the adult offspring, suggesting that the effects were mediated via the BZ receptor. These data have provided insight into the intricate processes of neuronal development; in particular the importance of target cell-nerve terminal interactions and the role of early developing receptors.