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Ampicillin administered to rabbits (20 mg/kg per day) over a period of three days subsequently provoked a death rate of 40%. No deaths were observed after treatment with gentamycin (10 mg/kg per day) or with a combination of ampicillin and gentamycin. On the fourth day weight loss in the three treated groups was 12%, 11% and 9%, respectively, compared to controls. At the same time food intake in the treated groups was only 15% to 20% of the amount consumed by controls. In the caecum, ampicillin treatment resulted in dominance of a strain of Enterobacter aerogenes. Gentamycin had no effect on bacterial flora, although in combination with ampicillin, the number of caecal bacteria (aerobic and anaerobic) was reduced. Flora modification might be responsible for accumulation of NH3 and an unbalance of free acids. Caecotrophy was inhibited by administration of ampicillin. When administered intramuscularly, ampicillin produced results comparable with those obtained orally, although gentamycin was ineffective.

Minocycline administered to rabbits per os or intramuscularly (30 mg/kg) over a period of three days led neither to digestive problems nor mortality. Administration per os left the growth curve unchanged. Intramuscular administration reduced rate of growth, and on the 15th day weight loss compared to controls was 3.2% or 11.7% depending on whether the place of administration was in the back muscles or in the thigh, and this despite a normal food intake. Minocycline did not modify microbial flora and level of ammonia in the caecum. Level of acetic acid was reduced by 50% on the fourth and 15th day after intramuscular administration of minocycline into the thigh. The depressive effect of minocycline on growth remains unexplained.

In order to assess drug renal kinetics in vivo, the two kidneys of seven ewes were surgically placed under the skin. Through the use of renal function tests and a series of biopsies, we found that the kidneys remained normal in their subcutaneous location. Gentamicin renal kinetics were evaluated in conscious animals by a series of biopsies. Histological controls showed only slight lesions due to biopsy; based upon plasma hydrocortisone concentration, there was no indication of chronic stress affecting the renal pharmacokinetics. We suggest that this model has great potential as a method for studying in vivo the kinetics of drug disposition in the renal tissue and assessing the residue level of a drug.

The purpose of this investigation was to determine the effects of a subclinical fascioliasis at various stages of its development (by week--4, 8, 12, and 16 weeks after the infestation by an oral administration of 150 metacercariae of Fasciola hepatica) on the activity of some hepatic drug-metabolizing systems in lamb. The parasitic pathology was ascertained at autopsy and by clinical observation of animals. Hepatic microsomal cytochrome P-450 content was significantly decreased (by 9-22%) in all infected groups of animals. In early stages of the parasitic disease, decreases in cytochrome b5 content (10-18%) and ethoxycoumarin O-deethylase (25%) were observed, whereas aminopyrine N-demethylase, benzphetamine N-demethylase, and aniline hydroxylase were significantly lowered by 8 to 16 weeks postinfection. Among investigated transferases, glutathione transferase was only decreased (28%) in animals killed 16 weeks after the infestation; in these animals a significant increase in microsomal gamma-glutamyltransferase was observed, probably related to the elevated plasma activity of this enzyme. By 8 weeks postinfection, a simultaneous increase in cytosolic calcium (38%) and decrease in cytosolic glutathione (22%) would correspond to an oxidative cell injury occurring in the course of fascioliasis. The consequences of the fascioliasis-induced decreases in liver-oxidative and conjugative liver drug metabolism are discussed.

1. The comparative distribution of cytochrome P-450 monooxygenase system, glucuronyltransferase, glutathione S-transferase and N-acetyltransferase was studied in the liver, lung and kidney of young male sheep. 2. The sheep liver was characterized by a lack in glutathione S-transferase activity with isoniazid as substrate. 3. The oxidative drug metabolizing enzymes of lung were generally close to those of liver; benzphetamine N-demethylase and ethoxycoumarin O-deethylase were even found to be higher in lung (213 and 148%, respectively). 4. Pulmonary conjugative and both renal oxidative and conjugative systems accounted only for 9-38% of hepatic corresponding enzymes. 5. The enzyme determination in various sampling sites of the three organs, demonstrated the homogeneous distribution of all investigated monooxygenases and transferases in liver, lung and kidney of sheep.

The growth of Byssochlamys nivea and P. granulatum was reduced by ochratoxin A (1 ppm, 10 ppm), whereas Aspergillus ochraceus growth and toxinogenesis were not affected by 1 and 10 ppm of patulin. When Penicillium granulatum and Asperigillus ochraceus were placed in the same medium the former grew and produced its toxin and ochratoxin production by the latter was weakened. Since patulin and ochratoxin can be found in the same substrate; the toxinogenic significance of in vitro strains is questionned.

0,1 and 1,9 p. 100 of French corn samples harvested in 1973 and 1974 contain respectively 4 to 42 ppb aflatoxin and 15 to 200 ppb ochratoxin A. Because the dilution of this product in the feed, such amounts could not be considered causing acute or chronic mycotoxicosis. In case of corn contamination by ochratoxin A, the analysis of technologic parameters conclude to question the drying corn with ears in cribs and the delayed drying after the reception of corn in storage corporation.