Compared kinetics of plasma creatine kinase activity in rabbits after intravenous injection of different preparations of skeletal muscle.

The purpose of this study was to compare the disposition parameters of creatine kinase (CK) in rabbits after intravenous bolus administration of 3 CK preparations: 1) purified CK; 2) CK obtained from a muscular extract after a 3,000 g centrifugation (ie with cell remains) (3,000 g CK); or 3) a 105,000 g centrifugation (ie the cytosolic soluble phase) (105,000 g CK). The plasma half-lives were not significantly different (approximately 9 h). In contrast, the clearance of 3,000 g CK (3.25 +/- 0.33 ml.kg-1.h-1) was significantly lower than that of the 2 others (7.00 +/- 0.49 ml.kg-1.h-1 and 4.63 +/- 0.65 ml.kg-1.h-1 for 105,000 g and purified CK, respectively). These findings suggest that purified CK preparation is not the most appropriate form for determination of enzyme pharmacokinetic parameters following muscle damage.

Variations of plasma creatine kinase in rabbits following repetitive blood sampling effects of pretreatment with acepromazine, carazolol and dantrolene.

Plasma creatine kinase activity increased significantly (P less than 0.001) in rabbits sampled every two hours for 12 hours (mean from 509 to 2242 U/l), but did not change when rabbits had been accustomed to laboratory handling procedures for two weeks. This increase was not alleviated or only moderately by pretreatment with acepromazine (per os, 2.5 mg.kg-1), carazolol (intravenously, 0.05 mg.kg-1) or dantrolene (intravenously, 1.0 mg.kg-1). Thus, when using plasma creatine kinase in rabbits, e.g. to test muscle damage or local tolerance of drugs, animals should be made familiar with laboratory procedures before any experiment.

Measurement of alpha-amylase activity in cat plasma: test of specificity of a chromogenic substrate, reference values.

Glucoamylase activity can interfere with the measurement of alpha-amylase activity in cat plasma. This can be avoided by the use of "blocked" substrates such as 4,6-O-benzylidene-4-nitrophenyl-alpha-D-maltoheptaoside. In 241 healthy cats, reference values were 586 +/- 241 U/L (m +/- standard deviation) at 30 degrees C; age, sex, overnight fasting, and mild hemolysis had no significant effect.

[Covalent fixation in vivo of trenbolone acetate and estradiol to hepatic DNA of the rat: comparative study of the fixation of tritiated molecules and post labeling with radiophosphorus]. / Fixation covalente in vivo de la trenbolone et de l'estradiol à l'ADN hépatique de rat: étude comparative de la fixation de molécules tritiées et du postmarquage au radiophosphore.

In vivo covalent binding of trenbolone and estradiol was assayed using either radiolabeled compounds or 32P-post labeling. The covalent binding index, as measured with tritiated molecules, was 2.4 for the alpha isomer of trenbolone, 5.4 for its beta isomer and 5.4 for 17-beta estradiol. Using 32P-post labeling at repeated medium doses or a single high dose did not allow any of the 3 compounds to reveal specific adducts in the background of adducts spontaneously formed in control animals. It can therefore be concluded that these steroids most probably do not have a direct genotoxic action.

[Anabolics and French legislation: history and the present]. / Anabolisants et législation française: historique et actualité.

In 1975, the French law on veterinary drug products was adopted. In 1976, the Ceyrac law prohibited the use of oestrogens. After various scandals, Parliament voted unanimously in favour of the "Rocard" law in 1984. This law defined the use of anabolics very strictly. In 1985, the EEC decided to ban anabolics. This ban has resulted in the illegal use of many kinds of substances, a situation which is difficult to control. This has exposed public health to risk, and has perturbed commercial rules and regulations within the EEC countries.

Determination of plasma alpha-amylase in the dog: a test of the specificity of new methods.

Commercially available chromogenic substrates for the assay of alpha-amylase were tested for specificity in dog plasma. Blocked alpha-4-nitrophenylmaltoheptaoside and non-blocked beta-4-nitrophenylmaltoheptaoside showed no interference with glucoamylase and were suitable for the measurement of alpha-amylase in dog plasma. In contrast, an alpha-4-nitrophenylmaltoheptaoside showed interference, and was therefore an inappropriate substrate. Reference values with the blocked substrate in a group of 82 non-selected 3 month- to 10 year-old male and female dogs were 355 +/- 131 U/l (mean +/- standard deviation) at 30 degrees C.

Hematological and plasma biochemical disturbances in experimental molybdenum toxicosis in sheep.

Two groups of 4 sheep received a daily iv injection of sodium heptamolybdate (100mg/day) or of saline for 2 weeks to study the hematological and plasma biochemical effects of molybdenum toxicosis. In molybdenum-dosed sheep, there was hypercupremia, mild anemia due to the decrease of copper concentration in the liver and moderate hepatocellular damage probably due to a direct toxic effect of molybdenum against the liver.

Fate and residues of trenbolone acetate in edible tissues from sheep amd calves implanted with tritium-labeled trenbolone acetate.

In order to study the fate and residues of trenbolone acetate in edible tissues, two groups of six animals from two ruminant species (ewes and calves) were implanted with [3H]trenbolone acetate. The distribution of extractable radioactive residues was measured in liver, kidney and muscle. We found that the largest proportion of residues was not extractable and thus was considered as covalently bound residues. The proportion of the main extractable metabolites (17 alpha-trenbolone, trendione, 17 beta-trenbolone) was measured. The evaluation of the distribution of trenbolone acetate metabolites directly soluble in water showed that unknown metabolite(s) were predominant. The covalent binding to nucleic acids was measured. It was so low that it was not detectable. The results are discussed in light of the data presented in the scientific report on anabolic agents in animal production from the European scientific working group.

In vivo covalent binding of 17-alpha-OH- and 17-beta-OH- trenbolone to rat liver DNA.

In vivo covalent binding to rat liver DNA was assayed with 2 major metabolites of trenbolone, alpha-OH-trenbolone (alpha-TB) and beta-OH-trenbolone (beta-TB), in male Sprague-Dawley rats. DNA purified by ultracentrifugation in cesium trifluoroacetate showed protein contamination less than 0.4% of DNA by weight. The mean results obtained for the covalent binding indexes were 2.4 +/- 0.3 for alpha-TB and 5.3 +/- 2 for beta-TB. The covalent binding of alpha-TB was linear as a function of dose, which was not the case for beta-TB. The higher affinity of beta-trenbolone for DNA contaminating proteins was not sufficient to explain the difference. When these results are compared with the genotoxicity tests already performed with trenbolone by several authors (almost all completely negative), it may be concluded that the very low levels of binding could not be regarded as responsible for a direct genotoxic action of trenbolone.

[Distribution of alanine and aspartate aminotransferases, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatases and creatine kinase in the main organs of adult goats and kids]. / Distribution de l'alanine et de l'aspartate aminotransférases, de la gamma-glutamyl transférase, de la lactate deshydrogénase, des phosphatases alcalines et de la créatine kinase dans les principaux organes de chèvres adultes et de chevreaux.

In adult ewes, the distribution of enzymes in the liver, kidney, spleen, pancreas, muscle, lung and myocardium was very similar to that in cows or sheep: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), lactate dehydrogenase (LDH) and creatine kinase (CK) were mainly in skeletal muscles and the myocardium, while gamma-glutamyl transferase (GGT) and alkaline phosphatases (PAL) predominated in the kidneys. Age-related changes of tissue enzyme patterns were dominated by a dramatic decrease of liver ALAT in adults whereas this enzyme was liver-specific in one month old animals; a decrease of muscle LDH and CK, and an increase of kidney GGT and ALP were also observed in adults.

Routine hematology and clinical chemistry in female dogs with benign and malignant mammary tumors.

Routine hematological and serum biochemical screening was done in 61 female dogs with benign mammary tumors and 51 female dogs with malignant mammary tumors. Most parameters were not significantly different from age-matched female controls; moreover, no significant difference could be observed between animals with benign and malignant tumors. It is concluded that routine hematology and biochemistry offer little diagnostic or prognostic benefit in female dogs with mammary tumors.

[Biochemical semiology of the liver in ruminants]. / Sémiologie biochimique du foie chez les ruminants.

Many different serum biochemical tests can help in the diagnosis of liver disturbances in ruminants. The best tests for hepato-cellular damage are the measurement of enzymes such as glutamate dehydrogenase, sorbitol dehydrogenase and, if available, arginase or ornithine carbamoyl transferase. Disturbances of biliary function can be investigated through the measurement of so-called "cholestasis enzyme markers" such as gammaglutamyl transferase or alkaline phosphatases; bilirubin and bile salts can also be helpful. Liver insufficiency can be approached through the measurement of serum albumin, fibrinogen and coagulation tests whereas inflammative and inductive processes are difficult to investigate. Moreover, liver clearances (bromosulfonephtalein or indocyanine green) can provide useful data about whole liver function.

Experimental acute sodium fluoride poisoning in sheep: renal, hepatic, and metabolic effects.

Sheep received a single intragastric dose of 0.5, 1.0, 1.5, or 2.0 mmol F-/kg. Mild signs occurred at 1.5 mmol F-/kg and the animals recovered 2 days later. With the 2.0 mmol F-/kg dose all animals showed dullness, anorexia, and mild diarrhea which decreased from the third day. Dose-related congestion of duodenum, liver, kidney, and lung was observed in all animals. For the two higher doses kidney degeneration and tubular necrosis were associated with glomerular inflammation. Serum fluoride had a dose-related increase and was still significantly elevated on Day 7 for sheep given doses higher than or equal to 1.0 mmol F-/kg. Serum calcium and glucose levels were significantly lowered for all doses on the first day and the decrease was dose-related. In sheep given 2.0 mmol F-/kg total proteins and sodium were significantly lowered, whereas potassium and urea were increased (p less than 0.05); alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were both lowered (p less than 0.01) on the first day and ALP was still lowered on Day 7. For the highest dose glutamate dehydrogenase (GDH) was increased on Days 1 and 7 and gamma-glutamyl transferase (GGT) was increased on Day 1 and lowered on Day 7. Diuresis was increased for the two higher doses in Day 3 or 4 following dosage. A dose-related increase of daily fluoride excretion occurred for all doses on Day 1 and fluoride excretion was still significantly elevated on Day 7 except for the lowest dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Application of whole-body autoradiography in toxicology.

Whole-body autoradiography enables the drugs and toxicants to be distributed throughout the animal. Good results are obtained with this technique. However, certain artifacts can occur that could lead to misinterpretation, and these must be known. These artifacts are described. From the metabolic point of view, autoradiography provides data on the distribution kinetics of a compound and the elimination of radioactivity in various organs. These data are a guide for quantitative research into the metabolism of a compound. From the toxicological point of view, it must be admitted that the main purpose of this technique is to reveal the sites of retention of radioactivity. Such specific organ retention could be the consequence of the activation of a minor metabolite into a very reactive compound. If this is so, it is a specific organ effect which could not be studied by other techniques and could lead the way to a more specific organ effect which could not be studied by other techniques and could lead the way to a more appropriate line of research in the study of chronic toxicity. However, it must be recalled that the fact that a compound is retained by a specific organ does not always mean that the compound exerts a toxic effect upon the said organ. With this technique, distribution study can be performed on pregnant animals, and it provides us with more data concerning the transplacental passage of radioactive metabolites. All these aspects of the technique clearly indicate that whole-body autoradiography should be insisted upon during the early stages of development of new molecules. Successive experiments could then lead to selecting the best experimental conditions for metabolic pharmacokinetics and studies in toxicology.

Enzyme patterns of the organs of the goose. Effects of fattening on liver enzymes.

The distribution of some enzymes in the organs of the goose was investigated: Creatine-kinase was specific for muscles, Glutamate Dehydrogenase for liver and Gamma-Glutamyl Transferase for pancreas and liver. The production of fatty liver induced an important dilution of liver enzymes except for Lactate Dehydrogenase which was only moderately lowered. This latter enzyme is probably one of the most interesting markers of liver disturbances while fattening is occurring.