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V Burgat-Sacaze

Publications and source records attributed to V Burgat-Sacaze.

At least 19 recordsLinked to original sources

[Covalently bound residues: theoretical aspects].

Covalently bound residues (CBRs) result from the covalent binding of the parent drug or its metabolites to endogenous macromolecules. They are not extractable from the tissues by exhaustive extraction, denaturation and solubilization techniques, and are not the result of endogenous incorporation. They can be detected in the non-extractable radioactivity which persists in tissues after administration of radiolabeled drugs. The characteristics of CBRs are discussed. Covalent binding is an association of a reactive metabolite (electrophile or free radicals) and endogenous molecules (proteins, lipids). This chemical reaction is non-specific and irreversible. Even if the covalent bond is cleaved, the compound released will not be the highly reactive intermediate metabolite. The covalently bound metabolites can have a potential toxic effect in the target species but they probably represent low toxicity for consumers. Pharmacokinetic analyses of CBRs have demonstrated their specific properties: 1) they make up the largest fraction of late residues, and 2) their bioavailability is low. Several examples are given to support these concepts.

Animals↗

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.

Animals↗

Protection against mercuric chloride nephrotoxicity by cold exposure in rats.

The influence of cold exposure (+ 1 degree C for 24 h) was studied in rats dosed i.p. with 0, 2.5 or 5.0 mumol HgCl2/kg. Cold exposure of controls caused an increased diuresis and solute elimination, except sodium, with almost no variations in urine alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT). Proximal tubule brush border damage was demonstrated by a marked increase in ALP and GGT in HgCl2-dose animals at room temperature. Cold exposure protected against this kidney damage.

Animals↗

Acute kidney disturbances by lead acetate in the rat.

Four groups of 5 male and 5 female rats were dosed i.p. with 0, 0.05, 0.15 and 0.30 mmol Pb2+/kg as neutral acetate. A minimal kidney damage shown by an increased urinary GGt was only observed in males at the highest dose. In all animals and for all doses natriuria was significantly decreased on the first day (from the 4th hour). Such disturbances evoke mild tubular disturbances but glomerular disturbances may also be involved.

Animals↗

[Allergenic residues of veterinary drugs in food (author's transl)].

Residues of veterinary drugs can be found in human food and be involved in allergic untoward reactions in consumers. The current french law on veterinary pharmacy allows to control this risk. Therefore, to evaluate this risk the following topics are considered: 1) origin of food contamination by allergenic compounds and characteristics of residues, 2) effects of these residues. Observations demonstrate that residues may elicit clinical reactions in sensitized individuals; on the contrary, an sensitizing effect is probably minor in pratice.

Anaphylaxis↗

Comparison of sodium and stannous fluoride nephrotoxicity.

Single i.p. injections of 0.5 mmol F-/kg and repeated i.p. injections of 0.25 mmol F-/kg as NaF or SnF2 to male rats showed that both compounds produced early lesions of kidney tubule demonstrated by an intense increase of urine gamma-glutamyl transferase (GGT). Disturbance of kidney function with an increase of diuresis and phosphaturia and a decrease of natriuria and kaliuria were more marked in SnF2-treated animals as was the decrease of urine GGT after a few days. These results indicate that tin nephrotoxicity adds to that of fluoride and antagonizes tubule regeneration.

Animals↗

[Gamma glutamyl transferase and cancer (author's transl)].

Attention has been drawn in recent years to the diagnostic interest offered by increases in serum gamma GT in the detection of liver metastases and various cancers in man. Although this analysis is not specific and presents a few false positive and negative results, it seems however profitable to include it either in detection or in supervision tests. Furthermore, in the rat and mouse, this enzyme practically absent from the adult liver, reappears during liver cancer Whatever the cause: this onco-foetal character may be useful to exploit in studies of experimental carcinogenesis, but does not seem to be a valid model for the increases observed in man.

Animals↗

[Conditions of methemoglobine dosage in veterinary toxicology (author's transl)].

Evolution of the percentage of methemoglobine in blood was studied to find a method of conserving samples. It is recommended that blood be frozen rapidly after sampling due to instability of the compound, and that this low temperature be maintained until analysis. Other processes have a limited effectiveness, namely dilutions in aqueous solution of NaCl (7%) or in phosphate buffer (pH 6.5) with hemolysis (saponine) and keeping at +4 degrees C.

Animals↗

Bound residues of veterinary drugs: bioavailability and toxicological implications.

Basic considerations dealing with the biological significance of drug residues and safety evaluation are studied. The specific problem of covalently bound residues is considered from three different points of view. (1) Analytical characteristics clearly distinguish between soluble residues, which deplete relatively fast, and bound material which is slowly eliminated from edible tissues of target animals. (2) These two residual fractions have not the same bioavailability. (3) Finally, toxicity assessment of bound residues is considered.

Animals↗

Methoxyethylmercury nephrotoxicity: effects on enzymuria and kidney function.

The fungicide, methoxyethylmercury chloride, was given in a saline solution to four groups of Sprague-Dawley C D rats (5 male, 5 female) as a single injection (IP) of 0, 0.5, 1.0, and 2.0 mg Hg/kg. In a three-day period, no changes were observed in urine collected every 24 h from rats given 0 or 0.5 mg Hg/kg; 1 mg Hg/kg induced only a transient increase of urine gamma glutamyl transferase (x 4) and alkaline phsophatase (x 2.5) on the day 2; 2.0 mg Hg/kg caused an early increase of enzymuria (day 1 and day 2) and a decrease of Na+, Cl-, K+, urea, and creatinin excretion. Urine enzymes and total mercury excretion were higher in males. These time-related variations of enzymuria, compared to previous results with Hg Cl2, could reflect the existence of metabolites more toxic than the native compound.

Alkaline Phosphatase↗

Acute kidney toxicity of sodium fluoride in the rat.

Single i.p injection of 0, 0.05, 0.10, 0.25, 0.50 and 1.00 mmol NaF/kg to male rats induced a dose-related increase of urine gamma-glutamyl transferase (GGT) elimination on the first day for all doses higher or equal to 0.25 mmol NaF/kg. Kidney damage began between 2--4 h following the injection and lasted only 12 h for the 0.50 mmol NaF/kg dose. There was an increase of diuresis and of phosphaturia even at lower doses.

Animals↗

[Elaboration of an in vivo model, in half life size, for aeronautical purposes].

Toxic effects of combustion products originating from plane cabin constituents are studied, in vivo, in Rats. The model associates an important combustion room, and an experience room containing eight revolving cages for Rats; these cages allow a remote control of the movements of the Rats which can be electrically stimulated and ejected. Such a device permits to study the incapacitance, i.e. the inability to move. For the combustion of a seat, without ventilation, incapacitation appears in 2 to 6 min. Biochemical screening demonstrates on increase of pCO2, carboxyhemoglobin and glycemia and a decrease of pO2.

Animals↗