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G Meyniel

Publications and source records attributed to G Meyniel.

82 records · Page 5Linked to original sources
PubMedDate not supplied

Metabolic disposition of 2-chloroethyl nitrosocarbamoylcystamine in rats.

The disposition and the metabolism of 2-chloroethyl nitrosocarbamoylcystamine (CNCC), a new antitumor agent, has been studied in rats. For this purpose, three separate labeled species of CNCC have been used. The tissue distribution and the elimination of the radioactivity were determined in animals after gavage with a single dose of each labeled species of CNCC (35 mumol/kg). It was observed, after analysis of plasma taken at timed intervals after administration, that little radioactivity co-chromatographed with the parent compound. These data suggest that CNCC undergoes an important first-pass metabolism, but chromatographic analysis provided evidence for the formation of four main metabolites. These biotransformation products were isolated from pooled plasma extracts of rats treated with 200 mumol/kg of unlabeled CNCC. They were identified by the combined use of mass spectrometry and chromatographic properties. These metabolites are sulfinyl and sulfonyl derivatives arising from the bioreduction of the disulfur bridge of CNCC with subsequent methylation and oxidation. These compounds are potentially active cytostatic agents. The evaluation of their antitumor activity is currently under investigation.

Animals↗
PubMedDate not supplied

Metabolism of 2-chloroethyl nitrosocarbamoylcystamine by rat liver subcellular fractions.

Previously we have shown that a new nitrosourea, 2-chloroethyl nitrosocarbamoylcystamine (CNCC), undergoes an extensive metabolism in the rat. Two pairs of plasma metabolites have been identified. This suggested our hypothesis that the metabolic pathway involves the reduction of the disulfur bridge followed by the methylation and the oxidation of the thiol groups. The two first intermediates, i.e. the unoxidized metabolites, could not be detected in vivo. Hence, to better understand and to confirm the proposed mechanism of biotransformation of CNCC, its in vitro metabolism has been studied. Incubation of CNCC with a rat liver homogenate or a 10,000g supernatant fraction leads to the formation of four pairs of metabolites. Among them we have identified the two first intermediates not found in vivo and the oxidized metabolites. These findings, together with the kinetics data, suggest that reduction, methylation, and oxidation are very rapid enzymatic reactions. We also show that, for completion of the reaction, the incubation mixture had to contain a cytosolic thioreductase, a microsomal and cytosolic S-methyltransferase, a microsomal oxidase, and an NADPH generating system. The sum of the amounts of metabolites found in the organic extratable material is less than the amount of CNCC metabolized. We conclude that the biotransformation of CNCC proceeds from two fast competitive mechanisms operative on both the disulfur and the nitroso groups.

Animals↗
PubMedDate not supplied

Main metabolites of 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats.

The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified.

Animals↗
PubMedDate not supplied

[Physiological exploration of the eustachian tube using labeled compounds. Applications in the control of treatment (author's transl)].

Sequential scintigraphy enables the qualitative and quantitative study of the drainage function of the Eustachian tube. Use is made of serum albumin labeled with technetium 99 m. After reviewing the various methods employed in an exploration of the functions of the Eustachian tube, and in particular the drainage function, the writers explain the method in detail (indicator, detection system, examination procedure, normal scintigraphic aspects) while stressing the control factors (onset of passage, speed and intensity of passage, length of time for the appearance of a trace on the pharynx, eventual aspects of blocking) and giving the basic characteristics; persistant spotting of the drum, transient image of the tube, partial stoppage at the ostium, and traces along the pharynx. The role of swallowing and the position of the head appear to be essential. Results obtained in various disorders of the middle ear, accessory cavities, the tube and the cavum are given in the form of tables. The writers then indicate the principal merits of the method: demonstration of the pathological role of the Eustachian tube in a work-up of transmission deafness, with its impact on treatment, the role of a deficient drainage function in surgical failures, and control of the efficacy of treatment, in particular crenotherapy. A study of the drainage function of the Eustachian tube, as a complement to the function of equalizing pressure, in an essential factor in formulating indications and in establishing the prognosis for tympanoplasties.

Adolescent↗