Search PubMed⌕ Search

Biomedical subjects

G Descotes

Publications and source records attributed to G Descotes.

At least 19 recordsLinked to original sources
PubMed2000

Sucrose tricarboxylate by sonocatalysed TEMPO-mediated oxidation.

Oxidation of sucrose by the NaOCl/TEMPO system provided sucrose tricarboxylate without the addition of sodium bromide as co-catalyst when high-frequency (500 kHz) ultrasound was applied, in contrast to very limited conversion without sonication. In the presence of sodium bromide, sonication also caused acceleration of the oxidation. The rate increase due to sonication of the oxidant system prior to sucrose addition suggests that ultrasound acts at the level of the formation of the nitrosonium ion, the active oxidising species in the catalytic cycle.

Antioxidants↗
PubMed2000

Ultrasound in carbohydrate chemistry: sonophysical glucose oligomerisation and sonocatalysed sucrose oxidation.

Both aspects of the interest in using ultrasound are illustrated by our results in the field of carbohydrate chemistry. The course of the heterogeneous reaction of glucose with hydrophobic alcohols in acidic medium is directed towards the oligomerisation of glucose because of the wetting of the glucose suspension due to the efficiency of the sonophysical mixing. On the other hand, a sonocatalysis is observed during the course of the oxidation of primary hydroxyl groups in homogeneous aqueous medium by the NaOCl/TEMPO system.

Journal Article↗
PubMed1999

An improved synthesis of an umbelliferyl 5-thioxylopyranoside, precursor of the antithrombotic drug Iliparcil.

4-Ethyl-2-oxo-2H-1-benzopyran-7-yl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, a synthetic intermediate of the orally active antithrombotic compound Iliparcil, has been prepared in 44-47% isolated yield. Different conditions were used for the glycosylation of 4-ethyl-2H-7-hydroxy-1-benzopyran-2-one 6 applying 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide (2), the analogous beta-chloride 3 or the alpha-trichloroacetimidate 5 as donors. With halides 2 and 3, the reaction was carried out in the presence of ZnO-ZnCl2 or ZnO alone. Both promoters are cheap, safe and therefore compatible with large-scale industrial processes.

Benzopyrans↗
PubMed1996

Extension of the 4-week safety study for detecting immune system impairment appears not necessary: example of cyclosporin A in rats.

A 4-week study was conducted to shed light on the question of whether compounds impairing immune homeostasis may escape the standard safety testing. Wistar rats were orally treated with cyclosporin A at dosages of 0 (control: olive oil), 1, 5 or 25 mg/kg/day. Ten rats/sex/group (study segment 1) were not immunized while six other rats/sex/group (study segment 2) were immunized 4 days before killing to perform a plaque forming cell (PFC) assay. All rats were subjected to routine safety evaluations (OECD guideline 407) and determination of IgM and IgG serum levels. Other immune parameters were evaluated using cells from spleen and mesenteric lymph nodes (segment 1). Effects on safety parameters were similar for immunized and non-immunized rats. A slight decrease of body weight gain (males, 25 mg/kg) accompanied slight clinical chemical and histomorphologic evidence of renal tubulotoxicity. Changes in safety parameters indicative of immune system alterations were: increased thymic corticomedullary ratio (> or = 5 mg/kg) and 25 mg/kg) minimal lymphopenia, low thymus weight, thymic cortical lymphocytolysis and low lymphoid cellularity of spleen and lymph nodes. They were associated with (males at > or = 1 mg/kg) dose-related decreases of T-cell receptor+ and CD4+ cells and increases of CD8+ cells, and decreased PFC (> or = 5 mg/kg) and lymphoproliferative responses to mitogens and alloantigens (25 mg/kg). There were no changes in natural killer activity. The conventional assay identified the drug as a potential immunomodulator. Specific immune assays (phenotyping, PFC) improved the threshold of detection. These results did not support the incorporation of specific immune tests in the standard 4-week study protocol.

Administration, Oral↗
PubMed1996

Induction of liver cytochrome P-450 (CYP) 3A in male and female rats by a steroidal androgen receptor antagonist, zanoterone.

The cytochrome P-450 (CYP) mediated hydroxylation of testosterone to 6 beta-, 7 alpha-, and 16 alpha-hydroxytestosterone (b beta-, 7 alpha-, and 16 alpha-OHT) and the dealkylation of ethoxycoumarin to 7-hydroxycoumarin (ECOD) and ethoxyresorufin to resorufin (EROD) were used to probe changes in CYP monooxygenase activities in liver microsomes from rats treated with the androgen receptor antagonist, zanoterone (Z). Phenobarbital (PB) and beta-naphthoflavone (beta-NF) were used as comparators. There were sex-related differences in the constitutive CYP activities and in the responses of CYP activities to Z. The greatest effect of Z administration was on 6 beta-OHT activity: It was increased up to 5.2-fold in males and 13.9-fold in females (Z high dose). The effect was larger than the produced by PB or beta-NF (< or = threefold increases). Z (high dose), PB, and beta-NF increased ECOD to a similar extent, e.g., about 1.3-fold in males and 1.2-2.9-fold in females. beta-NF increased EROD (11.2-fold males, 6.2-fold females) more than PB (3.4- to 4.6-fold) or Z (1.3- to 1.7-fold). Since hydroxylation of testosterone at the 6 beta position in rats and humans is catalyzed primarily by CYP isoforms from the 3A subfamily, the increase in 6 beta-OHT suggests that Z induced CYP 3A activity. These findings were confirmed with Western immunoblots with probes for rat CYP 1A1, 2B1/2, 2E1, 3A, and 4A. Z produced a three-to fourfold increase in the 3A isoform for both male and female rats. Results from this study suggest that in a clinical setting, Z therapy has the potential to induce CYPs of the 3A subfamily and in so doing alter the metabolism and clearance of drugs that are substrates for the 3A subfamily.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1996

Functional, biochemical, and morphological hepatobiliary effects in rats chronically exposed to a steroidal antiandrogen.

Yellow-brown deposits in intrahepatic bile ducts and portal macrophages were observed for male, but not female, Sprague- Dawley rats fed zanoterone, a steroidal antiandrogen, for >=3 months. The lesion did not affect biliary canaliculi and was associated with changes of biliary epithelium, portal chronic inflammation, and bile duct proliferation. Deposit formation was assumed to be related to a gender-related anomaly in bile composition and/or flow. Therefore, the pathogenesis of the lesion was investigated in male, female, and orchiectomized rat. Hepatobiliary structure and function were evaluated after 3 months of treatment and 3 months of reversibility. Drug biliary disposition was evaluated at 3 months. Sulfobromophthalein clearance, bile flow, and plasma concentration and biliary excretion rate of cholesterol were increased at the end of the treatment phase without significant sex-related differences. These effects are consistent with the hepatic enzyme induction potential of the drug, were accompanied by perivenous hepatocellular hypertrophy and increased liver weights, and were no longer observed at the end of the recovery phase. Histomorphologic evidence of cholestasis was observed for most intact and orchiectomized males, the lesion being slightly less pronounced for the latter. Deposits were present at the end of the recovery phase, but were confined to macrophages in all but one case. The lesion differed from a protoporphyria, or precipitates of bile pigments, cholesterol, or proteins. The drug was extensively metabolized with major gender-related differences. Glucuronides of a 16- hydroxy- and another unidentified metabolite were the major metabolites found in bile of males, while a 15-hydroxy-glucuronide was the major metabolite for females. The concentration and biliary excretion of the 16-hydroxy- glucuronide markedly increased after chronic exposure. A possible explanation for pigment deposition in males is that the drug is converted to a metabolite(s) which is excreted at a rate beyond the solubilization potential of bile and, therefore, precipitates in bile ducts.

Androgen Antagonists↗
PubMed1993

Nephrotoxicity of pravadoline maleate (WIN 48098-6) in dogs: evidence of maleic acid-induced acute tubular necrosis.

Single oral administration of pravadoline maleate (WIN 48098-6), the maleic acid salt of WIN 48098, induced acute tubular necrosis (ATN) in male and female beagle dogs at dosages > or = 40 mg/kg (WIN 48098 base (31 mg/kg) and maleic acid (9 mg/kg)). Subsequent oral studies were conducted with equimolar dosages of maleic acid and WIN 48098-7, the ethanesulfonate salt of WIN 48098, to determine the nephrotoxic moiety of WIN 48098-6. ATN was observed for dogs given only maleic acid at single oral dosages > or = 9 mg/kg. This result provided evidence that maleic acid was responsible for the nephrotoxicity observed in dogs given single oral dosages of WIN 48098-6. The induction of maleic acid-related nephrotoxicity in dogs may confound the interpretation of toxicologic studies of maleic acid salts of basic pharmaceutics, if the dosage of test article results in the delivery of dosages of maleic acid > or = 9 mg/kg. Furthermore, the results of these studies underscore the importance of establishing maximum no-observed-effect dosages and target organ toxicity profiles for acids and bases that are commonly used in the development of salts of pharmaceutics.

Animals↗
PubMed1990

[Periodate oxidation of sucrose derivatives].

The periodate oxidation of some derivatives of sucrose at primary positions is generally selective for the D-glucopyranoside group. A cleavage at C-2-C3 or C-3-C-4 positions was observed for the 6,1',6'-tri-O-trityl and 6,1',6'-tri-O-(tert-butyldemethylsilyl) derivatives, respectively. The periodate oxidation was more complete for all other derivatives with a cleavage at C-2-C-3 and C-3-C-4.

Carbohydrate Sequence↗
PubMed1990

The use of N-alkoxycarbonyl derivatives of 2-amino-2-deoxy-D-glucose as donors in glycosylation reactions.

1,3,4,6-Tetra-O-acetyl-2-alkoxycarbonylamino-2-deoxy-beta-D-glu copyranoses and 3,4,6-tri-O-acetyl-2-alkoxycarbonylamino-2-deoxy-alpha-D-glucopyra nosyl bromides have been used as donors in glycosylation reactions with model alcohols. beta-Glycosides were obtained in good yields and with a high degree of 1,2-trans stereoselectivity. An oxazolidinone was formed as the main product from the reaction of some of the glucopyranosyl bromides with alcohols of low reactivity, but the formation of all products could be interpreted by a strong participation of the alkoxycarbonylamino group.

Alcohols↗
PubMed1987

Synthesis, structure-activity relationships and a reaction mechanism for mutagenic N-nitroso derivatives of glycosylamines and Amadori compounds--model substances for N-nitrosated early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound were synthesized, together with their N-nitroso derivatives. Their structures were established by physico-chemical and spectroscopic data and elemental analyses. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentopyranosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (the Amadori compound) and N-3-ethylindole-D-xylopyranosylamine were shown to be direct-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to depend on the structure of the amine and the sugar moieties and to require the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arenediazonium cations. The formation of these compounds was detected by azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass spectrometric analyses. These data implicate arene(alkyl)diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines (and possibly of N-nitroso Amadori compounds), a little-explored class of N-nitroso compounds that may be formed in vivo.

Amino Sugars↗
PubMed1987

Synthesis, analysis and mutagenic activity of N-nitroso derivatives of glycosylamines and Amadori compounds: nitrosated model substances for the early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synthesized. The structures were ascertained by spectroscopy and elemental analysis. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (Amadori compound) and N-3-ethylindole-D-xylosylamine were shown to be directly-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to be dependent on the structure of the amine and the sugar moieties and requires the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arene diazonium cations. Their formation was detected via azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass-spectrometric analyses. Our data implicate arene (alkyl) diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines and N-nitroso Amadori compounds, a little explored class of N-nitroso compounds which may be formed in vivo.

Amino Sugars↗
PubMed1985

The immunological activity of plant toxins used in the preparation of immunotoxins--II. The immunodepressive activity of gelonin.

The immunological activity of Gelonin, a 30,000 dalton plant protein possessing close similarity to Ricin chain A as a protein synthesis inhibitor which may be of interest for the preparation of antibody-toxin conjugates, was studied in mice. At in vitro concentrations not affecting baseline radioactivity uptake, this substance reduced mitogen responses with the following order of sensitivity PHA less than ConA less than LPS. In microgram/ml concentrations it also markedly reduced macrophage-dependent cytotoxicity while not affecting NK activity. Macrophagic (but not NK) cytotoxicity and mitogen responses were similarly depressed after in vivo treatment. When given before (but not after) stimulus, Gelonin also reduced the primary responses to a T-dependent and, although to a lower degree, to a T-independent antigen, and decreased resistance to allogeneic tumor grafts and L. monocytogenes challenges. The immunopharmacological activity of this and similar substances should be considered in the design of antibody-toxin conjugates and in the evaluation of their therapeutic activity.

Animals↗
PubMed1983

Inhibition of endogenous nitrosation of proline in rats by lyophilized beer constituents.

Various amounts of lyophilized beer were administered to rats dosed with proline and sodium nitrite. N-Nitrosoproline (NPRO) excreted in the 24-h urine was monitored as an index of endogenous nitrosation. In vitro formation of NPRO was determined after 15-min incubation of the same precursor solutions. Both in vivo and in vitro nitrosation of proline was inhibited in a dose-dependent fashion by lyophilized beers of different brands; the effects in vitro were most pronounced at pH below 4. The highest inhibitory effect was with beers with a high total polyphenolic content. Our results demonstrate that ingredients present in this widely consumed beverage inhibit endogenous nitrosation.

Animals↗
PubMed1982

Drug immunotoxicological approaches with some selected medical products: cyclophosphamide, methylprednisolone, betamethasone, cefoxitine, minor tranquillizers.

Alterations of the normal immune response were estimated in C57B1/6 mice pretreated with cyclophosphamide, methylprednisolone sodium succinate, betamethasone sodium phosphate or cefoxitine as positive controls and three minor tranquillizers: dipotassium chlorazepate, diazepam and meprobamate. The specific immune response against sheep red blood cells (SRBC) was evaluated by numeration of the direct plaque-forming cells (PFC; humoral immunity) and by measurement of the footpad swelling (delayed-type hypersensitivity, DTH). In our experiments, the results with the positive controls were in the same order as those described by others, and at the dose levels used, these three minor tranquillizers did not really alter the specific humoral and cellular immune response against SRBC in the C57B1/6 mice.

Animals↗