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Biomedical subjects

H Joyeux

Publications and source records attributed to H Joyeux.

At least 19 recordsLinked to original sources
PubMed1992

Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture.

The expression of several forms of cytochrome P450 including P450 1A2, 2D6, 2E1, and 3A was investigated in human hepatocytes maintained in primary culture for 96 h in the absence or presence of 50 microM of various imidazole derivatives. These included ketoconazole, clotrimazole, miconazole, fluconazole, secnidazole and metronidazole. In addition, the typical inducers rifampicin and beta-naphthoflavone were used for comparison. Western and Northern blot analysis of microsomes and RNA prepared from these cultures as well as de novo synthesis experiments revealed that, among the imidazole derivatives tested, only clotrimazole was a strong rifampicin-like inducer of P450 3A. The expression of the other forms of P450 tested was not affected by the treatments. Analysis of the inhibition of 13 monoxygenase activities, including ethoxyresorufin and phenacetin O-deethylases, coumarin 7 alpha-, lauric acid 11- and 12-, mephenytoin 4-, debrisoquin 4-, and aniline hydroxylases, benzphetamine, aminopyrine, mephenytoin and erythromycin demethylases, and cyclosporin oxidase (representative of 10 different forms of P450 in human liver microsomes) revealed that ketoconazole was a strong and selective in vitro inhibitor of P450 3A (cyclosporin oxidase) with a Ki less than 1 microM. Clotrimazole and miconazole were also strong inhibitors of P450 3A-mediated activities in contrast to the other imidazole derivatives.

Blotting, Northern↗
PubMed1992

Thiazolidine-4-carboxylate and 2-phenylthiazolidine-4-carboxylate are active as cysteine precursors but have no effect on growth of a methionine-dependent tumor in rats.

Diets with partial replacement of sulfur amino acids by thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate were fed to normal and to rhabdomyosarcoma-bearing rats (methionine-dependent tumor) to evaluate their efficacy as cysteine precursors and as antitumor agents. Food intake, weight gain, food efficiency and plasma albumin and plasma sulfur amino acid concentrations were not different when these diets were compared with isosulfurous diets containing either methionine or N-acetylcysteine. 2-Phenylthiazolidine-4-carboxylate induced a lower plasma glutathione (GSH) level than the latter diets. Tumor-bearing rats had lower plasma GSH concentration. A negative linear relationship was found between plasma GSH levels and tumor weight and also the tumor weight: body weight ratio. This could mean that the tumor becomes the most important organ in the uptake of GSH. However, there was also a significant positive correlation between plasma GSH and albumin, suggesting a reduced GSH hepatic synthesis due to amino acid uptake by the tumor. There were no differences in tumor growth among rats receiving diets containing N-acetylcysteine, thiazolidine-4-carboxylate or 2-phenylthiazolidine-4-carboxylate.

Amino Acids↗
PubMed1992

Regulation of cytochrome P450IA1 gene expression in a human intestinal cell line, Caco-2.

The expression and inducibility of cytochrome P450IA1 isozyme was investigated in the human carcinoma cell line Caco-2 cultured between days 7 and 35 in the absence or the presence of various enzyme inducers such as 3-methylcholanthrene, beta-naphthoflavone (beta NF), dioxin, isosafrole, rifampycin, dexamethasone or phenobarbital. 7-Ethoxyresorufin O-deethylase activity (EROD) was maximal at day 25 when the differentiation of Caco-2 cells, characterized by the level of the brush border associated enzymes such as sucrase isomaltase and alkaline phosphatase, was higher. The inducibility of this enzyme activity was found to be maximal when cells were treated between days 7 and 10. After a 3-day treatment of Caco-2 cells with 50 microM beta NF, EROD achieved 36.6 +/- 14.6 pmol/min/mg compared to 2.5 +/- 1.1 pmol/min/mg in untreated cells. This enzyme activity appeared to be supported only by P450IA1 isozyme because: 1) EROD was quantitatively inhibited by alpha-naphthoflavone, a P450IA1-specific inhibitor; otherwise, phenacetin O-deethylation was completely abolished in the presence of alpha-naphthoflavone and not by furafylline, a P450IA2-specific inhibitor; 2) EROD was induced after treatment with 3-methylcholanthrene, beta NF and dioxin, which are P450IA1 inducers, but not by isosafrole, a P450IA2-specific inducer; 3) cytochrome P450IA1 apoprotein could be immunodetected by antibodies directed against rabbit cytochrome P450-LM6, orthologous to P450IA1, in polycyclic hydrocarbon-treated cells; 4) under the latter conditions, P450IA1 mRNA accumulation was specifically detected, but not P450IA2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoflavones↗
PubMed1992

Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes.

Prednisone, prednisolone, and methylprednisolone are currently administered in association with cyclosporin A in the postoperative treatment of transplant patients. The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes P450 (P450), including P450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96-144 hr, in the absence or presence of 50-100 microM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of P450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of P450 proteins and corresponding messages, and de novo synthesis and half-lives of these P450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of P450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these P450; 2) although corticosteroids are known to be metabolized in human liver, notably by P450 3A, partial or total inhibition of this P450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of P450 3A or the accumulation of other forms of P450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect P450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 +/- 12, 125 +/- 25, 190 +/- 38, and 210 +/- 42 microM for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells. These results support most of clinical reports dealing with mutual interactions between cyclosporin A and corticosteroids.

Adrenal Cortex Hormones↗
PubMed1991

Autotransplantation of the pylorus sphincter at the terminal abdominal colostomy. Experimental study in dogs.

A method for constructing a continent colostomy has been tried in dogs. The pylorus sphincter with blood supply by the left gastroepiploic vessels was transposed around or anastomosed to the terminal abdominal colostomy in five dogs. One dog had a colostomy without pylorus transplantation. Evaluation was by clinical (consistency and weight of fecal material and number of defecations per day), radiologic, and manometry studies. There was no difference in the clinical data. In all the dogs, the radiologic study demonstrated emptying of the contrast medium to the peristomal skin. By manometry one high-pressure zone was demonstrated, and, in all dogs with a transposed or anastomosed pyloric segment, the average resting pressure was superior to that of the control dog. However, the transposed pylorus sphincter alone was not sufficient to control continence.

Animals↗
PubMed1991

Skin test reactivity in patients suffering from lung and breast cancer.

Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer.

Adult↗
PubMed1991

Clinical, biological, and histological follow-up during intestinal adaptation after small-bowel resection in the dog.

Massive resections of the intestine including the ileocecal valve are associated with a high mortality. This model of short bowel in the dog consists of an extensive small-bowel resection (remaining jejunum 25 cm) associated with colectomy. Small-bowel adaptation is evidenced by increases of crypt depth (p = 0.02) and villus height (p = 0.001) in animals fed per os. Plasma glutamine levels decrease after surgery, while there is a significant decrease of plasma alanine levels (p less than 0.001). This model should allow to pursue investigations on the importance of glutamine as an essential fuel for intestinal mucosa regeneration.

Adaptation, Physiological↗
PubMed1991

[Possible role of sexual and gastrointestinal hormones on cancer of the digestive system].

This is a review of the most interesting studies on the possible role of sex and gut hormones in gastrointestinal (GI) carcinomas. Many experimental and some human studies suggest that sex and gut peptides may have a growth effect on normal or neoplastic gut cells. It may be possible in the future to develop strategies for patients with GI cancers that will be based upon hormonal manipulation in a manner similar to current strategies that are at present employed in the treatment of patients with breast cancer.

Animals↗
PubMed1991

[Spontaneous rupture of the liver during triplet pregnancy following in vitro fertilization].

The authors present an observation of a spontaneous rupture of the liver happening during the 8th month of gestation of a triple pregnancy obtained by in-vitro fertilization. The diagnosis was done with some delay but evolution was successful for the mother and all her children. It is elective ligation of the right branch of the hepatic artery which produced the hemostasis.

Adult↗
PubMed1990

Lingual fibrosarcoma induced by 7, 12-dimethylbenzanthracene in the rat.

A single injection of 5 mg of 7, 12-dimethylbenzanthracene (DMBA) resulted in a high incidence of lingual fibrosarcoma in 67 Wistar rats. No metastases were found. We studied the influence of age and sex on the incidence, latency of tumors, loss of weight and the spontaneous survival of animals. The method described offers an experimental model for the study of cachexia resulting from upper digestive and respiratory tract cancer.

9,10-Dimethyl-1,2-benzanthracene↗