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H Joyeux

Publications and source records attributed to H Joyeux.

At least 19 recordsLinked to original sources

[Semi-automatic measurements of hepatic lobes. Application to study of liver volumes. Analysis of 50 computed tomography of normal liver].

OBJECTIVE: Healthy and pathological hepatic volumetry can be of great interest in Liver pathology and treatment. We studied the hepatic segmentation in order to verify if it is possible to estimate the volume of one lobe, when the volume of the other lobe or the total liver is known. PATIENTS AND METHODS: We studied 50 normal hepatic angiotomographies. For each exam and using the Couinaud classification, we measured the total hepatic volume, the right lobe, the left lobe and the caudate lobe volumes. We used a software called "Hepato" developed in order to quantify automatically CTScan images of the liver. We performed a linear regression analysis (least squares method) and calculated the determination coefficient to study the correlation between the different volumes. RESULTS: The mean total hepatic volume was 1497 cm3. We obtained for the right lobe 1231 cm3, 226 cm3 for left lobe, and 39 cm3 for the caudate lobe. Moreover there was a weak correlation between these volumes. CONCLUSION: Exact volume estimation of an hepatic lobe in one patient can not be obtained from the total hepatic volume. However, theses volumes can only be measured from three-dimensional images. Since classical image editing tools are time request, it becomes impossible to utilize them in a clinical routine to get the different volumes of the Liver. Thus, a software dedicated for liver parenchyma recognition is necessary.

Adult↗

Lipid-mediated transfection of normal adult human hepatocytes in primary culture.

The aim of this work was to develop a procedure for the lipid-mediated transfection of DNA into normal adult human hepatocytes in culture. Cells were plated in a serum-free culture medium at various cell densities, on plastic or collagen-coated dishes, both in the absence and in the presence of epidermal growth factor (EGF). The cells were incubated for various periods of time with mixtures of DNA-lipofectin or DNA-3 beta[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) liposomes, and the efficiency of transfection was assessed by measuring the activity of reporter genes, beta-galactosidase or chloramphenicol acetyl-transferase (CAT). For comparison, similar experiments were carried out with human cell lines including HepG2, Caco-2, and WRL68. The efficiency of transfection (in percentage of cells) was not significantly different after transfection with lipofectin or DC-chol and comprised between 0.04 and 1.7% (extreme values) for different cultures. The efficiency of transfection decreased as the age or density of the culture increased and increased in cultures treated with EGF. Direct measurement of the rate of DNA synthesis suggested that the efficiency of transfection was related to the number of cells entering the S phase. Under the same conditions, the efficiency of transfection was one to two orders of magnitude greater in the three cell lines. A plasmid harboring 660 bp of the 5'-flanking region of CYP1A1 (containing two xenobiotic enhancer elements) fused upstream of the promoter of thymidine kinase and the CAT reporter gene was constructed. When this plasmid was transfected in human hepatocytes, CAT activity was induced as expected. We conclude that normal adult human hepatocytes can be transfected with exogenous DNA and that the transfected construct is regulated in the manner expected from in vivo studies.

Adult↗

Oxidative metabolism of lansoprazole by human liver cytochromes P450.

The aim of this work was to identify the form(s) of human cytochrome P450 (P450) involved in the hepatic biotransformation of lansoprazole to its two main metabolites, i.e., the sulfone and the hydroxy derivative. In liver microsomes, the production of the sulfone of lansoprazole correlated with the level of P450 3A4, cyclosporin oxidase, and the production of the hydroxy derivative, as well as of omeprazole sulfone. The production of hydroxylansoprazole moderately correlated with the level of P450 3A4, cyclosporin oxidase, and (S)-mephenytoin 4'-hydroxylase. The production of the sulfone and of the hydroxy derivative of lansoprazole was significantly inhibited by anti-P450 3A4 antibodies, by cyclosporin and ketoconazole, and by tolbutamide. Anti-P450 2C8 and 2C3 antibodies moderately inhibited the biotransformation of lansoprazole, whereas they completely inhibited (S)-mephenytoin 4'-hydroxylase activity under the same conditions. In primary cultures of human hepatocytes, the biotransformation of lansoprazole and the oxidation of cyclosporin were strongly increased by rifampicin and phenobarbital, whereas (S)-mephenytoin 4'-hydroxylation was not. beta-Naphthoflavone did not induce the formation of the sulfones but stimulated the production of hydroxylansoprazole. Among several forms of cDNA-expressed human P450s, 3A4 generated significant amounts of the sulfones of lansoprazole and omeprazole and 2C18 was active for the production of hydroxylansoprazole but inactive in the 4'-hydroxylation of (S)-mephenytoin. We conclude that P450 3A4 is the major enzyme involved in the production of the sulfone of lansoprazole and that this P450, as well as P450 2C18 and/or another 2C-related form, could contribute to the production of hydroxylansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Total and prolonged parenteral nutrition at the hospital and at the patient's home: its socio-economic importance].

Total parenteral nutrition with "All in one" nutritive mixtures is used in France from 1970. These advances ensure a more simple treatment for intensive care units. Nutritive mixtures provide the caloric and nitrogen daily requirements added with micronutrients (electrolytes, trace elements and vitamins) and this technique allows home parenteral nutrition. "All in one" nutritive mixtures have reduced the infectious complications and the industrial quality control during parenteral solutes admixing has decreased again this infectious risk. So, nutritive mixtures result in sparing of nurse time, material for preparation and antibiotic costs. Moreover, although the costs of home parenteral nutrition are considerable, this technique still reduces annual costs by 50% to 70%, avoids prolonged hospitalization and allows the patients to resume a more normal existence at home. Development of new technologies and nutritive mixtures for specific malnutrition are now required to improve treatment of these patients with insufficiency digestive tract.

Ambulatory Care↗

Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture.

The ability of several gastric antiulcer drugs including lansoprazole, cimetidine and ranitidine to affect the expression of human liver microsomal cytochromes P450 comparatively to omeprazole, reported previously to be a CYP1A inducer, was evaluated in primary cultures of human hepatocytes. Poly (A)+ RNA and microsomes extracted from the cells were analyzed in Northern and Western blots with specific cDNA probes and antibodies, and assayed for form-specific monoxygenase activities. Lansoprazole induced both CYP1A1 and CYP1A2 as omeprazole and did not apparently bind to the aryl hydrocarbon receptor with high affinity. Omeprazole sulfone was not an inducer of CYP1A. Omeprazole, omeprazole sulfone and lansoprazole induced CYP3A in approximately 50% of tested cultures, whereas 100% of tested cultures responded to omeprazole and to rifampicin in terms of CYP1A and CYP3A induction, respectively. Finally, cimetidine and ranitidine were not inducers. We conclude that omeprazole and lansoprazole constitute a new class of mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture and that the induction of CYP3A in response to these molecules could be polymorphic in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Repeated hepatic resections for liver metastases from colon carcinoma. Montpellier Cancer Institute experience.

The main cause of death after hepatic resection for colorectal liver metastases is tumor recurrence. An improvement in survival may be achieved by resection of recurrent hepatic metastases as previously reported. In this paper we report our experience with 13 repeated liver resections in 11 patients. The post-operative mortality was 8% and the morbidity was 23% with two biliary tract fistulas and one recurrent pleural effusion. The median survival time from the first hepatic resection was 23 months, but differed according to the length of the disease-free interval (more than 1 year and less than 1 year: 49 and 17 months, respectively (P < 0.05). Our results suggest that repeated hepatic resection is technically a safe procedure and may be beneficial to selected patients. All candidates should be carefully evaluated pre-operatively for extrahepatic disease.

Adult↗

Importance of the paracellular pathway for the transport of a new bisphosphonate using the human CACO-2 monolayers model.

The transport of a new bisphosphonate, Tiludronate, was investigated on the human adenocarcinoma cell line, CACO-2. Experiments were performed 7-16 days after cells achieved confluence, conditions under which they form well-differentiated monolayers joined by tight junctions. Tiludronate transport rate across CACO-2 monolayers was independent of the temperature (4 degrees versus 37 degrees), of the polarity of the cell membrane (apical-to-basolateral versus basolateral-to-apical), and of the presence of metabolic poisons (sodium azide). Its transport was enhanced by either the presence of EGTA in the incubation buffer, i.e. when extracellular Ca2+ concentration was reduced, or by the pretreatment of monolayers with EGTA, i.e. when the intercellular spaces and the tight junctions were widened. Based on these different observations, we could suggest that Tiludronate mainly used the paracellular pathway to cross the intestinal epithelium. An increase in the Tiludronate permeability coefficient was also observed following treatment of cells with high Tiludronate concentrations, as a consequence of the direct effect of this compound on the extracellular Ca2+ ions. Hence, for high drug concentrations, i.e. 20 mM, we observed a decrease in free extracellular Ca2+ concentration, an increase in the transepithelial electrical resistance and an increase in the transport of [14C]polyethyleneglycol ([14C]PEG400), a probe for the paracellular pathway. The results indicate that Tiludronate is transported across CACO-2 monolayers by the paracellular route. Moreover, it can affect its own transport by its concentration-dependent effect on tight junction widening.

Azides↗

Conservative treatment for low rectal carcinoma by local excision with or without radiotherapy.

Thirty-seven patients with low rectal carcinoma were treated by transanal resection between January 1979 and December 1988. Adjuvant radiotherapy was used in eight patients before operation, in 13 after operation and six patients had both preoperative and postoperative radiotherapy. The selection criteria for transanal resection were low, superficial tumours treated conservatively with curative intent (group 1, 18 patients) or patients medically unfit for (12) or refusing (seven) abdominoperineal resection (APR) (group 2, 19 patients). In group 1, the local recurrence rate was 11 per cent with an overall 5-year survival rate of 100 per cent. In group 2, the local recurrence rate was 53 per cent with an overall 5-year survival rate of 35 per cent. There was no postoperative mortality and minimal morbidity. Salvage of local failure was by APR in six patients. The survival rate after local recurrence was 70 per cent at 1 year and 30 per cent at 5 years. Transanal resection can be proposed as a curative procedure for selected low, small, minimally infiltrating and well differentiated adenocarcinomas. Local control might be improved by postoperative radiotherapy for Astler-Coller stage B1 tumours or those above 3 cm in diameter. Further trials should examine the results of high-dose (60 Gy) preoperative radiotherapy so that transanal resection might be employed for favourable post-irradiation stage (0 or A) lesions. This new strategy will benefit from a better evaluation of tumour response after primary radiotherapy and an improved assessment of histological excision margins.

Adult↗

The role of hormonal and dietary factors in pancreatic carcinogenesis.

The pancreatic cancer continues to represent an important problem, as a cancer with extremely poor prognosis. To date more than 16 chemicals have been shown to induce pancreatic tumors, in animal models. The tumors developed in rats are essentially of acinar type and those in hamsters mostly of ductal type. Many studies proved the direct or indirect role of hormonal and dietary factors in pancreatic cancer. The development of alternative treatments according to biological and biochemical steps of carcinogenesis is available as adjuvant treatment. We present herein an overview of current experimental and clinical results in order to understand the evolution, histogenesis and biological behaviour of pancreatic cancer.

Adenocarcinoma↗

Treatment of fistulas of the gastrointestinal tract with total parenteral nutrition and octreotide in patients with carcinoma.

The development of a fistula is a serious postoperative complication. Conservative medical treatment with total parenteral nutrition, skin care and intensive infection control usually succeeds in closing fistulas (60 to 75 percent), but the treatment is of long duration (two to three months), high cost and high morbidity related to prolonged hospitalization. We have used octreotide, a long half-life stomatostatin analog, in 40 patients from two European university centers with postoperative enterocutaneous fistulas. Twenty-two patients had low fistula output and 28 patients had high fistula output. Spontaneous closure was achieved in 77.5 percent of the patients after a mean of 13.6 days. One patient died. Glucose intolerance, which has been reported with stomatostatin treatment of fistulas, was not observed. Previous chemotherapy or radiotherapy or low albumin level (23 grams per deciliter) negatively influenced fistula closure. As an adjunct treatment to primary care (total parenteral nutrition, skin care and infection control), octreotide is efficient in reducing fistula output and accelerating spontaneous fistulas closure.

Adult↗

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↗

Plasma and jejunal glutamine levels after extensive small bowel resection in dogs.

Recent studies have demonstrated that glutamine may be required for mucosal growth and that it is widely utilised by the intestinal tract after surgery. This study has evaluated the effect of massive small bowel resection on plasma and jejunal glutamine and related amino-acids level evolution after surgery. Transection was performed in 6 dogs (control group) and enterectomy in 10 dogs leaving 25cm of jejunum, associated with colectomy (group 1). Plasma glutamine levels decreased on D2 (p = 0.03) in the resected group while a significant decrease of plasma alanine levels was observed on D2 (p = 0.002), D4, D6 and D8 (p < 0.001). Intestinal mucosa glutamic acid content was increased on D8 in this group (p < 0.001). No changes were observed in the control group. These results suggest that glutamine is a required substrate after massive small bowel resection which could improve the intestinal adaptation encountered after enterectomy.

Journal Article↗

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↗

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↗