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Biomedical subjects

Pierre Déchelotte

Publications and source records attributed to Pierre Déchelotte.

At least 19 recordsLinked to original sources
PubMed2006

Oxysterol nuclear receptor LXRbeta regulates cholesterol homeostasis and contractile function in mouse uterus.

The uterus is an organ where lipid distribution plays a critical role for its function. Here we show that nuclear receptor for oxysterols LXRbeta prevents accumulation of cholesteryl esters in mouse myometrium by controlling expression of genes involved in cholesterol efflux and storage (abca1 and abcg1). Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased in wild-type mice, whereas under basal conditions, lxralpha;beta(-/-) mice exhibited a marked decrease in abcg1 accumulation. This change resulted in a phenotype of cholesteryl ester accumulation. Besides, a defect of contractile activity induced by oxytocin or PGF2alpha was observed in mice lacking LXRbeta. These results imply that LXRbeta provides a safety valve to limit cholesteryl ester levels as a basal protective mechanism in the uterus against cholesterol accumulation and is necessary for a correct induction of contractions.

ATP Binding Cassette Transporter 1↗
PubMed2006

Effects of intragastric L-arginine administration on proximal stomach tone under basal conditions and after an intragastric diet.

Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment.L-Arg administration was associated with significantly higher increases in barostat bag volumes at both dosages, 30 g (117+/-16 ml) and 15 g (67+/-15 ml), compared to placebo (46+/-11 ml; P < 0.05). In response to the polymeric diet the 30-g L-Arg challenge was associated with a smaller increase in intrabag volume, whereas postinfusion final volumes did not differ in the three treatment conditions. Antral areas were not different at any time of measurement among the three challenges. Bloating and diarrhea were observed after 30-g L-Arg administration in five subjects of eight. Short-term L-Arg administration was able to induce proximal stomach relaxation that allowed a secondary response to enteral feeding only at the 15-g dosage. This 15-g dosage was as well tolerated as the placebo and was associated with no significant changes in gastric emptying patterns.

Adult↗
PubMed2006

Undernutrition is predictive of early mortality after palliative self-expanding metal stent insertion in patients with inoperable or recurrent esophageal cancer.

BACKGROUND: Self-expanding metallic stents (SEMS) are a first-line therapeutic procedure in the palliative treatment of dysphagia in patients with esophageal cancer. However, the impact of SEMS insertion on patient nutritional status has never been assessed. OBJECTIVE: To evaluate the nutritional status of patients after insertion of a SEMS and the impact of a preexisting undernutrition status on survival. DESIGN: Retrospective observational study. PATIENTS: A total of 120 patients treated in a single center by insertion of a SEMS for relief of dysphagia in the palliative treatment of esophageal cancer were retrospectively included. MAIN OUTCOME MEASUREMENTS: Efficacy of SEMS was assessed by the Ogilvie's dysphagia score. Patient nutritional and clinical statuses were evaluated at SEMS insertion, and patients were regularly followed until death. Independent predictive factors of early 30-day mortality were researched. RESULTS: Dysphagia scores decreased after SEMS insertion in 89.1% of patients, with median scores decreasing from 3.0 to 1.0 (P < .05). There was a significant decrease in body mass index (BMI) (P < .04), serum albumin level (P < .01), and World Health Organization (WHO) performance index (P < .02) at a 1-month evaluation. Serum albumin level, BMI <18 kg/m(2), and WHO performance index >2 at SEMS insertion were independent predictive factors of 30-day mortality. CONCLUSIONS: This study suggested that palliative stent placement in esophageal cancer was effective to relieve dysphagia but was not followed by an improvement of nutritional parameters. Moreover, it underlined the key role played by undernutrition on survival.

Adenocarcinoma↗
PubMed2006

Regulation of proteolysis by cytokines in the human intestinal epithelial cell line HCT-8: role of IFNgamma.

Protein metabolism contributes in the regulation of gut barrier function, which may be altered during inflammatory states. There are three major proteolytic pathways in mammalian cells: lysosomal, Ca(2+)-activated and ubiquitin-proteasome. The regulation of proteolytic activities during inflammation remains unknown in intestine. Intestinal epithelial cells, HCT-8, were stimulated by IL-1beta, IFNgamma and TNFalpha each alone or in combination (Cytomix). Proteolytic activities were assessed using fluorogenic substrates and specific inhibitors, protein expressions by Western blot. Lysosomal and Ca(2+)-activated pathways were not significantly altered by any treatment. In contrast, the activity of ubiquitin-proteasome system was stimulated by IFNgamma and Cytomix (155, 160 versus 100, P<0.05, respectively) but remained unaffected by IL-1beta and TNFalpha. Free ubiquitin expression, but not ubiquitinated proteins, was enhanced by IFNgamma and Cytomix. The expression of proteasome 20S alpha1 subunit, a constitutive proteasome 20S subunit, was not altered, beta5 subunit expression was weakly decreased by Cytomix and inducible beta5i subunit expression was markedly increased in response to IFNgamma and to Cytomix (202, 206 versus 100, P<0.05, respectively). In conclusion, lysosomal, Ca(2+)-activated and constitutive proteasome activities were not affected by IL-1beta, IFNgamma and TNFalpha alone or in combination, in HCT-8 cells. These results suggest that IFNgamma, but not IL-1beta and TNFalpha, increases immunoproteasome, which might contribute to enhanced antigen presentation during inflammatory bowel diseases.

Acetylcysteine↗
PubMed2006

Proteomic analysis of glutamine-treated human intestinal epithelial HCT-8 cells under basal and inflammatory conditions.

Glutamine (Gln) promotes intestinal growth and maintains gut structure and function, especially in situations of injury and during inflammation. Several mechanisms could contribute to Gln protective effects on gut. Proteomics enable us to characterize differentially expressed proteins in tissues in response to modifications of the biological or nutritional environment. Gln effects on the human intestinal epithelial HCT-8 cell line proteome were assessed under basal and proinflammatory conditions. The 2-DE gels were obtained and compared. Proteins were identified by MS and using databases. About 1200 spots were detected in both 2- and 10-mM Gln concentrations. Under basal conditions, 24 proteins were differentially expressed in response to Gln. Half of these proteins were implicated in protein biosynthesis or proteolysis and 20% in membrane trafficking. Under proinflammatory conditions, 27 proteins were up- or down-regulated by Gln 10 mM. From these proteins, 40% were involved in protein biosynthesis or proteolysis, 16% in membrane trafficking, 8% in cell cycle and apoptosis mechanisms and 8% in nucleic acid metabolism. This study provides the first holistic picture of proteome modulation by Gln in a human enterocytic cell line under basal and proinflammatory conditions, and supports further evaluation of nutritional modulation of intestinal proteome in humans.

Cell Line↗
PubMed2006

Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination.

Glutamine, the most abundant amino acid in the human body, plays several important roles in the intestine. Recent studies showed that glutamine regulates protein metabolism and intestinal inflammation among other mechanisms by reducing proinflammatory cytokine release. Because regulation of the inflammatory response was shown to be linked to proteolysis regulation, we hypothesized that glutamine pretreatment could act on IL-8 production in human intestinal epithelial cells through the regulation of inhibitor kappaB (IkappaB) ubiquitination. The HCT-8 cells were pretreated for 24 h with 0.6, 2, or 10 mmol/L glutamine. IL-8 concentration and IkappaB (free and ubiquitinated) expressions were assessed by ELISA and immunoblotting, respectively. A pretreatment with 10 mmol/L glutamine decreased IL-8 production under both basal and proinflammatory conditions (both P < 0.05). In the presence of a proteasome inhibitor (MG132), the ubiquitin-IkappaBalpha complex expression was not significantly modified by glutamine under basal conditions but decreased significantly under proinflammatory conditions (P < 0.05). After the addition of 10 mmol/L of glutamine, the free IkappaBalpha expression increased under basal and stimulated conditions (both P < 0.05). A glutamine pretreatment of 10 mmol/L did not affect ubiquitin expression or proteasome activity. This study indicates that glutamine pretreatment may reduce the intestinal inflammatory response by limiting the proteolysis of IkappaBalpha.

Cells, Cultured↗
PubMed2006

L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study.

OBJECTIVE: Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. DESIGN: Prospective, double-blind, controlled, randomized trial. SETTING: ICUs in 16 hospitals in France. PATIENTS: One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). INTERVENTIONS: Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days. MEASUREMENTS AND MAIN RESULTS: Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group. CONCLUSIONS: TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.

Analysis of Variance↗
PubMed2005

L-Arginine modulates CXC chemokines in the human intestinal epithelial cell line HCT-8 by the NO pathway.

Arginine has immunomodulating properties in different animal models but its effects in human intestine remain unknown. This study examined whether arginine modulates inflammatory mediators as chemokines and nitric oxide (NO) in the human intestinal epithelial cell line HCT-8 induced by cytokines. Under basal conditions, arginine did not influence iNOS protein expression, NO and chemokine production and mRNA levels (P>0.05 for all). Stimulation with cytokines-induced a significant increase of NO and chemokine production, iNOS and chemokine mRNA level and iNOS protein expression. Under inflammatory conditions, arginine increased 30% NO production (P<0.05) but did not influence iNOS mRNA level or iNOS protein expression. Under stimulated conditions, arginine decreased IL-8 and Mig mRNA level (57% and 39%, for 0.1 vs. 2 mmol/l l-arginine, P<0.05, respectively), and production (respectively, 28 and 23%, both P<0.05). IP-10 and I-TAC mRNA level and production were not significantly influenced by arginine. Under inflammatory conditions, l-arginine as well as a NO donor (sodium nitroprusside (SNP)) increased NO production, which was inversely correlated with IL-8 production (r'=-0.66, P=0.007 for arginine; r'=-0.79, P<0.0001 for SNP). Use of NG-Methyl-l-arginine acetate, a NOS inhibitor which prevents arginine-induced NO production, suppressed the arginine-induced IL-8 inhibition (P<0.05). In HCT-8 cells, arginine enhanced cytokine-induced NO production, reduced IL-8 and Mig production and mRNA level and had no effects on other assessed chemokines. In conclusion, arginine-induced IL-8 inhibition in HCT-8 cells involves NO pathway under inflammatory conditions. These data suggest that arginine-enriched enteral nutrition may have significant influence on inflammatory response in human intestine.

Adenocarcinoma↗
PubMed2005

Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation.

BACKGROUND: The scarcity of human ovarian tissue is a major problem in developing research on ovarian cryopreservation. We were interested in ovarian cortex surrounding benign ovarian cysts harvested during their requisite operations. METHODS: Ovarian tissue was collected from 25 women (mean age = 27.7 +/- 1.0 SEM) and frozen in serum-free cryoprotective medium. Histological and viability analysis were performed on fresh and frozen-thawed slices of tissue. RESULTS: Dermoid (n = 7), endometriosis (n = 13) and serous (n = 5) cysts were observed. Follicular densities (expressed per mm3) in ovarian cortex surrounding dermoid cysts were higher than in endometriosis and serous cysts for both histological (median of follicular densities: 13.04, 0.31 and 0.89 respectively) and viability analysis (2.93, 0.05 and 0.71 respectively). Freezing-thawing did not result in gross abnormality of follicle population either in number or morphology (80% of follicles preserved a normal pattern). However, a slight decrease of the density of living follicles (expressed per mm2) was reported. CONCLUSIONS: Ovarian cortex surrounding ovarian cysts, especially dermoid cysts, could be considered a source of ovarian tissue for future research. In our study, the cryopreservation procedure resulted in high follicular survival assessed by both histological and viability analysis. Nevertheless, further studies of in vivo and in vitro follicular maturation are needed to strengthen this model.

Adult↗
PubMed2005

Effect of glutamine on water and sodium absorption in human jejunum at baseline and during PGE1-induced secretion.

Glutamine, a major fuel for enterocytes, stimulates water and sodium absorption in animal models of secretory diarrhea, but data in humans are still limited. The aim of this study was to investigate the effect of glutamine on jejunal absorption during hypersecretion in humans. In six healthy adults, the effects of glutamine on jejunal absorption were assessed with a triple-lumen tube on two occasions, at baseline and during PGE(1)-induced hypersecretion (0.1 microg.kg(-1).min(-1)) in a random order. Isoosmolar solutions containing polyethylene glycol 4000 as nonabsorbable marker were infused in the jejunum at 10 ml/min over 1-h periods: saline (sodium chloride 308 mmol/l), glucose-mannitol 45:45 mM, glucose 90 mM, alanine-glucose 45:45 mM, glutamine-glucose 45:45 mM, and glutamine 90 mM. Net absorptive and secretory fluxes were measured at steady state. At baseline, glutamine- and alanine-containing solutions induced a threefold increase of water and sodium absorption (P < 0.05); 90 mM glutamine stimulated water absorption more than 90 mM glucose (3.6 +/- 0.6 vs. 1.9 +/- 0.3 ml.min(-1).30 cm(-1), P < 0.05). PGE(1)-induced hypersecretion was reduced (P < 0.05) by solutions of alanine-glucose, glutamine-glucose, and glutamine 90 mM (P < 0.05) and reversed to absorption by alanine-glucose and glutamine-glucose. Glutamine and alanine absorption was nearly complete and was not influenced by PGE(1). In conclusion, glutamine stimulates water and electrolyte absorption in human jejunum, even during experimental hypersecretion. In addition to the metabolic effects of glutamine, these results support the evaluation of glutamine-containing solutions for the rehydration and the nutritional support of patients with secretory diarrhea.

Adsorption↗
PubMed2005

The role of glutamine in intensive care unit patients: mechanisms of action and clinical outcome.

Patients in the intensive care unit are at high risk of glutamine depletion and subsequent complications. Several controlled studies and a meta-analysis have concluded that glutamine supplementation has beneficial effects on the clinical outcome of critically ill and surgical patients. These results may be explained by glutamine's influences on the inflammatory response, oxidative stress, cell protection, and the gut barrier. In addition, glutamine may also improve glucose metabolism by reducing insulin resistance.

Critical Care↗
PubMed2004

Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations.

Tpit is a T box transcription factor important for terminal differentiation of pituitary proopiomelanocortin-expressing cells. We demonstrated that human and mouse mutations of the TPIT gene cause a neonatal-onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid replacement, IAD can lead to neonatal death by acute adrenal insufficiency. This clinical entity was not previously well characterized because of the small number of published cases. Since identification of the first TPIT mutations, we have enlarged our series of neonatal IAD patients to 27 patients from 21 unrelated families. We found TPIT mutations in 17 of 27 patients. We identified 10 different TPIT mutations, with one mutation found in five unrelated families. All patients appeared to be homozygous or compound heterozygous for TPIT mutations, and their unaffected parents are heterozygous carriers, confirming a recessive mode of transmission. We compared the clinical and biological phenotype of the 17 IAD patients carrying a TPIT mutation with the 10 IAD patients with normal TPIT-coding sequences. This series of neonatal IAD patients revealed a highly homogeneous clinical presentation, suggesting that this disease may be an underestimated cause of neonatal death. Identification of TPIT gene mutations as the principal molecular cause of neonatal IAD permits prenatal diagnosis for families at risk for the purpose of early glucocorticoid replacement therapy.

Adolescent↗
PubMed2004

[Trophoblastic gestational disease: a placental site trophoblastic tumor and an epithelioid trophoblastic tumor].

Placental site trophoblastic tumor and epithelioid trophoblastic tumor are rare gestational trophoblastic tumors. They both appear in the same context and follow the same course. We report two cases in patients aged 44 and 20 years. These lesions usually affect young women with a history of multiple gestations. Clinical manifestations include vaginal bleeding, uterine mass, and moderate elevation of serum beta human chorionic gonadotrophin levels. These morphologically distinct trophoblastic proliferations usually have a favorable course if complete excision is performed.

Adult↗
PubMed2004

[Hematodermic CD4/CD56 neoplasm].

Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been initially proposed by the French Study Group on Cutaneous Lymphomas which established the primary anatomoclinical and pathogenic and cytogenic bases of the disease in 1999. This descriptive and provisional name allowed conceptualizing the entity by its main clinical and phenotypical characteristics. The first case in the literature goes back to 1994. Since that time, several other cases have been published. The expression of CD56 led most of the authors to propose an NK-cell lineage origin. In the last WHO classification of lymphomas, the entity was indexed under the name of "blastic NK-cell lymphoma". However, the authors underlined that there were currently no clues to the etiology of blastic NK-cell lymphoma and that the precise lineage of this disease was still unresolved. At the clinical level the main characteristics of the disease are the skin tropism and the occurrence of a leukemic phase at any time during the course of the disease. The median age is 59 but pediatric cases do exist. At the morphological level skin biopsy shows a monomorphous cell proliferation simulating a pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic criteria which require frozen tissue. Currently, the main characteristics are the expression of CD4 and CD56 antigens while the main defined lineage specific markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The origin of the tumor cells still remains uncertain but the plasmacytoid dendritic cell is presently a very serious candidate. The tumor cells share a great phenotypical homology and particularly the expression of the CD123 antigen. Functional homologies have also been demonstrated with tumor cells in vitro. Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of survival is 14 months irrespective of the treatment given. Conventional chemotherapies used for the treatment of aggressive lymphomas or acute myeloid leukemias are quickly inefficient.

Adolescent↗
PubMed2004

Frozen section in laparoscopic management of macroscopically suspicious ovarian masses.

STUDY OBJECTIVE: To study the usefulness of and applications for frozen section in the laparoscopic management of adnexal masses. DESIGN: Historical prospective study (Canadian Task Force classification II-3). SETTING: Large tertiary care hospital with university affiliation. PATIENTS: One hundred forty-one women undergoing laparoscopy for a suspicious adnexal mass. INTERVENTION: Adnexal masses suspicious on ultrasound were managed by laparoscopy. After laparoscopic diagnosis, frozen sections were used to confirm a diagnosis of malignancy. Treatment was performed by laparoscopy whenever feasible. MEASUREMENTS AND MAIN RESULTS: The results of frozen section were compared with the results of permanent sections, and the consequences of the intraoperative diagnosis on the surgical management were evaluated. The frozen section diagnosis was correct in 125 of the 141 patients (88.7%). In one patient, the result was false negative. Specifically, frozen section diagnosis was correct in 96.8% of cases when a cyst or biopsy was sent for pathologic examination and in 86.4% when the whole adnexa was sent. It was correct in 93% of the cases involving tumors smaller than 100 mm and in 74% of larger tumors. It was correct in 92.3% of the women younger than 50 years and in 81.6% of women older than age 50. Intraoperative pathologic diagnosis was correct in 95.5% of benign tumors, 77.8% of low-malignancy tumors, and 75% of cancer cases. CONCLUSION: Frozen section is a useful examination for surgical management decision making; however, the limitations and the difficulties should be taken into account.

Adult↗
PubMed2003

Phytoestrogen-rich diets modulate expression of Brca1 and Brca2 tumor suppressor genes in mammary glands of female Wistar rats.

Phytoestrogens are natural compounds with anticancer, proliferation, differentiation, and chemopreventive effects, for which several mechanisms have been proposed. In the present study, modulation of Brca1 and Brca2 expression by different phytoestrogen-rich diets has been investigated in ovariectomized Wistar rats. Two hundred mammary glands were harvested in three independent experiments. Brca1 and Brca2 mRNAs were quantified by real-time quantitative reverse transcription-PCR, and their proteins by immunohistochemistry. The first experiment compared the influence of different phytoestrogens [flax-seed, isoflavones (IFs), or rutin]. A 10% increase in Brca1 mRNA expression was shown after flax-seed consumption, whereas no variation was noted for Brca2 mRNA, nor for Brca1 and Brca2 proteins. In the second experiment, two soy IFs sources (Novasoy or Soylife) were given at different concentrations to the animals. Only Brca2 mRNA was increased and only at high doses. Finally, the effect of IFs was compared with that of estradiol. An increase in mRNA for both genes was noted after estradiol treatment and with the highest dose of IFs. In conclusion, our results show that IFs, given in the diet at different doses, are able to increase Brca1 and Brca2 mRNA in ovariectomized female Wistar rat. However, no variation in Brca1 or Brca2 protein expression was demonstrated, whatever the experimental conditions were.

Animals↗
PubMed2003

Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa.

Effects of glutamine on whole body and intestinal protein synthesis and on intestinal proteolysis were assessed in humans. Two groups of healthy volunteers received in a random order enteral glutamine (0.8 mmol.kg body wt(-1)x h(-1)) compared either to saline or isonitrogenous amino acids. Intravenous [2H5]phenylalanine and [13C]leucine were simultaneously infused. After gas chromatography-mass spectrometry analysis, whole body protein turnover was estimated from traced plasma amino acid fluxes and the fractional synthesis rate (FSR) of gut mucosal protein was calculated from protein and intracellular phenylalanine and leucine enrichments in duodenal biopsies. mRNA levels for ubiquitin, cathepsin D, and m-calpain were analyzed in biopsies by RT-PCR. Glutamine significantly increased mucosal protein FSR compared with saline. Glutamine and amino acids had similar effects on FSR. The mRNA level for ubiquitin was significantly decreased after glutamine infusion compared with saline and amino acids, whereas cathepsin D and m-calpain mRNA levels were not affected. Enteral glutamine stimulates mucosal protein synthesis and may attenuate ubiquitin-dependent proteolysis and thus improve protein balance in human gut.

Adult↗