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Biomedical subjects

Philippe Ducrotté

Publications and source records attributed to Philippe Ducrotté.

At least 19 recordsLinked to original sources
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

Concomitant variations of gastric tone and duodenal motility in humans: results of a placebo-controlled study assessing octreotide and sumatriptan.

OBJECTIVE: To describe the concomitant effects of octreotide and sumatriptan on fundic tone and duodenal phase III activity. MATERIAL AND METHODS: A double-blind study was performed in nine volunteers, studied for 2 h after receiving 50 microg octreotide, 6 mg sumatriptan or placebo. Fundic tone variations were assessed by barostat while antroduodenal motility was studied concomitantly using manometry. RESULTS: A rapid increase in intrabag volume was observed in all but one subject after both sumatriptan and octreotide administration, while only two subjects exhibited a volume variation after placebo, p<0.01. A significant decrease in the number of phasic contractions was observed after octreotide, while sumatriptan reduced only wave amplitudes (p<0.05). A total of 13 concomitant duodenal phase III-like activities were observed in the duodenum after octreotide, 3 after sumatriptan and 4 after placebo, all followed by spontaneous fundic relaxation with disappearance of phasic contractions, p<0.05. Spontaneous phase III activities were different from phases III-like activities after octreotide in velocity and duration (p<0.05). CONCLUSIONS: Octreotide induced concomitant fundic relaxation, disappearance of phasic contractions and duodenal phase III-like activity. Sumatriptan relaxed the proximal stomach and reduced the amplitude of fundic phasic contractions without affecting concomitant antroduodenal phase III activity.

Adult↗
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

Transient neonatal Cryptosporidium parvum infection triggers long-term jejunal hypersensitivity to distension in immunocompetent rats.

In 5-day-old immunocompetent Sprague-Dawley rats infected with either 10(2) or 10(5) Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.

Animals↗
PubMed2006

Does the treatment of gastroesophageal reflux disease (GERD) meet patients' needs? A survey-based study.

OBJECTIVE: Symptoms of gastroesophageal reflux disease (GERD) affect approximately 20% of people on a weekly basis. A number of different therapies are prescribed to control the disease. This survey-based study was carried out to assess patients' and physicians' perceptions of GERD and its treatment. METHODS: Randomly selected general practitioners (GPs) from five countries (USA, UK, Japan, Germany and France) took part in a faceto-face interview, using a standard questionnaire, concerning the last four GERD patients (those taking GERD medication) who had consulted them and who consented to be interviewed. Those patients were then interviewed via telephone, also using a standard questionnaire. RESULTS: Completed questionnaires were available for 927 of the 1044 patients who were identified. The mean length of time that patients suffered GERD symptoms prior to consultation was more than 1.5 years, with 52.3% of those consulting a GP stating the reason they sought medical attention was that 'symptoms were too uncomfortable to bear'. Only 36% of patients receiving prescription therapy reported that they were currently asymptomatic; 20.5% of patients were also taking at least one over-the-counter (OTC) medication. CONCLUSIONS: In the primary care setting, many patients receiving GERD therapy do not have fully controlled symptoms. It is recommended that GPs question patients routinely about persistent symptoms on therapy, and OTC use, in order that effective treatment choices are made in the management of GERD.

Attitude of Health Personnel↗
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

Factors that affect gastric passage of video capsule.

BACKGROUND: Gastric retention and delayed gastric emptying of the video capsule are major limitations. We retrospectively studied gastric transit time, gastric retention, and completeness of capsule endoscopy (CE) in relation to the conditions in which it was performed. METHODS: From May 2002 to September 2004, CE was performed in 190 patients (92 men; mean age, 58.4 years, range 16-91 years). Patients were stratified according to the way CE was performed (hospital day setting, outpatient, or ongoing hospitalization), and the recordings were analyzed to measure gastric retention, gastric transit time, and the completeness of the examinations. RESULTS: CE examination was performed in a hospital day setting in 100 patients, in an outpatient setting in 61, and during hospitalization in 29. Gastric retention of the capsule occurred in 8 of 190 patients (4.2%) (5 women, 3 men; mean age, 37.9 years). Gastric retention occurred during hospitalization in 7/29 (24.1%) and in hospital day setting in one of 100. Ongoing hospitalization was statistically associated with an increased risk of gastric capsule retention (p < 0.0001). The cecum was reached in 165/190 (87%), and ongoing hospitalization was associated with a lower rate of complete examinations (p < 0.001). Small-bowel transit time was similar, regardless of the circumstances of CE performance. CONCLUSIONS: Ongoing hospitalization is a major cause of gastric retention and incomplete examination by CE. Therefore, CE performance during ongoing hospitalization may require the use of a prokinetic agent.

Adolescent↗
PubMed2005

Prevalence of functional gastrointestinal disorders in a population of subjects consulting for gastroesophageal reflux disease in general practice.

AIMS: To establish the prevalence of functional gastrointestinal (GI) disorders in adult patients with symptoms of gastroesophageal reflux disease (GERD) and to assess the impact of GERD treatment on functional GI disorders in medical practice in France. METHODS: 3318 patients with GERD symptoms (mean age 53 yr; 1726 women and 1592 men) were involved in the survey. A questionnaire on demographic data, GERD features, presence of functional GI disorders and their features, and impact of GERD treatment on functional GI disorders was performed by the physician. The size of the different groups was compared using either a chi2 test or a Mantel-Haenszel analysis, on a case by case basis. RESULTS: Seventy-two percent of patients with GERD had associated functional GI disorders, with a mean of 4.1 +/- 1.9 functional digestive symptoms per patient. Gas, flatulence, transit disorders and abdominal distension were the most commonly reported symptoms. Among patients with functional GI symptoms, 27% had symptoms suggestive of irritable bowel syndrome (IBS), 16% were suggestive of dyspepsia while 57% had both upper and lower functional digestive symptoms. According to the patients, GERD treatment had a positive impact (significant to complete improvement) on their functional GI disorders in about one-third of patients particularly in those with dyspeptic-type symptoms. CONCLUSIONS: Functional GI disorders are particularly common in adult patients suffering from GERD, with a three times higher prevalence than in the general population.

Family Practice↗
PubMed2005

Gastric tone variations during gastric infusion of fiber-supplemented formulas.

BACKGROUND AND AIM: Despite gastric feeding being a common method of artificial nutritional support, little is known about the effects of enteral nutrition on fundic motor function. The objective of this study was to assess variations of fundic tone and their relation to antroduodenal motility before, during and after nasogastric feeding supplemented or not with fibers. METHOD: Double-blinded studies were performed in random order with the three different diets (2100 kJ) in eight volunteers: fiber free (FF), insoluble fiber (IF) or mixed fiber (MF). Fundic tone was recorded by barostat concomitantly with antroduodenal manometry. RESULTS: Before the infusion, seven spontaneous fundic relaxations occurred during the 24 studies. Concomitantly or less than 2 min before these relaxations, phase III of the migrating motor complex (MMC) with a duodenal onset was recorded. Only the 17 studies without spontaneous fundic relaxation (4 FF, 6 MF, 7 IF) were suitable for the assessment of fundic response to infusion. Disappearance of the volume waves at the beginning and during the whole infusion was observed in 11/17 studies (FF 50%, MF 66% and IF 71%, NS), but a proximal gastric relaxation following the beginning of the infusion occurred in only three individuals, one with the FF and two with IF. When it occurred, fundic relaxation was observed within 2 min and was not different from those observed spontaneously. CONCLUSION: Gastric infusion of a polymeric diet, supplemented or not with fiber, did not promote fundic relaxation in most of the cases but often induced a disappearance of gastric volume waves.

Adult↗
PubMed2004

[New-generation proton pump inhibitors: progress in the treatment of peptic acid diseases?].

EFFECTS AND INCONVENIENCIES OF THE OLDER PRODUCTS: The proton pump inhibitors (PPIs) are now universally considered the treatment of choice for management of gastric-acid-related diseases, mainly gastro-oesophageal reflux disease (GERD). These drugs share similar properties: general structure, acid-activation step, covalent binding to the proton pump of the gastric parietal cell via the production of covalent disulphide bonds, relatively stable inhibition of H+,K+-ATPase. However, the older PPIs (omeprazole, lansoprazole et pantoprazole) have notable limitations. These drugs exhibit substantial interpatient variability and may have significant interactions with other drugs. These first-generation PPIs also do not achieve a rapid and sustained suppression of gastric acid, leading to the development of new acid-pump antagonists. The new-generation PPIs, esomeprazole and rabeprazole, offer several pharmacokinetic advantages: lower oxidative hepatic metabolism rate via the CYP 2C19 reducing the activity variations due to genetic polymorphisms and decreasing the risk of significant drug-drug interactions (advantages mainly for rabeprazole), lower metabolic clearance of esomeprazole (S-enantiomer of omeprazole) increasing plasma concentrations and acid suppression of this new PPI, higher accumulation of rabeprazole in the parietal cell due to its higher pKa. Gastric pH studies and therapeutic trials have demonstrated significant advantages of esomeprazole and rabeprazole compared with the older PPIs, which omeprazole is the prototype: a greater inhibition of acid secretion, a more rapid onset of action to provide reflux symptoms relief over 24 hours with lower GERD-related cost for rabeprazole, a sustained acid suppression, cost-effectiveness advantages for esomeprazole in the healing and maintenance of erosive esophagitis compared with lansoprazole, reduced potential for clinically significant drug-drug interactions with rabeprazole compared with omeprazole and esomeprazole. Due to their properties, esomeprazole and rabeprazole are the best candidates for "on demand" treatment of GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Glutamine and CXC chemokines IL-8, Mig, IP-10 and I-TAC in human intestinal epithelial cells.

BACKGROUNDS & AIMS: Chemokines are a family of small proteins involved in immune and inflammatory responses. Human intestinal epithelial cells act as a sentinel in the immune response and produce CXC chemokines such as IL-8, Mig, IP-10 and I-TAC. Glutamine has various effects on immuno-inflammatory response in human intestine. METHODS: The present study aimed to determine the effect of glutamine on the IL-8, Mig, IP-10 and I-TAC production by ELISA and their mRNA level by RT-PCR (expressed as % gapdh) in two human intestinal epithelial cell lines Caco-2/TC7 and HCT-8 under basal conditions or during stimulation with combined cytokines. RESULTS: Under basal conditions, studied chemokines were not influenced by glutamine. When intestinal epithelial cells were stimulated with cytokines, increasing concentrations of glutamine from 2 to 10 mM in HCT-8 cells significantly decreased I-TAC and IP-10 mRNA level (respectively 219 to 182%; P < 0.01; 257 to 176%; P < 0.05) and I-TAC and IP-10 production (respectively 21.2 to 13.0; P < 0.05; 696 to 548 ng/prot mg; P < 0.01). Glutamine also reduced IP-10 mRNA level (186 to 135%, P < 0.05) in cytokines-stimulated Caco-2/TC7 cells. CONCLUSIONS: Down-regulation of CXC chemokines by glutamine could contribute to its therapeutic potential in intestinal inflammation and during critical illness.

Bacterial Infections↗
PubMed2004

[Lower gastrointestinal bleeding due to ileal lipoma. Diagnosis contribution of contrast enhanced helical CT].

Jejunoileal gastrointestinal hemorrhage is uncommon and difficult to diagnose. Ileal lipoma is an unusual cause of jejunoileal bleeding. We report the case of a 45-Year-old patient admitted for acute gastrointestinal bleeding. The patient was taking aspirin at admission. A bleeding intussuscepted ileal lipoma was localized with a contrast enhanced helical computed tomography. This diagnosis was confirmed by laparotomy.

Gastrointestinal Hemorrhage↗