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Bruno Bonaz

Publications and source records attributed to Bruno Bonaz.

At least 19 recordsLinked to original sources
PubMed2007

Corticotropin-releasing factor receptors and stress-related alterations of gut motor function.

Over the past few decades, corticotropin-releasing factor (CRF) signaling pathways have been shown to be the main coordinators of the endocrine, behavioral, and immune responses to stress. Emerging evidence also links the activation of CRF receptors type 1 and type 2 with stress-related alterations of gut motor function. Here, we review the role of CRF receptors in both the brain and the gut as part of key mechanisms through which various stressors impact propulsive activity of the gastrointestinal system. We also examine how these mechanisms translate into the development of new approaches for irritable bowel syndrome, a multifactorial disorder for which stress has been implicated in the pathophysiology.

Anxiety↗
PubMed2006

Technical and functional results after laparoscopic rectopexy to the promontory for complete rectal prolapse. Prospective study in 54 consecutive patients.

INTRODUCTION: Laparoscopic rectopexy for complete rectal prolapse offers short-term advantages compared with operations performed by laparotomy. The aim of this prospective study was to report technical and functional outcome after laparoscopic rectopexy to the promontory in consecutive patients operated on by a single surgeon. PATIENTS AND METHODS: From May 1996 to July 2004, 54 consecutive patients (47 women), median age 53 years (range: 16-84 years), underwent laparoscopic rectopexy to the promontory for complete rectal prolapse. Preoperative evaluation included physical examination, dynamic videoproctography and, in patients with constipation, colonic transit time (with radiopaque markers). Postoperative evaluation included the same examinations and a simple global quality-of-life questionnaire. RESULTS: Conversion to laparotomy was required for three patients during the learning curve. Median duration of operation was 157 minutes (range: 50-370). There was no mortality and morbidity was 5.5% (brachial plexus palsy in two patients and urinary tract infection in one). Median hospital stay was 3.5 days (range: 1-11). There were 4 recurrences (7.4%). Functional outcome at 12 months showed the presence of constipation in 20.3% of patients (persistence in eight and de novo in three) and the presence of outlet obstruction in 25.9% of patients (persistence in six and de novo in eight). Anal continence improved in 72.4% of the 29 patients who complained of this symptom. The global quality-of-life questionnaire showed a satisfactory result in 96% of patients. CONCLUSION: Laparoscopic rectopexy to the promontory is a safe and efficient procedure to treat complete rectal prolapse; morbidity is low. Functional outcome is at least equivalent to that obtained with open procedures in terms of continence, constipation and outlet obstruction.

Adolescent↗
PubMed2006

Sacral neuromodulation in the treatment of severe anal incontinence. Forty consecutive cases treated in one institution.

INTRODUCTION: Sacral neuromodulation is a recognized therapeutic option in severe anal incontinence from neurogenic origins, when medical treatment has failed. METHODS: We report the results of this procedure applied in 40 consecutive patients operated on by a single surgeon from August 2001 to June 2004. Mean duration of incontinence was 5 years. There were 33 women and 7 men of mean age 59 (range 29-89). All patients had had medical treatment, 26 had had physiotherapy and 9 had been previously operated on for that problem. Neuromodulation consisted in a temporary electrical stimulation test followed by implantation of a stimulator in case of efficacy. RESULTS: Twenty nine patients had a positive test and were implanted. Ten had a negative test and one is waiting for implantation. From the 29 patients, 23 had uneventful postoperative course. Incontinence score varied from 17 before neuromodulation to 6 after in the 24 patients who were improved. Mean resting pressure, mean maximum squeeze pressure and mean duration of squeeze pressure did not change from pre to postoperative period. CONCLUSION: Sacral neuromodulation is a safe and efficacious procedure in properly selected anal incontinent patients. However, we observed no correlation between clinical and manometric data.

Adult↗
PubMed2005

Endogenous expression and in vitro study of CRF-related peptides and CRF receptors in the rat gastric antrum.

In vivo studies suggest that corticotrophin-releasing factor (CRF) and CRF-like peptides, urocortin 1 (UCN 1) and UCN 2, inhibit gastric emptying and stimulate colonic motility through CRF2 and CRF1 receptors, respectively. We evaluated expression and functions of CRF, UCN 1, UCN 2 and CRF1 and CRF2 receptors in the rat gastric antrum. Tissues were processed for immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In vitro studies were performed to test the functional significance of CRF, UCN 1 and UCN 2. Some experiments were realized in the presence of specific CRF1 or CRF2 receptors antagonists. CRF1 and CRF2 receptors-like immunoreactivity (CRF1 and CRF2 receptors-LI) was localized in fibers and neurons of the myenteric ganglia. CRF1 and CRF2 receptors-LI was also found in nerve fibers distributed in the muscle layers. CRF- and UCN 1-LI was observed in neuronal cell bodies of the myenteric ganglia and in numerous nerve fibers running parallel to smooth muscle cells. Quantitative RT-PCR demonstrated UCN 2, CRF1 and CRF2 receptors expressions in both muscle layers and mucosa of the gastric antrum. Functional studies showed that CRF, UCN 1 and UCN 2 decreased antral phasic contractions. CRF(1) receptor antagonist (CP-154,526) did not block CRF-like peptides-induced inhibition of antral motility. In contrast, a CRF2 receptor antagonist (Astressin2-B) blocked the effects of CRF-like peptides on the antral muscle contractions. These results demonstrate (1) the presence of CRF, UCN and CRF1 and CRF2 receptors in the rat gastric antrum; (2) that, in vitro, CRF-like peptides inhibit phasic contractions of the antrum through CRF2 receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of gastric motility through CRF2 receptor.

Animals↗
PubMed2005

Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat.

Nor-trimebutine is the main metabolite of trimebutine that is used in the treatment of patients with irritable bowel syndrome. Nor-trimebutine has a blocking activity on sodium channels and a potent local anesthetic effect. These properties were used to investigate the effect of nor-trimebutine on spinal neuronal activation induced by models of noxious somato-visceral stimulus and acute colonic inflammation. Nor-trimebutine was administered in rats either subcutaneously 30 min before intraperitoneal administration of acetic acid or intracolonically 30 min before intracolonic infusion of trinitrobenzenesulfonic acid. Abdominal contractions were counted for 1 h as a marker of abdominal pain. c-fos expression was used as a marker of neuronal activation and revealed by immunohistochemistry 1h after intraperitoneal acetic acid injection and 2 h after colonic inflammation. Nor-trimebutine decreased Fos expression in the thoraco-lumbar (peritoneal irritation) and lumbo-sacral (colonic inflammation) spinal cord in laminae I, IIo V, VII and X. This effect was also observed in the sacral parasympathetic nucleus after colonic inflammation. Nor-trimebutine induced a significant decrease of abdominal contractions following intraperitoneal acetic acid injection. These data may explain the effectiveness of trimebutine in the therapy of abdominal pain in the irritable bowel syndrome.

Abdominal Pain↗
PubMed2005

Bombesin receptor subtype-3 is expressed by the enteric nervous system and by interstitial cells of Cajal in the rat gastrointestinal tract.

Bombesin receptor subtype-3 (BRS-3), a G-protein-coupled orphan receptor, shares 47% and 55% homology with other known mammalian bombesin receptors. Despite the molecular characterization of BRS-3, its function remains unclear as a consequence of its low affinity for bombesin and the absence of an identified natural ligand. Although the other mammalian bombesin receptors are widely distributed in the gut and central nervous system, expression of BRS-3 in the gastrointestinal tract has not been previously described. We report the expression of BRS-3 mRNA and protein in the tunica muscularis of the rat gastrointestinal tract. The mRNA expression pattern was studied by reverse transcription followed by quantitative polymerase chain reaction. To identify the cellular sites of expression of BRS-3, we performed immunocytochemistry by using a N-terminus-specific affinity-purified antiserum. BRS-3 was found to be widely expressed in the rat gastrointestinal tract at both the mRNA and protein levels. BRS-3-like immunoreactivity (BRS-3-LI) was localized in neurons of the myenteric and submucosal ganglia, being primarily concentrated near the neuronal plasma membrane, and in fibers distributed in the longitudinal and circular muscle layers. In addition, BRS-3-LI was observed in the cell bodies and processes of c-kit+ interstitial cells of Cajal. These data have functional applications for the effects mediated by the activation of BRS-3 on gut motility through distinct neuronal and non-neuronal pathways.

Animals↗
PubMed2005

Expression and effects of metabotropic CRF1 and CRF2 receptors in rat small intestine.

Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1 and CRF2; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF1 and CRF2 receptors in the rat small intestine (i.e., duodenum and ileum). CRF(1-2)-like immunoreactivity (CRF(1-2)-LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF(1-2)-LI was found in nerve fibers of the longitudinal and circular muscle layers, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF2 than CRF1 in the ileum, whereas CRF1 expression was higher than CRF2 expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF1 antagonists (CP-154,526 and SSR125543Q) blocked CRF-like peptide-induced activation of duodenal motility but did not block CRF-like peptide-induced inhibition of ileal motility. In contrast, a CRF2 inhibitor (astressin2-B) blocked the effects of CRF-like peptides on ileal muscle contractions but did not influence CRF-like peptide-induced activation of duodenal motility. These results demonstrate the presence of CRF(1-2) in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1 receptor while inhibiting phasic contractions of the ileum through CRF2 receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of small intestinal motility through CRF receptors.

Animals↗
PubMed2005

Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma de novo.

BACKGROUND: Data concerning small bowel adenocarcinoma (SBA) in Crohn's disease (CD) come from case reports and small retrospective series. The aim of this study was to further describe SBA in patients with CD and compare it with SBA de novo. METHODS: Twenty patients with CD with SBA recruited in French university hospitals were studied and compared with 40 patients with SBA de novo recruited from a population-based registry. SBA occurred after a median time of 15 years of CD and was located within the inflamed areas of the ileum (n=19) or jejunum (n=1), whereas in patients with SBA de novo, it was distributed all along the small intestine. Median age at diagnosis of SBA was 47 years (range, 33-72 yr) in patients with CD and 68 years (range, 41-95 yr) in those with SBA de novo. RESULTS: The cumulative risk of SBA, assessed in a subgroup of patients, was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. SBA accounted for 25% and 45% of the risk of gastrointestinal carcinoma after 10 and 25 years of CD, respectively. Diagnosis was made preoperatively in 1/20 patients with CD and 22/40 patients with SBA de novo. Signet ring cells were found in 35% of patients with CD but not in patients with SBA de novo. Relative survival was not significantly different in these 2 categories of patients (54 versus 37% and 35 versus 30% in patients with and without CD at 2 and 5 yr, respectively). CONCLUSIONS: SBA in CD is different from SBA de novo. It arises from longstanding ileal inflammation and is difficult to diagnose. SBA cumulative risk increases after 10 years of CD and is likely to cause premature mortality in patients with early-onset CD.

Adenocarcinoma↗
PubMed2004

Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis.

We aimed to characterize neuronal and corticotropin-releasing factor (CRF) pathways at the acute phase of a model of colitis in rats. Male rats received an intracolonic injection of either vehicle (controls) or trinitrobenzenesulfonic acid (TNBS) and were killed 1, 2, 3, 4, 6, 12, or 24 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF1 receptor, and CRF2alpha,beta receptors were assayed by in situ hybridization histochemistry. Localization of these transcripts within CRF-immunoreactive (CRF-ir) neurons of the paraventricular nucleus (PVN) of the hypothalamus was also determined. Intracolonic TNBS induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioral, and neuroendocrine response to a stimulus (PVN, amygdala, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract) and in circumventricular organs (lamina terminalis, subfornical organ, area postrema). CRF pathways, particularly in the PVN, were activated in this model as represented by a robust signal of c-fos and CRF1 receptor transcripts in the PVN and numerous CRF-ir neurons expressed c-fos or CRF1 receptor transcripts in the PVN of TNBS-treated animals. No expression of CRF2 receptor transcripts was observed in the PVN, either in basal conditions or after TNBS. These neuroanatomical data argue for an involvement of CRF pathways, through CRF1 receptor, within the PVN in TNBS-induced colitis.

Animals↗
PubMed2004

c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats.

We aimed to characterize neuronal and corticotrophin-releasing (CRF) pathways in a model of somato-visceral pain in rats. Male rats received an intraperitoneal (i.p.) injection of either vehicle (controls) or acetic acid (AA) and were sacrificed 1, 2, 3, 4, or 6 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF(1), CRF(2 alpha,beta) receptors were assayed by in situ hybridisation histochemistry. Localization of these transcripts within CRF-immunoreactive (i.r.) neurons of the paraventricular nucleus (PVN) of the hypothalamus was also determined. AA i.p. induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioural and neuroendocrine response to pain. Some of these nuclei are involved in the control of digestive motility, as represented by the PVN, locus coeruleus and nucleus tractus solitarius. CRF pathways, in particular in the PVN, are activated in this model. Indeed, a robust signal of c-fos and CRF(1) transcripts was observed in the PVN and numerous CRF-i.r. neurons expressed c-fos or CRF(1) transcripts in the PVN of AA-treated animals. In contrast, no expression of CRF(2) transcripts was observed in the PVN either in basal conditions or after AA i.p. These data argue for an activation of CRF pathways within the PVN in this model of somato-visceral pain. The use of CRF antagonists, particularly of the CRF(1) type, should have an interest in somato-visceral pain pathology.

Acetic Acid↗
PubMed2004

Irritable bowel syndrome in France: a common, debilitating and costly disorder.

OBJECTIVE: This epidemiological investigation aims to measure the prevalence of irritable bowel syndrome (IBS) in the general population using the Rome II criteria and to evaluate the medical management including treatments and the impact of IBS on patient life. METHODS: A nationally representative sample of 20,000 French subjects, aged 18 years and over, were interviewed by SOFRES (French Public Opinion Poll Institute) in May 2001. In a second phase (June/July 2001), a 48-question self-administered questionnaire was given to the subjects who have been selected during the first phase as suffering from IBS (Rome II criteria). RESULTS: The prevalence of IBS was 4.7% (confidence interval, 4.36-5.04% with 5% risk) with a predominance in women (5.7% versus 3.7%, P < 0.01). The abdominal pain was often longstanding (> 5 years, 50%), intense (43%) and nocturnal (35%). During the most recent painful episode the levels of associated transit problems were almost equally divided between diarrhoea (36%), constipation (29%) and alternate episodes of both (31%). Apart from pain, bloating was given as the most frequent (73%) and most troublesome (24%) symptom. Since the onset, 80% of subjects with IBS had consulted a doctor (90% consulted a general physician, 57% a gastroenterologist, 50% both) and of these, 80% consulted within the previous 12 months. Sixty-seven per cent of subjects underwent additional investigations since the start of their illness (average of 3.4 examinations per patient examined: colonoscopy, 34.1%; laboratory tests, 34%; and abdominal ultrasound, 27.7%). Over the previous 12 months, 8% of the subjects had been admitted to hospital (average length of stay, 6.6 days), 11% of employed subjects had to take time off, 93% of subjects had taken prescribed medication (87%), but 43% of people thought it was ineffective. The effect on daily life was considerable (score, 6.2/10; close to the score for flu, 7/10). Two-thirds of the individuals changed their diet; 54% said it affected their social life and 29% their professional life. Seventy-four per cent of patients trusted their doctor, with a satisfaction index of 63%, but 45% of patients would like to have more information on IBS. CONCLUSION: This study confirmed that the Rome II criteria detected IBS with a prevalence of 4.7%. The recruited subjects had severe symptoms (frequency, intensity and duration) that had a considerable effect on their daily life. The high level of referrals and initial consultations in all categories and the patient's attitudes towards the illness and its treatment emphasize the relative ineffectiveness of care for patients suffering from IBS.

Adult↗