Guy E. Boeckxstaens

University of Leuven, Louvain, Flanders, Belgium

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Publications (227)1846.82 Total impact

  • An Moonen, Guy Boeckxstaens
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    ABSTRACT: The mechanical properties of the esophagogastric junction (EGJ) are of major importance for the competence of the EGJ. Although manometry reliably measures sphincter pressure, no information is provided on distensibility, a crucial determinant of flow across the EGJ. Recently, a new technique, impedance planimetry, was introduced allowing accurate measurement of compliance or distensibility. This review discusses the recent advances in this area and highlights the clinical relevance of this new technique evaluating the mechanical properties of the esophageal wall and EGJ.
    Gastrointestinal Endoscopy Clinics of North America 10/2014;
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    ABSTRACT: Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ$beta$1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 × 10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQ$alpha$1 at position 41 (lysine encoded by HLA-DQA1*01:03; P = 5.60 × 10(-10)) and of HLA-DQ$beta$1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P = 1.20 × 10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.
    Nature Genetics 07/2014; 46(8):901-904. · 35.21 Impact Factor
  • An Moonen, Guy Boeckxstaens
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    ABSTRACT: Achalasia is the best characterized primary esophageal motility disorder of the esophagus and typically presents with absent peristalsis of the esophageal body and a failure of the lower esophageal sphincter to relax upon swallowing on manometry, associated with progressively severe dysphagia, regurgitation, aspiration, chest pain, and weight loss. The diagnosis is suggested by barium swallow and endoscopy, and confirmed by manometry. As there is no curative treatment for achalasia, treatment is confined to disruption of the lower esophageal sphincter to improve bolus passage. Treatment modalities available for this purpose include pneumatic dilation, laparoscopic Heller myotomy and since recently peroral endoscopic myotomy or POEM. In this review, we will discuss the current diagnosis, management, and treatment options of achalasia.
    Journal of Clinical Gastroenterology 07/2014; 48(6):484-490. · 3.20 Impact Factor
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    ABSTRACT: Based on the discomfort/pain threshold during rectal distension, Irritable Bowel Syndrome (IBS) patients may be subtyped as normo- or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that visceral sensitivity is linked to the degree of neuronal activation. Normo- and hypersensitive IBS patients were distinguished by their discomfort/pain threshold to rectal balloon distension with a barostat. Using potentiometric and Ca(2+) dye imaging, we recorded the response of guinea pig enteric submucous and mouse dorsal root ganglion (DRG) neurons, respectively, to mucosal biopsy supernatants from normosensitive (n = 12 tested in enteric neurons, n = 9 tested in DRG) and hypersensitive IBS (n = 9, tested in both types of neurons) patients. In addition, we analyzed the association between neuronal activation and individual discomfort/pain pressure thresholds. IBS supernatants evoked Ca(2+) transients in DRG neurons and spike discharge in submucous neurons. Submucous and DRG neurons showed significantly stronger responses to supernatants from hypersensitive IBS patients as reflected by higher spike frequency or stronger [Ca(2+)]i transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca(2+)]i transients and proportion of responding neurons significantly correlated with the individual discomfort/pain thresholds of the IBS patients. Supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons. The level of activation correlated with the individual discomfort/pain threshold pressure values. These findings support our hypothesis that visceral sensitivity is linked to activation of peripheral neurons by biopsy supernatants. This article is protected by copyright. All rights reserved.
    Experimental physiology 06/2014; · 3.17 Impact Factor
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    ABSTRACT: Background Postoperative ileus (POI) is characterized by impaired gastrointestinal motility resulting from intestinal handling-associated inflammation. The introduction of laparoscopic surgery has dramatically reduced the duration of POI. However, it remains unclear to what extent this results in a reduction of intestinal inflammation. The aim of the present study is to compare the degree of intestinal inflammation and gastrointestinal transit following laparoscopic surgery and open abdominal surgery.Methods Mice were subjected to laparoscopic surgery or laparotomy alone or, in combination with standardized intestinal manipulation of the small bowel (IM). Gastrointestinal transit and intestinal inflammation were assessed 24 h after surgery by the number of myeloperoxidase (MPO) positive cells and the level of cytokine expression. The recovery time and the degree of inflammation were also analyzed in patients subjected to colectomy under open conditions (laparotomy) or laparoscopic conditions.Key ResultsMice undergoing IM by laparotomy (open IM), but not by laparoscopy (Lap IM) developed a significant delay in gastrointestinal transit compared to laparotomy or laparoscopy alone. In addition, there was significant intestinal inflammation only after open IM. Similarly, cytokine levels in peritoneal lavage fluid were lower while recovery time was faster in patients subjected to colectomy under laparoscopic conditions compared to open colectomy.Conclusions & InferencesOur data confirms that intestinal inflammation is underlying the delayed gastrointestinal transit observed after open surgery. Most importantly, we demonstrate that intestinal inflammation under laparoscopic conditions is significantly lower compared to open surgery, most likely explaining the faster recovery following laparoscopic surgery.
    Neurogastroenterology and Motility 06/2014; · 2.94 Impact Factor
  • Tim Vanuytsel, Jan F Tack, Guy E Boeckxstaens
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    ABSTRACT: Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.
    Journal of Gastroenterology 05/2014; · 3.79 Impact Factor
  • Wout O Rohof, Roelof J Bennink, Guy E Boeckxstaens
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    ABSTRACT: The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 male; 55±2.1 years old) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring following a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of 99mTc-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated and its pH was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was significantly reduced in those on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n=6) than in those who were (n=16) (0.9 [range 0.7-1.2] vs 4.0 [range 1.6-5.9]; P<.001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r=0.72, P<.01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 04/2014; · 5.64 Impact Factor
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    ABSTRACT: The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.
    Gut 03/2014; · 10.73 Impact Factor
  • Guy E Boeckxstaens, Wout O Rohof
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    ABSTRACT: Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding of these factors has significantly improved in recent years, with increased understanding of the acid pocket and hiatal hernia and how these factors interact. Although our insight has significantly increased over the past years, more studies are required to better understand symptom generation in GERD, especially in patients with therapy-resistant symptoms.
    Gastroenterology clinics of North America 03/2014; 43(1):15-25. · 2.56 Impact Factor
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    ABSTRACT: Irritable bowel syndrome is a prevalent and chronic disorder, characterized by recurrent abdominal pain/discomfort, bloating and altered bowel habits. This condition affects an estimated 10-15% of the population worldwide and impacts heavily on a patient's daily life and ability to work, as well as healthcare resource utilization. Drug therapy aimed at correcting the primary symptoms of diarrhea/constipation/bloating may have little effect on abdominal pain, which results from visceral hypersensitivity. Smooth muscle relaxants or antispasmodics decrease the tone and contractility of intestinal smooth muscle, effectively managing abdominal pain. Otilonium bromide has been widely used worldwide and has been found to be safe and well tolerated, and superior to placebo for the reduction of symptoms and the prevention of symptom relapse in patients with irritable bowel syndrome.
    Expert review of gastroenterology & hepatology 02/2014; 8(2):131-7.
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    ABSTRACT: [This corrects the article on p. e85304 in vol. 9.].
    PLoS ONE 01/2014; 9(1). · 3.53 Impact Factor
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    ABSTRACT: Electrical stimulation of the vagus nerve suppresses intestinal inflammation and normalizes gut motility in a mouse model of postoperative ileus. The exact anatomical interaction between the vagus nerve and the intestinal immune system remains however a matter of debate. In the present study, we provide additional evidence on the direct and indirect vagal innervation of the spleen and analyzed the anatomical evidence for neuroimmune modulation of macrophages by vagal preganglionic and enteric postganglionic nerve fibers within the intestine. Dextran conjugates were used to label vagal preganglionic (motor) fibers projecting to the small intestine and spleen. Moreover, identification of the neurochemical phenotype of the vagal efferent fibers and enteric neurons was performed by immunofluorescent labeling. F4/80 antibody was used to label resident macrophages. Our anterograde tracing experiments did not reveal dextran-labeled vagal fibers or terminals in the mesenteric ganglion or spleen. Vagal efferent fibers were confined within the myenteric plexus region of the small intestine and mainly endings around nNOS, VIP and ChAT positive enteric neurons. nNOS, VIP and ChAT positive fibers were found in close proximity of intestinal resident macrophages carrying α7 nicotinic receptors. Of note, VIP receptors were found on resident macrophages located in close proximity of VIP positive nerve fibers. In the present study, we show that the vagus nerve does not directly interact with resident macrophages in the gut or spleen. Instead, the vagus nerve preferentially interacts with nNOS, VIP and ChAT enteric neurons located within the gut muscularis with nerve endings in close proximity of the resident macrophages.
    PLoS ONE 01/2014; 9(1):e87785. · 3.53 Impact Factor
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    ABSTRACT: Postoperative ileus is characterized by a transient impairment of the gastrointestinal motility after abdominal surgery. The intestinal inflammation, triggered by handling of the intestine, is the main factor responsible for the prolonged dysmotility of the gastrointestinal tract. Secondary lymphoid organs of the intestine were identified as essential components in the dissemination of inflammation to the entire gastrointestinal tract also called field effect. The involvement of the spleen, however, remains unclear.
    PLoS ONE 01/2014; 9(7):e102211. · 3.53 Impact Factor
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    The American Journal of Gastroenterology 01/2014; 109(1):137. · 9.21 Impact Factor
  • Wout O. Rohof, Roelof J. Bennink, Guy E. Boeckxstaens
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    ABSTRACT: Background & Aims The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Methods Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 male; 55±2.1 years old) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring following a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of 99mTc-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated and its pH was measured. Results The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was significantly reduced in those on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n=6) than in those who were (n=16) (0.9 [range 0.7–1.2] vs 4.0 [range 1.6–5.9]; P<.001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r=0.72, P<.01). Conclusion Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD.
    Clinical Gastroenterology and Hepatology. 01/2014;
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    ABSTRACT: Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors predisposing to achalasia have been poorly documented, we assessed whether single nucleotide polymorphisms (SNPs) in genes mediating immune response and neuronal function contribute to achalasia susceptibility. 391 SNPs covering 190 immune and 67 neuronal genes were genotyped in an exploratory cohort from Central Europe (589 achalasia patients, 794 healthy volunteers (HVs)). 24 SNPs (p<0.05) were validated in an Italian (160 achalasia patients, 278 HVs) and Spanish cohort (281 achalasia patients, 296 HVs). 16 SNPs in linkage disequilibrium (LD) with rs1799724 (r(2)>0.2) were genotyped in the exploratory cohort. Genotype distributions of patients (1030) and HVs (1368) were compared using Cochran-Armitage trend test. The rs1799724 SNP located between the lymphotoxin-α (LTA) and tumour necrosis factor-α (TNFα) genes was significantly associated with achalasia and withstood correction for testing multiple SNPs (p=1.17E-4, OR=1.41 (1.18 to 1.67)). SNPs in high LD with rs1799724 were associated with achalasia. Three SNPs located in myosin-5B, adrenergic receptor-β-2 and interleukin-13 (IL13) showed nominally significant association to achalasia that was strengthened by replication. Our study provides evidence for rs1799724 at the LTA/TNFα locus as a susceptibility factor for idiopathic achalasia. Additional studies are needed to dissect which genetic variants in the LTA/TNFα locus are disease-causing and confirm other variants as potential susceptibility factors for achalasia.
    Gut 11/2013; · 10.73 Impact Factor
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    ABSTRACT: OBJECTIVES:Abnormal pain perception or visceral hypersensitivity (VH) is considered to be an important mechanism underlying symptoms in a subgroup of irritable bowel syndrome (IBS) patients. Increased TRPV1 (transient receptor potential cation channel subfamily V member 1) expression in rectal biopsies of IBS patients suggests a potentially important role for this nociceptor in the pathophysiology of IBS. However, evidence underscoring the involvement of TRPV1 in visceral perception in IBS is lacking. The objective of this study was to evaluate the role of TRPV1 in VH to rectal distension and clinical symptoms in patients with IBS.METHODS:A total of 48 IBS patients and 25 healthy volunteers (HVs) were invited to undergo subsequent assessment of sensitivity to rectal distensions and rectal capsaicin applications. Visceral sensitivity was evaluated by rectal distension at 3, 9, and 21 mm Hg above minimal distension pressure (MDP). Capsaicin was applied to the rectal mucosa (0.01%, 0.1%, or solvent only in random order). Visceral sensations (urge to defecate, pain, burning, and warmth sensation) were scored on a 100-mm visual analog scale (VAS). TRPV1 expression in rectal biopsies was determined by immunohistochemistry and real-time PCR.RESULTS:A total of 23 IBS patients (48%) were hypersensitive to rectal distensions (VH-IBS). A concentration-dependent increase of urge and pain perception was present in HVs and IBS patients during capsaicin 0.01 and 0.1% applications. VH-IBS patients experienced a significantly increased perception of pain, but not urge, during capsaicin applications compared with normosensitive patients (ns-IBS) and HVs. Increased pain perception was significantly associated with anxiety and VH, symptoms scores of abdominal pain, loose stools, and stool frequency. Anxiety experienced during the experimental procedure was enhanced in VH-IBS patients but not in ns-IBS or HVs. However, rectal TRPV1 expression was similar in VH-IBS, ns-IBS, and HVs on both mRNA and protein expression levels. TRPV1 expression levels did not correlate with pain perception to capsaicin or clinical symptoms in IBS patients or the subgroups.CONCLUSIONS:IBS patients with VH to rectal distension reveal increased pain perception to rectal application of capsaicin, as well as an increased anxiety response. No evidence for TRPV1 upregulation could be demonstrated. As both VH and anxiety are independently associated with increased pain perception to rectal capsaicin application, our data suggest that both peripheral and central factors are involved, with increased receptor sensitivity as a speculative possibility.Am J Gastroenterol advance online publication, 5 November 2013; doi:10.1038/ajg.2013.371.
    The American Journal of Gastroenterology 11/2013; · 9.21 Impact Factor
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    ABSTRACT: Approximately 30% of patients with gastroesophageal reflux disease (GERD) have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability and possibly the position of the gastric acid pocket might underlie a partial response to PPI. To what extent these mechanisms interact and contribute to PPI resistant symptoms has however not been investigated previously. In 18 GERD patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the LES. Mucosal permeability of 4 esophageal biopsies per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance (TEER) and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH-impedance following a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs. PPI partial responders 4.2 ± 0.4 p=0.54) or in the position of the acid pocket was observed in PPI partial responders compared to PPI responders. In addition, permeability of esophageal mucosa was similar in both groups, as demonstrated by a similar TEER and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent compared to PPI responders, and were more sensitive to balloon distension, both in the upper and the lower esophagus. PPI resistant symptoms are most likely explained by increased proximal reflux in a hypersensitive esophagus, and less likely by increased mucosal permeability or the position of the acid pocket.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2013; · 5.64 Impact Factor
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    ABSTRACT: Intestinal permeability and psychological stress have been implicated in the pathophysiology of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms. Small intestinal permeability was quantified by a 2 h lactulose-mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of electroshocks. In a second study, five test conditions were investigated in 13 volunteers: control; after pretreatment with disodium cromoglycate (DSCG); administration of CRH; DSCG+CRH and DSCG+public speech. Indomethacin, as a positive comparator (0.071±0.040 vs 0.030±0.022; p<0.0001), and public speech (0.059±0.040; p<0.01), but not the shock protocol increased intestinal permeability. Similarly, salivary cortisol was only increased after public speech. Subgroup analysis demonstrated that the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol. CRH increased the lactulose-mannitol ratio (0.042±0.021 vs 0.028±0.009; p=0.02), which was inhibited by the mast cell stabiliser DSCG. Finally, intestinal permeability was unaltered by public speech with DSCG pretreatment. Acute psychological stress increases small intestinal permeability in humans. Peripheral CRH reproduces the effect of stress and DSCG blocks the effect of both stress and CRH, suggesting the involvement of mast cells. These findings provide new insight into the complex interplay between the central nervous system and GI function in man.
    Gut 10/2013; · 10.73 Impact Factor
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    ABSTRACT: Idiopathic rhinitis (IR) is a prevalent condition for which capsaicin nasal spray is the most effective treatment. However, the mechanisms underlying IR and the therapeutic action of capsaicin remain unknown. We sought to investigate the molecular and cellular bases of IR and the therapeutic action of capsaicin. Fourteen patients with IR and 12 healthy control subjects (HCs) were treated with intranasal capsaicin. The therapeutic effect was assessed in patients with IR by using visual analog scale and therapeutic response evaluation scores, and nasal hyperreactivity was evaluated by means of cold dry air provocation. Nasal samples served to measure the levels of neuromediators and expression of chemosensory cation channels, protein gene product 9.5 (PGP 9.5), and the mast cell marker c-kit. The effects of capsaicin were also tested in vitro on human nasal epithelial cells and mast cells. Patients with IR had higher baseline transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) expression in the nasal mucosa and higher concentrations of substance P (SP) in nasal secretions than HCs. Symptomatic relief was observed in 11 of 14 patients with IR after capsaicin treatment. Expression of TRPV1; transient receptor potential cation channel subfamily M, receptor 8 (TRPM8); and PGP 9.5 was only reduced in patients with IR after capsaicin treatment. Capsaicin did not alter c-KIT expression or nasal epithelial morphology in patients with IR and HCs nor did it induce apoptosis or necrosis in cultured human nasal epithelial cells and mast cells. IR features an overexpression of TRPV1 in the nasal mucosa and increased SP levels in nasal secretions. Capsaicin exerts its therapeutic action by ablating the TRPV1-SP nociceptive signaling pathway in the nasal mucosa.
    The Journal of allergy and clinical immunology 10/2013; · 12.05 Impact Factor

Publication Stats

3k Citations
1,846.82 Total Impact Points

Institutions

  • 2011–2014
    • University of Leuven
      • Translational Research Center for Gastrointestinal Disorders (TARGID)
      Louvain, Flanders, Belgium
    • Temple University
      • Section of Gastroenterology
      Philadelphia, PA, United States
  • 2008–2014
    • Universitair Ziekenhuis Leuven
      • Department of Gastroenterology
      Louvain, Flanders, Belgium
  • 2013
    • Northwestern University
      • Division of Hospital Medicine
      Evanston, IL, United States
  • 1997–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Gastroenterology and Hepatology
      • • Tytgat Institute for Liver and Intestinal Research
      • • Academic Medical Center
      • • Department of Surgery
      Amsterdam, North Holland, Netherlands
  • 2010
    • AstraZeneca
      Tukholma, Stockholm, Sweden
  • 2007
    • University of Oxford
      Oxford, England, United Kingdom
    • Zaans Medical Centre
      Zaandam, North Holland, Netherlands
  • 2003–2007
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2001–2006
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 1990–1995
    • University of Antwerp
      • Faculty of Medicine
      Antwerpen, VLG, Belgium