Francesco De Giorgi

Effects of long‐term PPI treatment on producing bowel symptoms and SIBO

Eur J Clin Invest 2011; 41 (4): 380–386

Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells

Objective Enteric glial cells (EGC) have been suggested to participate in host–bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in host–bacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production. Design Primary cultures of human EGC were exposed to pathogenic (enteroinvasive Escherichia coli; EIEC) and probiotic (Lactobacillus paracasei F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors. Results EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC. Conclusions Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.

Correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease

Background & aims Oesophageal acidification induces dyspeptic symptoms in healthy individuals. This study aimed to evaluate the correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease. Methods A total of 68 patients with dominant symptoms of heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic symptoms participated in the study. The severity of dyspepsia and reflux-related symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was performed in all patients at baseline and after 4 weeks of therapy with esomeprazole 40 mg. Results Oesophageal basal acid exposure was pathological in 43 patients and normal in 25 patients, with a similar prevalence and severity of individual dyspeptic symptoms in the two groups. A significant correlation between reflux and dyspepsia scores was observed in the subgroup of patients with normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07, respectively). After esomeprazole, a reduction in severity of dyspepsia (≥50% with respect to baseline) was observed, independent of improvement of reflux-associated symptoms. Improvement in dyspepsia was, however, similar in patients with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively, P=NS). Conclusion Dyspeptic symptoms coexist in a subset of nonerosive reflux disease patients, but prevalence and severity of the symptoms seems to be independent of oesophageal acid exposure.

Symptoms and pathophysiological correlations in patients with constipation and functional dyspepsia.

Introduction: Patients with constipation often report dyspeptic symptoms, but whether constipation is associated with specific dyspeptic symptoms and altered gastrointestinal (GI) motility, remains to be established. Our aim was to study symptoms association and GI motility parameters in patients with constipation and functional dyspepsia. Patients and Method: 42 patients with different symptoms and severity of constipation and dyspepsia were enrolled. Scintigraphic gastric emptying, colonic transit time and gallbladder contraction were studied in all subjects. Results: No significant association was observed between individual symptoms of constipation and dyspepsia. Patients with more severe constipation did not have higher dyspepsia severity scores. Colonic transit time, gastric half emptying and gallbladder contraction were not significantly correlated. Although patients with severe nausea had faster colonic transit than those with absent/mild symptom (19 ± 2 vs. 48 ± 7 h; p < 0.05), the multivariate analysis only revealed a significant association between severe postprandial fullness, delayed t1/2 (OR 1.05, CI 1–1.1) and impaired gallbladder contraction (OR 0.94, CI 0.89–0.99). Conclusions: Constipation was not associated with severity, or any particular dyspeptic symptom. Although motor abnormalities of both colon and proximal GI tract regions existed in the subset of constipated dyspeptic patients, they did not seem associated with the genesis of different dyspeptic symptoms.

Esophageal acid exposure and altered neurocardiac function in GERD patients with idiopathic arrhytmias

under i7 years (mean age i2 yxs) and 352 adults (i78 men, mean age 53 yrs). The children presented a mean of 2.4 years (range 0-11) after symptom onset, while adults did so after 62 years (range 0,5-40; p = 0.01 t-test). Presenting symptoms in children and adults respecnvely were dysphagia (100/99%, n.s.), regurgitation (73/70%, n.s.), retrostemal pain (42140%, n.s), pyrosis (4/24%, p=0.01), cough (31/18%, n.s.) and weight loss (27/47% >5 kg, n.s.). Esophageal manometry showed no difference between both groups. Barium swallow showed dilation in 65% and 81%(n.s.); all patients in both groups had a typical bird beak with stasis of contrast. Endoscopy showed dilation in 58% and 76% (p =0,05), tertiary contractions in 11% and 21% (n.s) and food retention in 77% and 74%(n.s.). In 16 children pneumo-dilation failed after a mean 32 months, compared with 86 failures after a mean 38 months in adults (p = 0.00 ] ). Statistical analysis of presenting symptoms, diagnostic delay, patient characteristics and clinical features in relation to treatment success revealed only age as a predictor of outcome; in comparing the two groups as well as within the adult group younger age adversely effects success of pneumo-dilation. CONCLUSION Children generally present with similar clinical symptoms as adults, with exception of pyrosis. Diagnosuc eva[nation shows more frequent esophageal dilation in adults at barium swallow and endoscopy and the delay until diagnosis is shorter in children than in adults. Young age adversely affects outcome of pneumo-dilation (p = 0.003), all other parameters am no predictors of balloon dilation outcome