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Background/aims: Partially hydrolyzed guar gum (PHGG) relieves symptoms in constipation-predominant irritable bowel syndrome (IBS) and may have prebiotic properties. However, the correlation between the effectiveness of PHGG and patient characteristics has not been examined. We aimed to investigate the effect of PHGG in symptom relief on constipation-predominant IBS according to gender, age, and body mass index (BMI)., Patients and Methods: Sixty-eight patients with IBS entered a 2-week run-in period, followed by a 4-week study period with PHGG. Patients completed a daily questionnaire to assess the presence of abdominal pain/discomfort, swelling, and the sensation of incomplete evacuation. The number of evacuations/day, the daily need for laxatives/enemas and stool consistency-form were also evaluated. All patients also underwent a colonic transit time (CTT) evaluation., Results: PHGG administration was associated with a significant improvement in symptom scores, use of laxatives/enemas, stool form/consistency and CTT. At the end of the study period and compared with baseline, the number of evacuations improved in women, patients aged ≥ 45 years and those with BMI ≥ 25 (P < 0.05 for all comparisons); abdominal bloating improved in males (P < 0.05), patients < 45 years (P < 0.01) and those with BMI < 25 (P < 0.05). A decrease in the number of perceived incomplete evacuations/day was reported in patients with a BMI ≥ 25 (P < 0.05). Reductions in laxative/enema use were recorded in females (P < 0.05), patients < 45 years (P < 0.01), and patients with BMI < 25 (P < 0.05)., Conclusions: Gender, age, and BMI seem to influence the effect of PHGG supplementation in constipated IBS patients. Further studies are needed to clarify the interaction of such parameters with a fiber-enriched diet.

Among the different signaling molecules released during reactive gliosis occurring in Alzheimer's disease (AD), the astrocyte-derived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (Aβ-) induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits Aβ-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease.

Unlabelled: Cyanoacrylate skin adhesive is increasingly used to ensure and stabilize wound closures. One of the documented favorable effects of these glues is to limit the risk of a surgical site infection by physically isolating the wound., Patients and Methods: From January 2005 to January 2013, 900 patients requiring surgical treatment in the Structure of Plastic Surgery of the University of Sienna were enrolled for the study and divided in two groups; 450 patients treated with glue versus 450 controls., Results: The cohort of patients treated with glue had lower incidence of wound infection and wound dehiscence. Approximately 375 work-hours were economized., Conclusion: Octyl-2-cyanoacrylate is a valuable aid for ensuring the success of surgery by reducing surgical site infections. The use of octyl-2-cyanoacrylate is easy, guarantying a major superficial protection without relevant contraindications and with evident saving of time and resources., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.

The risk of surgical site infection is always present in surgery; the use of prosthetic materials is linked to an increased possibility of infection. Breast augmentation and breast reconstruction with implants are gaining popularity in developing countries. Implant infection is the main complication related to breast aesthetic and reconstructive surgery. In the present paper, we reviewed the current microbiological knowledge about implant infections, with particular attention to risk factors, diagnosis, clinical management, and antibiotic prophylaxis, focusing on reports from developing countries. After breast aesthetic surgery, up to 2.9% of patients develop a surgical site infection, with an incidence of 1.7% for acute infections and 0.8% for late infections. The rate of surgical site infection after post-mastectomy breast reconstruction is usually higher, ranging from 1% to 53%. The clinical features are not constant, and bacterial culture with antibiogram is the gold standard for diagnosis and for identification of antibiotic resistance. While waiting for culture results, empiric therapy with vancomycin and extended-spectrum penicillins or cephalosporins is recommended. Some patients require removal of the infected prosthesis. The main methods to bring down the risk of infection are strict asepsis protocol, preoperative antibiotic prophylaxis, and irrigation of the surgical pocket and implant with an antibiotic solution.

Background: After a review of clinical cases of the Unit of Plastic Surgery of the University of Siena, Italy, we found that 22 patients undergoing lipofilling for breast recontruction needed less pain drugs compared to 18 patients which did not undergo lipofilling. In this work, the postoperative pain was analyzed in two groups of patients: a cohort treated with prosthesis and a cohort treated with prosthesis implant together with a lipofilling procedure., Patients and Methods: During the immediate postoperative period, a visual analog scale for pain was submitted to every patient every eight hours until they were discharged, then every day for a week, every two days during the second week and once a week in the first three months. The administration of analgesics was also registered., Results: Pain intensity was lower in the group treated with prosthesis and lipofilling., Conclusion: Fat transplant is a procedure well-tolerated by patients, resulting in a lower rate of pain., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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-DQβ1 (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-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.60×10(-10)) and of HLA-DQβ1 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.

Objective: Enteric glia activation has been reported to amplify intestinal inflammation via the enteroglial-specific S100B protein. This neurotrophin promotes macrophage recruitment in the mucosa, amplify colonic inflammation and interacts with toll-like receptors (TLR). Molecules inhibiting S100B-driven enteric activation might mitigate the course of ulcerative colitis (UC). This study aims to investigate the effects of palmitoylethanolammide (PEA), a drug able to counteract astroglial activation in the central nervous system, on intestinal inflammation, in humans and mice., Design: Mouse models of dextran sodium sulphate (DSS)-induced colitis, colonic biopsies deriving from UC patients and primary cultures of mouse and human enteric glial cells (EGC), have been used to assess the effects of PEA, alone or in the presence of specific PPARα or PPARγ antagonists, on: macroscopic signs of UC (DAI score, colon length, spleen weight, macrophages/neutrophils infiltration); the expression and release of proinflammatory markers typical of UC; TLR pathway in EGCs., Results: PEA treatment improves all macroscopic signs of UC and decreases the expression and release of all the proinflammatory markers tested. PEA anti-inflammatory effects are mediated by the selective targeting of the S100B/TLR4 axis on ECG, causing a downstream inhibition of nuclear factor kappa B (NF-kB)-dependent inflammation. Antagonists at PPARα, but not PPARγ, abolished PEA effects, in mice and in humans., Conclusions: Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS.

Background & Aims: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5., Methods: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls., Results: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS., Conclusions: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to evaluate the association between constipation severity, productivity losses and healthcare utilization in a national sample of Italian patients with chronic non-organic constipation (CC)., Methods: We enrolled 878 outpatients with CC. Clinical and demographic data were collected by physicians during clinical examinations. Patients completed a self-administered questionnaire (Patient Assessment of Constipation-Symptoms, PAC-SYM; Work Productivity and Activity Impairment; healthcare utilization, and Symptoms Checklist 90 Revised - Somatization Scale, SCL-90 R)., Results: Mean PAC-SYM score was 1.62 ± 0.69. Mean weekly sick time due to constipation was 2.7 ± 8.6 h and productivity losses due to presenteeism was 19.7% ± 22.3%. Adjusted productivity losses in patients with severe CC (PAC-SYM score 2.3-4.0) compared to patients with mild symptoms (PAC-SYM score 0.0-1.0) was Italian Purchase Power Parity US$ 6160. Constipation severity (PAC-SYM quintiles) was associated with higher healthcare utilization (RRPAC-SYM 4/01.84; p-value for linear trend <0.01). After adjustment for somatization scores, the association of constipation severity with productivity losses and healthcare utilization rates was attenuated yet statistically significant., Conclusions: We observed a graded increase in productivity losses and healthcare utilization with increasing constipation severity. Further studies should evaluate whether significant savings might be achieved with regimens aimed at reducing the constipation severity.

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.

Alcoholic beverages (ABs) and carbonated soft drinks (CSDs) are widely consumed worldwide. Given the high consumption of these beverages, the scientific community has increased its focus on their health impact. There is epidemiological evidence of a causal association between AB intake and digestive cancer, but the role of alcohol in determining cancer is not fully defined. Experimental studies have so far identified multiple mechanisms involved in carcinogenesis; ethanol itself is not carcinogenic but available data suggest that acetaldehyde (AA) and reactive oxygen species-both products of ethanol metabolism-have a genotoxic effect promoting carcinogenesis. Other carcinogenetic mechanisms include nutritional deficits, changes in DNA methylation, and impaired immune surveillance. As CSDs are often suspected to cause certain gastrointestinal disorders, consequently, some researchers have hypothesized their involvement in gastrointestinal cancers. Of all the ingredients, carbon dioxide is prevalently involved in the alteration of gastrointestinal physiology by a direct mucosal effect and indirect effects mediated by the mechanical pressure determined by gas. The role of sugar or artificial sweeteners is also debated as factors involved in the carcinogenic processes. However, several surveys have failed to show any associations between CSDs and esophageal, gastric, or colon cancers. On the other hand, a slight correlation between risk of pancreatic cancer and CSD consumption has been found.

Motility disorders of the upper gastrointestinal tract encompass a wide range of different diseases. Esophageal achalasia and functional dyspepsia are representative disorders of impaired motility of the esophagus and stomach, respectively. In spite of their variable prevalence, what both diseases have in common is poor knowledge of their etiology and pathophysiology. There is some evidence showing that there is a genetic predisposition towards these diseases, especially for achalasia. Many authors have investigated the possible genes involved, stressing the autoimmune or the neurological hypothesis, but there is very little data available. Similarly, studies supporting a post-infective etiology, based on an altered immune response in susceptible individuals, need to be validated. Further association studies can help to explain this complex picture and find new therapeutic targets. The aim of this review is to summarize current knowledge of genetics in motility disorders of the upper gastrointestinal tract, addressing how genetics contributes to the development of achalasia and functional dyspepsia respectively.

Background: Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS., Materials and Methods: Patients with DD or IBS, matched for age and gender (1/1) were consecutively recruited. Data on demographic parameters, voluptuary habits, inheritance of disease and symptoms were collected. Moreover, the association between pain > 24 h, and clinical parameters were evaluated., Results: Ninety patients with DD and 90 patients with IBS (DD: F/M: 46/44; age: 50.9 years; IBS: 46/44; 50.4) were selected from an overall population of 1275 patients. Only nine patients with DD (10%) fulfilled the criteria for IBS diagnosis. Abdominal pain > 24 h was more prevalent in SDD than in patients with IBS (20 vs. 6 patients; P < 0.01). Furthermore, compared with IBS, patients with DD showed more episodes of pain > 24 h requiring medical attention (80% vs. 33%; P < 0.01)., Conclusions: Abdominal pain lasting for more than 24 h discriminates patients with DD compared with those with IBS. Identifying this symptom could be an appropriate strategy to define the diagnosis and management., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Data on factors affecting treatment satisfaction in European women with chronic constipation are limited., Objective: To assess factors associated with treatment satisfaction among European women with chronic constipation., Methods: A 2011-2012 internet survey was conducted in men and women from 12 European countries. Respondents analysed were female with self-reported chronic constipation (≥1 symptoms for ≥6 months of lumpy/hard stools, feeling of incomplete evacuation, and pain during defecation, as well as <3 bowel movements/week). For laxative users, satisfaction with treatment, factors affecting satisfaction, and interactions with healthcare professionals were collected., Results and Conclusions: In total, 4805/50,319 participants fulfilled the inclusion criteria (female with chronic constipation). Of the laxative users (1575/4805), 57% (n = 896) were satisfied with their treatment, while 26% were neutral, and 17% dissatisfied. Dissatisfied respondents visited their GP less frequently in the past 12 months, were more likely to obtain over-the-counter laxatives, and took a dose higher than recommended more frequently than those satisfied. Respondents were most satisfied with ease of use of treatment and least satisfied with relief from bloating. Newer treatments aimed at alleviating symptoms, particularly bloating, are required for respondents neutral or dissatisfied with their current treatment.

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.

Little is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

This minireview highlights the importance of cannabidiol (CBD) as a promising drug for the therapy of inflammatory bowel diseases (IBD). Actual pharmacological treatments for IBD should be enlarged toward the search for low-toxicityand low-cost drugs that may be given alone or in combination with the conventional anti-IBD drugs to increase their efficacy in the therapy of relapsing forms of colitis. In the past, Cannabis preparations have been considered new promising pharmacological tools in view of their anti-inflammatory role in IBD as well as other gut disturbances. However, their use in the clinical therapy has been strongly limited by their psychotropic effects. CBD is a very promising compound since it shares the typical cannabinoid beneficial effects on gut lacking any psychotropic effects. For years, its activity has been enigmatic for gastroenterologists and pharmacologists, but now it is evident that this compound may interact at extra-cannabinoid system receptor sites, such as peroxisome proliferator-activated receptor-gamma. This strategic interaction makes CBD as a potential candidate for the development of a new class of anti-IBD drugs., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Iron deficiency anemia frequently occurs in gastrectomized patients., Methods: Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured., Results: In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations)., Conclusions: In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results., (Copyright © 2013 S. Karger AG, Basel.)

Background: Mental stress (MS) may alter gastric sensory-motor function. The aim of the study was to assess postprandial autonomic nervous system activity and stress hormones in response to acute mental stress in dyspeptic patients., Methods: A total of 25 patients with postprandial distress syndrome (PDS; 11 mol L(-1), age 35.9 ± 9.3 years) and 12 healthy controls (5 mol L(-1), age 25.8 ± 4.6 years) underwent electrogastrography and (13) C-octanoate gastric emptying study using a 480 kcal solid meal. Heart rate variability (LF/HF ratio) and corticotrophin-releasing factor, adrenocorticotropic hormone (ACTH), and cortisol serum levels were also evaluated. Dyspeptic symptoms were scored by analogue visual scale and expressed as symptoms total score (TS). The protocol was repeated twice in each subject, with and without a mental stress test before the meal., Key Results: Mental stress significantly increased postprandial symptoms severity in patients (TS: stress 111 ± 18 vs basal 50 ± 10; P < 0.05). Low-/high-frequency component ratio was significantly higher in patients after MS at 120 min (stress 5.46 ± 0.41 vs basal 3.41 ± 0.64; P < 0.01) and 180 min (stress 5.29 ± 0.2 vs basal 3.58 ± 0.19; P < 0.05). During stress session, in patients we found a significantly higher ACTH level than baseline at 30, 60, 90, 150, 210, 240, and 270 min and a significantly higher cortisol level at 30, 60, 90, 120, 210, and 270 min. Gastric emptying rate and electrical activity were not influenced by MS., Conclusions & Inferences: In PDS patients, administration of MS before meal increases symptoms severity by inducing sympathetic hyperactivity and increased stress hormones levels. As the gastric emptying looks not altered, we conclude that these neurohormonal responses mainly affect sensitive function., (© 2012 Blackwell Publishing Ltd.)

Background: Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS)-induced acute colitis., Methods: Mice were divided into: control group, colitis group (4% DSS for four days) and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg). Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP) preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine., Results: Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP., Conclusions: Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.

Background: In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs)., Aim: To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs., Methods: This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year., Results: The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P<0·0001), especially for dyspepsia (from 9·5% to 13·7%; P<0·0001) and chronic treatments (from 23·4% to 29·4%; P<0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P<0·0001). Calendar years, long-term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P<0·0001)., Conclusions: The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs., (© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease., Methods: This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria., Results: A total of 598 patients (50 % female, age 69 years), 71 % with newly diagnosed symptomatic uncomplicated diverticular disease and 29 % with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78 % of the patients. Recurrent short-lived abdominal pain (<24 h) was present in 70 % (relieved by evacuation in 73 %), prolonged abdominal pain (>24 h) in 27 %, and recurrent abdominal bloating in 61 % of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13 % of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7 % of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain., Conclusions: Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.

The gastrointestinal system can be considered the gateway for food entry in our body. Rather than being a passive player, it is now clear that gut strongly influence the feeding behavior and contribute to maintain energy balance with different signals. The aim of this review is to summarize the current knowledge about the role of gastrointestinal tract in the control of food intake, by focusing on the interplay existing between the enteric nervous system and gastrointestinal hormones and their ability to modulate digestive motility and sensitivity. Also the latest advances about the contribution of gut microbiota and gastrointestinal taste receptors are described. From the reported data it clearly emerges that gut hormones together with nervous signals likely contribute to the regulation of energy balance and modulate food intake through the control of digestive motility and sensations. The close linkage among gastrointestinal hormones, the gut and the central nervous systems appears very intriguing and has induced the development of a new field of research: the gastroendocrinology.

Background: There is conflicting data on the effects of carbon dioxide contained in beverages on stomach functions. We aimed to verify the effect of a pre-meal administration of a 300 ml non-caloric carbonated beverage (B+CO2) compared to water or a beverage without CO2 (B-CO2), during a solid (SM) and a liquid meal (LM) on: a) gastric volume, b) caloric intake, c) ghrelin and cholecystokinin (CCK) release in healthy subjects., Methods: After drinking the beverages (Water, B-CO2, B+CO2), ten healthy subjects (4 women, aged 22-30 years; BMI 23 ± 1) were asked to consume either an SM or an LM, at a constant rate (110 kcal/5 min). Total gastric volumes (TGV) were evaluated by Magnetic Resonance Imaging after drinking the beverage and at maximum satiety (MS). Total kcal intake at MS was evaluated. Ghrelin and CCK were measured by enzyme immunoassay until 120 min after the meal. Statistical calculations were carried out by paired T-test and analysis of variance (ANOVA). The data is expressed as mean ± SEM., Results: TGV after B+CO2 consumption was significantly higher than after B-CO2 or water (p < 0.05), but at MS, it was no different either during the SM or the LM. Total kcal intake did not differ at MS after any of the beverages tested, with either the SM (Water: 783 ± 77 kcals; B-CO2: 837 ± 66; B+CO2: 774 ± 66) or the LM (630 ± 111; 585 ± 88; 588 ± 95). Area under curve of ghrelin was significantly (p < 0.05) lower (13.8 ± 3.3 ng/ml/min) during SM following B-CO2 compared to B+CO2 and water (26.2 ± 4.5; 27.1 ± 5.1). No significant differences were found for ghrelin during LM, and for CCK during both SM and LM after all beverages., Conclusions: The increase in gastric volume following a 300 ml pre-meal carbonated beverage did not affect food intake whether a solid or liquid meal was given. The consistency of the meal and the carbonated beverage seemed to influence ghrelin release, but were unable, under our experimental conditions, to modify food intake in terms of quantity. Further studies are needed to verify if other food and beverage combinations are able to modify satiation.

Background: Diverticular disease of the colon is a common disorder, characterized by recurrent symptoms and complications such as diverticulitis, requiring hospital admissions and surgery., Objective: This study aimed to systematically review the evidence for medical therapy of diverticular disease in reducing symptoms and preventing acute diverticulitis., Data Sources: MEDLINE and Embase databases (1966 to February 2010)., Study Selection: The studies selected were prospective clinical trials on uncomplicated diverticular disease of the colon., Interventions: Four investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria., Main Outcome Measures: The main outcomes measured were improvement in symptoms, complete remission of symptoms, and prevention of acute diverticulitis., Results: We identified 31 studies, including 6 placebo-controlled trials. The methodological quality of these studies was suboptimal. Only 10 trials provided a detailed description of the patient history, 8 assessed symptoms by the use of a validated questionnaire, and 14 appropriately defined inclusion and exclusion criteria. Only one long-term double-blind placebo-controlled study was identified. This reported a significant improvement in symptoms and greater prevalence of symptom-free patients at 1 year with fiber plus rifaximin in comparison with fiber alone. The efficacy of treatment in preventing acute diverticulitis was evaluated in 11 randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and failed to show a significant difference between treatments. However, cumulative data from these trials revealed a significant benefit following rifaximin and fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P = .012), but with a number needed to treat of 57, to prevent an attack of acute diverticulitis., Limitations: : Heterogeneity of the study design, patients' characteristics, regimens and combination of studied treatment, and outcome reporting precluded the pooling of results and limited interpretation., Conclusions: The treatment for diverticular disease relies mainly on data from uncontrolled studies. Treatment showed some evidence of improvement in symptoms, but its role in the prevention of acute diverticulitis remains to be defined.

Background: Enteric glial cells (EGCs) have been recently indicated as key regulators of intestinal inflammation in animals. Whether or not this is true and how these cells participate to inflammatory responses in humans is unknown., Methods: We isolated primary EGCs from human small bowel and then, we purified and characterized those using specific glial markers, such as S100B and glial fibrillary acidic protein (GFAP). To mimic an inflammatory scenario, we exposed EGCs to exogenous stimuli, such as lipopolysaccharide and interferon-gamma (LPS and IFN-γ), alone or in combination, to evaluate glial activation [measuring GFAP, S100B level together with c-fos, major histocompatibility complex (MHC) class II, inducible nitric oxide (iNOS) proteins expression and nitric oxide (NO) production] and proliferation, respectively., Key Results: We showed that, when challenged with a combination of LPS and IFN-γ, EGCs are significantly activated, as indicated by their positivity to c-fos and MHC class II. Similarly, pro-inflammatory stimuli significantly increase the cell proliferation rate, the expression of both S100B and GFAP, and the NO production consequent to the induction of EGCs-derived iNOS protein, with the last being dependent on S100B-RAGE (receptor for advanced glycation endproducts) interaction., Conclusions & Inferences: Our data provide the first evidence that human EGCs directly respond to pro-inflammatory stimuli by changing their expression profile and by proliferating. The finding that stimulated EGCs are able to produce NO points to a role of this cell population in the scenario of intestinal inflammation., (© 2011 Blackwell Publishing Ltd.)

Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed.

Chronic intestinal pseudo-obstruction (CIPO) is a rare disease due to a severe gastrointestinal motility disorder which may mimic, on both clinical and radiological grounds, mechanical obstruction. We report a case of a 26-year-old woman who presented to our institution for plain abdominal radiography for referred long-lasting constipation with recurrent episodes of abdominal pain and distension. At X-ray, performed both in the upright and supine position, an isolated air-fluid level was depicted in the left flank, together with a number of radiological signs suggestive of pneumoperitoneum. First, subphrenic radiolucency could be observed in the upright film. Second, the intestinal wall of some jejunal loops appeared to be outlined in the right flank. Third, the inferior cardiac border was clearly depicted in the upright film. The patient however had no evidence of peritoneal signs but only hypoactive bowel movements. Unenhanced multi-detector computed tomography (MDCT) of the abdomen and pelvis was therefore performed. MDCT revealed abnormal air-driven distension of the small and large bowel, without evidence of extra-luminal air. All radiological signs of pneumoperitoneum turned out to be false-positive results. The patient was submitted to pan-colonoscopy and to anorectal manometry to rule out Hirshprung's disease, and was finally discharged with a diagnosis of CIPO.

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1 of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6-/MUM1+/CD138- and BCL6+/MUM1+/CD138- or BCL6-/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV- patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system.

We report a case of cellular neurothekeoma with unusual clinicopathological features in which neuroendocrine markers, determined by immunohistochemistry were observed. Histologically, the tumor showed a micronodular architecture with hypercellular lobules composed of slightly spindled to epithelioid cells, with nuclear atypia or pleomorphism and extension into fat, skeletal muscle. Neoplastic cells were immunoreactive for NKI/C3, CD68, CD10, and smooth-muscle actin, whereas S100 and HMB-45 staining was negative. An intriguing feature was the strong expression by tumor cells of different neuroendocrine markers. Clinical follow up showed no local recurrences after five months despite the presence of positive margins. The presence of atypical histopathological features may cause diagnostic problems with malignant mesenchymal tumors, nevo-melanocytic lesions, and fibrohistiocytic tumors. The immunohistochemical profile including the positive staining for neuroendocrine markers may suggest divergent differentiation or an origin from myofibroblast and neuroendocrine cells.

Aim: To estimate the economic consequences for society arising from populations with poorly treated gastroesophageal reflux disease (GERD) and Barrett's esophagus in Germany, Italy and Spain., Methods: The following epidemiologic data were used: total population figures, the prevalence and incidence of GERD and its complications, and data on patients with poorly treated GERD, as well as data on treatment costs and active workers' presenteeism and absenteeism. These data were used to calculate the economic consequences arising from the population with poorly treated GERD and Barrett's esophagus for the healthcare system and employers in each country., Results: The size of the population with poorly treated GERD with Barrett's esophagus was estimated to be 29,678 in Spain, 19,327 in Germany and 10,079 in Italy. Costs for the healthcare systems in Spain, Germany and Italy for the population with poorly treated GERD with Barrett's esophagus were estimated to be €18, 12 and 7 million, respectively, for each country. Total costs for absenteeism and presenteeism for employers due to poorly treated GERD with Barrett's esophagus were €10 million for Germany, €1 million for Italy and none for Spain., Conclusion: Costs due to poorly treated GERD with Barrett's esophagus represent a substantial burden for the healthcare systems of all three studied countries. Costs for employers owing to absenteeism or presenteeism of employees were low or no costs were found.

Background: Gastroesophageal reflux disease (GERD), including erosive reflux disease and non-erosive reflux disease (NERD), is a chronic disease with a significant negative effect on quality of life. State-of-the-art treatment involves proton pump inhibitors (PPIs). However, relapse of symptoms occurs in the majority of the patients who require recurrent or continuous therapy. Although PPIs are well tolerated, little information is available about gastrointestinal side effects., Aim: To evaluate the effects of long-term PPI treatment on development of bowel symptoms and/or small intestinal bacterial overgrowth (SIBO)., Methods: Patients with NERD not complaining of bowel symptoms were selected by upper endoscopy, 24-h pH-metry and a structured questionnaire concerning severity and frequency of bloating, flatulence, abdominal pain, diarrhoea and constipation. Patients were treated with esomeprazole 20 mg bid for 6 months. Prior to and after 8 weeks and 6 months of therapy, patients received the structured questionnaire and underwent evaluation of SIBO by glucose hydrogen breath test (GHBT)., Results: Forty-two patients with NERD were selected out of 554 eligible patients. After 8 weeks of PPI treatment, patients complained of bloating, flatulence, abdominal pain and diarrhoea in 43%, 17%, 7% and 2%, respectively. After 6 months, the incidence of bowel symptoms further increased and GHBT was found positive in 11/42 (26%) patients. By a post hoc analysis, a significant (P < 0·05) percentage of patients (8/42) met Rome III criteria for irritable bowel syndrome., Conclusions: Prolonged PPI treatment may produce bowel symptoms and SIBO; therefore, the strategy of step-down or on-demand PPI therapy should be encouraged in GERD., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system (CNS). In recent years, the role of enteric glial cells (EGCs) has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the S100B protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, S100B overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. S100B-mediated pro-inflammatory effects are not limited to the brain: S100B overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and S100B protein occurring in intestinal inflammation deriving from such.

Aim: The standard therapeutic approach for symptomatic uncomplicated diverticular disease (DD) remains to be defined, and only a few studies have tested the efficacy of probiotics in these patients., Methods: Patients with symptomatic uncomplicated DD were randomized to a control arm, i.e., (group A, [N.=16], high-fibre diet alone), or to Group B ([n=18], twice daily 1 sachet of probiotic + high-fibre diet), or group C ([N.=16], twice daily 2 sachets of probiotic + high-fibre diet). The probiotic Genefilus F19© containing Lactobacillus paracasei sub. paracasei F19 was administered for 14 days/month for 6 months. The primary endpoint under consideration was a decrease in abdominal pain and bloating intensity after treatment., Results: Bloating decreased significantly in Groups B and C VAS score group B: 4.6 ± 2.6 vs. 2.3 ± 2.0, P<0.05, group C: 3.9 ± 2.9 vs. 1.8 ± 2.1, P<0.05). The decrease in abdominal pain within 24 hours in these groups did not reach statistical significance. During treatment, none of the group B (N.=4) or group C patients (N=3) with abdominal pain >24 hours reported the recurrence of this symptom, while the 3 group A patients reported at least one episode (P=0.016). No significant difference regarding abdominal pain <24 hours and bloating was observed between the two groups of patients treated with a low or high probiotic dose., Conclusion: Lactobacillus paracasei F19, in association with a high-fibre diet, is effective in reducing abdominal bloating and prolonged abdominal pain in symptomatic uncomplicated diverticular disease, and could thus be a promising option in the treatment of these patients.

Aim: To investigate the effect of appendectomy and cigarette smoking on the clinical course of diverticulosis., Materials and Methods: A retrospective case-control study of 207 consecutive patients (45.8% male mean age 64.0 years), 150 with asymptomatic diverticulosis, and 57 with acute diverticulitis. Diagnosis of diverticulosis was defined on the basis of clinical and colonoscopic criteria, diverticulitis was defined by means of clinical, colonoscopic and computerised tomography criteria. Logistic regression function was used to define the relationship between the dependent variable (diverticulitis) and several covariates: sex, age, body mass index, smoking habit, and history of appendectomy., Results: According to the final model, the risk of diverticulitis was 4.94-fold higher (95% confidence interval: 1.98-12.37) in patients with a history of appendectomy with emergency resection, compared to patients not submitted to appendectomy or with a history of elective resection (P < 0.001); and 2.79-fold higher (95% confidence interval: 1.30-5.96) in smokers than in non-smokers (P = 0.008). The effects of the two determinants were found to be independent, thus the cumulative risk of diverticulitis was 13.78-fold higher for smokers with a history of emergency surgical treatment., Conclusion: Smoking and emergency appendectomy are important predictive factors for the clinical course of diverticulosis., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.

Oeosinophilic gastroenteritis is a chronic and rare disorder characterised by massive oeosinophilic tissue infiltration involving one or more segments of the digestive tract. The management of patients with oeosinophilic gastroenteritis is complex and the therapeutic response often poor. Here we discuss the clinical case and management of a 23-year-old man with oeosinophilic gastroenteritis since the first year of life and the decision to prescribe lifelong total parenteral nutrition.

Background/aims: No comparative studies are available, as yet, in Italy, concerning the prevalence of irritable bowel syndrome (IBS) in urban and rural areas. The aim is to compare the prevalence of IBS in Italian urban and rural areas., Methods: 950 subjects were randomly selected from each area and completed a questionnaire regarding demographic data and the Rome II questionnaire., Results: The prevalence of IBS was significantly (p<0.05) higher in the urban (9.9%), than in the rural area (4.4%). In the urban area, a significantly higher prevalence of IBS was observed in females than in males, 67/490 (13.7%) vs 27/460 (5.9%) (p<0.05), while no gender differences were present in the rural population., Conclusion: In the urban area, we found a higher prevalence of IBS, and a significantly higher prevalence of IBS in females than in males, while no gender differences were present in the rural population.

Aim: To assess the management and outcome of nonerosive gastro-esophageal reflux disease (NERD) patients who were identified retrospectively, after a 5-year follow-up., Methods: We included patients with gastro-esophageal reflux disease (GERD) symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years (range 3.5-7 years) by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis., Results: 260 patients (137 women) were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 (40%). 70% received a maintenance treatment, which was proton pump inhibitor (PPI) in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of follow-up were observed. A progression to erosive gastro-esophageal reflux disease (ERD) was found in 58/193 (30.0%) of patients undergoing repeat endoscopy; 72% of these were Los Angeles grade A-B., Conclusion: This study shows that progression to ERD occurs in about 5% of NERD cases per year, despite therapy. Only two factors consistently and independently influence progression: smoking and absence of PPI therapy.

A wealth of information has appeared on non-scientific publications, some suggesting a positive effect of carbonated beverages on gastrointestinal diseases or health, and others a negative one. The evaluation of the properties of carbonated beverages mainly involves the carbon dioxide with which they are charged. Scientific evidence suggests that the main interactions between carbon dioxide and the gastrointestinal system occur in the oral cavity, the esophagus and the stomach. The impact of carbonation determines modification in terms of the mouthfeel of beverages and has a minor role in tooth erosion. Some surveys showed a weak association between carbonated beverages and gastroesophageal reflux disease; however, the methodology employed was often inadequate and, on the overall, the evidence available on this topic is contradictory. Influence on stomach function appears related to both mechanical and chemical effects. Symptoms related to a gastric mechanical distress appear only when drinking more than 300 ml of a carbonated fluid. In conclusion there is now sufficient scientific evidence to understand the physiological impact of carbonated beverages on the gastrointestinal system, while providing a basis for further investigation on the related pathophysiological aspects. However, more studies are needed, particularly intervention trials, to support any claim on the possible beneficial effects of carbonated beverages on the gastrointestinal system, and clarify how they affect digestion. More epidemiological and mechanistic studies are also needed to evaluate the possible drawbacks of their consumption in terms of risk of tooth erosion and gastric distress.

In the central nervous system glial-derived S100B protein has been associated with inflammation via nitric oxide (NO) production. As the role of enteroglial cells in inflammatory bowel disease has been poorly investigated in humans, we evaluated the association of S100B and NO production in ulcerative colitis (UC). S100B mRNA and protein expression, inducible NO synthase (iNOS) expression, and NO production were evaluated in rectal biopsies from 30 controls and 35 UC patients. To verify the correlation between S100B and NO production, biopsies were exposed to S100B, in the presence or absence of specific receptor for advanced glycation end-products (RAGE) blocking antibody, to measure iNOS expression and nitrite production. S100B and iNOS expression were evaluated after incubation of biopsies with lipopolysaccharides (LPS) + interferon-gamma (IFN-gamma) in the presence of anti-RAGE or anti-S100B antibodies or budesonide. S100B mRNA and protein expression, iNOS expression and NO production were significantly higher in the rectal mucosa of patients compared to that of controls. Exogenous S100B induced a significant increase in both iNOS expression and NO production in controls and UC patients; this increase was inhibited by specific anti-RAGE blocking antibody. Incubation with LPS + IFN-gamma induced a significant increase in S100B mRNA and protein expression, together with increased iNOS expression and NO production. LPS + IFN-gamma-induced S100B up-regulation was not affected by budesonide, while iNOS expression and NO production were significantly inhibited by both specific anti-RAGE and anti-S100B blocking antibodies. Enteroglial-derived S100B up-regulation in UC participates in NO production, involving RAGE in a steroid insensitive pathway.

Background and Aims: Transglutaminases are tissue enzymes involved in different neuronal processes including maintenance and signalling. However, their up-regulation elicited by a variety of noxae contributes to neurodegeneration. This study tested the hypothesis that experimental inflammation evoked transglutaminase up-regulation in myenteric neurons and that this event had an impact on neuronal survival., Methods: Rats with or without trinitro-benzene-sulphonic acid-induced colitis were used. One week after colitis induction, longitudinal muscle-myenteric plexus preparations were obtained from left colon to assess tissue-transglutaminase activity, protein and mRNA expression. Double labelling immunofluorescence using antibodies to neuron-specific enolase and transglutaminase was performed to identify myenteric neurons expressing transglutaminase. Additional sets of experiments evaluated the involvement of transglutaminase in the apoptotic process of cultured myenteric neurons., Results: Compared to controls, rats with colitis showed several tranglutaminase/neuron-specific enolase positive myenteric neurons. Western blot analysis and RT-PCR confirmed that in rats with colitis, the increased neuronal transglutaminase-immunoreactivity was associated with an increased enzyme expression. Similarly, transglutaminase activity was significantly higher than in controls (1100+/-280 m U/g vs. 725+/-119 m U/g, p<0.05). In cultured myenteric neurons incubation with the specific transglutaminase inducer, retinoic acid, significantly increased neuronal apoptosis, whereas the presence of cystamine significantly reduced the number of apoptotic neurons., Conclusions: Experimental colitis evoked transglutaminase up-regulation and increased activity in myenteric neurons. This mechanism enhances neuronal susceptibility to apoptosis and could contribute to neuropathic changes during gut inflammation.