Epidemiologic characteristics of Helicobacter pylori infection in southeast Hungary.

BACKGROUND: Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori (H. pylori) infection in Western Europe. AIM: To obtain data regarding the prevalence of H. pylori in Csongrád and Békés Counties in Hungary, evaluate the differences in its prevalence between urban and rural areas, and establish factors associated with positive seroprevalence. METHODS: One-thousand and one healthy blood donors [male/female: 501/500, mean age: 40 (19-65) years] were enrolled in this study. Subjects were tested for H. pylori IgG antibody positivity via enzyme-linked immunosorbent assay. Subgroup analysis by age, gender, smoking habits, alcohol consumption, and urban vs non-urban residence was also performed. RESULTS: The overall seropositivity of H. pylori was 32%. It was higher in males (34.93% vs 29.2%, P = 0.0521) and in rural areas (36.2% vs 27.94%, P = 0.0051). Agricultural/industrial workers were more likely to be positive for infection than office workers (38.35% vs 30.11%, P = 0.0095) and rural subjects in Békés County than those in Csongrád County (43.36% vs 33.33%, P = 0.0015). CONCLUSION: Although the prevalence of H. pylori infection decreased in recent decades in Southeast Hungary, it remains high in middle-aged rural populations. Generally accepted risk factors for H. pylori positivity appeared to be valid for the studied population.

Role of ion transporters in the bile acid-induced esophageal injury.

Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury.

A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the leading malignancies worldwide, therefore cheap noninvasive screening methods are of great importance. Matrix-metalloproteinase-9 (MMP-9) has a role in the progression of CRC, and its level is elevated in tumour biopsies. Faecal MMP-9 levels are increased in active ulcerative colitis patients, but in CRC patients, they have never been measured. We aimed to assess the faecal MMP-9 levels in patients undergoing total colonoscopy according to endoscopic and histological diagnosis. METHODS: One hundred and nine patients provided faecal samples for MMP-9 analysis. A total colonoscopy was performed; suspicious lesions were evaluated by histology. Faecal MMP-9 levels were measured by ELISA. RESULTS: The number of patients allocated to different groups were: negative/diverticulosis: 34 (referred to as controls); hyperplastic polyps: 15; adenomas: 32 (22 at high risk); and CRC: 28. Faecal MMP-9 was significantly increased in CRC compared with all other groups (P<0.001). Faecal MMP-9 was suitable to distinguish CRC patients from controls (sensitivity: 89.3%; specificity: 91.2%). By means of a lower cutoff level, faecal MMP-9 identified high-risk adenomas besides CRC (sensitivity: 76%; specificity: 85.3%). This lower cutoff level screened 59% of high-risk adenomas. CONCLUSIONS: Faecal MMP-9 may be a promising new noninvasive marker in CRC.

New-onset type 2 diabetes mellitus--A high-risk group suitable for the screening of pancreatic cancer?

BACKGROUND: Type 2 diabetes mellitus is widely considered to be associated with pancreatic cancer. OBJECTIVE: To determine the incidence of pancreatic cancer in new-onset type 2 diabetic patients by measuring the serum level of CA 19-9 and performing abdominal ultrasonography (US). PATIENTS AND METHODS: Consecutive type 2 diabetic patients in whom diabetes was diagnosed within 36 months were included in this prospective study. Serum CA 19-9 measurement and US were performed in all patients. If any of two was positive, abdominal computer tomography (CT) was carried out. Endoscopic ultrasound-guided fine needle aspiration or direct surgical referral was performed on patients with CT-identified lesions. RESULTS: A total of 115 patients were enrolled. CA 19-9 was elevated in 10 patients but pancreatic cancer diagnosed in neither of them. Pancreatic cancer was revealed by morphological means in three patients without elevated CA 19-9 level. The sensitivity, specificity, positive-, negative predictive values and validity were 0%, 90.4%, 0%, 97.9% and 87.9% for CA 19-9, 66.7%, 100%, 100%, 99% and 99% for US, respectively. The value of the Standardized Incidence Ratio for pancreatic cancer in new-onset type-2 diabetic patients was 198.6 (95% CI = 6.25-46.9). CONCLUSIONS: The prevalence of pancreatic cancer in patients with new-onset type-2 diabetes is significantly higher than that in the general population and screening is beneficial for detecting PaC in this patient population. CA 19-9 and US is not reliable screening modality for pancreatic cancer screening in this population.

The diagnostic value of a new fecal marker, matrix metalloprotease-9, in different types of inflammatory bowel diseases.

BACKGROUND: Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohn's disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD. METHODS: Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay. RESULTS: Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis. CONCLUSIONS: This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation.

Faecal matrix metalloprotease-9 is a more sensitive marker for diagnosing pouchitis than faecal calprotectin: results from a pilot study.

BACKGROUND: Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. AIM: This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. PATIENTS AND METHODS: Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. RESULTS: Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. DISCUSSION: Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.

Role of antispasmodics in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.

Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS.

OBJECTIVES: Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies. METHODS: Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN. RESULTS: We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64. CONCLUSIONS: These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.

Fecal MMP-9: a new noninvasive differential diagnostic and activity marker in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by frequent relapses, with the presence of colorectal inflammation and mucosal lesions. Matrix-metalloprotease 9 (MMP-9) is elevated in colonic biopsies, urine, and blood plasma of UC patients. MMP-9 has been suggested as a predictor of UC in the urine of children; however, 20% of the controls tested positive. So far, fecal MMP-9 levels have never been measured. Our aims were: 1) to compare fecal MMP-9 levels in UC patients to control subjects and a functional gastrointestinal disorder characterized by diarrhea (IBS-D); 2) to test the correlation between UC disease activity and fecal levels of MMP-9; and 3) to correlate fecal MMP-9 levels with a known fecal marker of UC activity, calprotectin. METHODS: UC (n = 47), IBS-D (n = 23) patients, and control subjects (n = 24) provided fecal samples for MMP-9 analysis. In UC patients, disease severity was evaluated by the Mayo score. Fecal MMP-9 and calprotectin levels were measured by enzyme-linked immunosorbent assay and lateral flow assay, respectively. RESULTS: MMP-9 was undetectable or ≤0.22 ng/mL in the feces of all controls and IBS-D patients. In UC patients, fecal MMP-9 levels significantly correlated with the overall Mayo score (P < 0.001), the endoscopic score (P < 0.001), and the serum C-reactive protein levels (P = 0.002). Additionally, in UC patients fecal MMP-9 levels showed a significant correlation with a known disease activity marker, fecal calprotectin (P = 0.014). CONCLUSIONS: These results highlight fecal MMP-9 as a useful tool in the differential diagnosis of diarrheic disorders and in the noninvasive evaluation of disease activity and mucosal healing in UC.

Leaky gut in patients with diarrhea-predominant irritable bowel syndrome and inactive ulcerative colitis.

BACKGROUND/AIMS: Defective epithelial barrier has been implicated in the pathogenesis of irritable bowel syndrome (IBS) and inflammatory bowel diseases. The aim of this study was to investigate gut permeability in patients with inactive ulcerative colitis (UC) and in patients with IBS. METHODS: IBS patients of the diarrhea-predominant (IBS-D) and of the constipation-predominant subgroup (IBS-C), patients with inactive UC and healthy subjects were enrolled. Gut permeability was evaluated by measuring 24-hour urine excretion of orally administered (51)Cr-EDTA. Clinical symptoms were evaluated in IBS-D patients and correlated to colonic permeability. RESULTS: There was a significant decrease in the proximal small intestinal permeability in IBS-C patients compared to controls (0.26 ± 0.05 vs. 0.63 ± 0.1%; p < 0.05). Distal small intestinal permeability showed no significant difference in the studied group of patients compared to controls. Colonic permeability of IBS-D and inactive UC patients was significantly increased compared to controls (2.68 ± 0.35 and 3.74 ± 0.49 vs. 1.04 ± 0.18%; p < 0.05, p < 0.001). Colonic permeability of IBS-D patients correlated with stool frequency. CONCLUSIONS: Elevated gut permeability is localized to the colon both in IBS-D and in inactive UC patients.

The evaluation of oesophageal function in patients with different types of oesophageal metaplasia.

AIM: To evaluate the oesophageal function in patients with different types of oesophageal metaplasia and in cases with dysplasia on the basis of the Montreal definition of gastro-oesophageal reflux disease. PATIENTS AND METHODS: 270 consecutive patients [M/F 151/119, mean age 54.2 years (19-84)] with endoscopic and histological evidence of oesophageal metaplasia were prospectively studied: patients with specialized intestinal metaplasia (SIM, n = 109) and patients without SIM (n = 161). Patients with SIM were subdivided into a dysplasia-positive (n = 34) and a dysplasia-negative (n = 75) group. All patients underwent reflux symptom analysis, oesophageal manometry, and simultaneous 24-hour pH and biliary reflux monitoring. RESULTS: Patients with SIM were significantly older and had a significantly higher body mass index than patients without SIM. A significant male predominance was observed in patients with SIM and dysplasia compared to the dysplasia-negative group. The clinical symptom spectrum and the prevalence of erosive oesophageal lesions were similar in all groups. Patients with SIM had longer metaplastic segments, which was further increased in the dysplasia-positive group. During oesophageal manometry, pH and biliary reflux monitoring, patients with SIM had more severe alterations than patients without SIM, and these were further increased in patients with SIM and dysplasia. CONCLUSIONS: Patients with SIM had more severe oesophageal function abnormalities than those with other types of oesophageal metaplasia (e.g. gastric). The oesophageal function was further impaired if dysplasia was present in the metaplastic mucosa.

Luminal cathepsin g and protease-activated receptor 4: a duet involved in alterations of the colonic epithelial barrier in ulcerative colitis.

Impairment of the colonic epithelial barrier and neutrophil infiltration are common features of inflammatory bowel disease. Luminal proteases affect colonic permeability through protease-activated receptors (PARs). We evaluated: (i) whether fecal supernatants from patients with ulcerative colitis (UC) trigger alterations of colonic paracellular permeability and inflammation, and (ii) the roles of cathepsin G (Cat-G), a neutrophil serine protease, and its selective receptor, PAR(4), in these processes. Expression levels of both PAR(4) and Cat-G were determined in colonic biopsies from UC and healthy subjects. The effects of UC fecal supernatants on colonic paracellular permeability were measured in murine colonic strips. Involvement of Cat-G and PAR(4) was evaluated using pepducin P4pal-10 and specific Cat-G inhibitor (SCGI), respectively. In addition, the effect of PAR(4)-activating peptide was assessed. UC fecal supernatants, either untreated or pretreated with SCGI, were infused into mice, and myeloperoxidase activity was determined. PAR(4) was found to be overexpressed in UC colonic biopsies. Increased colonic paracellular permeability that was triggered by UC fecal supernatants was blocked by both SCGI (77%) and P4pal-10 (85%). Intracolonic infusion of UC fecal supernatants into mice increased myeloperoxidase activity. This effect was abolished by SCGI. These observations support that both Cat-G and PAR(4) play key roles in generating and/or amplifying relapses in UC and provide a rationale for the development of new therapeutic agents in the treatment of this disease.

Fecal proteases from diarrheic-IBS and ulcerative colitis patients exert opposite effect on visceral sensitivity in mice.

Elevated colonic luminal serine-protease (Ser-P) activity of diarrhea-predominant IBS (IBS-D) patients evokes a proteinase-activated receptor (PAR)-2-mediated colonic hypersensitivity in mice. Despite similarly elevated Ser-P levels in feces, patients with IBD exhibit visceral hypo- or normosensitivity to rectal distension, as opposed to IBS-D. To explain these discrepancies we studied the effect of colonic infusion of fecal supernatants from ulcerative colitis (UC) patients to colorectal mechanical sensitivity of mice and explored the involvement of PAR-4 and its activator Cathepsin-G (Cat-G). Fecal protease activities were assayed in healthy subjects, IBS-D and UC patients in presence or not of antiproteases or Cat-G inhibitor. Following intracolonic infusion of fecal supernatants from healthy subjects, IBS-D and UC patients or PAR-4 activating peptide (PAR-4-AP) or Cat-G, EMG response to colorectal balloon distension was recorded in mice. This nociceptive response was also determined after treatment with pepducin (PAR-4 antagonist) on UC supernatant or after a preincubation with antiproteases or Cat-G inhibitor. In contrast to IBS-D supernatant, UC supernatant promoted colonic hyposensitivity to distension, an effect mimicked by PAR-4-AP or Cat-G. UC supernatant-induced hypoalgesia was inhibited by a cocktail of antiproteases. However, blockade of PAR-4 or Cat-G inhibition resulted in colonic hypersensitivity similar to that observed after IBS-D supernatant infusion. Despite similarly elevated Ser-P activities, IBS-D and UC fecal supernatant display visceral pro- and antinociceptive effects in mice, respectively. Visceral hyposensitivity induced by fecal supernatant from UC patients results from PAR-4 activation by cathepsin-G, counterbalancing the pronociceptive effect of simultaneous PAR-2 activation.

Asthma and gastroesophageal reflux: clinical evaluation of esophago-bronchial reflex and proximal reflux.

AIMS: To evaluate the prevalence of proximal reflux and esophago-bronchial reflex (EBR) in patients with asthma, and to compare the symptom spectrum, esophageal acid sensitivity, pH monitoring, and the endoscopic and manometric parameters of EBR-positive and -negative patients with asthma. PATIENTS AND METHODS: Forty-three consecutive patients with recent diagnoses of asthma and 20 patients with chronic cough but without asthma were prospectively submitted to detailed reflux and respiratory symptom analysis, upper gastrointestinal endoscopy, esophageal manometry, Bernstein test and double-channel intra-esophageal pH monitoring. The presence of EBR was studied by combined esophageal acid (0.1 N HCl) perfusion and methacholine test. RESULTS: Patients with asthma had significantly more proximal acid reflux than controls. Patients with EBR positivity were more likely to have an acid-sensitive esophagus and had more acid reflux especially in the supine period at the distal measurement point. Other parameters were similar. CONCLUSIONS: Patients with asthma had significantly more proximal acid reflux than those with chronic cough. The combination of the methacholine test with esophageal acid perfusion is able to establish the presence of EBR, however prospective therapeutic trials are needed to confirm its clinical value. The increased amount of acid reflux during the supine period in patients with EBR may indicate a role for appropriate nighttime acid suppressive therapy.

Increased prevalence of gallstone disease and impaired gallbladder motility in patients with Barrett's esophagus.

The prevalence of gallstones in patients with Barrett's esophagus (BE) and their gallbladder motility relative to that of healthy volunteers and GERD patients without BE were investigated. Of the 707 patients reviewed, 203 (125 males and 78 females) had BE. The prevalence of gallstones was significantly higher in the patients with BE than in those without BE (34 vs. 20%, respectively). The gallbladder functions of 22 patients with GERD, 27 patients with BE and 21 healthy volunteers were assessed by ultrasonography before and after a test meal. The patients with BE had significantly higher fasting volume and residual volume, but lower ejection volume, ejection fraction and ejection rate values than those of the healthy controls. None of the ultrasonographic parameters of patients without BE were significantly different from those of the controls. Patients with BE have a more complex gastrointestinal motility disorder that involves the gallbladder, and this makes this subset of patients with GERD more prone to gallstone disease.

A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: The pathogenesis of irritable bowel syndrome (IBS) remains only partially understood, and no specific or universally effective patient management procedure has been developed to date. Our study was designed to evaluate if colonic luminal serine-proteases may be a relevant pathophysiologic marker of IBS. METHODS: Fecal samples of 38 IBS patients, 15 patients with ulcerative colitis (UC), and 15 healthy controls were studied. Fecal serine-protease activity was determined photometrically by using azocasein as a proteolytic substrate; fecal pancreatic elastase-1 and mast cell tryptase content were measured by enzyme-linked immunosorbent assay. Fecal secretory leukocyte protease inhibitor concentration was determined by enzyme-linked immunosorbent assay in control subjects and in patients with diarrhea-predominant IBS. RESULTS: Fecal serine-protease activity was 3-fold higher in patients with diarrhea-predominant IBS than in both controls and IBS patients with either constipation or alternating bowel habits. Fecal serine-protease activity was not correlated with the frequency of bowel movements in all groups. Increased serine-protease activity also was detected in stools of UC patients. No significant difference was observed in the fecal mast cell tryptase and pancreatic elastase concentrations between all groups, or in the fecal secretory leukocyte protease inhibitor concentration between controls and diarrhea-predominant IBS patients. CONCLUSIONS: Fecal serine-protease activity is increased markedly in patients with diarrhea-predominant IBS. This increase, however, is not coupled with changes in either mast cell tryptase or pancreatic elastase concentrations. Thus, serine-protease activity in the colon may be a pathophysiologic factor in the development of diarrhea-predominant IBS.

Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats.

BACKGROUND: Low-grade inflammation may play a role in the pathogenesis of irritable bowel syndrome (IBS). Although corticosteroids are potent inhibitors of inflammatory processes, only one study with corticosteroids in patients with postinfectious IBS exists, which suggests that prednisolone is not an effective treatment for IBS symptoms. AIM: To evaluate whether dexamethasone treatment prevents protease-activated receptor-2 (PAR-2) activation-induced visceral hyperalgesia and increased permeability in rats, and to determine whether the effects involve colonic mast cells. METHODS: Abdominal contractions provoked by rectal distension were recorded in rats equipped with intramuscular electrodes. Changes in visceral hypersensitivity provoked by intracolonic administration of PAR-2-activating peptide (SLIGRL; H-serine-leucine-isoleucine-glycine-arginine-leucine-OH), changes in colonic mucosal rat mast cell protease-II (RMCP-II) content, mast cell count and PAR-2 expression were measured after a 4-day treatment with dexamethasone (1 mg/day/rat intraperitoneally) or its vehicle (water). The effect of mast cell stabiliser (doxantrazole, 1 mg/kg intraperitoneally, 2 h before and 6 h after intracolonic infusion of SLIGRL) on SLIGRL-induced visceral hyperalgesia was also assessed. The effects of SLIGRL and a mast cell degranulator (compound 48/80) on the permeability of colonic strips from vehicle- or dexamethasone-treated rats were investigated in Ussing chambers. RESULTS: 4 days of dexamethasone as well as doxantrazole diminished the SLIGRL-induced hyperalgesia for all volumes of distension. This effect of dexamethasone was accompanied by a reduced responsiveness of colonic permeability to compound 48/80, and decreased RMCP-II content and mast cell number. Dexamethasone treatment did not influence colonic mucosal PAR-2 expression and permeability responsiveness to SLIGRL. CONCLUSIONS: Dexamethasone treatment improves PAR-2 agonist-induced visceral hypersensitivity but does not prevent PAR-2 agonist-induced increase in colonic permeability in rats. This effect is coupled with a reduction of colonic mast cell number and RMCP-II contents.

Prevalence of respiratory symptoms and diseases associated with gastroesophageal reflux disease.

AIM: Investigation of the prevalence of respiratory symptoms and diseases associated with gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: 299 subjects with GERD were submitted to upper gastrointestinal endoscopy and 24-hour esophageal pH monitoring and a symptom analysis. RESULTS: Chronic respiratory symptoms or diseases were present in 18% (56/299). Chronic cough was observed in 42/56 patients, while typical reflux symptoms such as heartburn and acid regurgitation were observed in 30/56 and 24/56 cases, respectively. The prevalence of airway diseases was chronic bronchitis 12/56, asthma 10/56, recurrent pneumonia 10/56, chronic sinusitis 7/56 and chronic laryngitis 1/56. In patients with respiratory complications pathologic acid reflux was established in 29/51 cases on the basis of the DeMeester score, while 17/51 had pathologic postprandial, nocturnal or diurnal reflux events. Upper gastrointestinal endoscopy revealed a normal esophageal mucosa in 6/56, Savary-Miller stage I esophagitis in 23/56, stage II in 15/56, stage III in 5/56 and stage IV in 6/56 patients. CONCLUSIONS: These investigations have demonstrated an abnormal 24-hour pH score in about half of the patients with GERD-associated respiratory complications, and indicated that short reflux events are characteristic of the reflux activity in one third of this population.