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Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome

UNLABELLED Visceral hyperalgesia has been suggested to play a role in the development of symptoms presented by irritable bowel syndrome patients. Otilonium bromide was developed to block smooth muscle Ca release to control cramping pain of these patients. AIMS to determine whether otilonium bromide can influence sensory thresholds of patients suffering from irritable bowel syndrome. METHODS 15 patients with Rome-II positive IBS were tested by Synectics Visceral Stimulator Barostat using rapid phasic distension (870 ml/min). The sensory threshold for first sensation, stool, pain and maximum tolerable volume and pressure were measured. All of the parameters were tested before and 1 week after the initiation of otilonium bromide (Spasmomen, Berlin Chemie, 3x40 mg) therapy. RESULTS The perceptual thresholds for first sensation, stool, pain and maximum tolerable distention were, 8.8+/-1.7 Hgmm, 19.2+/-2.1 Hgmm, 26.3+/-2.8 Hgmm, 28.7+/-2.8 Hgmm for pressure, 90+/-21 ml, 145+/-28 ml, 208+/-25 ml, 213+/-28 ml for volume, before treatment, respectively. Otilonium bromide treatment did not influence the thresholds for first sensation and stool, 7.4+/-1.4 Hgmm, 20.7+/-4.6 Hgmm and 83+/-21 ml, 178+/-35.8 ml, respectively. The pressure threshold of pain was significantly higher 1 week after treatment (26.3+/-2.8 Hgmm vs. 29.1+/-5.5 Hgmm, P<0.05), but the volume threshold of this sensation remained unchanged (208+/-25 ml vs. 234+/-39 ml, not significant). The pressure (28.7+/-2.8 Hgmm vs. 38.1+/-3.4 Hgmm, P<0.05) and volume (213+/-28 ml vs. 278+/-27 ml, P<0.05) thresholds for maximum tolerable volume were increased by 7 days otilonium bromide treatment. CONCLUSION These data suggest that otilonium bromide enhances sensory thresholds to recto-sigmoideal distention.

Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett’s esophagus

UNLABELLED The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barretts esophagus. METHODS The diagnosis of Barretts esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. RESULTS Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barretts esophagus. CONCLUSION Impaired esophageal sensory motor function may serve as one etiologic role in the development of Barretts esophagus.

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity

BACKGROUND the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS the observation was carried out in 49 patients with Crohns disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohns disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohns Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Vagus-mediated activation of mucosal mast cells in the stomach: Effect of ketotifen on gastric mucosal lesion formation and acid secretion induced by a high dose of intracisternal TRH analogue

TRH analogue, RX 77368, injected intracisternally (i.c.) at high dose (3 microg/rat) produces gastric mucosal lesion formation through vagal-dependent pathway. The gastric mucosal hyperemia induced by i.c. RX 77368 was shown to be mediated by muscarinic vagal efferent fibres and mast cells. Furthermore, electrical vagal stimulation was observed to induce gastric mucosal mast cell degranulation. The aim of the study was to assess the influence of ketotifen, a mast cell stabilizer, on RX 77368-induced gastric lesion formation and gastric acid secretion. RX 77368 (3 microg, i.c.) or vehicle (10 microL, i.c.) was delivered 240 min prior to the sacrifice of the animals. Ketotifen or vehicle (0.9% NaCl, 0.5 mL) was injected intraperitoneally (i.p.) at a dose of 10 mg x kg(-1) 30 min before RX 77368 injection. The extent of mucosal damage was planimetrically measured by a video image analyzer (ASK Ltd., Budapest) device. In the gastric acid secretion studies, the rats were pretreated with ketotifen (10 mg x kg(-1), i.p.) or vehicle (0.9% NaCl, 0.5 mL, i.p.), 30 min later pylorus-ligation was performed and RX 77368 (3 microg, i.c.) or vehicle (0.9% NaCl, 10 microL, i.c.) was injected. The rats were killed 240 min after i.c. injection, and the gastric acid secretion was measured through the titration of gastric contents with 0.1 N NaOH to pH 7.0. RX 77368 (3 microg, i.c.) resulted in a gastric mucosal lesion formation involving 8.2% of the corpus mucosa (n = 7). Ketotifen elicited an 85% inhibition on the development of mucosal lesions (n = 7, P < 0.001) whereas ketotifen alone had no effect on the lesion formation in the mucosa (n = 7). The RX 77368 induced increase of gastric acid secretion was not influenced by ketotifen pretreatment in 4-h pylorus-ligated animals. Central vagal activation induced mucosal lesion formation is mediated by the activation of mucosal mast cells in the stomach. Mast cell inhibition by ketotifen does not influence gastric acid secretion induced by i.c. TRH analogue in 4-h pylorus-ligated rats.

One year follow-up of patients after successful helicobacter pylori eradication therapy

UNLABELLED The aim of this study was to investigate the Helicobacter pylori (Hp) status of patients who underwent successful eradication therapy 1 year prior to the study and to evaluate their current symptoms. METHODS all of the patients were initially evaluated by oesophago-gastro-bulboscopy and the Hp status was determined by at least two different methods [rapid urease test, histology or urea breath test (UBT)]. The Hp infection was treated with a 1-week triple therapy protocol, and the UBT was repeated 4-6 weeks later. We invited back 110 patients who had negative post-eradication UBT results 12+/-3 months prior to the study period. UBT was repeated and a questionnaire was completed about the previous and present complaints and medication. RESULTS 80 of the 110 patients (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease, 36 patients had gastritis or duodenitis without erosive lesions, and 19 patients had erosive form of gastritis or duodenitis initially. All of the patients except one in the erosive gastritis group had negative control UBT 1 year after the eradication, which means 1.25% recurrence rate within 1 year. The eradication therapy completely revealed the symptoms of 16 patients in the ulcer group (64%), 13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10 patients with erosive gastroduodenitis (52%), but this was only temporary. One year after the eradication therapy seven of the ulcer patients (28%), 11 patients with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis (37%) were symptom-free. Most of the patients had epigastric pain (44%), heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10 patients with gastroduodenitis (28%) and five patients with erosive gastroduodenitis (26%) were taking H(2)-blockers regularly. CONCLUSION the 1-month post-eradication UBT was probable true negative in all of the evaluated cases, since 79 patients (98.75%) were also negative after 1 year. The Hp recurrence rate is very low (1.25%) in a 1-year period. The symptoms were relieved shortly after eradication therapy in the majority of patients with ulcer disease or erosive lesions. However, significantly smaller portion of the patients with gastroduodenitis became symptom-free. Only about one third of the treated patients remained symptom-free 1 year after the eradication.

Adipose tissue infiltration in minor salivary glands of patients with Sjögren’s syndrome: Lack of significant correlation with the disease. An image analysis of 174 cases*

Abstract Fatty infiltration in minor salivary gland biopsies and its correlation to systemic autoimmune diseases are controversial in the literature. Presence and extent of fatty infiltration in minor salivary glands of 107 Sjögren’s syndrome patients and 67 age-matched sicca controls were compared with statistical analyses. No significant difference was found regarding the presence or the extent of fatty infiltration between the two groups. Fatty infiltration seems to be unrelated to Sjögren’s syndrome thus its examination in salivary gland biopsy samples cannot improve the diagnostic accuracy of the disease.

Image analysis of fatty infiltration in labial salivary gland biopsies: extent and its correlation to age, obesity and diabetes

BACKGROUND Fatty infiltration of minor salivary gland parenchyma is relatively frequent, but not extensively examined histopathological phenomenon in biopsy samples. Its extent and relation to several suspected background diseases are not well understood. METHODS In this study, we examined the presence and extent of fatty infiltration on digitally scanned versions of the periodic acid/Schiff-stained minor salivary gland slides of 275 patients. As a result of the image analysis, fatty infiltration was expressed in per cent of the whole selected area. The presence and extent of this change were compared to age, diabetes mellitus and body mass index in various statistical analyses. RESULTS Significantly higher age and body mass index values were found in the fatty infiltration positive than in the negative group. We also found that not only the number of fatty infiltration positive cases was increased significantly in the gradually worsened body mass index groups, but the extent of fatty infiltration also increased as the obesity worsened. Age also showed significant correlation with the extent of fatty infiltration. DISCUSSION All of these findings support that the age (which seemed the only independent variable) shows strong correlation with the presence of the fatty infiltration but obesity may also play important role in the development and the extent of this change. Because of its frequency in elderly, at least partly, the fatty infiltration might be responsible for the xerostomia. We also think that presence of fatty infiltration should be mentioned in the histopathological report of salivary gland biopsies.