bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Lipopolysaccharide Protects Gastric Mucosa against Acute Injury in Rats by Activation of Genes for Cyclooxygenases and Endogenous Prostaglandins
Authors: Konturek Peter Ch. , Brzozowski Tomasz , Konturek Stanislaw J. , Taut Astrid , Kwiecien Slawomir , Pajdo Robert , Sliwowski Zbigniew , Hahn Eckhart G.
Published: April 2003

Lipopolysaccharides (LPS) derived from gram-negative bacteria were reported to impair gastrointestinal mucosal integrity, but the results obtained are controversial. This study was undertaken to determine the effects of short-term administration of LPS on gastric secretion and gastric damage induced by 100% ethanol and to assess the role of the gene expression of two isoforms of cyclooxygenase (COX), constitutive (COX-1) and inducible (COX-2), and endogenous prostaglandins (PG) on these effects of LPS. Fasted rats received vehicle (control) or LPS (0.1–40 mg/kg i.g. or i.p.) without or with pretreatment with nonselective inhibitors of COX activity, indomethacin (5 mg/kg i.p.) and meloxicam (2 mg/kg i.g.), or the selective COX-2 inhibitor NS-398 (10 mg/kg i.g.), followed by intragastric application of 100% ethanol. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by the H2-gas clearance technique, mucosal PGE2 generation was measured by radioimmunoassay, and expression of COX-1 and COX-1 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR with [32P]dCTP and immunohistochemistry. LPS applied intraperitoneally in various doses (0.1–10 mg/kg), dose dependently inhibited gastric acid and pepsin secretion and significantly reduced the area of gastric lesions induced by ethanol, and this was accompanied by an attenuation of the ethanol-induced fall in GBF and increased mucosal generation of PGE2. LPS applied in higher doses, such as 20 or 40 mg/kg, that caused systemic hypotension failed to protect the mucosa against 100% ethanol. Suppression of mucosal PGE2 generation by indomethacin or meloxicam, significantly reduced the inhibitory action of LPS on gastric secretion and abolished LPS-induced gastroprotection and elevation of GBF. NS-398 did not influence PGE2 generation, but significantly attenuated the protection and hyperemia induced by LPS suggesting that COX-2-derived products play an important role in gastroprotection. The expression of COX-1 mRNA, as determined by RT-PCR, quantitative RT-PCR and immunohistochemistry was found in intact gastric mucosa and after LPS administration. In contrast, the expression of COX-2 mRNA was undetectable in intact gastric mucosa but appeared in this mucosa 2, 4 and 8 h after LPS administration. COX-2 mRNA was not detected in rats treated with ethanol but, when LPS was applied before ethanol, the enhanced expression of COX-2 was detected without affecting COX-1 mRNA expression. We conclude that acute parenteral LPS affords gastroprotection against ethanol-damage through an increase in gastric microcirculation and overexpression of COX-2 and enhanced endogenous PG release.
Neurogenic Control of the Ovine Gallbladder: Ultrastructural and Functional Study
Authors: Khoursheed Moussa , Krajci Dimitrolos , Oriowo Mabayoje A. , Kadavil Elizabeth , Philip Elizabeth K. , Thulesius Olav
Published: April 2003

The purpose of this study was to investigate the ultrastructure of the local nerve supply of ovine gallbladders as well as the functional characteristics of inhibitory nerves. We used electron microscopy of thin sections of ovine gallbladders and in vitro isometric tension recording using gallbladder strips. Specifically, we measured contractile and inhibitory responses induced by transmural electrical field stimulation (EFS). We found a ganglionated plexus with intramural nerve cells and interconnecting axons. Clear and large dense-core vesicles colocalized in axons close to smooth muscle cells. EFS elicited gallbladder contractions which were converted to relaxation after atropine. EFS-induced relaxation was reduced by the nitric oxide (NO) synthase inhibitor, L-NOARG and blocked by propranolol and/or tetrodotoxin. In conclusion, enteric ganglia and neurones with synaptic vesicles (clear and dense core) were detected close to smooth muscle bundles. Neural inhibition of gallbladder contraction was mediated by β-adrenoceptors coupled to NO generation.
Gastro-Oesophageal Reflux Disease
Authors: Dent John
Published: April 2003

New approaches to the grading of reflux oesophagitis and the definition of reflux disease have been proposed which should improve the precision of descriptions of this common problem. Endoscopy and 24-hour pH monitoring studies, though of great value, have significant limitations for assessment of reflux disease. Only about one third of reflux disease patients have oesophageal mucosal erosion or ulceration. Analysis of symptoms is probably the most useful method for diagnosis. Further research is needed into the best strategies for maximising the potential of symptom analysis. In the pathogenesis of reflux disease, Helicobacter pylori infection is not a major factor but the interaction of H. pylori gastritis and eradication therapy are important areas of great current interest. Troublesome reflux disease arises primarily from abnormally frequent gastro-oesophageal reflux, though heightened oesophageal mucosal sensitivity and defective oesophageal clearance play a role in some patients. Transient lower oesophageal sphincter relaxation appears to be the most important mechanism of reflux. This distinctive, swallow-independent type of lower oesophageal sphincter relaxation has a complex triggering system, apparently located in the brain stem. Medical and surgical treatments of reflux disease are now well characterised and have improved very substantially over recent years. Drugs that inhibit the occurrence of transient lower oesophageal sphincter relaxation are an intriguing possible future therapy.
Advances in Laparoscopic Surgery
Authors: Périssat J. , Collet D. , Monguillon N.
Published: April 2003

After a brief account of the origins of laparoscopy and of its development into an interventional technique thanks to technical improvement, the author gives a dynamic state of the art in laparoscopic surgery, beginning with a description of his original classification method for laparoscopic procedures according to their level of use. Before tackling the highly controversial issue of laparoscopic surgery for cancer, he reviews in detail the various operations successfully performed by laparoscopy for the treatment of nonmalignant abdominal disorders and acute syndromes, all the while checking their results against those obtained with their open counterparts. As the various procedures are described, the interest of the laparoscopic approach becomes clearly visible, based on the excellent view of the operative field that allows diagnostic accuracy, thus avoiding unnecessary operations, and precise dissection with minimal damage. However, the laparoscopic approach is highly dependent on the surgeon’s proficiency, itself depending on experience and therefore on the frequency of occurrence of the disorder, and on the progress in and availability of adequate equipments. The last chapter looks into the future of this ever-expanding approach and defines two great trends in its evolution, one accessible to the individual surgeon, the gradual adaptation of open procedures into laparoscopic ones, the other at the institutional level, in view of the huge financial support involved if high technologies are to be systematically integrated in this new surgery. What will the future be like?
Role of Photodynamic Therapy in the Management of Gastrointestinal Cancer
Authors: Kubba A.K.
Published: April 2003

Background: Surgery for cancer of the gastrointestinal tract is associated with high morbidity and mortality, especially in older patients. A significant proportion of patients cannot be cured and would be referred for palliative therapy. Others may have early cancer but are deemed unfit for surgery. Chemotherapy and external radiotherapy are suitable for only a proportion of patients. Therefore, photodynamic therapy may have a role in the management of these patients. It was the possibility of achieving selective tumour necrosis with sparing of normal tissue that made this treatment extremely appealing compared to other conventional tumour therapy. Method: The literature is reviewed (after an extensive Medline search 1975–1997) regarding the scientific basis of photodynamic therapy and the clinical experience to date with this therapy in the management of malignancies of the gastrointestinal tract. Results and Conclusions: Photodynamic therapy holds the promise of an eradication form of treatment for early cancer especially for patients deemed unfit for other treatment. It may also prove a useful supplement to other techniques in order to eliminate small residual areas of tumour left after the main bulk has been removed by other methods. The use of photodynamic therapy in the palliative management of gastrointestinal tract cancer is likely to be limited.
Local Downregulation of Enterochromaffin-Like Cell Histamine Formation in Ulcer Healing: A Study in Rats
Authors: Mei Qi , Sundler Frank
Published: April 2003

Background and Aims: Although enterochromaffin-like (ECL) cells are the major source of histamine for the regulation of gastric acid secretion, their role in ulcer healing has not been fully investigated. The present study aimed to investigate changes in ECL cell components as well as markers for somatostatin cells, parietal cells and macrophages during the healing of experimental ulcers in rats. Methods: Standardised ulcer was induced directly in the rat gastric mucosa by brief application of acetic acid. At different time intervals following ulcer induction (1–15 days), histamine, histidine decarboxylase (HDC), chromogranin A, pancreastatin, vesicular monoamine transporter 2 (VMAT-2), H-K-ATPase, somatostatin as well as ED1 and ED2 (macrophage markers) were localised by immunocytochemistry. ED1- and histamine-immunoreactive cells were counted at different time points. HDC- and VMAT-2-immunoreactive cells were demonstrated by double staining and counted. The mRNA of HDC, chromogranin A and somatostatin was demonstrated by in situ hybridisation and quantitated by computerised image analysis. Results: HDC immunoreactivity and mRNA were markedly reduced in the ECL cells at the ulcer margin from day 1 following ulcer induction and onwards; after day 5 HDC immunoreactivity and mRNA rose gradually and had almost normalised by day 15. This local and transient downregulation of HDC was accompanied by a similar decrease in ECL cell histamine. In contrast to HDC and histamine, other ECL cell components (chromogranin A, pancreastatin, VMAT-2) as well as somatostatin and H-K ATPase were still demonstrable at the ulcer margin and displayed no major changes at any time point studied. Of the macrophage markers, ED1, but not ED2, could be identified at the ulcer margin, and the number of ED1-immunoreactive cells was high in the ulcer margin from day 1 to day 5 after ulcer induction. The increase in ED1-positive cells and the decrease in HDC-expressing cells were coincident in time and localisation. Conclusion: The present results revealed a local and transient downregulation of HDC in the ECL cells at the ulcer margin. This may account for the decrease in ECL cell histamine observed. The local infiltration of macrophages into the ulcer margin suggests that inflammatory mediators are involved in the local suppression of ECL cell activity during ulcer healing.
Superoxide: A Major Factor for Stress Protein Induction in Reoxygenation Injury in the Intestinal Cell Line Caco-2
Authors: Gebhardt Boris R. , Ries Jürgen , Caspary Wolfgang F. , Boehles Hansjosef , Stein Jürgen
Published: April 2003

Background/Aims: Acute intestinal ischemia is followed by cellular destruction and loss of mucosal barrier function. Posthypoxic injury of cellular proteins leads to the synthesis of heat shock proteins. The role of oxygen radicals in this process, however, is not fully established. Methods: In the present study, using the intestinal cell line Caco-2, we investigated the relationship between the synthesis of the heat shock protein HSP70, detected by Western blot and oxygen radicals as well as lactate dehydrogenase (LDH) release, as measured in photometrical tests. Results: Various periods of hypoxia and 30 min of reoxygenation resulted in an increased generation of superoxide as measured by the tetrazolium base 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazoliumbromide. The inhibitor of superoxide dismutase (SOD), diethyldithiocarbamate (DDC) increased and addition of SOD decreased intracellular superoxide levels. HSP70 synthesis was detectable after 2 h of hypoxia. Similar to superoxide production, DDC increased and SOD reduced the HSP70 synthesis. In contrast, the increased LDH release from the cells observed after hypoxia was not significantly altered by DDC and SOD. Conclusion: The production of superoxide correlates with HSP70 induction, but not with LDH release. We conclude that hypoxia/reoxygenation induces heat shock protein production, a result of protein damage, by increased superoxide generation, whereas superoxide does not correlate with membrane damage in Caco-2 cells.
Sequential Treatment of Anemia in Ulcerative Colitis with Intravenous Iron and Erythropoietin
Authors: Gasche Christoph , Dejaco Clemens , Reinisch Walter , Tillinger Wolfgang , Waldhoer Thomas , Fueger Gerhard F. , Lochs Herbert , Gangl Alfred
Published: April 2003

Background: Intravenous iron and erythropoietin have been shown to be effective in Crohn’s disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second. Patients and Methods: Twenty patients with ulcerative colitis-associated anemia (hemoglobin ≤10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin ≥2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, ≤10.5 g/dl as partial response. A hemoglobin increase <2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks. Results: During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6 ± 2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5 ± 1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4 ± 1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3 ± 1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl). Conclusion: Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.
Gallbladder Volume in Adults and Its Relationship to Age, Sex, Body Mass Index, Body Surface Area and Gallstones
Authors: Caroli-Bosc F.X. , Pugliese P. , Peten E.P. , Demarquay J.F. , Montet J.C. , Hastier P. , Staccini P. , Delmont J.P.
Published: April 2003

Background/Aims: The role of a large gallbladder volume with regard to a predisposition for gallstones is unknown. It is possible that an increase in gallbladder volume could result in impaired gallbladder motility and bile stasis. We looked for factors affecting gallbladder volume in a random population in the southeast of France. Methods: To assess the relationship between gallbladder volume and gallstones, 528 subjects over the age of 30 were studied (72 with lithiasis). Age, sex, body mass index, body surface area and gallbladder volume were collected for each subject. A linear regression analysis was performed to look for significant variables. Results: The overall adjusted prevalence of cholelithiasis was 13.9% in our population. On linear regression analysis, two variables (age and surface area) were found to be independently correlated with gallbladder volume. Gallbladder volume was significantly increased in subjects over 50 years (p < 0.001). There was a positive correlation between gallbladder volume and body surface area (r = 0.33, p < 0.001). In this study, the presence or absence of gallstones did not significantly affect the gallbladder volume. Conclusions: We report that there is dilatation of the gallbladder with age and with an increase in body surface area. Whether this could represent risk factors for the occurrence of gallstone remains uncertain.
Portal Hyperglutamatemia after Dietary Supplementation with Monosodium Glutamate in Pigs
Authors: Blachier François , Guihot-Joubrel Gwénaële , Vaugelade Pierre , Le Boucher Jacques , Bernard Françoise , Duée Pierre-Henri , Cynober Luc
Published: April 2003

The aim of the present work was to examine in pigs the effect of a dietary supplementation with the flavor enhancer monosodium glutamate (MSG) on intestinal amino acid metabolism. For this purpose, pigs weighing 60 ± 2 kg received a standard meal twice a day for 1 week, supplemented with either 10 g MSG per meal or, as control experiments, an isonitrogenous amount of glycine together with an equal amount of sodium in the form of NaCl, the animals being their own control in all experiments. At the end of this period, pigs received a MSG or glycine-NaCl-supplemented meal and samples of portal and arterial blood were collected for amino acid analysis in plasma. The results demonstrate after MSG supplementation rapid significant increases in glutamate concentration in the portal and arterial blood plasma after a test meal which resulted in a positive portoarterial difference. In comparison, after glycine-NaCl supplementation, glutamate concentrations were almost identical in portal and arterial plasma. Furthermore, significant increased aspartate concentration in the portal blood plasma was observed after MSG supplementation when compared with control experiments. When enterocytes were isolated at the end of the supplementation period from the jejunum and examined for their metabolic capacities towards L-glutamate and L-glutamine, it was found that metabolism did not differ according to the supplement used, with glutamate and glutamine being oxidized and transaminated at a similar level. It is concluded that the portal hyperglutamatemia observed shortly after the ingestion of a MSG- supplemented meal is likely due to the saturation of the intestinal capacity to metabolize glutamate with no measurable adaptation of the metabolic pathways controlling glutamate metabolism in enterocytes.
Successful Symptomatic Management of a Patient with Ménétrier’s Disease with Long-Term Antibiotic Treatment
Authors: Raderer Markus , Oberhuber Georg , Templ Eva , Wagner Ludwig , Pötzi Regina , Wrba Friedrich , Hejna Michael , Base Wolfgang
Published: April 2003

We present the case of a 79-year-old female patient with criteria typical for Ménétrier’s disease, i.e. enlargement of the gastric folds due to foveolar hyperplasia associated with severe protein-loss along with epigastric pain, nausea, vomiting and weight loss. Gastrin levels were within the normal range, but elevated Helicobacter pylori antibody titers (83 μg/ml) were indicative of a recent infection. Histologic examination of a gastric polyp, which was removed in toto, revealed the presence of early gastric cancer of the mucosal type. After initiation of antibiotic treatment with clarithromycin (3 × 250 mg/day) and metronidazole (2 × 500 mg/day) in combination with lansoprazole (30 mg/day), the patient’s condition improved rapidly along with abrogation of protein loss. Under maintenance treatment as indicated above, the patient has been free of symptoms now for a period of more than 2 years. On repetitive endoscopic follow-up, there was no change in gastric mucosa morphology either endoscopically or histologically, and also no evidence of recurrence of a malignant lesion. We conclude that this therapeutic regimen represented an effective alternative to surgical intervention in this patient and should be considered in similar cases.
Coincidence of Crohn’s Disease and a High-Risk Gastrointestinal Stromal Tumor of the Terminal Ileum
Authors: Pfeffel Franz , Stiglbauer Wolfgang , Depisch Dieter , Oberhuber Georg , Raderer Markus , Scheithauer Werner
Published: April 2003

A 51-year-old male patient presented with characteristic radiologic features of Crohn’s disease in the terminal ileum plus a large tumorous lesion in the right lower abdomen. Because of rapid crescent symptoms of bowel obstruction, the patient underwent surgery revealing a high-risk gastrointestinal stromal tumor (GIST) of the terminal ileum within an area of Crohn’s ileitis. Whereas the association of chronic inflammatory bowel disease (IBD) and gastrointestinal adenocarcinoma is well known, other primary intestinal tumors are rare in these patients, particularly at the time of onset of clinical symptoms. This is the 3rd patient reported in the literature with a sarcoma complicating IBD, and in fact, the first description of the coincidence of Crohn’s disease and GIST. Though the present case is likely to be a mere coincidence of two pathologically distinct entities (without any potential causal relationship), it should remind one of the possibility of small bowel ‘Crohn’s carcinoma’ in patients with a sudden change in symptomatology as well as in those in whom intestinal obstruction fails to resolve with adequate therapy.
The Antacid Talcid Adsorbs and Neutralizes All Proteins Secreted by H. pylori Including VacA Cytotoxin: A New Mechanism for Its Ulcer-Healing Action?
Authors: Tarnawski A. , Pai R. , Itani R. , Wyle F.A.
Published: April 2003

Background and Aim: Helicobacter pylori culture supernatant containing VacA cytotoxin significantly inhibits gastric cell proliferation and delays healing of experimental gastric ulcers. Since cell proliferation is crucial for ulcer healing, the removal of inhibitory effects of H. pylori secreted cytotoxin would have a beneficial effect on the healing process. In this study, we determined whether the antacid Talcid can adsorb, remove, or neutralize H. pylori derived VacA cytotoxin responsible for the above deleterious actions. Methods: Supernatants of viable H. pylori isogenic strains producing VacA cytotoxin [VacA(+)] and with disrupted cytotoxin gene not producing cytotoxin [VacA(–)] were incubated with either placebo, Talcid 10 mg/ml, omeprazole 10 mg/ml (positive control) for 1–24 h. Treated supernatants were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate proteins. We also studied the effect of supernatants on epidermal growth factor stimulated Kato III cell proliferation using BrdU labeling. Results: Talcid very effectively removed from the H. pylori culture supernatant the ∼90 kD VacA(+) cytotoxin at 3 and 24 h (99.5% removal vs. placebo-treated control; p < 0.001). It also removed all other proteins, including 66-kD urease and 58-kD heat shock protein, secreted by both VacA(+) and VacA(–) H. pylori strains. Omeprazole was completely ineffective in this regard. Preincubation with Talcid completely abolished the inhibitory effect of VacA(+) H. pylori culture supernatant on epidermal growth factor stimulated Kato III cell proliferation. Conclusion: Adsorption and neutralization by Talcid of all H. pylori secreted proteins may explain, at least in part, the ulcer-healing action of this drug.
Ampullary Hamartoma: A Rare Cause of Biliary Obstruction
Authors: Allgaier Hans-Peter , Schwacha Henning , Kleinschmidt Manuela , Thimme Robert , Schöffel Ulrich , Blum Hubert E.
Published: April 2003

Tumors of the papilla of Vater are very rare. Despite advanced imaging techniques the distinction between benign and malignant tumors remains very difficult. Because most ampullary and periampullary tumors are malignant, primary management is surgical. Here we report the case of a 65-year-old man with biliary obstruction caused by an ampullary hamartoma simulating cancer. The correct diagnosis was not established until surgery.
Effects of Dexamethasone and Linoleic Acid on Hepatic Secretion of Biliary Lipids and Anionic Polypeptide Factor: In vivo and in vitro Studies
Authors: Domingo N. , Debono E. , Reynier M.O. , Crotte C. , Thorin B. , Charbonnier M. , Clerc T. , Grillasca J. , Chanussot F. , Lafont H.
Published: April 2003

Synthetic glucocorticoids, such as dexamethasone, and diets enriched with unsaturated fatty acids have been shown to stimulate hepatic bile salt synthesis. This fact led us to investigate the effects of dexamethasone and linoleic acid supplementation on bile secretion. Cholesterol (Ch) and phospholipid secretions are bile acid dependent. Ch and phospholipid in bile are also highly bound to a small apoprotein, the anionic polypeptide factor (APF). In bile, APF may play a physiological role in stabilizing cholesterol:phospholipid vesicles and might also be important in the regulatory process of bile lipid secretion. In order to study the factors influencing bile secretion, the biliary secretion rates of bile lipids and APF were experimentally modulated in perfused rat liver (PRL) and HepG2 cells. As expected, dexamethasone induced an increase in the biliary secretion rate of bile salts (BS) in the two models (PRL: 34 up to 67 nmol/l/min/g liver; HepG2 cells: 234% vs. 100% in controls). The bile secretion rates for phospholipids (PRL: from 5 down to 1.5 nmol/l/min/g liver; HepG2 cells: 93 vs. 100% in controls) and APF (PRL: from 0.34 down to 0.12 µg/l/min/g liver; cells: 86 vs. 100% in controls) rapidly decreased independently from those of BS. The data from experimental cell models supplemented with linoleic acid indicated a correlation between the BS and APF levels (APF: 71 and 63%; BS: 161 and 197% vs. 100% in controls). The phospholipid level was regulated independently from that of APF and BS and increased (106 and 111% vs. 100% in controls), while Ch remained nevertheless unchanged. Our data showed that dexamethasone induced changes in bile and that linoleic acid clearly impaired the regulation exerted by the dexamethasone on bile lipids.
Analysis of β-Catenin Gene Mutations in Pancreatic Tumors
Authors: Gerdes Berthold , Ramaswamy Annette , Simon Babette , Pietsch Torsten , Bastian Daniel , Kersting Michael , Moll Roland , Bartsch Detlef
Published: April 2003

Background/Aim: Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been described in a subset of pancreatic carcinomas. The APC gene modulates the β-catenin-Tcf pathway. The major player in this pathway is the β-catenin protein encoded by the β-catenin gene. A variety of different tumors, including colon, prostate, endometrial, and hepatocellular carcinomas, carry mutations in exon 3 of the β-catenin gene. The aim of this study was to determine the role of the β-catenin gene in the genesis of exocrine and endocrine tumors of the pancreas. Methods: 78 ductal pancreatic adenocarcinomas, 14 ductal pancreatic cancer cell lines, and 33 endocrine pancreatic tumors were evaluated for mutations in exon 3 of the β-catenin gene by single-strand conformation polymorphism analysis and direct DNA sequencing. In addition, 40 ductal pancreatic adenocarcinomas were analyzed for intracellular β-catenin accumulation by immunohistochemistry, indicating alterations of the β-catenin gene. Results: Neither the 111 exocrine and endocrine pancreatic tumors nor the 14 pancreatic cancer cell lines carried mutations in exon 3 of the β-catenin gene. Intracellular β-catenin accumulation was not identified in any of the 40 pancreatic adenocarcinomas. Conclusion: These data suggest that the β-catenin gene as the major player of the β-catenin-Tcf pathway does not play an important role in the genesis of pancreatic tumors.
Morphine Contracts the Guinea Pig Ileal Circular Muscle by Interfering with a Nitric Oxide Mediated Tonic Inhibition
Authors: Lénárd Jr. László , Halmai Vilmos , Barthó Loránd
Published: April 2003

The effect of morphine was examined on the circular muscle of guinea pig ileal segments in vitro, with special regard to its interaction with enteric nitric oxide (NO) releasing neurons. In the presence of atropine (10–6 M), morphine (10–6 M) caused tonic contraction (approximately 7% of the maximal spasm) which was reversed by naloxone (10–6 M). Tetrodotoxin (TTX; 10–6 M) also caused contraction (14% of maximum); morphine completely lost its effect in the presence of TTX. Likewise, the NO synthase inhibitor NG-nitro-L-arginine (L-NOARG, 10–4 M) elicited a tonic circular muscle contraction (12% of maximum) and completely prevented the excitatory action of TTX or morphine. The NO donor sodium nitroprusside (10–7 to 10–4 M) caused relaxation. In longitudinally oriented preparations in the presence of atropine (10–6 M), no change in tone was observed upon administration of morphine (10–6 M), TTX (10–6 M), or L-NOARG (10–4 M). In the circular muscle in the absence of atropine, cholecystokinin octapeptide (CCK-8; 10–9 M) evoked a tonic-phasic contractile response which spontaneously faded away within 3 min. L-NOARG (10–4 M) failed to affect intensity or duration of the response to CCK-8. It is concluded that NO-releasing myenteric neurons exert a tonic inhibitory influence upon the circular, but not longitudinal muscle of the guinea pig ileum. Morphine and TTX probably contract the circular muscle by reducing the amount of NO released. A release of NO seems to play no role in the contractile effect of CCK-8 or in its spontaneous termination.
Gastric Compliance, Sensation, and the Relaxation Response to a Nitric Oxide Donor in Health and Reflux Oesophagitis
Authors: Newton Magda , Kamm MichaelA. , Burnham W.Rodney , Roy Amanda , Roeloffs JanM.M. , Akkermans LouisM.A.
Published: April 2003

Background/Aims: The gastric fundus affects afferent control of lower oesophageal sphincter function. Nitric oxide is an important relaxant of the fundus. We postulated that gastric distensibility, compliance and nitric oxide sensitivity may be altered in patients with gastro-oesophageal reflux disease (GERD). Methods: 9 patients with erosive oesophagitis (6 males; median age 55 years) and 16 healthy controls (9 males; median age 36 years) were studied fasting with a gastric barostat. Minimal distending pressure (MDP) and gastric compliance (Δv/Δp) were determined by increasing intrabag pressure in 2-mm Hg increments. The pressures required to produce initial sensation and maximum tolerated sensation were recorded. With the intrabag pressure set at MDP +2 mm Hg, 500 μg sublingual glyceryl trinitrate was administered and the percentage change in intrabag volume from initial volume recorded. Results: The MDP was significantly greater in patients than controls (7.5 vs. 6.7 mm Hg median; p = 0.02). Gastric compliance was similar in both groups (57.8 vs. 67.2 ml/mm Hg; p = 0.4). There was no difference between groups in the pressure at first intragastric sensation (11.2 vs. 10.3 mm Hg above MDP; p = 0.5) or in the maximal tolerated pressure (15.8 vs. 14.3 mm Hg above MDP; p = 0.2). The proportional change in gastric volume from baseline in response to glyceryl trinitrate was smaller in patients than controls (66 (3–200) vs. 120 (26–1,053)%; p = 0.02). Conclusions: Gastric MDP may be altered in GERD, but gastric compliance and sensitivity to distension are normal. Major gastric relaxation occurs in response to a nitric oxide donor, but this appears to be diminished in patients with GERD. Upper gut nitrinergic mechanisms may be altered in oesophageal reflux disease.
Gastroesophageal Reflux Disease: Prevalence, Clinical, Endoscopic and Histopathological Findings in 1,128 Consecutive Patients Referred for Endoscopy due to Dyspeptic and Reflux Symptoms
Authors: Voutilainen Markku , Sipponen Pentti , Mecklin Jukka-Pekka , Juhola Matti , Färkkilä Martti
Published: April 2003

Background and Aims: Gastroesophageal reflux disease (GERD) reportedly has increased in prevalence while Helicobacter pylori infection and peptic ulcer disease have been on the decrease. The aim of the present study was to examine the prevalence of GERD as well as the clinical, endoscopic and histologic variables that associate with GERD in patients referred for endoscopy. Patients and Methods: The study population was drawn from 1,562 consecutive patients referred for endoscopy. The exclusion criteria were previous H. pylori eradication, gastric surgery, anemia and weight loss. Thus 1,128 patients were enrolled in the present study. Results: Of the 1,128 patients, 199 (18%) were referred for endoscopy due to heartburn and/or regurgitation. GERD, defined as chronic (>6 months) heartburn and/or regurgitation with or without erosive esophagitis, Barrett’s esophagus, esophageal ulcer or stricture, was detected in 248 (22%) patients. Of the 248 GERD patients, 81 (33%) had endoscopy-negative GERD, but of those aged <50 years (n = 67), 57 (85%) were endoscopy-negative. The overall incidence of GERD was 307 per 100,000 population/year and that of endoscopy-positive GERD 207/100,000/year. The positive and negative predictive values of heartburn and regurgitation for endoscopy-positive GERD were 0.37 (95% CI 0.31–0.44) and 0.90 (95% CI 0.88–0.92), respectively. Independent risk factors for GERD were male sex (OR 1.9, 95% CI 1.3–2.7), previous medication for upper gastrointestinal symptoms (OR 2.7, 95% CI 1.7–4.1), the use of nonsteroidal anti-inflammatory drugs (NSAIDs; OR 2.0, 95% CI 1.3–3.0), histologic esophagitis (OR 2.2, 95% CI 1.5–3.2) and incomplete intestinal metaplasia at the gastroesophageal junction (OR 1.7, 95% CI 1.0–3.1). Chronic gastritis was protective against GERD (OR 0.7, 95% CI 0.5–0.9). No association was observed between GERD and H. pylori infection. The risk of patients aged <50 years (n = 407) of having major lesion (Barrett’s esophagus, esophageal stricture, peptic ulcer, esophageal/gastric carcinoma) was significantly lower than that of patients aged >50 years (n = 721; OR 0.5, 95% CI 0.3–0.9, p = 0.01). Conclusions: The correlation between reflux symptoms and endoscopy-positive GERD is poor and most GERD patients aged <50 years have endoscopy-negative GERD. The use of NSAIDs is a risk factor for GERD, whereas chronic gastritis, but not H. pylori infection, may protect against GERD. Incomplete intestinal metaplasia at the gastroesophageal junction is associated with GERD.
Protective Effect of Lafutidine against Indomethacin-Induced Intestinal Ulceration in Rats: Relation to Capsaicin-Sensitive Sensory Neurons
Authors: Kato Shinichi , Tanaka Akiko , Kunikata Tomonori , Umeda Masakazu , Takeuchi Koji
Published: April 2003

Background/Aim: We examined the prophylactic effect of lafutidine, a novel histamine H2-receptor antagonist [(±)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2 butenyl]acetamide], on indomethacin-induced small intestinal ulcers in rats and investigated the relation of this action to capsaicin-sensitive sensory neurons. Methods and Results: Subcutaneously administered indomethacin (10 mg/kg) provoked ulceration in the small intestine, mainly the jejunum and ileum, accompanied by increases in myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well as the enterobacterial numbers invading the mucosa. Intestinal ulcerogenic response to indomethacin was prevented by 16,16-dimethyl prostaglandin E2 (10 μg/kg, p.o.) and capsaicin (10 mg/kg, p.o.) as well as ampicillin (800 mg/kg, p.o.), but not omeprazole (100 mg/kg, p.o.). Likewise, lafutidine (1–10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.), reduced the occurrence of intestinal ulcers in response to indomethacin in a dose-dependent manner, and a significant effect was observed at 3 mg/kg or greater. The protective action of lafutidine as well as capsaicin was almost totally abolished by chemical ablation of capsaicin-sensitive sensory neurons. Both lafutidine and capsaicin significantly suppressed the increases in MPO and iNOS activities as well as enterobacterial numbers in the mucosa. These agents also significantly enhanced mucus secretion in the small intestine. Conclusion: These results suggest that lafutidine protects the small intestine against ulceration via stimulation of capsaicin-sensitive sensory neurons. This action may be attributable to inhibition of enterobacterial invasion in the intestinal mucosa, probably by increasing the mucus secretion.
Regulation of PepT1 Peptide Transporter Expression in the Rat Small Intestine under Malnourished Conditions
Authors: Ihara Takashi , Tsujikawa Tomoyuki , Fujiyama Yoshihide , Bamba Tadao
Published: April 2003

Background and Aims: Many investigations suggested that peptide nutrition had a clinical advantage for nitrogen absorption. Recently, the cDNA encoding the H+/peptide cotransporter PepT1 was cloned. However, the regulatory mechanism of PepT1 expression under malnourished conditions has not been elucidated. The aim of this study was to clarify regulatory mechanisms of PepT1 expression. Methods: Sprague-Dawley rats were starved for 4 days, semistarved (50% amount of control) for 10 days, or given total parenteral nutrition (TPN) for 10 days. Rats with free feeding were used as control. Among those groups, the changes of PepT1 mRNA level in the jejunal mucosa and PepT1 protein density at the brush-border membranes were examined by Northern blot and by Western blot analysis, respectively. Results: Both starvation and TPN treatment caused a significant decrease in mucosal weight by 41 and 50% respectively. PepT1 mRNA level increased to 179% in the starved group and also to 161 and 164% in the TPN and semistarved groups, respectively. In contrast, sodium-dependent glucose transporter 1 mRNA expression showed no significant change. PepT1 protein density showed similar changes with the mRNA. Conclusions: PepT1 gene expression was significantly enhanced under the malnourished conditions in spite of atrophic changes of intestinal mucosa.
Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics
Authors: Schiedermaier Peter , Hansen Stephan , Asdonk Dirk , Brensing Karl-August , Sauerbruch Tilman
Published: April 2003

Background: Recently, the beneficial effects of ursodeoxycholic acid (UDCA) on the portal hypertensive state have been demonstrated in patients with primary biliary cirrhosis. However, it is not known whether UDCA has direct or indirect effects on the vascular smooth muscles in humans, thereby leading to a change in splanchnic or systemic hemodynamics. Aims: We therefore evaluated the hemodynamic effects of UDCA as to its established effect on gallbladder motility under fasting and postprandial conditions in healthy volunteers. Methods: In a double-blind, cross-over study of 20 healthy volunteers, placebo or UDCA (750 mg/d) were randomly administered over 4 weeks with an interim 4-week washout period. Portal blood flow, cardiac output and gallbladder motility were measured using echo-Doppler and b-mode sonography before and after placebo and verum, respectively. ECG, blood pressure, heart rate and blood chemistry were also measured. Results: UDCA did not significantly change fasting portal flow or meal-induced portal hyperemia. Both fasting and postprandial gallbladder volumes increased (26.5 ± 6.0 vs. 40.7 ± 13.8 ml, p < 0.05, and 11.2 ± 6.2 vs. 14.8 ± 6.7 ml, p < 0.05). Diastolic blood pressure decreased under UDCA (71.2 ± 8.7 vs. 66.5 ± 6.5 mm Hg, p < 0.05). Serum levels of chloride and γ-glutamyltransferase decreased slightly, while alkaline phosphatase increased. Conclusions: UDCA affected systemic but not portal hemodynamics. The increase in gallbladder volume is obviously mediated by factors that do not influence the splanchnic vascular bed.
Influence of a Highly Purified Senna Extract on Colonic Epithelium
Authors: van Gorkom Britta A.P. , Karrenbeld Arend , van der Sluis Tineke , Koudstaal Jan , de Vries Elisabeth G.E. , Kleibeuker Jan H.
Published: April 2003

Background: Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls. Aims: To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression. Methods: Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2′-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically. Results: Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased. Conclusion: Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.
Clinical Patterns of Crohn’s Disease in Greece: A Follow-Up Study of 155 Cases
Authors: Triantafillidis John K. , Emmanouilidis Anastasios , Manousos Orestis , Nicolakis Dimitrios , Kogevinas Manolis
Published: April 2003

The aim of this prospective study was to elucidate the clinical features and natural history of Crohn’s disease in Greece. One hundred and fifty-five Greek patients with definite diagnosis of Crohn’s disease were followed-up for a mean period of 9.7 years and evaluated for clinical patterns and course of illness. The male/female ratio was 1.58:1. The peak incidence of the disease was observed between 20 and 30 years of age. The majority of patients were urban dwellers and of higher socio-economic level compared to the general population of Greece. In almost 50% of the patients symptoms of the disease started below the age of 30, although in almost one in every 5 cases, symptoms appeared after the age of 50. Familial clustering of inflammatory bowel disease was observed in 1.3%. The pattern of anatomic involvement was: ileocolic 33.3%, colon 33.3% and small bowel 33.3%. The kind of predominant symptoms at the time of diagnosis was related to the anatomic location of the disease. At least one extraintestinal manifestation appeared in 42% of patients. Perianal disease was noticed in 21.3% with fistulae and abscesses being the most common manifestation. Fifty-one percent of patients were operated upon at least once during the follow-up period because of acute abdomen, bad response to conservative treatment and fistulae and abscesses. Emergency operation was required in 17.3% of the patients. Evolution to cancer was observed in 3 patients (2%). During the follow-up period of 9.7 ± 6.5 years, 18 patients (11.6%) died. A considerable mortality was noticed in the surgically treated group of patients, while in the nonoperated group the disease was running with milder symptoms. It is concluded that some of the clinicoepidemiological characteristics of patients with Crohn’s disease in Greece are in accordance with those reported from western as well as the neighboring Mediterranean countries. However, other parameters such as the higher incidence of the disease in males, the low incidence of familial clustering, and the low incidence of perianal disease, underline the importance of environmental, genetic and other factors on the evolution and behavior of the disease in different parts of the world.
Helicobacter pylori and Gastric Erosions
Authors: Lehmann Frank S. , Renner Eberhard L , Meyer-Wyss Beat , Wilder-Smith Clive H. , Mazzucchelli Luca , Ruchti Charles , Drewe Jürgen , Beglinger Christoph , Merk Hans S.
Published: April 2003

Background/Aims: Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers. Methods: 175 asymptomatic subjects underwent upper gastrointestinal endoscopy. Antral biopsies were taken for bacterial cultures, histology and quick urease (CLO) test. A 13C-urea breath test was performed after endoscopy. NSAID intake, alcohol consumption and smoking habits were also recorded in each subject. Results: 33 (19%) of 175 asymptomatic volunteers had macroscopic lesions on upper gastrointestinal endoscopy, 7 were H. pylori positive, 26 were H. pylori negative. Gastric erosions occurred in 8% (14 subjects) of all volunteers. 10 subjects were H. pylori negative and 4 H. pylori positive. In 11 volunteers, gastric erosions were restricted to the prepyloric antrum. Only 1 of 14 subjects had a history of NSAID intake and 6 subjects were alcohol abstainers. Conclusion: We conclude that gastric erosions occur in a considerable amount of asymptomatic volunteers. They are predominantly localized in the prepyloric antrum and are most likely not associated with H. pylori infection, NSAID intake, smoking or alcohol consumption.
Involvement of CCK in the Paraventricular Nucleus of the Hypothalamus in the CNS Regulation of Colonic Motility
Authors: Mönnikes H. , Tebbe J. , Grote C. , Sonntag A. , Pluntke K. , Sturm K. , Arnold R.
Published: April 2003

The effects of cholecystokinin octapeptide (CCK8), the CCK-A receptor antagonist, MK-329, and the CCK-B receptor antagonist, L-365, 260, microinfused into the paraventricular nucleus of hypothalamus (PVN) on colonic motor function was investigated in awake rats, chronically implanted with a microinjection cannula into the PVN and a catheter into the proximal colon. In fasted rats, bilateral microinfusion of CCK8 at doses of 1.5 and 3.0 μg/rat into the PVN stimulated colonic transit, as shown by a significant increase in the geometric center by 47 and 54%, respectively. This effect of CCK8 was site-specific to the PVN, since microinjection of the peptide into sites outside of but adjacent to PVN had no effect. In non-fasted rats, L-365,260 bilaterally microinjected into the PVN at a dose of 1.5 μg/rat inhibited propulsive colonic motor function; colonic transit time significantly increased by 73% in comparison to the control condition. Microinfusion of the CCK-A antagonist into in the PVN did not affect colonic transit. These results show that the PVN is a responsive site for the central CCK8-induced modulation of colonic motility. The data suggest, that endogenous CCK in the paraventricular nucleus of the hypothalamus unfolds a stimulatory effect on colonic transit through action on CCK-B receptors.