bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Epidermal Growth Factor and TransformingGrowth Factor-β<sub>1</sub> Expression in Hormone-Induced Acute Pancreatitis in Rats
Authors: Konturek Peter Ch. , Dembinski Artur , Warzecha Zygmunt , Ihlm Astrid , Ceranowicz Piotr , Konturek Stanislaw J. , Stachura Jerzy , Hahn Eckhart G. 
Published: April 2003

Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP) suggested that these substances play an important role in pancreatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regeneration, has not been investigated. The aim of this study was to compare the gene and immunohistochemical expression of EGF and TGF-β<sub>1</sub>, cell proliferation, and biochemical parameters in AP induced by infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at 0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion. Pancreatic tissue DNA synthesis, cell proliferation, histological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and TGF-β<sub>1</sub> was evaluated by reverse transcription-polymerase chain reaction. During 10 days of the study after induction of AP a gradual normalization of biochemical and histological parameters was observed. DNA synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradually decreased reaching at day 10 the values similar to those of vehicle-treated control rats. In these control rats the EGF mRNA or immunohistochemical expression was not detected, while the TGF-β<sub>1</sub> expression was weak. After induction of AP, the mRNA and immunohistochemical expression of EGF showed an increase during the initial 5 days, while those of TGF-β<sub>1</sub> showed a marked increase between 0 and 48 h and then again at day 10. We confirm that: (1) the expression of TGF-β<sub>1</sub> during AP is biphasic with an initial increase probably related to pancreatic damage and inhibition of cell proliferation and with the later phase of increase accompanied by the stimulation of the synthesis of extracellular matrix components and (2) AP is accompanied by an induction of synthesis of EGF that occurs in the initial phase of AP, probably limiting the extent of AP, and enhancing the stimulation of the pancreatic repair and regeneration.
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 H<sub>2</sub>-gas clearance technique, mucosal PGE<sub>2</sub> 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 [<sup>32</sup>P]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 PGE<sub>2</sub>. 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 PGE<sub>2</sub> 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 PGE<sub>2</sub> 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.
Local Downregulation of Enterochromaffin-Like Cell Histamine Formation in Ulcer Healing: A Study in Rats
Authors: Mei Qi , Sundler Frank 
Published: April 2003

<i>Background and Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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. <i>Conclusion:</i> 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

<i>Background/Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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. <i>Conclusion:</i> 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.
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 <i>L</i>-glutamate and <i>L</i>-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.
The Antacid Talcid Adsorbs and Neutralizes All Proteins Secreted by <i>H. pylori</i> Including VacA Cytotoxin: A New Mechanism for Its Ulcer-Healing Action?
Authors: Tarnawski A. , Pai R. , Itani R. , Wyle F.A. 
Published: April 2003

<i>Background and Aim:</i> <i>Helicobacter pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i> derived VacA cytotoxin responsible for the above deleterious actions. <i>Methods:</i> Supernatants of viable <i>H. pylori</i> 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. <i>Results:</i> Talcid very effectively removed from the <i>H. pylori</i> 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(–) <i>H. pylori</i> strains. Omeprazole was completely ineffective in this regard. Preincubation with Talcid completely abolished the inhibitory effect of VacA(+) <i>H. pylori</i> culture supernatant on epidermal growth factor stimulated Kato III cell proliferation. <i>Conclusion:</i> Adsorption and neutralization by Talcid of all <i>H. pylori</i> secreted proteins may explain, at least in part, the ulcer-healing action of this drug.
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<sup>–6</sup> M), morphine (10<sup>–6</sup> M) caused tonic contraction (approximately 7% of the maximal spasm) which was reversed by naloxone (10<sup>–6</sup> M). Tetrodotoxin (TTX; 10<sup>–6</sup> M) also caused contraction (14% of maximum); morphine completely lost its effect in the presence of TTX. Likewise, the NO synthase inhibitor N<sup>G</sup>-nitro-L-arginine (L-NOARG, 10<sup>–4</sup> 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<sup>–7</sup> to 10<sup>–4</sup> M) caused relaxation. In longitudinally oriented preparations in the presence of atropine (10<sup>–6</sup> M), no change in tone was observed upon administration of morphine (10<sup>–6</sup> M), TTX (10<sup>–6</sup> M), or L-NOARG (10<sup>–4</sup> M). In the circular muscle in the absence of atropine, cholecystokinin octapeptide (CCK-8; 10<sup>–9</sup> M) evoked a tonic-phasic contractile response which spontaneously faded away within 3 min. L-NOARG (10<sup>–4</sup> 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

<i>Background/Aims:</i> 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). <i>Methods:</i> 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. <i>Results:</i> 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). <i>Conclusions:</i> 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

<i>Background and Aims:</i> Gastroesophageal reflux disease (GERD) reportedly has increased in prevalence while <i>Helicobacter pylori</i> 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. <i>Patients and Methods:</i> The study population was drawn from 1,562 consecutive patients referred for endoscopy. The exclusion criteria were previous <i>H. pylori</i> eradication, gastric surgery, anemia and weight loss. Thus 1,128 patients were enrolled in the present study. <i>Results:</i> 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 <i>H. pylori</i> 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). <i>Conclusions:</i> 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 <i>H. pylori</i> 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

<i>Background/Aim:</i> We examined the prophylactic effect of lafutidine, a novel histamine H<sub>2</sub>-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. <i>Methods and Results:</i> 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 E<sub>2</sub> (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. <i>Conclusion:</i> 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.