piperidines and Gastritis

Lafutidine is a novel histamine H(2)-receptor antagonist used primarily as an antisecretory agent in Japan. Previous human studies have not assessed its gastroprotective effects. The purpose of the present study was to determine the effects of lafutidine on the human gastric mucus layer using both histological and biochemical methods.. Of the 14 patients scheduled for gastrectomy who consented to participate, seven were given 14 days of lafutidine 20 mg/day (lafutidine group) and the others received no medication (control group). The surface mucus gel layer in Carnoy-fixed tissue sections was examined immunohistochemically. Both the thickness of the mucus layer and its mucin content were measured in gastric corpus mucosa.. There was no detectable difference between the groups in the grade of gastritis or the immunohistochemical staining characteristics. The laminated structure of the surface mucus gel layer was retained after administration of lafutidine and it was thicker than the layer in the control group. The surface layer in the lafutidine group had three-fold more mucin than that in the control group. There was no difference between the two groups in the mucin content of the deep mucosa.. Lafutidine, given at clinical dosages, not only inhibits acid secretion but also strengthens the mucus barrier of the human gastric mucosa.

Topics: Acetamides; Administration, Oral; Adult; Aged; Anti-Ulcer Agents; Female; Gastric Mucosa; Gastritis; Histamine H2 Antagonists; Humans; Male; Middle Aged; Mucus; Piperidines; Pyridines; Severity of Illness Index; Stomach Neoplasms; Treatment Outcome

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients' feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Dyspepsia; Female; Gastric Mucosa; Gastritis; Humans; Male; Middle Aged; Piperidines

Spices have been used for thousands of years, and recent studies suggest that certain spices confer beneficial effects on gastric disorders. The purpose of this study was to evaluate possible chemopreventive effects of spice-derived compounds on Helicobacter pylori (H. pylori)-induced gastritis.. We examined the inhibitory effects of curcumin, capsaicin, and piperine on H. pylori in vitro by determining the colony-forming units and real-time RT-PCR in H. pylori stimulated AGS gastric cancer cells. For in vivo analysis, 6-week-old SPF male Mongolian gerbils were infected with H. pylori, fed diets containing 5000 ppm curcumin, 100 ppm capsaicin, or 100 ppm piperine, and sacrificed after 13 weeks.. All three compounds inhibited in vitro proliferation of H. pylori, with curcumin being the most effective. Infiltration of neutrophils and mononuclear cells was suppressed by piperine both in the antrum and corpus of H. pylori-infected gerbils. Capsaicin also decreased neutrophils in the antrum and corpus and mononuclear cell infiltration and heterotopic proliferative glands in the corpus. mRNA expression of Tnf-α and formation of phospho-IκB-α in the antrum were reduced by both capsaicin and piperine. In addition, piperine suppressed expression of Il-1β, Ifn-γ, Il-6, and iNos, while H. pylori UreA and other virulence factors were not significantly attenuated by any compounds.. These results suggest that capsaicin and piperine have anti-inflammatory effects on H. pylori-induced gastritis in gerbils independent of direct antibacterial effects and may thus have potential for use in the chemoprevention of H. pylori-associated gastric carcinogenesis.

Topics: Alkaloids; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Benzodioxoles; Capsaicin; Chemoprevention; Colony Count, Microbial; Diet Therapy; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Piperidines; Polyunsaturated Alkamides; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Stomach

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Line; Chemotaxis, Leukocyte; Diclofenac; Epithelial Cells; Gastric Acid; Gastric Mucosa; Gastritis; Humans; Microscopy, Fluorescence; Mitochondria; Neutrophil Infiltration; Organophosphorus Compounds; Oxidative Stress; Piperidines; Rats, Sprague-Dawley; Superoxides

Helicobacter pylori causes a lifelong infection and provides a model of bacterial adaptation and persistent colonization. Adenosine is an anti-inflammatory mediator that limits tissue damage during inflammation. We studied the role of adenosine in the T-cell-mediated regulation of gastritis and bacterial persistence. After 4 h of activation, human T helper (Th) cells increased A(2A) adenosine receptor (A(2A)AR) mRNA level (sevenfold). A(2A)AR was the predominant subtype expressed in resting and stimulated gastric or peripheral Th cells. Stimulation with ATL313, an A(2A)AR agonist, increased cyclic AMP (cAMP) accumulation and reduced interleukin-2 (IL-2) production by 20-50%. ATL313 also attenuated tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production, which was inhibited by an A(2A)AR antagonist. Infection of IL-10-deficient mice with H. pylori is cleared spontaneously due to the marked inflammation. Administration of ATL313 during infection reduced gastritis and pro-inflammatory cytokine responses while bacterial load increased. In contrast, infection of A(2A)AR-deficient mice enhanced gastritis. Thus, A(2A)AR limits the pro-inflammatory effects of Th cells and favor chronic Helicobacter infection.

Topics: Adenosine A2 Receptor Agonists; Animals; CD4 Antigens; Cyclic AMP; Cytokines; Gastric Mucosa; Gastritis; Helicobacter felis; Helicobacter Infections; Helicobacter pylori; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Lymphocyte Activation; Mice; Mice, Knockout; Piperidines; Receptor, Adenosine A2A; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha

Leptin, a multifunctional hormone that regulates food intake and energy expenditure, has emerged recently as an important modulator of gastric mucosal responses to Helicobacter pylori infection. We applied the animal model of H. pylori LPS-induced gastritis to investigate the role of endothelin-1 (ET-1) in the mucosal leptin production. We show that the histologic pattern of inflammation reached a maximum on the fourth day following the LPS and was reflected in a marked increase in the mucosal level of ET-1 and leptin. Therapeutic administration of phosphoramidon, an inhibitor of ECE-1 activity, led to a 61.2% decline in the mucosal ET-1 level and a 64.1% reduction in leptin, while the severity of mucosal inflammatory involvement increased by 28.6%. A drop in the level of leptin and the increase in severity of the inflammatory involvement elicited by the LPS was also attained in the presence of ET(A) receptor antagonist BQ610, but not the ET(B) receptor antagonist BQ788. Moreover, administration of ERK inhibitor, PD98059, in the presence of ET(B) receptor antagonist, but not the ET(A) receptor antagonist, caused reduction in the mucosal leptin level. Our findings are the first to implicate ET-1 as a key factor in up-regulation of gastric mucosal leptin-associated H. pylori infection. We also show that the effect of ET-1 on leptin production is a consequence of ET(A) receptor activation.

Topics: Animals; Aspartic Acid Endopeptidases; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Gastric Mucosa; Gastritis; Glycopeptides; Helicobacter pylori; Leptin; Lipopolysaccharides; Metalloendopeptidases; Oligopeptides; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Up-Regulation

Helicobacter pylori may increase or inhibit gastric acid. We studied acid variations and plasma gastrin in cats harboring Helicobacter felis, harboring H. pylori, or free of gastric pathogens with reference to thioperamide (H(3) receptor antagonist) and SR-27417A (PAF receptor antagonist). In cats harboring H. felis, gastric mucosa were histologically normal. After H. felis eradication, pentagastrin-stimulated acid secretion was increased (40%) compared with the situation before eradication. Thioperamide abolished this inhibitory effect of H. felis, whereas SR-27417A did not. Basal and meal-stimulated plasma gastrin levels were not affected by eradication therapy. Acid secretion was inhibited (-80%) in week 3, increased from weeks 5 to 9, and remained constant for up to 42 weeks after H. pylori infection. SR-27417A had no effect on acid secretion before week 8 but inhibited it thereafter, and thioperamide increased it (20%) only before week 7 in those cats. Helicobacter inhibits gastric acid via an H(3) receptor pathway. Inflammatory mediators are thus involved in adaptation to the inhibitory effects of H. pylori on acid secretion.

Topics: Animals; Anti-Bacterial Agents; Cats; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter; Helicobacter Infections; Helicobacter pylori; Histamine Antagonists; Kinetics; Pentagastrin; Piperidines; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Histamine H3; Thiazoles; Urease

We previously reported that the gastric mucosa emits fluorescence of porphyrins at the onset of gastric lesions induced by hemorrhagic shock. In this study, we investigated whether the fluorescent substance concerns with the gastric mucosal injuries induced by diflofenac, a nonsteroidal antiinflammatory drug (NSAID). In the gastric mucosa treated with diclofenac, lesions were generated and myeloperoxidase activity increased. Diclofenac administration also increased thiobarbituric acid-reactive substances, a index of tissue peroxidation. After diclofenac treatment, the gastric mucosal fluorescence intensities rose. HPLC analysis demonstrated that the fluorescent substances were mesoporphyrin and protoporphyrin, which were the same as found in hemorrhagic shock. Pretreatment of the tissue with radical scavenging substances, catalase and troxipide, restrained the increase of mucosal fluorescence intensity, tissue peroxidation, and lesion formation. These findings indicate that diclofenac treatment induced the generation of porphyrins as well as tissue peroxidation in gastric mucosal tissue. This study suggests that autofluorescence observation is a useful tool to identify diclofenac-induced gastric injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Catalase; Chromatography, High Pressure Liquid; Diclofenac; Disease Models, Animal; Fluorescence; Free Radical Scavengers; Gastric Mucosa; Gastritis; Lipid Peroxidation; Male; Piperidines; Porphyrins; Rats; Rats, Wistar; Spectrometry, Fluorescence

Oral administration of an ammonia solution (0.01%) or a sodium taurocholate solution (TCA solution, 5 mM) as drinking water for 4 weeks or 13 weeks, respectively, resulted in gastric mucosal thinning and decreased parietal cell numbers. Oral administration of TCA solution also caused cell infiltration in the lamina propria of the mucosa and mucosal fibrosis. When lafutidine (3, 10 mg/kg) was administered orally once daily for one week after the withdrawal of ammonia or TCA solution, the recovery of the mucosal thickness in the fundic gland area and the parietal cell number were significantly accelerated, and the recovery of mucosal thickness in the pyloric gland area also tended to be accelerated. Lafutidine at 10 mg/kg for 1 week had no influence on normal mucosal thickness and parietal cell numbers. At the doses that produce equal or greater acid antisecretory effect than lafutidine, oral administration of cimetidine (30 mg/kg) and famotidine (1 mg/kg) had no effect on either of these atrophy indexes. These results demonstrate that lafutidine, unlike cimetidine and famotidine, can accelerate the healing of mucosal injuries in ammonia- and TCA-induced chronic gastritis models.

Topics: Acetamides; Ammonia; Animals; Anti-Ulcer Agents; Cell Count; Chronic Disease; Cimetidine; Famotidine; Gastric Mucosa; Gastritis; Humans; Male; Parietal Cells, Gastric; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Taurocholic Acid

In order to evaluate the symptomatic efficacy of cisapride on motility disorders often associated with mild inflammatory changes of the upper gastrointestinal tract, the authors carried out a comparison between two groups of patients (15 patients in each group, 10 males and 5 females) with histologic antral gastritis, treated respectively with famotidine 40 mg/day per os plus cisapride 10 mg ter/die per os, and famotidine alone. While the endoscopic evaluation performed four weeks later did not show a significant difference between the two groups, both macroscopically and microscopically, cisapride was able to ameliorate all those symptoms presumably provoked by delayed gastric emptying.

Topics: Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Famotidine; Female; Gastritis; Gastrointestinal Motility; Humans; Male; Piperidines; Pyloric Antrum

This paper identifies the symptom profile associated with the four main diagnoses of functional digestive disorders (dyspepsia, gastro-oesophageal reflux disease (GORD), gastritis, and constipation) made by general practitioners in Belgium. Results are also presented from a multicentre study in which the effects of cisapride, administered as an oral tablet or suspension, were evaluated in patients with these functional digestive disorders. Analysis of symptom patterns revealed that early satiety and postprandial abdominal bloating were the most prominent symptoms, followed by eructation (belching), heartburn, regurgitation, postprandial epigastric burning or discomfort, and nausea. These symptoms occurred in all diagnostic groups. However, different symptom patterns were associated with each of the disorders; for example, heartburn and regurgitation were the core symptoms in patients diagnosed as having GORD, early satiety and abdominal bloating were characteristic of patients diagnosed with dyspepsia, and fasting or postprandial pain were characteristic of patients given the diagnosis of gastritis. Therefore, it appears that these diagnoses used by general practitioners in Belgium closely correspond to reflux-like, dysmotility-like and ulcer-like dyspepsia, as defined by an international working party. Cisapride improved the core symptoms in about 80% of patients with GORD or dyspepsia, relieved all epigastric symptoms in about 80% of patients with gastritis, and significantly decreased the use of laxatives and increased stool frequency in constipated patients. Cisapride was well tolerated and thus appears to be a useful option in the treatment of functional digestive disorders in a general practice setting.

Topics: Adult; Aged; Belgium; Cisapride; Cluster Analysis; Constipation; Dyspepsia; Family Practice; Female; Follow-Up Studies; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Male; Middle Aged; Piperidines; Treatment Outcome

Topics: Adult; Aged; Asthma; Biliary Tract Diseases; Dioxoles; Drug Tolerance; Duodenal Diseases; Dysmenorrhea; Esophagitis; Female; Gastritis; Heart Diseases; Humans; Kidney Calculi; Male; Middle Aged; Migraine Disorders; Muscles; Piperidines; Spasm

Topics: Cholinergic Antagonists; Disease; Duodenum; Gastritis; Humans; Parasympatholytics; Peptic Ulcer; Piperidines; Stomach Diseases