piperidines and Helicobacter-Infections

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bicarbonates; Carnosine; Chalcone; Chalcones; Diterpenes; Enprostil; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Mucus; Organometallic Compounds; Peptic Ulcer; Piperidines; Prostaglandins; Sucralfate

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2-4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.

Topics: Antiemetics; Asia; Cisapride; Disease Management; Domperidone; Dyspepsia; Endoscopy; Gastrointestinal Agents; Helicobacter Infections; Histamine H2 Antagonists; Humans; Pacific Islands; Piperidines

Dyspepsia affects one in four Australians; of those who present in general practice, the majority will have functional or non-ulcer dyspepsia, with no structural explanation for their symptoms. Older patients who present for the first time with dyspepsia, and those with 'alarm features' deserve immediate investigation (preferably by upper endoscopy), to exclude cancer, peptic ulcer or oesophagitis. Other patients may be given empiric therapy (for example, a prokinetic or H2 blocker) initially, but require investigation if this fails. The role of Helicobacter pylori infection in functional dyspepsia is uncertain.

Topics: Adult; Aged; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Child; Cholelithiasis; Chronic Disease; Cisapride; Diagnosis, Differential; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metoclopramide; Peptic Ulcer; Piperidines; Stomach Neoplasms

Topics: Anti-Ulcer Agents; Cisapride; Drug Resistance; Helicobacter Infections; Histamine H2 Antagonists; Humans; Piperidines; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Stomach Ulcer; Sucralfate

Symptoms of functional dyspepsia are frequent; the prevalence of dyspepsia (defined as pain or discomfort centred in the upper abdomen) in the general population approaches 25%. By definition, patients with functional dyspepsia do not have a structural or biochemical explanation for their symptoms. Disorders of function (e.g. delayed gastric emptying) are detectable in a proportion of patients but remain poorly understood. Nevertheless, the current rationale for drug treatment is based on altering pathophysiological mechanisms which are believed to be associated with the development of symptoms. Although the placebo response rates approach 60%, prokinetics, acid-suppressing agents and bismuth-containing compounds have been shown to be significantly better than placebo in reducing symptoms. Antacids are widely used, but no controlled study has been able to demonstrate a significant benefit over placebo. The efficacy of sucralfate is uncertain. Rational guidelines on which drug should be used for a given patient are lacking, although approaches based on symptom profiles have been proposed; the duration of treatment needed to achieve long-lasting relief of symptoms is also poorly defined. Identifying optimal treatment for the individual patient, therefore, continues to be largely a trial and error process. Further research efforts are needed to elucidate the pathophysiological basis of functional dyspepsia so that specific therapy can be tailored to underlying pathophysiological disturbances.

Topics: Cisapride; Dopamine Antagonists; Dyspepsia; Gastric Acid; Gastrointestinal Agents; Gastrointestinal Motility; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists

Lafutidine is an H2-receptor antagonist with gastroprotective action through capsaicin-sensitive afferent neurons and relatively inexpensive compare to proton-pump inhibitors (PPIs). A 7-day course of PPIs-amoxicillin-metronidazole is recommended as standard second-line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second-line eradication using the H2-receptor antagonist lafutidine as a substitute for a PPI..  Fifty-two patients who failed in first-line eradication using PPI-amoxicillin-clarithromycin were randomly assigned to a 7-day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ-AM) or a 7-day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT-AM) as second-line therapy. Eradication was assessed by the (13) C urea breath test. A drug susceptibility test was performed before the second-line therapy..   Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT-AM and RPZ-AM groups were 96% (95%CI = 88.6-100%). There were no severe adverse events in either group.. Lafutidine plus metronidazole-amoxicillin as second-line therapy provided a high eradication rate and safe treatment similar to a PPI-based regimen. Lafutidine-based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Pilot Projects; Piperidines; Pyridines; Rabeprazole; Time Factors; Young Adult

Lafutidine is a novel H(2)-receptor antagonist with gastroprotective activity that includes enhancement of gastric mucosal blood flow. The aim of the present study was to test the efficacy of 7- or 14-day lafutidine-clarithromycin-amoxicillin therapy versus a lansoprazole-based regimen for Helicobacter pylori eradication.. Four hundred and sixty-three patients with H. pylori-infected peptic ulcer disease were randomized to one of four regimens: (1) lafutidine (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LFT group) or (2) for 14 days (the 14LFT group); (3) lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LPZ group); or (4) for 14 days (the 14LPZ group). The eradication rates, drug compliance, and adverse effects among the four regimens were compared.. The eradication rates by the intention-to-treat and per-protocol analyses in the 7LFT and 7LPZ groups were 76.5% and 81.6%, and 76.9% and 82.0% (p = .94 and .95), respectively. The eradication rates by intention-to-treat and per-protocol analyses in the 14LFT and 14LPZ groups were 78.2% and 82.2%, and 80.4% and 85.9% (p = .70 and .49), respectively. The treatment duration for 7 days or 14 days did not affect the eradication rates. In addition, the adverse effect rates and discontinuation rates were similar among the four groups. Furthermore, the ulcer cure rate and symptom response rate were similar in the lafutidine and lansoprazole groups.. The results of this study showed that lafutidine-clarithromycin-amoxicillin therapy was a safe and effective as lansoprazole-based triple therapy for the eradication rate of H. pylori, and could be considered as an additional treatment option.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Female; Helicobacter Infections; Helicobacter pylori; Humans; Korea; Lansoprazole; Male; Middle Aged; Piperidines; Pyridines; Time Factors; Treatment Outcome

Even with the most effective treatment, Helicobacter pylori eradication is difficult in some patients. Therefore, patients sometimes require acid-suppressive therapy without H. pylori eradication. It has been reported that ranitidine inhibits neutrophil activation, whereas famotidine does not. However, few studies have been published concerning the activation of neutrophils before and after treatment using clinical doses of histamine-2 receptor antagonists in patients with H. pylori infection.. To examine the effects of neutrophil activation after treatment with three different histamine-2 receptor antagonists.. This prospective, open-label, randomised, parallel-group study was conducted. Thirty patients with H. pylori infection were enrolled. These subjects were randomly assigned to receive one of the following treatments: (a) 150 mg ranitidine, (b) 20mg famotidine, or (c) 10 mg lafutidine b.d., for 4 weeks. Before and after histamine-2 receptor antagonist treatment, histological findings, myeloperoxidase activity, and interleukin-8 in the gastric mucosa were evaluated.. On the basis of the histological findings between before and after histamine-2 receptor antagonist treatment, no significant differences were found in any groups. Similarly, there were no significant differences in myeloperoxidase activity or interleukin-8 levels.. In patients with H. pylori, when used at clinical doses, any histamine-2 receptor antagonists can be used without concerning about inhibition of neutrophil activation.

Topics: Acetamides; Adult; Dyspepsia; Famotidine; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Peroxidase; Piperidines; Pyridines; Ranitidine

To investigate the therapeutic effects of triple therapy combining lafutidine with clarithromycin and amoxicillin on H pylori infection and the resolution of gastroesophageal symptoms after eradication.. We conducted a randomized, multicenter, open-label controlled trial to compare the effectiveness of a triple therapy of lafutidine, clarithromycin, and amoxicillin (lafutidine group) with that of a triple therapy of lansoprazole, clarithromycin, and amoxicillin (lansoprazole group) in patients with H pylori infection. The study group comprised 22 patients with gastric ulcers and 18 patients with duodenal ulcers who had H pylori infection.. H pylori eradication rates were similar in the lafutidine group (14/20, 70%) and the lansoprazole group (14/20, 70%). Gastroesophageal reflux and abdominal symptoms improved after eradication therapy in both groups, whereas abdominal discomfort, diarrhea, and constipation were unchanged. H pylori status had no apparent effect on improvement of gastroesophageal reflux or abdominal symptoms after treatment. Adverse events were similar in both groups.. The triple therapy including lafutidine is equivalent to triple therapy including lansoprazole in terms of H pylori eradication rates and improvement in gastroesophageal reflux and abdominal symptoms. These results are attributed to the fact that lafutidine has strong, continuous antisecretory activity, unaffected by CYP2C19 polymorphisms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Infective Agents; Clarithromycin; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Male; Middle Aged; Piperidines; Pyridines

The attenuated anti-secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whether Helicobacter pylori infection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine.. To investigate the occurrence of the tolerance phenomenon in subjects with and without H. pylori infection during the continuous administration of lafutidine and famotidine.. Subjects were 20 healthy male volunteers (seven H. pylori positive and 13 H. pylori negative cases). All subjects were examined by ambulatory intragastric pH monitoring five times without medication, on the first and 15th day of the administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a cross-over fashion.. The tolerance phenomenon was not observed in H. pylori-positive subjects during the 15-day-long administration of both H2RAs. In contrast, the tolerance phenomenon was observed in H. pylori negative subjects, which has been previously reported.. This study demonstrated that H. pylori infection affects the tolerance phenomenon during continuous administration of H2RAs.

Topics: Acetamides; Adult; Ambulatory Care; Circadian Rhythm; Cross-Over Studies; Cross-Sectional Studies; Drug Tolerance; Famotidine; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Piperidines; Pyridines

The sensitivity of the urea breath test (UBT) has been reported to be influenced by the administration of omeprazole, lansoprazole and ranitidine. However, it is unclear whether other H2 receptor antagonists (H2RA), except ranitidine, and rebamipide, a mucosal protective agent, affect UBT sensitivity. The aim of this study is to clarify the effects of lansoprazole, famotidine, roxatidine and rebamipide administration on UBT sensitivity.. Subjects comprised 30 volunteers with Helicobacter pylori infection. All subjects were examined by the 13C-UBT on four occasions: (i) without medication (control); (ii) after the administration of 30 mg lansoprazole (u.i.d) for 14 days; (iii) after the administration of 100 mg rebamipide (t.i.d) for 14 days; and (iv) after the administration of 20 mg famotidine or 75 mg roxatidine (b.i.d) for 14 days. In the H2RA study, individuals were randomized into two groups of 15 subjects and were administered either famotidine or roxatidine.. Five of the 30 cases administered lansoprazole and one of the 15 cases given roxatidine gave a false-negative UBT result. No negative UBT results were observed in patients administered famotidine or rebamipide.. Patients showing negative UBT results during the administration of proton pump inhibitors and H2RA should be re-examined after the cessation of these drugs to confirm the true negativity of H. pylori infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Alanine; Anti-Ulcer Agents; Breath Tests; False Negative Reactions; Famotidine; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Omeprazole; Piperidines; Predictive Value of Tests; Quinolones; Urea

In contrast to the growing amount of data concerning proton pump inhibitor-based triple therapy for Helicobacter pylori infection, it is still controversial whether proton pump inhibitor can be replaced by H2 receptor antagonist without compromising efficacy. Lafutidine is a novel potent H2 receptor antagonist with gastroprotective activities such as enhancement of gastric mucosal blood flow.. 122 outpatients with positive cultures and subsequent successful cultivation of H. pylori for antimicrobial susceptibility tests were randomized to receive a 7-day course of either lafutidine (20 mg twice daily) or lansoprazole (30 mg twice daily), plus clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Eradication was considered successful if the rapid urease test, culture, histology and [13]C-urea breath test were all negative at least 4 weeks after cessation of therapy. Cytochrome p450 2C19 genotype status using polymerase chain reaction-restriction fragment length polymorphism was also studied.. On intention-to-treat basis, H. pylori cure was achieved in 52 of 61 (85.2%) patients and 49 of 61 (80.3%) patients for the lafutidine- and lansoprazole-based therapies, respectively. The predicted 95% confidential intervals for the 4.9% of the difference were -1.8-11.6%. Using per protocol analysis, the eradication rates were 88.2% (52/59) and 84.5% (49/58), respectively. The predicted 95% confidential intervals for the 3.7% of the difference were -2.6-10.0%. Adverse events were observed in five and six patients, from the lafutidine and lansoprazole groups, respectively, but they were generally mild. Genetic predisposition of cytochrome p450 2C19 had no significant influence on treatment outcome in both regimens.. The lafutidine-clarithromycin-amoxicillin therapy yielded satisfactory results for eradicating H. pylori, which was comparable with those of the lansoprazole-based regimen with the same drug combination.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Clarithromycin; Cytochrome P-450 CYP2C19; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Penicillins; Piperidines; Prospective Studies; Pyridines

Functional dyspepsia is recognized as a common disorder in clinical practice. The aim of this study was to determine the efficacy and adverse effects of cisapride compared to a placebo in patients from a general practice with functional dyspepsia (FD). Secondly we investigated whether Helicobacter pylori-positive FD patients present with specific symptoms and determined the efficacy of cisapride for FD patients with H. pylori.. In a placebo-controlled double-blind study, patients were randomized to receive fixed doses of either cisapride (10 mg three times daily) or placebo. Symptoms were evaluated after 2 and 4 weeks of treatment. The selection of FD patients,collection of data, and evaluation of symptoms as well as adverse effects were performed by general practitioners. Dyspeptic patients were referred to the Gastroenterology Department in order to exclude ulcers, oesophagitis, pancreatitis and gallstones. Biopsies of gastric mucosa were taken for histological examination and H. pylori culture.. 121 patients entered this study (61 took cisapride, 60 placebo). There were 113 patients (56 cisapride, 57 placebo) available for analysis of the efficacy and 120 patients (61 cisapride, 59 placebo) for evaluation of adverse effects.In total 102 biopsies were tested for the presence of gastritis by histological examination. There were 30 H. pylori-positive cultures among 111 patients.. After 4 weeks a statistically significant reduction in symptoms was found, but it was similar in the two groups. No symptoms specific for H. pylori-positive patients were found. There was not a significant difference in the response to cisapride between H. pylori-positive and H. pylori-negative patients. The difference in overall (63%) response in the cisapride group and the 44% response in the placebo group did not reach statistical significance.. No significant difference was found between placebo and cisapride in the treatment of FD in general practice. H. pylori-positive patients did not present with specific symptoms nor did they exhibit a different response to cisapride.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cisapride; Diagnosis, Differential; Double-Blind Method; Dyspepsia; Family Practice; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Piperidines

Topics: Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Omeprazole; Organometallic Compounds; Piperidines; Roxithromycin

Fifty-three patients with previously uninvestigated chronic dyspepsia symptoms in the absence of gastrointestinal or extra-gastrointestinal disease (functional dyspepsia) underwent antral and duodenal mucosal biopsies to detect the role of such samplings in the presence of normal endoscopic findings. Patients were enrolled in a randomized, placebo-controlled, double-blind trial, receiving either eradicating treatment (colloidal bismuth subcitrate plus metronidazole) or placebo if they had Helicobacter pylori-associated gastritis (20 patients), or cisapride or placebo if they had normal antral mucosa (28 cases). Unsuspected celiac sprue was found in one patient. Eradicating treatment ameliorated histological gastritis (p = 0.01). However, owing to great placebo efficacy, symptom remission rates following a 1-month wash-out period in both treatment groups were no higher than that in controls. Independent of the initial randomization, an extremely low symptom recurrence rate was observed during a drug-free follow-up study equivalent to the mean duration of symptoms before enrollment. We conclude that in functional dyspepsia, bulbar and antral biopsies are not useful in clinical management, equivalent symptom relief can be achieved in patients randomly assigned to both drugs and placebos, and such improvement can be long lasting in the absence of any maintenance treatment. We believe the prevalence of unsuspected villous atrophy and the therapeutic role of investigation-based reassurance deserve further assessment.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Cisapride; Double-Blind Method; Duodenum; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Piperidines; Pyloric Antrum

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

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

Many drugs have been reported to interact with repaglinide in patients with type 2 diabetes mellitus, resulting in hypoglycemia. However, to our knowledge, an interaction between clarithromycin and repaglinide in these patients has not been previously reported. We describe an 80-year-old man with end-stage renal disease and well-controlled type 2 diabetes (hemoglobin A1c < 7%) who was hospitalized for treatment of severe hypoglycemia. He had been receiving repaglinide 0.5 mg 3 times/day for the previous 2 years. Clarithromycin 500 mg twice/day had been started for Helicobacter pylori infection several days before admission. Within 48 hours of starting the drug, he developed severe hypoglycemia, which resolved with intravenous glucose administration. However, 48 hours later, the patient again experienced hypoglycemia and was unresponsive. Intravenous glucose administration again resolved the problem. Repaglinide was discontinued, and no further hypoglycemic episodes occurred. Clinicians should be aware of this possible clarithromycin-repaglinide interaction; in particular, in elderly patients with type 2 diabetes who are taking repaglinide and begin clarithromycin therapy, blood glucose levels should be monitored closely for potential dosage adjustment of repaglinide.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blood Glucose; Carbamates; Clarithromycin; Diabetes Mellitus, Type 2; Drug Interactions; Helicobacter Infections; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Piperidines

Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction for measurements of short-circuit current by a previously validated technique. Short-circuit current was measured before and after application of graded cumulative doses of 5-HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5-HT receptor antagonists: ketanserin, ondansetron, or SB-204070 (1-butyl-4 piperidinmethyl-8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-carboxylate HCl). Histological examination was performed on duodenal biopsies. Helicobacter urease testing and histological examination determined Helicobacter pylori infection. 5-HT induced a dose-dependent and bumetanide-sensitive short-circuit current, which was independent of the presence of Helicobacter pylori infection. All the three 5-HT receptor antagonists failed to significantly effect basal and 5-HT-induced short-circuit current. Our results indicate that in human duodenum 1) 5-HT is a potent stimulator of bumetanide-sensitive secretion, 2) the serotonergic receptor subtype, which acts as the main mediator of 5-HT-induced secretion is different from the 5-HT(2), 5-HT(3), and the 5-HT(4) subtype and, 3) the sensitivity to 5-HT is not altered by Helicobacter pylori infection.

Topics: Adult; Aged; Bumetanide; Dioxanes; Duodenum; Female; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Intestinal Secretions; Ion Transport; Ketanserin; Male; Middle Aged; Ondansetron; Piperidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Sodium Potassium Chloride Symporter Inhibitors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Benzimidazoles; Gastric Acid; Gastric Acidity Determination; Heartburn; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Omeprazole; Piperidines; Prognosis; Proton Pump Inhibitors; Pyridines; Rabeprazole; Severity of Illness Index; Treatment Outcome

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

Neutrophils are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastroduodenal diseases on account of their potent biological functions as effector cells. Troxipide, a new antiulcer compound used for patients with gastric ulcer or gastritis, has been shown to inhibit migration and activation of guinea pig neutrophils, but little is known about the pharmacological effects on human neutrophils.. To study the effects of troxipide on chemotactic migration and superoxide generation by human neutrophils.. The chemotactic response of neutrophils was determined in a multi-well chamber with a polycarbonate filter and the generation of O2- by neutrophils was measured using a chemiluminescence method. Concentrations of troxipide in gastric mucosa were measured by high-performance liquid chromatography.. Incubation of neutrophils with 10(-6) to 10(4) M troxipide caused inhibition of recombinant interleukin-8-induced migration. These concentrations of troxipide also inhibited superoxide generation by neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine or platelet activating factor. These phenomena were not simply due to the direct cytotoxic effects since the above concentrations of troxipide did not induce neutrophil apoptosis. The concentrations of troxipide detected in the gastric mucosa after oral administration were in the range able to inhibit chemotactic migration and superoxide generation by neutrophils in vitro.. These results suggest that troxipide may exert its therapeutic effect in patients with gastric ulcer or gastritis by inhibiting inflammatory responses and mucosal injury mediated by neutrophils in gastric mucosa.

Topics: Adult; Anti-Ulcer Agents; Cell Culture Techniques; Cell Movement; Chemotaxis; Chromatography, High Pressure Liquid; Helicobacter Infections; Humans; Inflammation; Intestinal Mucosa; Neutrophils; Piperidines; Stomach Ulcer; Superoxides