sofalcone 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

Topics: Amoxicillin; Anti-Ulcer Agents; Chalcone; Chalcones; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Peptic Ulcer; Treatment Outcome

According to reports in Japanese patients, 1 week of Helicobacter pylori eradication therapy alone is not adequate for healing of gastric ulcers; 7-8 weeks of anti-ulcer therapy are subsequently required. We compared a gastroprotective drug, sofalcone, and an H(2)-receptor antagonist, cimetidine, in terms of promoting ulcer healing after 7 weeks of administration following 1 week of eradication therapy.. Eradication therapy was administered to 64 patients with H. pylori-positive active gastric ulcer at least 10 mm in diameter, after which 32 patients each received 7 weeks of ulcer treatment with sofalcone (300 mg/day) or cimetidine (800 mg/day).. The H. pylori eradication rate was 81.3% (intention-to-treat: ITT) and 81.3% (per protocol: PP) in the sofalcone group, and 62.5% (ITT) and 64.5% (PP) in the cimetidine group. The ulcer healing rate after 8 weeks was 71.9% (ITT) and 71.9% (PP) in the sofalcone group, and 71.9% (ITT) and 71.0% (PP) in the cimetidine group. The rate of a flat pattern of scarred mucosa was 43.5% (ITT) and 43.5% (PP) in the sofalcone group, and 47.8% (ITT) and 50.0% (PP) in the cimetidine group. No significant differences were seen between the two groups in terms of H. pylori eradication rate, ulcer healing rate and flat pattern rate.. Sofalcone promoted gastric ulcer healing during 7 weeks of treatment following 1 week of eradication therapy, and the healing rate was equivalent to that of cimetidine. Symptom disappearance rates were significantly better in the sofalcone group than in the cimetidine group. This may be a useful way of using a gastroprotective drug in the H. pylori era.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Chalcones; Chi-Square Distribution; Cimetidine; Endoscopy, Digestive System; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Stomach Ulcer; Time Factors; Treatment Outcome; Wound Healing

The mucoprotective agents, sofalcone and polaprezinc have anti-Helicobacter pylori (H pylori) activities. We determined the therapeutic effects of sofalcone and polaprezinc when combined with rabeprazole, amoxicillin and clarithromycin for Helicobacter pylori infection.. One hundred and sixty-five consecutive outpatients with peptic ulcer and H pylori infection were randomly assigned to one of the following three groups and medicated for 7 d. Group A: triple therapy with rabeprazole (10 mg twice daily), clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Group B: sofalcone (100 mg thrice daily) plus the triple therapy. Group C: polaprezinc (150 mg twice daily) plus the triple therapy. Eradication was considered successful if (13)C-urea breath test was negative at least 4 wk after cessation of eradication regimens or successive famotidine in the cases of active peptic ulcer.. On intention-to-treat basis, H pylori cure was achieved in 43 of 55 (78.2%) patients, 47 of 54 (87.0%) and 45 of 56 (80.4%) for the groups A, B and C respectively. Using per protocol analysis, the eradication rates were 81.1% (43/53), 94.0% (47/50) and 84.9% (45/53) respectively. There was a significant difference in the cure rates between group A and B. Adverse events occurred in 10, 12 and 11 patients, from groups A, B and C respectively, but the events were generally mild.. The addition of sofalcone, but not polaprezinc, significantly increased the cure rate of H pylori infection when combined with the rabeprazole-amoxicillin-clarithromycin regimen.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Benzimidazoles; Chalcone; Chalcones; Clarithromycin; Drug Therapy, Combination; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Peptic Ulcer; Rabeprazole

To assess the effects of the mucoprotective drug sofalcone, which has direct and indirect effects on Helicobacter pylori in vitro, the eradication rate, adverse effects, and the quality of healing peptic ulcers were evaluated. Each study patient was given 500 mg t.i.d. amoxicillin and 200 mg t.i.d. clarithromycin. In addition, three different treatment regimens were compared: a standard dose (20 mg q.d.) of the proton pump inhibitor omeprazole (OAC), a double dose (20 mg b.i.d.) of omeprazole (Ox2AC), and a standard dose of omeprazole and a standard dose (100 mg t.i.d.) of sofalcone (OACS). Thirty-one H. pylori-positive patients were treated with OAC, 37 with Ox2AC, and 41 with OACS therapy. With an intention-to-treat analysis, the eradication rates were 74.2% for OAC, 86.2% for Ox2AC, and 85.0% for OACS therapy. The incidence of side effects was 9.6% for patients given OAC therapy, 86.5% for Ox2AC, and only 7.5% for OACS-treated patients, which was significantly lower than the incidence in the Ox2AC group. High-quality peptic ulcer scars were observed after eradication therapy which included solfacone. Although it is necessary to conduct a randomized double-blind study to obtain definitive conclusions, our results indicate that this novel quadruple eradication therapy with solfacone is an efficacious regimen with a high eradication rate and positive effects on ulcer healing, combined with a low incidence of adverse events.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Chalcone; Chalcones; Clarithromycin; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Penicillins; Peptic Ulcer; Treatment Outcome

To clarify the efficacy of combination therapy with clarithromycin and sofalcone for eradication of Helicobacter pylori.. We studied 42 patients with H. pylori-positive gastroduodenal diseases, who were divided into two groups according to treatment period. Group 1 comprised 27 patients (seven with gastric ulcers, 14 with duodenal ulcers and six with gastritis) treated with a combination of clarithromycin (200 mg, three times a day) + sofalcone (100 mg, three times a day) for 3 weeks. Group 2 comprised 15 patients with chronic active gastritis treated with the same doses of clarithromycin + sofalcone but for only 2 weeks (group 2). The H. pylori status of all patients was assessed by culture, rapid urease test and histological examination at the end of treatment and 4 weeks after the end of treatment. The gastritis score, the index of intracellular periodic acid-Schiff-positive substance in the antral mucosa and the ammonia concentration in gastric secretions were also estimated before and after treatment.. In group 1, with over half the patients excluded from the follow-up, H. pylori was eradicated in nine out of 13 patients (69.2%) compared with six out of the complete group of 15 (40.0%) patients in group 2, without serious side effects. In these patients, significant improvements were seen in the gastritis score (P < 0.025), the index of periodic acid-Schiff-positive substances in the antral mucosa (P < 0.025) and the ammonia concentration in gastric secretions (P < 0.02) after treatment.. These results suggest that modification of the treatment regimen is needed, with higher doses of clarithromycin and combination therapy with proton-pump inhibition.

Topics: Ammonia; Anti-Bacterial Agents; Anti-Ulcer Agents; Chalcone; Chalcones; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Gastric Mucosa; Gastrointestinal Diseases; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Microbial Sensitivity Tests; Treatment Outcome

Sofalcone has been reported to exert anti-ulcer and gastroprotective actions, but its exact mechanism of action remains unknown. In our laboratory, we found that indomethacin-induced gastric ulcers become worse when associated with Helicobacter pylori infection.. We employed the H. pylori-infected gnotobiotic murine model to examine the effect of sofalcone on indomethacin-induced gastric ulcers in the presence of H. pylori infection. In vitro experiments were also done to evaluate the effects of sofalcone on H. pylori growth, adherence of H. pylori to the MKN45 cells (a human gastric epithelial cell line), and these cells' IL-8 production in the presence of H. pylori.. We found that sofalcone produced a significant improvement in ulcer size as well as a substantial reduction in the number of H. pylori colonies in H. pylori-infected gnotobiotic mice. In vitro sofalcone has a significant bacteriocidal effect against H. pylori and can also significantly prevent adherence of this bacterium to MKN45 cells, thus remarkably reducing IL-8 production of these cells in response to stimulation by H. pylori.. Our results suggest that sofalcone can improve ulcer healing by the mechanisms mentioned above.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cell Adhesion; Chalcone; Chalcones; Disease Models, Animal; Helicobacter Infections; Helicobacter pylori; Humans; Indomethacin; Interleukin-8; Mice; Mice, Inbred BALB C; Stomach Ulcer

Eradication therapy for Helicobacter pylori (H. pylori) has been established. However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d, 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high preUBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT subgroup.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Breath Tests; Carbon Isotopes; Chalcone; Chalcones; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Proton Pump Inhibitors; Stomach Ulcer; Treatment Outcome; Urea; Urease

"Reflux" gastritis after gastrectomy is associated with various symptoms that are often detrimental to the patients' quality of life. However, prevention of the reflux does not always bring relief from the symptoms of gastritis. Helicobacter pylori (H. pylori) is now considered one of the most important pathogenetic factors in gastritis. The association between H. pylori infection and reflux gastritis after gastrectomy was investigated in the present study.. In total, 115 patients who had undergone gastrectomy were entered in this study. Five biopsy specimens from the gastric remnant were taken during upper GI endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. The histological degree of gastritis was determined according to the score system of Rauws et al.. Forty-six patients (40%) demonstrated H. pylori infection in their stomachs. The prevalence of the infection was significantly higher in patients with conventional gastrectomy than in those with subtotal gastrectomy. The prevalence of H. pylori infection was significantly lower in patients who had undergone gastrectomy more than 4 yr ago. The histological gastritis score in patients with H. pylori infection was significantly higher than in those without H. pylori infection. Furthermore, the eradication of H. pylori in patients with both serious gastritis symptoms and no bile reflux improved the symptoms and significantly decreased the histological gastritis score.. The results suggest that H. pylori is a factor in the pathogenesis of reflux gastritis after gastrectomy.

Topics: Amoxicillin; Anti-Ulcer Agents; Chalcone; Chalcones; Drug Therapy, Combination; Female; Gastric Mucosa; Gastric Stump; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Penicillins; Postgastrectomy Syndromes; Prevalence; Risk Factors

It is difficult to regard sofalcone as a single drug for the treatment of Helicobacter pylori infection. However, sofalcone exerts multiple effects against H. pylori: it has antibacterial activity, induces morphological changes, inhibits adhesion to gastric mucin and inhibits lipolytic activity. The safety profile of sofalcone even on long-term administration is well established. Therefore, it may be possible to establish a new triple therapy for H. pylori infection using sofalcone combined with antibacterial drugs and proton pump inhibitors.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Chalcone; Chalcones; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Microbial Sensitivity Tests

To investigate the mechanism of action of a series of potential combination therapies for use against Helicobacter pylori.. The effects of certain anti-ulcer agents on the antimicrobial activity of antibiotics effective against H. pylori were determined in vitro.. H. pylori was cultured on Skirrow's agar. Amoxycillin, clarithromycin, erythromycin and tetracycline were used. The anti-ulcer agents studied comprised aluminum chloride, sofalcone [2'-carboxymethyl 4,4'-bis(3-methyl-2-butenyloxy)chalcone] and zinc chloride. Urease activity was measured by the urease-indophenol method. The minimum inhibitory concentration was determined by a plating method, with H. pylori streaked on plates containing various concentrations of the antibiotics plus sublethal doses of the anti-ulcer agents.. This in vitro study showed that sofalcone had a direct antibacterial effect and, in addition, inhibited the adhesive property of H. pylori. It did not inhibit the antimicrobial activity of the antibiotics amoxycillin, clarithromycin, erythromycin or tetracycline against H. pylori. The metal ions had inhibitory effects on the antimicrobial activity of amoxycillin, erythromycin and tetracycline, but not on that of clarithromycin.. This study suggests that sofalcone is a suitable candidate for combination therapy.

Topics: Aluminum Chloride; Aluminum Compounds; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Chalcone; Chalcones; Chlorides; Clarithromycin; Drug Interactions; Drug Therapy, Combination; Erythromycin; Helicobacter Infections; Helicobacter pylori; Humans; Microbial Sensitivity Tests; Tetracycline; Zinc Compounds