Alimentary Pharmacology & Therapeutics Symposium Series最新文献

Summary

Background

Recently, it has been proved in Japan that granulocyte and monocyte adsorption apheresis (GCAP) and leukocytapheresis (LCAP) are effective and safe for patients with moderate to severe ulcerative colitis (UC).

Aim

To investigate the efficacy of GCAP and LCAP in patients with active UC, and the use of endoscopic findings in predicting efficacy, especially in refractory and steroid-dependent cases.

Subjects and methods

Thirty-four patients with active UC (24 refractory to conventional therapy and 10 steroid-dependent) were treated with GCAP (n = 21) or LCAP (n = 13). The patients received one or two GCAP or LCAP sessions per week for 5 consecutive weeks, with colonoscopy before and after each session.

Results

About 70% of the patients achieved a clinical response, and no severe adverse effects were observed. Most steroid-dependent patients or patients who had side effects due to steroids were controlled successfully. Endoscopically, 14 of 16 cases with shallow ulcers and erosion throughout the colon and 10 of 15 with deep ulcerations responded to treatment. However, three with massive ulceration of the whole mucosa did not respond.

Conclusions

GCAP or LCAP are valuable therapies for refractory or steroid-dependent UC, and endoscopic findings are helpful in predicting clinical effectiveness.

Summary

Background

Ghrelin, a recently discovered peptide hormone, has been shown to be produced mainly by the A-like cells of the gastric mucosa. Ghrelin not only stimulates growth hormone (GH) release but also promotes gastric motility. While the effect of ghrelin on the gastric acid secretion in rats has been reported, no such reports appeared to date from studies in humans.

Aim

To investigate the effect of ghrelin administration on the gastric pH in humans, using a novel wireless pH capsule (Bravo, Medtronic, Shoreview, MN, USA).

Methods

Four healthy volunteers (male; average age, 35.0 years; Helicobacter pylori-negative) were enrolled. The pH capsule was attached endoscopically to the gastric mucosa and the data were transmitted to a portable receiver. Thirty minutes after a stabilization period, synthetic ghrelin (5 μg/kg body weight) was injected intravenously into the subjects and the data were monitored for more than 120 min while the subjects lay supine.

Results

The average minimum gastric pH in four cases (1.2 ± 0.10) was significantly decreased after injection of ghrelin, as compared with the basal pH value (1.8 ± 0.06). The serum gastrin level, however, showed no change after the ghrelin injection.

Conclusion

These results suggest that exogenous ghrelin could enhance gastric acid secretion in humans.

Summary

Background

The [¹³C]-ethanol breath test (EBT) has been proposed as a novel non-invasive laboratory test to detect the degradation of ethanol into CO₂. However, this method has not yet been evaluated clinically.

Aim

To investigate the factors that influence [¹³C]-EBT.

Methods

Twenty-six healthy volunteers were instructed to drink 100 mL of beer (4 g ethanol) containing 100 μL of [¹³C]-ethanol. Breath samples were collected every 15 min before and after the intake of ethanol solution and ¹³CO₂-enrichment was measured using mass spectrometry. CO₂ excretion was then calculated, and the results were evaluated using kinetic parameters (T_max, C_max, AUC).

Results

T _max (min) was significantly shorter in men than in women but not C_max and AUC. Infection with H. pylori had no impact on all kinetic parameters. Genetic alcohol dehydrogenase (ADH) polymorphisms did not affect ¹³CO₂ excretion, but C_max (11.1 ± 3.4% dose/h, n = 16) and AUC (10.5 ± 3.4% dose) were slightly increased in aldehyde dehydrogenase (ALDH)-deficient individuals (heterozygote of ALDH2*2) (13.2 ± 3.2 and 12.9 ± 4.5, respectively; n = 10).

Conclusions

[¹³C]-EBT is capable of assessing the metabolic processing of 100 mL beer in a non-invasive way. Kinetic parameters are partially influenced by ALDH polymorphism but not by gender, H. pylori infection or ADH polymorphism.

Summary

Background

CagA⁺Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.

Aim

To investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.

Methods

A total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.

Results

Anti-CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti-CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P < 0.01). Mean anti-titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA-antibody-negative patients (93%;13/14) than from CagA-antibody-positive patients (29%; 4/14, P = 0.0007).

Conclusions

Host–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.

Summary

Background

Ghrelin is a novel appetite-promoting peptide secreted primarily from the A-like cells in the gastric fundic mucosa. As gastric inflammation caused by Helicobacter pylori infection extends, the number of ghrelin-producing A-like cells is diminished and gastric ghrelin content decreases significantly. We previously reported that plasma levels of ghrelin, which correlated well with the serum levels of pepsinogen (PG) I and PG I/II ratio, decreased as gastric mucosal atrophy increased in non-ulcerogenic conditions and that plasma ghrelin level increased in rats with cysteamine-induced duodenal ulcer.

Aim

To investigate the plasma levels of ghrelin in patients with peptic ulcer disease.

Patients and Methods

Two hundred and eighty-six patients with epigastric symptoms, who underwent upper gastrointestinal endoscopy, were enrolled. Blood samples were collected after a 12-h fast before endoscopy. Patients were divided into four groups, namely chronic gastritis with high PG (n = 197), chronic gastritis with low PG (n = 58), duodenal ulcer (n = 14) and gastric ulcer (n = 17) and plasma concentrations of total and active ghrelin as well as serum concentrations of PG I and PG II were measured by radioimmunoassay. Six patients with duodenal ulcer and seven with gastric ulcer were also examined after ulcer healing.

Results

Plasma ghrelin levels were significantly higher in patients with duodenal ulcer or gastric ulcer than in those without ulcers. Elevated plasma total ghrelin levels did not significantly change after the healing of ulcers.

Conclusions

Plasma ghrelin levels were significantly higher in patients with peptic ulcer than in those with gastritis without ulcer. This finding suggests a possible relationship between mucosal injury susceptibility and elevated fasting plasma ghrelin.

Summary

Aim

This large-scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan.

Methods

This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow-up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection.

Results

Three-thousand twenty-one patients were enrolled. The median follow-up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62).

Conclusion

This large-scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.

Summary

Background

A number of studies have indicated that Helicobacter pylori eradication therapy helps prevent secondary cancers in the stomach.

Aim

To investigate the risk of secondary cancer in the residual stomach after gastrectomy by comparing molecular biomarkers from stomach mucosa biopsies and the pH of gastric juice between H. pylori patients with and without gastrectomy.

Methods

Conventional H. pylori eradication therapy was administered to 22 patients who had undergone gastrectomy and to 37 un-operated patients. We measured pH levels of gastric juice, and collected stomach mucosa biopsy specimens by gastrointestinal fiberscopy. The mRNA expression levels of interleukin-1β, interleukin-8 and cyclo-oxygenase 2 in the biopsy tissues were measured by real-time polymerase chain reaction.

Results

Interleukin-1β levels in the antrum of un-operated H. pylori-positive patients showed a reverse correlation with pH levels in the gastric lumen (correlation coefficient: −0.50, P = 0.007). After eradication, pH levels were strongly associated with interleukin-1β mRNA levels, r = 0.83, P = 0.01, which, in the remnant stomach mucosa, decreased from 22.5 to 4.6 in the anastomosis and from 3.1 to 2.4 in the upper corpus, with a simultaneous and statistically significant decrease in pH.

Conclusions

Interleukin-1β mRNA levels correlated with pH levels in the remnant stomach. This indicates that eradication therapy may contribute not only to a reduction in these cancer-associated cytokines, but also to an improvement in the internal environment of the remnant stomach.