F. Takeshima

Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in rats

Background: Ghrelin may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not yet been clearly defined. The present study was designed to investigate whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent neurones and directly affects the enteric neuromuscular function. Methods: Gastric emptying of nutrient solids was assessed after intravenous administration of saline or ghrelin in conscious rats. The effects of ghrelin on gastric emptying were also examined in rats pretreated with capsaicin. Gastric emptying and intestinal transit of non-caloric liquids were evaluated using [Formula: See Text]Cr solution. The effects of ghrelin on spontaneous contractile activities of isolated strips from stomach and jejunum were also investigated and the influence of ghrelin on motor responses to carbachol and electrical field stimulation was examined. Results: Ghrelin significantly accelerated gastric emptying of both nutrient solids and non-caloric liquids in conscious rats. The intestinal transit of non-caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin prevented the ghrelin-induced acceleration of gastric emptying of nutrient solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions of strips of gastric body, gastric antrum and jejunum. However, electrical field stimulation-induced contractions were significantly enhanced by ghrelin in the gastric body. Conclusions: The results suggest that the stimulatory effects of ghrelin on gastric motility are mediated by direct stimulation of the enteric neural pathway and capsaicin-sensitive afferent neurones.

A Close Relationship between Helicobacter pylori Infection and Gastric Xanthoma

BACKGROUND Although the pathogenesis of gastric xanthoma (GX) remains unclear, an association of GX with atrophic gastritis has been reported. Helicobacter pylori is closely related to atrophic gastritis. The aim of this study was to investigate the relationship among GX, H. pylori, and atrophic gastritis. METHODS Sixty-seven patients with GX were assessed for H. pylori infection by serum anti-H. pylori IgG antibody, in addition to the rapid urease test, culture, and histologic examination using biopsy specimens of the antrum and corpus. The findings were compared with 67 age- and sex-matched control subjects without GX. The distribution of atrophic gastritis was assessed endoscopically. The severity of atrophic gastritis was determined endoscopically and histologically. Serum pepsinogen (PG) levels were also measured. Immunohistochemical staining of GX samples for H. pylori antigen was performed. H. pylori clinical isolates from patients with GX and controls were assessed for cagA by means of polymerase chain reaction. RESULTS The prevalence of H. pylori was significantly higher in patients with GX than in controls (94% and 72%, respectively). A significantly more extensive atrophic gastritis was present in patients with GX, as determined endoscopically and histologically, than in controls. Serum PG-I levels and the PG-I/PG-II ratio were significantly lower in the GX group than in the control group. H. pylori antigens were frequently identified in the cytoplasm of xanthoma cells in H. pylori-positive specimens of GX (54 of 63 specimens, 86%), whereas no immunoreactivity for H. pylori antigens was detected in H. pylori-negative specimens of GX. There was no significant difference in the positive rate of cagA between the two groups. CONCLUSIONS Our results identified a close relationship among H. pylori infection, GX, and atrophic gastritis. A proportion of GXs may be provoked by H. pylori infection.

Expression of Interleukin 6 and Its Receptor in Human Gastric and Colorectal Cancers

Interleukin 6 (IL-6) is a pleiotropic cytokine with many physiological functions. The present study was designed to determine the expression of IL-6 and its receptor (IL-6R) in human gastric and colorectal cancers. Nine gastric- and nine colorectal cancer cell lines were analysed. The IL-6 gene was expressed in two gastric cancer cell lines and one colorectal cancer cell line; however, most of the cancer cell lines studied expressed the IL-6R gene. The level of IL-6 secretion in the gastric cancer cell lines correlated with the level of soluble IL-6R secretion, and was significantly higher (> ~100 pg/ml) than the level of IL-6 secretion in the colorectal cancer cell lines (> ~50 pg/ml). These results suggest that IL-6 may act in a paracrine fashion rather than an autocrine fashion in these cell lines.

Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry.

H. Isomoto, M. Miyazaki, Y. Mizuta, F. Takeshima, K. Murase, K. Inoue, K. Yamasaki, I. Murata, T. Koji & S. Kohno Second Dept. of Internal Medicine and Dept. of Histology and Cell Biology, Nagasaki University School of Medicine; Internal Medicine, Shunkaikai Inoue Hospital; Internal Medicine, Nagasaki Municipal Medical Center; and Dept. of Pharmacotherapeutics, Nagasaki University Graduate School of Pharmaceutical Sciences; Nagasaki, JapanBACKGROUND The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa. METHODS H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression. RESULTS NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8. CONCLUSIONS H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.

Micronutrient Status and Glutathione Peroxidase in Bedridden Patients on Tube Feeding

Deficiency of micronutrients, especially selenium, is common in critically ill patients. We investigated the micronutrient status (selenium, zinc, copper and manganese) and glutathione peroxidase (GSH-Px) activity in 30 tube-fed patients and 21 hospitalized non-tube-fed control patients. Serum levels of selenium, copper and manganese in tube-fed patients were significantly lower than in control patients (selenium: 4.85 ± 1.38 μg/dl versus 8.67 ± 1.45 μg/dl; copper: 44.7 ± 36.9 μg/dl versus 92.1 ± 21.2 μg/dl; manganese 0.59 ± 0.41 μg/dl versus 1.52 ± 0.59 μg/dl). However, zinc and log GSH-Px in the serum were similar in the two groups. Serum selenium concentration correlated with the daily intake of selenium in tube-fed patients, but zinc, copper and manganese concentrations did not correlate with the daily intake of the respective trace elements in tube-fed patients. Blood GSH-Px activity correlated positively with serum selenium concentrations in the control patients, but not in tube-fed patients. These results demonstrate that selenium content of enteral feed appears to be insufficient to maintain normal serum levels in elderly bedridden patients. Our findings emphasize the importance of monitoring micronutrient status in patients on enteral feeding to avoid trace element deficiencies

Familial Crohn's disease with systemic lupus erythematosus.

We describe a young Japanese woman who was diagnosed with Crohns disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohns disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohns disease with SLE), patients with Crohns disease who develop such clinical findings might need evaluation for SLE.

Comparison of the microbicidal activities of superoxidized and ozonated water in the disinfection of endoscopes

The microbicidal activities of super-oxidized water (electrolysed strong acid water [ESAW] or electrolysed weak acid water [EWAW]), ozonated water, 0.05% chlorhexidine and 2% glutaraldehyde were tested against seven strains of clinical micro-organism isolates. Following incubation of bacterial suspensions in ESAW and EWAW for 10 s, the number of micro-organisms was reduced below the detection limit. The microbicidal activities of ESAW and EWAW were similar to that of glutaraldehyde, and superior to ozonated water and 0.05% chlorhexidine. The microbicidal activities of ESAW, EWAW and ozonated water were markedly diminished in the presence of albumin. Microbial contamination of upper gastrointestinal endoscopes was detected after 90 endoscopic procedures, but treatment of the endoscope with ESAW, EWAW or ozonated water eradicated the microbes. These results indicate that ESAW and EWAW are effective disinfectants after mechanical cleaning of upper gastrointestinal endoscopes, and can, therefore, be used in the endoscopy unit.

Polymorphism of CYP2C19 and Gastric Emptying in Patients with Proton Pump Inhibitor-Resistant Gastric Ulcers

The aim of the present study was to investigate whether CYP2C19 polymorphism status and gastric emptying are related to healing in patients with gastric ulcers. We studied the CYP2C19 status in seven patients with proton pump inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy volunteers using polymerase chain reaction restriction fragment length polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The frequency of phenotypes, indicated by genotypes, did not differ significantly between the three patient groups. The peak time of 13C excretion in patients with PPI-resistant ulcers was significantly longer than that of patients with PPI-sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric emptying, but not CYP2C19 polymorphism, is likely to be an important factor in the delayed healing of patients with PPI-resistant gastric ulcer.