Atsushi Furusawa

Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin concentrations of human stomach

Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric mucosa and gastric juice withHelicobacter pylori infection were measured in the human stomach. One hundred seventy-one patients (106 males, 65 females;, mean age, 52.0; range, 19–84 years) were registered. Gastric juice and mucosa were obtained with the usual endoscopy procedure. Somatostatin concentration was measured by radioimmunoassay. The irsomatostatin concentrations in theH. pylori-negative group were significantly higher than in the positive group gastric mucosa, whereas its levels in gastric juice tended to decrease withH. pylori infection. There was an inverse correlation between luminal ammonia levels and ir-somatostatin concentrations of the gastric mucosa. On the other hand, ir-somatostatin concentrations of the gastric mucosa significantly decreased with chronic and active inflammatory change. This decrease was not correlated with the grade of active inflammation, which was in close relation, toH. pylori infection, but with the grade of chronic inflammation. These results indicate thatH. pylori may reduce ir-somatostatin concentrations of the human stomach and that its effect is partly mediated via luminal ammonia produced byH. pylori.

Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), β-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohns disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4–5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6–12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.

Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn's disease: An immunocytochemical study

The phenotypes and ultrastructure of macrophages and dendritic cells in aphthoid lesions of the colon were immunocytochemically observed in patients with Crohns disease. Biopsy specimens were endoscopically obtained from both aphthoid and advanced lesions in Crohns disease patients. Biopsy specimens obtained from patients with infectious colitis and from normal individuals served as controls. Aphthoid lesions contained densely aggregated CD68+ macrophages, which were surrounded by numerous ID-1+ dendritic cells. In the normal controls and infectious colitis patients, however, a few scattered CD68+ macrophages and ID-1+ dendritic cells were noted beneath the surface epithelium. CD3+ lymphocytes were significantly increased in both aphthoid and advanced lesions of Crohns disease, but the CD4/CD8 ratio was similar in all groups studied. The double immunoperoxidase staining method revealed that both CD68+ macrophages and ID-1+ dendritic cells in the aphthoid lesions simultaneously expressed ICAM-1 and HLA-DR antigens. Electronmicroscopic observation revealed that CD68+ macrophages had numerous vesicles and lysosomal granules and few projections, and that ID-1+ dendritic cells had appreciable cytoplasmic protrusions with a few vacuoles. These findings suggested that the colonic mucosa in Crohns disease contained two types of macrophage/dendritic cells in the same lineage that expressed intercellular adhesion molecules and class-II MHC antigens. It also appeared that the aphthoid lesions of Crohns disease featured an increase in macrophages and dendritic cells consistent with immunological activation.

Effect of luminal administration of thyrotropin-releasing hormone or somatostatin on gastric pH and interaction of these peptides in rats

SummaryThe effect of intraluminal administration of thyrotropin-releasing hormone (TRH) on gastric pH and release of luminal somatostatin, and a possible interrelationship between TRH and somatostatin in the rat stomach were studied. TRH was administered into the stomach via an intragastric tube at various doses (50 pg/kg-10 μg/kg) and gastric pH was measured after 15 min. The intraluminal administration of TRH significantly decreased gastric pH at doses over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH administration caused a significant increase in immunoreactive-somatostatin (ir-somatostatin) concentrations in the gastric wall and a significant decrease in ir-somatostatin concentrations in the gastric juice. On the other hand, intraluminal administration of somatostatin caused a significant increase in ir-TRH concentrations in the gastric wall and a significant decrease in ir-TRH concentrations in the gastric juice, and significantly raised gastric pH at 5 min. These findings suggest that luminal TRH may exert a regulatory effect on gastric acid secretion, and that TRH may have a possible interaction with somatostatin in the modulation of gastric acid secretion.

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4°C for 1–3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.

The effects of histamine on the concentrations of immunoreactive thyrotropin-releasing hormone in the stomach and hypothalamus in rats.

SummaryThe effects of histamine and its related compounds on the concentrations of immunoreactive thyrotropin-releasing hormone (ir-TRH) in the stomach, gastric juice and hypothalamus in rats were studied. Histamine, ranitidine or ethanolamine was injected intraperitoneally, and the rats were decapitated at various times after the injection. Ir-TRH concentrations in the stomach, gastric juice and hypothalamus were measured by a radioimmunoassay. Ir-TRH concentrations in the stomach decreased significantly after histamine injection and increased significantly after ranitidine injection in a dose-dependent manner, but did not change with ethanolamine. Ir-TRH concentrations in the gastric juice increased in a dose-dependent manner, peaking at 30 min after histamine injection, and its effect was blocked with ranitidine. Ir-TRH concentrations in the hypothalamus elevated significantly after histamine injection and reduced significantly after ranitidine injection, but did not change with ethanolamine. The effects of histamine on ir-TRH concentrations in the stomach and hypothalamus were significantly blocked with ranitidine, but not with ethanol-amine. These findings suggest that histamine stimulates ir-TRH release from the stomach and inhibits ir-TRH release from the hypothalamus, and that these effects of histamine on ir-TRH release are mediated via an H2-receptor.

The role of thyrotropin-releasing hormone (TRH) in the pathogenesis of water-immersion stress in rats—inhibition of TRH release from the stomach by atropine, ranitidine or omeprazole—

SummaryThe role of thyrotropin-releasing hormone (TRH) in the development of gastric erosions and ulcers induced by water-immersion stress was studied. Intraperitoneally administered bethanechol induced a decrease in the gastric wall immunoreactive TRH (ir-TRH) concentrations and an increase in gastric juice ir-TRH concentrations in a dose-related manner, while atropine induced an increase in gastric wall ir-TRH concentrations and a decrease in gastric juice ir-TRH concentrations under non-stress condition. Intraperitoneally administered omeprazole did not influence gastric wall ir-TRH concentrations but elevated gastric pH. Water-immersion stress induced a decrease in gastric wall ir-TRH concentrations and an increase in gastric juice ir-TRH concentrations with a decrease in gastric pH prior to ulcer formation. Pretreatment with atropine or ranitidine inhibited the development of stress ulcers, reduced changes in ir-TRH concentrations in the gastric wall and gastric juice, and induced an increase in gastric pH. Omeprazole inhibited stress ulcer formation and changes in gastric wall and gastric juice ir-TRH concentrations. These results suggest that TRH release from the stomach wall into gastric juice is of importance in the pathogenesis of stress ulcer and that its release is mediated by both muscarinergic and histaminergic (H2) systems. Furthermore, omeprazole has an inhibitory effect on TRH release under stress ulcer.

Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach

The effects of serotonin and its related compounds on immunoreactive thyrotropin-releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir-TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors.

Effects of water-immersion-induced stress and intraperitoneal administration of brain-gut peptides upon immunoreactive thyrotropin-releasing hormone and prostaglandin E2 concentrations in the rat stomach

SummaryThe effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water-immersion caused a significant decrease in immunoreactive-TRH (irTRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of irTRH in the stomach was significantly decreased after VIP injection,whereas it was significantly increased after β-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after β-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat.

Successful Hyperbaric Oxygen Therapy of Pneumatosis Cystoides Intestinals : A Report of Two Cases

Abstract: Two patients with pneumatosis cystoides intestinalis (PCI) successfully treated with hyperbaric oxygen are described, The first patient was a 52‐year‐old male who presented with bloody stools and was diagnosed as having primary PCI. The second was a 61‐year‐old male whose occupation entailed prolonged exposure to trichloroethylene. Following hyperbaric oxygen therapy, the colonic gas cysts completely disappeared in both patients, and there has been no evidence of recurrence. The relevant literature from 1980 to 1992 is reviewed, and hyperbaric oxygen therapy for PCI is discussed in detail. The data accumulated thus far suggest that hyperbaric oxygen is superior to high‐flow oxygen breathing in PCI therapy.