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Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan.

The mechanisms by which Dai-kenchu-to (TJ-100), a kampo medicine, enhances gastrointestinal motility was investigated using isolated guinea pig ileum. TJ-100 induced contractions accompanied by autonomous contraction at a concentration of more than 3 x 10(-4) g/ml in a dose-related manner. The TJ-100-induced ileal contraction was suppressed by atropine and tetrodotoxin, but not by hexamethonium. This effect was partially suppressed in the presence of high concentrations of ICS 205-930, a serotonin 4 (5-HT4) receptor antagonist. In addition, TJ-100 showed an acetylcholine (ACh)-releasing action in the smooth muscle tissues of ileum. These results suggest that contractile response induced by TJ-100 is partially mediated by ACh released from the cholinergic nerve endings and that 5-HT4 receptors would be involved in the effect of TJ-100.

Oesophageal involvement of pemphigus vulgaris had been considered an exceptional event. However, our endoscopic study found oesophageal lesions in seven of eight (87·5%) patients with pemphigus vulgaris.

A 57-year-old woman with hypertension, mixed mitral valve disease, and atrial fibrillation was admitted to our hospital because of abdominal pain continuing for several hours. On the following day, colonoscopy was performed, and diffuse yellow-white pseudomembranous changes were seen in the right hemicolon, but there were no abnormal findings in the left hemicolon; 24 h after onset, a diagnosis of superior mesenteric arterial embolism was made on the computed tomography (CT) scan findings. Abdominal angiography was performed and showed complete occlusion of the superior mesenteric artery (SMA). Then conservative treatment, using per-catheteric thrombus aspiration, was done, followed by intraarterial injection of tissue type plasminogen activator. After the thrombo-aspiration, the filling deficit of the main artery had disappeared, and the branches on the right side were clearly delineated. After the treatment, the symptoms such as abdominal pain and diarrhea improved accordingly. She was discharged from the hospital 27 days later. Our case suggests that trans-catheter thrombo-aspiration is a possible alternative to open embolectomy for some cases of SMA embolism more than 10 h post-onset.

Recent studies have demonstrated relationships between cytokines and gastric acid secretion. The present study was performed in rats to elucidate the effects of interleukin-8 (IL-8) on gastric acid secretion through an increase in histamine release from the stomach. The experiments were performed in gastric lumen-perfused rats for the study of acid secretion and in totally isolated vascularly perfused rat stomach preparations for the study of histamine release. The histamine in the effluent was determined by radioimmunoassay. IL-8 (500 ng) significantly enhanced gastrin-stimulated acid secretion. IL-8, at a concentration of 500 ng/20 ml per 10 min, did not alter basal histamine release, but at 100 ng/20 ml and 500 ng/20 ml it dose-dependently increased gastrin-stimulated histamine release. IL-8 enhances gastrin-stimulated acid secretion and histamine release from the rat stomach, which may explain the enhancing effect of IL-8 on gastric acid secretion.

In recent studies, the involvement of mast cells in the pathogenesis of Helicobacter pylori infection was suggested. In the present study, using isolated canine gastric mucosal mast cells, we undertook to elucidate the effects of interleukin-8 (IL-8) and H. pylori on histamine release from these cells. Enriched canine gastric mucosal mast cells (50% target cells) were incubated in Hanks medium with IL-8, or water extract or sonicate of H. pylori for 15 min at 37 degrees C. The content of histamine in the supernatants and the cell pellets after centrifugation was assayed with a histamine radioimmunoassay (RIA) kit. IL-8 (50 ng/ml) and concanavalin A (20 microg/ml) significantly increased histamine release from enriched gastric mucosal mast cells. Dose-dependent stimulation of histamine release by IL-8 (5-50 ng/ml) was also seen. Water extract and sonicate of H. pylori (10(8) bacteria) increased histamine release from mast cells. A concentration-dependent stimulation of histamine release by water extract or sonicate was also seen. The maximal response of histamine release was seen at the highest concentration of the water extract or sonicate. The results indicated that IL-8 and H. pylori had stimulatory effects on histamine release from canine gastric mucosal mast cells. The results imply that IL-8 and soluble factors of H. pylori may accelerate inflammation of the gastric mucosa via histamine release from mast cells.

Until recently, the secretion of gastric acid, which plays an important role in the pathogenesis of peptic ulcer, was thought to be controlled by diet, the autonomic nerves and gut hormones. However, peptic ulcer is now known to be caused by the infection with Helicobacter pylori (H. pylori), so it is possible that inflammation modifies the secretion of gastric acid. We used gastric-lumen-perfused rats to first examine the effect of interleukin-8 (IL-8) on acid secretion and then the involvement of free radicals and neutrophils in the action of IL-8. IL-8 enhanced tetragastrin-stimulated acid secretion and free radical scavengers or inhibitors and the pretreatment with anti-rat neutrophil serum inhibited this effect, which indicates that IL-8 enhances gastrin-stimulated acid secretion and that neutrophil-derived hydroxyl radicals mediate the IL-8-induced increase in acid secretion.

Endogenous prostaglandin E2 has been indicated to have an important role in preventing gastric mucosal damage from noxious agents (i.e., in adaptive cytoprotection). However, the response of endogenous prostaglandin E2 to a mild irritant is controversial. In this study, we attempted to determine whether pretreatment with a low concentration of ethanol could induce endogenous prostaglandin E2 production by isolated canine fundic mucosal cells and to identify cells that are responsible for an increase of prostaglandin E2 production. Canine fundic mucosa was digested by collagenase, dispase, and EDTA. The cells were separated into five fractions with an elutriator rotor. Pretreatment with 5% ethanol induced a significant increase of prostagladin E2 release only from the secondary small-sized cell fraction, which was rich in mast cells and endocrine cells, and not from the other four fractions. Further cell separation by density gradient centrifugation revealed that the mast cell-enriched fraction (54%) was responsible for the increase of prostaglandin E2 release induced by the pretreatment with 5% ethanol. The results suggest that mast cells of the gastric mucosa play an important role in the production of endogenous prostaglandin E2 in adaptive cytoprotection.

Recent studies have demonstrated a relationship between cytokines and gastric acid secretion. However, details of the mechanism underlying that relationship have not been elucidated. For this study, an in vivo experiment was undertaken to investigate the possibility that IL-8 would be involved in the mechanism of gastric acid secretion. Gastric lumen-perfused rats were prepared and the stomachs were perfused with a saline solution. The effluent was collected at 15-min intervals and assayed for titratable acid against 0.01 M NaOH. IL-8 (200 ng/rat) given intravenously did not influence basal acid output in rats. However, when IL-8 was administered by injection during continuous tetragastrin infusion (4 microg/kg/hr) acid output increased significantly (P < 0.01). The acid output during the first hour following IL-8 injection was 43.6% higher than prior to the injection. Acid output during the second hour was lower than during the first hour. However, successive injection of IL-8 again increased tetragastrin-stimulated acid output by 23.4% (P < 0.05). IL-8 injection did not change histamine-stimulated acid output. The results indicate that IL-8 has the effect of enhancing gastrin-stimulated acid secretion and might have an important role in the pathophysiology of gastric acid secretion in vivo.