Gastroprotective and vasodilatory effects of epidermal growth factor: the role of sensory afferent neurons.

Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and gastroprotective effects via capsaicin-sensitive afferent neurons, including the release of calcitonin gene-related peptide (CGRP). We examined the protective and vasodilatory effects of EGF on the gastric mucosa and its interaction with sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric EGF (10 or 30 microg) significantly reduced gastric mucosal lesions induced by intragastric 60% ethanol (50.6% by 10 microg EGF and 70.0% by 30 microg EGF). The protective effect of EGF was significantly inhibited by pretreatment with capsaicin desensitization, human CGRP1 antagonist hCGRP-(8-37), or N(omega)-nitro-L-arginine methyl ester (L-NAME). Intravital microscopy showed that topically applied EGF (10-1,000 microg/ml) dilated the gastric mucosal arterioles dose dependently and that this vasodilatory effect was significantly inhibited by equivalent pretreatments. These findings suggest that EGF plays a protective role against ethanol-induced gastric mucosal injury, possibly by dilating the gastric mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO mechanisms.

Effect of diet on changes in small intestinal blood flow following intracolonic administration of indomethacin to rats.

Liquid diet (LD) is known to be protective against indomethacin-induced enteropathy, which is thought to be associated with ischemic change. We tested the hypothesis that the solid component of diet modulates small intestinal blood flow (SIBF) following indomethacin administration. In the first experiment, male Wistar rats were divided into 18-hr-fasted and normal diet groups. Indomethacin (20 mg/kg) or vehicle was administered intracolonically. SIBF was measured on both the mesenteric and antimesenteric sides of the intestine, using the hydrogen gas clearance method. In the second experiment, rats were given LD alone or LD with increasing concentration of soluble/insoluble fiber for seven days. The baseline SIBF was significantly higher in the groups with normal diet and LD with fiber than in the fasting and LD groups. Following indomethacin administration, SIBF gradually decreased in the groups with normal diet and LD with insoluble fiber, while neither liquid diet nor fasting reduced SIBF. There was no difference in SIBF between the mesenteric and antimesenteric sides of the intestine in any group. Our findings suggest that solid components of diet increase basal SIBF and decrease SIBF following indomethacin administration.

Rapidly growing primary gastric B-cell lymphoma after eradication of Helicobacter pylori.

Helicobacter pylori (H. pylori) infection plays a decisive role in primary gastric B-cell lymphoma especially of mucosa-associated lymphoid tissue (MALT)-type. We treated a 47-year-old male patient with primary gastric B-cell lymphoma associated with H. pylori infection. Although antibiotic therapy for eradication of H. pylori caused great improvement in the low-grade MALT lymphoma-like lesion, the small areas of high-grade lesion rapidly formed a new bulky mass in only 8 weeks. This suggests that eradication of H. pylori is not effective for high-grade lymphoma.

Crystallization and preliminary X-ray study of iso-2 azurin from the methylotrophic bacterium, Methylomonas J.

The obligate methylotroph Methylomonas J possesses two distinct azurins. The iso-2 azurin, which functions as an electron acceptor for methylamine dehydrogenase, has been crystallized using two kinds of precipitants: PEG 4000 and ammonium sulfate. The crystals precipitated with PEG belong to the monoclinic system, space group P21, with unit-cell parameters a = 32.96, b = 33.67, c = 47.34 A and beta = 101.35 degrees. The crystals precipitated with ammonium sulfate belong to the orthorhombic system, space group C2221, with unit-cell parameters a = 31.52, b = 62.49 and c = 135.41 A. The crystals diffract to 1.6 and 1.9 A resolution, respectively, and were suitable for X-ray crystallographic studies. A Patterson search is being conducted using the recently reported structure of Alcaligenes xylosoxidans NCIMB 11015 as a starting model.

Calcitonin gene-related peptide affords gastric mucosal protection by activating potassium channel in Wistar rat.

BACKGROUND & AIMS: Calcitonin gene-related peptide (CGRP) protects the gastric mucosa against injurious stimuli in various experimental models. The underlying mechanism could be the increase in gastric mucosal blood flow (GMBF). A number of endogenous vasodilators exert their effects through the activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels on vascular smooth muscle. The present experiments were performed to elucidate whether CGRP increases GMBF through the activation of KATP channels and whether the channels are involved in the protection by CGRP of gastric mucosa. METHODS: GMBF was determined by the hydrogen-clearance technique in male Wistar rats. Mucosal lesions were produced by intragastric superfusion with 0.15N HCland 15% ethanol for 40 minutes. Effects of an agonist (Y-26763, intra-arterially) and an inhibitor (glibenclamide, intravenously) of KATP channels were tested. RESULTS: Y-26763 increased GMBF, which was abolished by glibenclamide, and a CGRP-induced increase in GMBF was attenuated by glibenclamide. Macroscopic and microscopic lesions were exacerbated by human CGRP-(8-37) (a CGRP-1 receptor antagonist; intra-arterially) and glibenclamide but were ameliorated by exogenous CGRP (intra-arterially). CONCLUSIONS: CGRP protects the gastric mucosa against ulcerogenic stimuli, at least in part, through the activation of KATP channels in rats.

Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease.

To determine fatty acid patterns in Crohn's disease, we measured various serum fatty acids by gas chromatography in 20 patients with the disease and compared them with those in 18 healthy controls. All the patients had been free from any nutritional supplementation during preceding six months or had no history of intestinal resection. Eight of the patients were affected in the small bowel only, three in the large bowel only, and the remaining nine in both the small and large bowel. Both serum concentrations and percentages of C20:4n6, C20:5n3, C22:0, C22:6n3, total n3 polyunsaturated fatty acids, and total polyunsaturated fatty acids were lower in the patients than in the controls. Both essential fatty acids (C18:2n6, C18:3n3) and C20:3n9 levels were not different between the two groups. Among nine fatty acids that correlated with the Crohn's disease activity index, C20:5n3 and total n3 polyunsaturated fatty acids showed the most significant negative correlations. These findings suggest that essential fatty acid deficiency rarely occurs in Crohn's disease and also that n3 polyunsaturated fatty acids may be relevant to the activity of the disease.

Is vitamin E depleted in Crohn's disease at initial diagnosis?

We measured serum and red blood cell concentrations of vitamin E and serum lipid concentrations in 13 inpatients at the initial diagnosis of Crohn's disease and compared them with those of 12 healthy controls. Although the serum concentrations of vitamin E were significantly lower in the patients with Crohn's disease than in the controls, the red blood cell concentrations of this vitamin did not differ between the two groups. The serum concentrations of total lipids and total cholesterol were decreased in the patients with Crohn's disease. A significant correlation was found between the red blood cell concentration of vitamin E and the serum vitamin E/serum total lipids ratio in both the groups. There was no correlation between the Crohn's disease activity index and serum or red blood cell levels of vitamin E. These findings suggest that the lowered serum vitamin E levels in patients with Crohn's disease are a symptom of hypolipidemia, and that vitamin E deficiency may not actually become a serious problem in patients diagnosed with Crohn's disease.