Digestion

Lieber, Charles S.

doi: 10.1159/000201445pmid: 9243114

Helicobacter pylori has now been propelled into the forefront of gastroenterology, particularly the treatment of gastroduodenal ulcer, whereas its role in gastritis is still widely ignored, although this disease sparked much of the original observations. Forty years ago, it was shown for the first time that antibiotics can eliminate gastric ammonia production in man which suggested that this was due to eradication of bacterial urease activity. It was also found that the gastric juice ammonia concentration correlates with hypo- or anacidity in uremics and with mucosal inflammation in subjects with gastritis. In patients with nonalcoholic and alcoholic gastritis, the histology as well as the symptoms of gastritis were strikingly improved by antibiotic treatment. Beneficial effects of eradication of gastric urease activity and the resulting decreased ammonia production were also shown in patients with hepatic encephalopathy. Broader studies and clinical applications of these earlier findings are now warranted.

Talamini, Giorgio; Zamboni, Giuseppe; Cavallini, Giorgio

doi: 10.1159/000201446pmid: 9243115

Objective: Duodenal ulcer is regarded as the end result of alterations in which Helicobacter pylori (HP) plays a major role as a pathogenetic agent. The aim of this prospective study was to evaluate duodenal ulcer risk factors such as alcohol intake, smoking, use of non-steroidal anti-inflammatory drugs, age and sex in relation to HP colonization density. Patients and Methods. 495 patients consecutively examined by diagnostic upper digestive endoscopy were assessed; none of them had had previous upper digestive endoscopy or peptic ulcer, recent antiulcer-antibiotic treatment, upper gastrointestinal surgery, or cancer. The HP colonization on antral bioptic specimens was graded semi-quantitatively as follows: HP--(absence of HP); HP+-- (focal presence of small amounts of HP); HP++- (intermediate situation between HP+-- and HP+ + +), and HP+ + + (diffuse presence of large amounts of HP). Results: Logistic regression analysis identified only male sex (odds ratio 1.88, p < 0.02), smoking more than 10 cigarettes/day (odds ratio 2.53, p < 0.01), and HP grade (HP+-- odds ratio 0.79, p = NS; HP+ + – odds ratio 2.42, p < 0.02; HP+ + + odds ratio 3.66, p < 0.001) as independent risk factors of duodenal ulcer. Conclusion: The duodenal ulcer risk was found to correlate with HP density, male sex, and smoking, but not with non-steroidal anti-inflammatory drug use.

Heise, Walter; Arastéh, Keikawus; Mostertz, Peter; Skörde, Jürgen; Schmidt, Wolfgang; Obst, Christopher; Koeppen, Michael; Weiss, Rudolf; Grosse, Gernot; Niedobitek, Fred; L’Age, Manfred

doi: 10.1159/000201447pmid: 9243116

Kinoshita, Yoshikazu; Kishi, Kiyohiko; Asahara, Masakyo; Matsushima, Yumi; Wang, He-Yao; Miyazawa, Keiji; Kitamura, Naomi; Chiba, Tsutomu

doi: 10.1159/000201448pmid: 9243117

The hepatocyte growth factor has been reported to be a potent mitogen of various epithelial cells, including gastric mucosal cells. Therefore, production and activation of hepatocyte growth factor in the gastric wall were investigated to speculate on the possible role of this factor in the healing of gastric ulcer in rats. Indomethacin-induced gastric mucosal lesions and acetic acid induced ulcers were employed as models of acute gastric lesions and chronic ulcer, respectively. Immunoblot and Northern blot analyses indicate that experimentally induced gastric mucosal lesions stimulate not only the production of hepatocyte growth factor, but also the conversion to its active form. This conversion was accompanied by increased gene expression of hepatocyte growth factor activator in the stomach. In rats with acute mucosal lesions, hepatocyte growth factor activator mRNA was most abundant 6 h after induction of mucosal lesions. On the other hand, hepatocyte growth factor and hepatocyte growth factor activator mRNA levels were elevated until 15 days after the induction of chronic ulcers. In summary, it has been clarified that not only production, but also activation of hepatocyte growth factor is stimulated during gastric ulcer healing.

Uno, Hironori; Arakawa, Tetsuo; Fukuda, Takashi; Higuchi, Kazuhide; Kobayashi, Kenzo

doi: 10.1159/000201449pmid: 9243118

We investigated the role of capsaicin-sensitive sensory nerves (CPSNs), nitric oxide (NO), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in gastric adaptive and receptive relaxation in isolated guinea-pig stomachs. Changes in intragastric volume and pressure were recorded simultaneously in isolated stomachs in baths containing atropine and guaneth-idine. Adaptive relaxation was induced by luminal distention, and receptive relaxation was induced by electrical vagal stimulation. We found that desensitization to capsaicin inhibited adaptive relaxation, but not vagally induced relaxation. Extraluminal capsaicin induced gastric relaxation. Adaptive relaxation and capsaicin-induced relaxation were reduced by both tetrodotoxin and N^G-nitro-L-arginine (LNNA), but not by hexamethonium. The effect of LNNA was partially reversed by co-incubation with L-arginine. Neither CGRP_(8-37) nor VIP_(10-28) inhibited all responses of adaptive relaxation, vagally induced and capsaicin-induced relaxation. These findings suggest that activation of CPSNs may be involved in adaptive relaxation, and that NO, but not CGRP or VIP, may be involved in the mechanisms of adaptive relaxation and receptive relaxation.

Printz, H.; Schlenzka, R.; Reguadt, P.; Tscherny, M.; Wagner, A.C.C.; Eissele, R.; Rothmund, M.; Arnold, R.; Göke, B.

doi: 10.1159/000201450pmid: 9243119

To evaluate whether the small bowel can be distracted by mechanical stress in analogy to limb lengthening by osteodistraction, a gut-lengthening apparatus was designed. This distractor was placed at the antimesenterical side of a defined jejunum segment in rabbits. Distraction was performed by 1 mm lengthening of the distractor once daily using extracorporal screws. An effective gut lengthening was achieved of 9.9 ± 0.5 mm (∼ 100%) within 3 weeks. Treated animals gained weight and remained in good general condition. Fasting plasma levels of cholecystokinin, neurotensin, glucagon-like peptide-1, gastric inhibitory polypeptide, and insulin remained unaffected. Postoperative factor XIII levels were significantly diminished and gastrin was elevated during gut distraction. DNA and protein concentrations in the mucosa of the distracted gut segments corresponded to controls. Mucosal lactase and saccharase activities were reduced. In the distracted bowel segments total tunica muscularis thickness was more than doubled due to muscle cell hypertrophy. In distracted segments villous width was increased. Detection of proliferating mucosal crypt cells utilizing BrdUrd labeling revealed no effects. In conclusion, small gut lengthening by mechanical distraction is possible without major changes in gut morphology. This technique may hint a novel experimental approach for the treatment of short bowel syndrome.

Kapraali, Marjo; Söderman, Charlotte; Marín, Luis; Johansson, Olle; Theodorsson, Elvar; Uribe, Andrés

doi: 10.1159/000201451pmid: 9243120

Groups of Sprague-Dawley rats were given placebo or prostaglandin E₂ (PGE₂) at 25 or 5,000 μg/kg or 15, R,15-methyl-PGE₂ (MePGE₂) at 5 or 50 μg/ kg, twice daily, orally, for 1 month. Histological sections from the proximal duodenum were processed for immunohistochemistry and the volume density of immunoreactive endocrine cells was determined using point-counting grids. The surface density of the villous lining was estimated by using a cycloid test system. Thereafter, the total volumes of endocrine cells and the total surface area of the villous lining were calculated after estimating the mucosal volume. The volume density of serotonin-immunoreactive cells was increased in the duodenum of rats given 25 or 5,000 μg/kg PGE₂ (p < 0.05). The total volume of these cells increased in the animals given 25 μg/kg PGE₂ (p < 0.05). The total volume of gastrin/CCK-immunoreactive cells was higher in rats given 25 μg/kg PGE₂ or 50 μg/kg MePGE₂ than in controls (p < 0.05). The volume density of somatostatin-immunoreactive cells increased in rats given 5 μg/kg MePGE₂, but the total volumes were not different between the groups. The area of somatostatin-immunoreactive cell profiles was enlarged in the animals given 5,000 μg/kg PGE₂ (p < 0.05). The mucosal volume was enlarged by prostaglandins. The epithelial thickness increased in rats given the highest doses of PGE₂ (p < 0.05). The concentration of motilin-like immunoreactivity increased in the duodenum of rats given 5 μg/kg MePGE₂ (p < 0.05). We conclude that oral administration of PGE₂ for 1 month increased the total volumes of serotonin- and gastrin-CCK-immunoreactive cells and the tissue concentration of motilin-like immunoreactivity, which indicates that prostaglandins modulate endocrine cells in a stable steady-state condition.

Löser, C.; Fitting, T.; Fölsch, U.R.

doi: 10.1159/000201452pmid: 9243121

The present study was designed to investigate the inhibitory potency of the two novel S-adenosylmethionine decarboxylase (SAM-DC) inhibitors MDL 73811 and CGP 48664 on the camostate-induced pancreatic polyamine metabolism and especially intracellular spermidine accumulation as well as pancreatic growth in vivo. Male Wistar rats (180 g) were either treated with (1) the synthetic trypsin inhibitor camostate (200 mg/kg b. w. orally twice daily), (2) camostate + MDL 73811 (100 mg/kg b.w. i.p. twice daily), (3) camostate + CGP 48664 (5 mg/kg b.w. i.p. once daily) or (4) saline as controls. Animals (5-9 per group) were sacrificed after 1,2 and 5 days of treatment. MDL 73811 caused a long-lasting ( > 95%; p < 0.005) inhibition of SAM-DC followed by a significant (p < 0.005) increase in ornithine decarboxylase and putrescine, while spermine was decreased (p < 0.005). In contrast to MDL 73811, CGP 48664 had little effect in vivo. Despite potent inhibition of SAM-DC camostate-stimulated intracellular spermidine accumulation was not prevented by the simultaneous administration of MDL 73811. Consequently organ growth was not affected either. Since de novo synthesis of spermidine was effectively inhibited by MDL 73811, counterregulatory mechanisms (i.e. interconversion pathway, extracellular uptake) had to step in to maintain the intracellular balance of spermidine. The present data support the general concept of the importance of intracellular spermidine accumulation for the maintenance of pancreatic growth in vivo.

Radhakrishnan, S.; Zubaidi, Ghazi; Daniel, Mathew; Sachdev, G.K.; Mohan, A.N.

doi: 10.1159/000201453pmid: 9243122

Objective: Inflammatory bowel disease has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course in cases of ulcerative colitis (UC). The aim of the present study was to assess the incidence and disease pattern of UC in Oman. Method: A prospective study, over a period of 8 years (1987-1994), was performed to study 108 patients found to have UC. Results: The annual incidence of UC was 1.35/100,000. The disease was mainly seen in the middle and upper middle class group, and the majority were nonsmokers or exsmokers. There was no significant difference in the incidence of the disease between nationalities or sexes. Total colitis was seen in 18%, and a significant number had disease extending up to the splenic flexure. Proctitis was seen in 8%. Although, the extent of the disease was similar to reports from the West, these patients had fewer hospital admissions, blood transfusions and none of them suffered local complications such as toxic dilatation, perforation or severe bleeding. Sclerosing cholangitis occurred in 2 patients. Patients were followed up for a maximum period of up to 7 years after diagnosis and none developed dysplasia or cancer. Three patients had surgery mainly for failure of medical treatment. Conclusions: From this report it seems that UC occurs in Oman at a lower frequency compared to the West. Although, the extent of the disease was similar to Europeans, these patients had less severe disease with fewer complications.

Tateishi, H.; Mitsuyama, K.; Toyonaga, A.; Tomoyose, M.; Tanikawa, K.

doi: 10.1159/000201454pmid: 9243123

There is now clear evidence supporting the role of cytokines in the clinical and immunopathological manifestations of human inflammotory bowel disease. The purpose of the present study was to determine the possible role of a cytokine network in a rat model of trinitrobenzene sulfonic acid-induced colitis and to examine its relation to intestinal permeability. After a rapid increase in the intestinal permeability of Evans blue in the colon, tumor necrosis factor-α increased transiently, and interleukin-1 and interleukin-6 followed thereafter. The majority of tumor necrosis factor-α- and interleukin-1-producing cells observed by immunofluorescent staining was revealed to be macrophages. Repeated injections of interleukin-1 receptor antagonist led to a modest decrease in myeloperoxidase activity and colon weight. These findings suggest that enhanced pro-inflammatory cytokine production from intestinal macrophages accompanied by increased intestinal permeability may contribute to intestinal and systemic features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade of pro-inflammatory cytokines may help reduce intestinal inflammation.