Digestion

Arnold, R.

doi: 10.1159/000201346pmid: N/A

doi: 10.1159/000201347pmid: N/A

Blum, André L.

doi: 10.1159/000201348pmid: 8886571

Technology has propelled gastric physiology and pathophysiology since 1825, the year when the French Academy of Science tried to attribute a prize to the best paper on digestive physiology. I have analyzed the contributions of Ismar Boas, as well as my personal experience in studying gastric mucosal permeability, gastric secretion, a vaccine directed agaist Helicobacter pylori and the metabolism of this pathogen. In addition, I have examined the interplay between sociopolitical events and research activities, the role of suppressed minorities in research, the falacies of falsification strategies, the dependence of valid results from unorthodox experimental approaches and creative elements. Some of the older gastric researchers expressed solitary views – an attitude which may have helped them to make novel and valid observations.

Sommi, P.; Ricci, V.; Fiocca, R.; Romano, M.; Ivey, K.J.; Cova, E.; Solcia, E.; Ventura, U.

doi: 10.1159/000201349pmid: 8886572

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain. The effect of VacA and ammonia was evaluated with and without addition of 10 mM urea, a physiological concentration for the human stomach, and with and without addition of 0.5 mg/ml acetohydroxamic acid (AHA), an urease inhibitor. Our data show that: (1) both urease-positive H. pylori strains caused cell vacuolation in the absence of urea, the VacA-positive strain being approximatively twice as potent as the VacA-negative strain; (2) addition of urea to the culture medium caused an approximatively 3-fold increase in the vacuolating activity of both urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert any vacuolating effect, either in the presence or in the absence of urea; (4) the ratio between cell vacuolation induced by VacA-positive and VacA-negative strains was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and about 6 in the presence of AHA, either with or without urea added. The increment of vacuolation is likely due to an interaction between AHA and VacA. In conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when physiological levels of urea are present in the incubation medium. This finding suggests that all urease-positive H. pylori strains, both with and without VacA expression, should be considered as potentially cytotoxic for the human gastric mucosa, although VacA enhances the severity of cell damage.

Modlin, Irvin M.; Zhu, Zhao-hua; Tang, Laura H.; Kidd, Mark; Lawton, Gary P.; Miu, Kun; Powers, Robert E.; Goldenring, James R.; Pasikhov, Dmitry; Soroka, Carol J.

doi: 10.1159/000201351pmid: 8886574

Background/Aims: Hypergastrinemia, induced by sustained suppression of gastric acid secretion, is associated with gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumor formation. We examined the effect of a selective Hi-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to determine whether histamine might modulate ECL cell generation. Methods: The rodent mastomys received the H₂-antagonist loxtidine (2 g/l drinking water) alone or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120 days. Controls received water or terfenadine alone. Serum gastrin levels and tissue histamine content were assayed by radioimmu-noassays, and tissue chromogranin levels determined (Western blot analysis). In vivo cell proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days) incorporation. Gastric mucosal thickness was determined, ECL cell number was assessed, and the percentage of proliferating ECL cells quantitated. To evaluate the direct action on ECL cells we then studied the effect of terfenadine on histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation (∼ 90% pure) of ECL cells. Results: Loxtidine increased serum gastrin levels, mucosal thickness, tissue chromogranin levels, tissue histamine content, BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect. The high dose in combination with loxtidine significantly inhibited the increase in tissue chromogranin levels, tissue histamine content, ECL cell number and proliferating ECL cells (p < 0.05), but did not alter other parameters, compared to loxtidine alone. The low dose did not alter the loxtidine-induced changes. In pure isolated ECL cells, terfenadine did not alter histamine secretion either alone or in combination with gastrin (10 nM). DNA synthesis was significantly inhibited by terfenadine (IC₅₀ 10^-10M). Conclusions: Terfenadine specifically inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and significantly inhibited ECL cell DNA synthesis in vitro. We postulate that histamine, through an H₁ receptor, positively modulates gastric ECL cell proliferation.

Kato, Kimitoshi; Yang, Hong; Taché, Yvette

doi: 10.1159/000201352pmid: 8886575

The influence of central vagal activation induced by the thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally on gastric mucosal injury produced by 60% ethanol (4 ml·kg^-1) was investigated in urethane-anesthetized rats. RX 77368 (3, 10 and 30 ng) inhibits dose dependently macroscopic gastric damage induced by intragastric administration of 60% ethanol by 18,43 and 77%, respectively. The cytoprotective effect of intracisternal RX 77368 (30 ng) was completely blocked by cervical vagotomy, atropine (2 mg·kg^-1 s.c), and CGRP_8-37 (100 μg·kg^-1 i.v.) and partially inhibited by indomethacin (5mg·kg-¹ i.p.). Vagotomy, atropine, indomethacin and CGRP8-37 alone did not modify gastric mucosal lesions induced by ethanol in rats injected intracisternally with saline. The present data show that intracisternal injection of TRH analog in urethane-anesthetized rats protects against ethanol-induced gastric injury through vagal cholinergic dependent pathways which recruit prostaglandins and CGRP mechanisms.

Okada, Akihiko; Kinoshita, Yoshikazu; Maekawa, Torn; Hassan, Sazzad; Kawanami, Chiharu; Asahara, Masakyo; Matsushima, Yumi; Kishi, Kiyohiko; Nakata, Hirohisa; Naribayashi, Yoko; Chiba, Tsutomu

doi: 10.1159/000201353pmid:

Fu, Kai; Sarras, Jr., Michael P.; De Lisle, Robert C.; Andrews, Glen K.

doi: 10.1159/000201354pmid: 8886577

The pancreatitis-associated proteins (PAPs) are major pancreatic secretory proteins during acute pancreatitis. However, mechanisms of regulation of PAP gene expression are poorly understood, and there is a lack of information regarding mouse PAP gene expression. Herein, we employed Northern blotting and RNase protection assays to measure mouse PAP-I mRNA levels in the normal pancreas and intestine, and in the pancreas during caerulein-induced acute pancreatitis. Unexpectedly, we found that mouse PAP-I mRNA levels are constitutively high in the adult pancreas, as well as in the small intestine. Furthermore, mouse pancreatic PAP-I mRNA levels are rapidly and dramatically down-regulated (3 h) after the initiation of caerulein injections, but slowly return to high levels by 72 h. Interestingly, we found that pancreatic PAP-I mRNA levels are also transiently and dramatically down-regulated after L-buthionine-[S, R]-sulfoximine administration. Thus, a correlation between PAP-I mRNA levels and glutathione levels in the mouse pancreas was demonstrated.

Goll, Rasmus; Nielsen, Sørn Haagen; Holst, Jens Juul

doi: 10.1159/000201355pmid: 8886578

The release of motilin from an isolated preparation of pig duodenum has been studied. Three different types of stimuli were applied: electrical nerve stimulation, intraarterially administered peptides, and instillation of test solutions into the lumen of the duodenum. Furthermore, extracts of 20 different regions of the pig digestive system have been analyzed for motilin content. Analysis of the extracts only detected significant presence of motilin in the pig duodenum and jejunum (79 ± 15 and 60 ± 19 pmol/g). The stimulation experiments showed: (1) a significant noncholinergic depression of motilin release during electrical stimulation of the vagus nerve (nadir at 74 ± 5% of baseline level; (2) a significant elevation of motilin release in response to intraarterially administered vasoactive intestinal peptide (VIP) (peak at 330 ± 35% of baseline level), and (3) a significantly elevated motilin release in response to instillation of autologuous bile (peak at 170 ± 16% of baseline level) and hydrochloric acid (peak at 196 ± 42% of baseline level) into the duodenal lumen. In conclusion, luminal acidification and bile are important factors in stimulation of motilin release, whereas the vagally stimulated VIP release was insufficient to overcome the general inhibitory effect of vagus stimulation.

Herrmann-Rinke, Christine; Eissele, Rolf; Arnold, Rudolf; Göke, Burkhard

doi: 10.1159/000201356pmid: 8886579

The colon contains large numbers of endocrine cells. Insight into their physiological function is limited. This is due to the fact that no sufficient model of isolated endocrine colon cells is available. In the present study we introduce an isolated vascularly perfused colon model for in vitro studies. This model offers the advantage that it keeps the endocrine cells in their physiological orientation and environment. The gut mucosa is highly sensitive to ischemia. Therefore, a careful validation of its viability is crucial in gut organ preparations. This study demonstrates that, by utilizing an oxygenated vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of the colon is achieved for at least 1 h without obvious tissue injuries. During this time parameters such as perfusion pressure, venous lactate dehydrogenase release, glucose consumption, lactate output, oxygen consumption, perfusate loss by the preparation, and morphology were analyzed. Dependent on stimulation, the endocrine L cells of the colon released glucagon-like peptide-I upon arterial perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model for the isolated perfusion of the colon is introduced which is suitable for studies of endocrine colon cells.