Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.
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PMID:How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology. 939 59

Although Helicobacter pylori infection increases gastrin secretion, it is unknown whether this is a direct effect or requires activation of the immune system. We developed an H. pylori-infected human primary antral epithelial cell culture model to address this question. This culture protocol favors growth of H. pylori, and infected cultures could be maintained for up to 48 h. These cultures were enriched for gastrin (10-40%), somatostatin (2-5%), and gastric mucin (60-80%) cells but did not contain immunocytes. Bacterial attachment occurred in a random manner within 2 h of infection, although bacterial density was lower than in sections from infected patients. After 24 or 48 h, the bacterial microcolonies were similar in size to those seen in vivo, and at 24 h ultrastructural studies demonstrated well-developed pedestal formation underlying the bacteria. Coculture with H. pylori increased basal but not stimulated gastrin secretion at all time points >2 h. In conclusion, a newly developed cell culture model has been used to characterize the interactions between H. pylori and normal human antral epithelial cells.
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PMID:Helicobacter pylori-infected human antral primary cell cultures: effect on gastrin cell function. 972 49

Tham et al. show that Helicobacter pylori infection lowers the density of immunoreactive somatostatin cells (D-cells) in the antral mucosa and elevates plasma gastrin concentrations. According to current hypothesis, the lack of inhibition by somatostatin allows excessive release of gastrin, which stimulates acid secretion and thus causes duodenal ulcers. The cytokine tumour necrosis factor-alpha which is released in H. pylori gastritis inhibits D-cells in culture and may be responsible. Why do not all infected persons get duodenal ulcers? Recent work shows that more aggressive strains of H. pylori have greater effects on somatostatin/gastrin physiology. Another variable is whether the infection causes corpusitis or not. Inflammation of the gastric corpus diminishes acid secretion, which greatly decreases the likelihood of duodenal ulcers but increases the risk of gastric cancer. Factors which promote corpusitis include diets with high salt content or lacking in antioxidant vitamins. Work in this area is elucidating how H. pylori causes different diseases. Hopefully this will allow us to predict and prevent its serious sequelae.
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PMID:Helicobacter pylori and somatostatin cells. 985 43

Quadruple therapy (with a proton pump inhibitor (PPI), metronidazole, tetracycline and bismuth) is generally reserved for second-line treatment; however, studies using this regimen for 7 days have found it to be effective even in metronidazole-resistant strains. Resistance is an ongoing problem with antimicrobial therapy but considerable progress has now been made into understanding the underlying genetic mechanisms of this process. Metronidazole resistance in Europe is usually in the range of 20-30% of strains but may be as high as 70% in some countries. One genetic mechanism involved is thought to be a mutation of the rdxA gene. Macrolide resistance appears to be on the increase in Europe, varying from 1% in some countries to 13% in others. The genetic mechanism involved has been shown to be a point mutation of a ribosomal RNA. Amoxicillin resistance is an emerging problem that has an adverse effect on eradication rates in clinical practice. Resistance has been shown to be caused by the absence of one of the four binding proteins in the cell wall. Few novel antibiotics have been developed for use in eradication therapy, although rifabutin, secnidazole and furazolidone have shown some success as part of combination therapy. Alternative therapies that have been tested include mucosal protective agents which have been used in place of a PPI in some eradication regimens with some success, and the somatostatin analog, octreotide, that has been used as part of quadruple therapy in place of a PPI and produced eradication rates of approximately 88%. The ultimate challenge is still to develop a safe and effective vaccine against Helicobacter pylori. Current and future research will also focus on identifying genetic targets for therapy, adhesion molecule analogs to prevent binding of the bacterium, and urease inhibitors. The current triple therapy treatment options available for the eradication of Helicobacter pylori infection are over 90% effective in susceptible organisms and there are very few medical conditions to which we can offer such efficacious treatment. Unfortunately, the recommendations made at consensus conferences are not always put into practice and physicians in primary care may be unaware of the true efficacy of eradication therapy. Treatment is very simple: three drugs, twice a day for 1 week. The main focus for both primary care physicians and gastroenterologists should be to reinforce the need for patient compliance, otherwise we will see an increase in antibiotic resistance. Patients should be prewarned that they may experience some mild side effects and should be encouraged to complete the course of treatment. The real challenge for the future will be the management of patients who do not respond to first-line treatment. This paper will focus on potential problems with therapy, such as antibiotic resistance, and possible future solutions, such as novel antibiotics and vaccines.
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PMID:Challenges to therapy in the future. 1082 51

The association between Helicobacter pylori infection and gastric motility abnormalities is still controversial, partly because of the lack of an appropriate animal model. H. heilmannii type 1 (Hh1), a spiral bacterium that infects the stomach of both man and pigs, easily colonises and induces an inflammatory response in the gastric mucosa of rodents. For these reasons, the present study investigated the relationship between gastric motility in rats experimentally infected with Hh1 and correlated the results with serum gastrin and gastric somatostatin concentrations, as these hormones seem to be involved in gastric motility. Ten rats were inoculated with gastric mucus from an Hh1-positive pig and 10 animals with gastric mucus from an Hh1-negative pig (control group). After 56 days, gastric emptying was studied in vivo by scintigraphy. The animals were then killed, blood samples were collected for serum gastrin measurement, strips of the gastric wall were obtained for an in-vitro motor study and fragments of the gastric antrum were obtained for somatostatin content evaluation, Hh1 diagnosis and histological study. There was a significant increase in gastric emptying in the test group compared with the controls as demonstrated by the in-vivo and in-vitro studies. Serum gastrin levels were significantly higher and somatostatin levels were lower in the test group than in the controls. In addition, infected animals showed evidence of gastritis on histological examination. Gastric motility is altered in rats infected with Hh1, a fact possibly related to concurrent abnormalities of gastrin and somatostatin secretion.
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PMID:Increased gastric emptying induced by Helicobacter heilmannii type 1 infection in rats. 1088 88

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.
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PMID:Altered gastrin regulation in mice infected with Helicobacter felis. 1096 8

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.
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PMID:Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection. 1111 84

Helicobacter pylori affects gastric secretion. This functional effect might have a morphometric counterpart. Therefore, the gastric cell secretory compartment was morphometrically assessed in different pathophysiologic conditions related to Helicobacter pylori infection. Nineteen Helicobacter pylori-positive nonduodenal ulcer subjects, 15 omeprazole chronically treated subjects, and 19 duodenal ulcer patients were studied against 19 controls. Somatostatin, gastrin, enterochromaffin-like, and parietal cell density was assessed in gastric biopsies. No differences in any cell type density were found between Helicobacter pylori-positive nonduodenal ulcer subjects and controls. On the contrary, differences were significant when comparing omeprazole and duodenal ulcer patients to controls (higher density of gastrin, enterochromaffin-like, and parietal cells, lower density of somatostatin cells). In duodenal ulcer a reversion to control values followed Helicobacter pylori eradication and ulcer healing. A direct linear correlation between enterochromaffin-like, gastrin, and parietal cell density was demonstrated. An almost complete map of mucosal cells involved in gastric secretion is provided by this study. The cell density pattern, identical to the omeprazole group, points to an impaired feedback control of secretion in duodenal ulcer. The reversion to control values after Helicobacter pylori eradication and ulcer healing demonstrates the pathogenetic role of Helicobacter pylori-host interaction in these changes.
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PMID:Impairment of gastric secretion modulation in duodenal ulcer and in long-term PPI treatment: quantitative morphologic findings and pathophysiologic implications. 1157 48

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones.
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PMID:Helicobacter pylori and gut hormones. 1187 70

Helicobacter pylori has been recognized as one of the most important factors that lead to chronic changes in the gastric mucosa. These changes have either direct or indirect impact on various intestinal hormones (gastrin, somatostatin, bombensin, cholecystokinin...) which regulate gastric secretion. Gastric secretion enhancement is mostly caused by higher concentration of serum gastrin. The mechanism in which the Helicobacter pylori infection influences the regulation of gastrin and other intestinal hormones is yet to be discovered. It is known that eradication of the Helicobacter pylori infection decreases serum gastrin concentration, thus decreasing gastric secretion and inflammatory changes of the gastric mucosa.
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PMID:[Hormonal regulation of gastric secretion and Helicobacter pylori]. 1259 9


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