Drugs online research references
Scand J Gastroenterol Suppl. 1990;178:85-92.
Potential hazards of long-term acid suppression.
Selway SA.
Glaxo Group Research Ltd., Ware, Hertfordshire, U.K.
Neuroendocrine cell (carcinoid) tumours have been reported in the acid-secreting part of the stomach of rodents after long-term administration of a range of potent chemically diverse antisecretory agents. Although evidence shows a link between the sequence of acid suppression, hypergastrinaemia, and neuroendocrine cell hyperplasia, other factors are also thought to be involved in neoplastic transformation. Prolonged hypochlorhydria or achlorhydria resulting in bacterial colonization of the stomach may allow the generation of carcinogenic substances. Other as yet unidentified trophic factors may be involved in tumour formation. In view of the potential risks associated with these agents, there must be concern about the possible consequences in man of marked suppression of acid. It seems wise to limit the use of these more potent agents to situations in which conventional therapy has failed and to short-term treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1980549&dopt=Abstract
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Digestion. 1986;35 Suppl 1:84-97.
Effect of short- and long-term feeding of omeprazole on rat gastric endocrine cells.
Creutzfeldt W, Stockmann F, Conlon JM, Folsch UR, Bonatz G, Wulfrath M.
Rats were tube-fed with omeprazole (40 mumol/kg body weight twice daily) for 30 and 60 days. As a result, fasting plasma gastrin levels were significantly elevated, while plasma somatostatin levels remained normal. Gastrin concentrations in the antral mucosa were unchanged after 30 days, but significantly elevated after 60 days. The relative stomach weight and the area of the antral and oxyntic mucosa increased significantly; however, the oxyntic mucosa thickness and the volume density of the parietal cells did not increase. Highly significant changes occurred in the endocrine cells of the antrum and corpus. The volume density of the argyrophilic (Grimelius technique) cells of the oxyntic mucosa increased time-dependently, and so did the volume density of the antral G cells, while the volume density of the antral D cells decreased. This resulted in a remarkable increase in the G/D cell ratio. All functional and morphological changes are reversed 42 days after omeprazole feeding for 60 days. The findings in the endocrine cells of the antral mucosa are explained by the omeprazole-induced permanent elevation of the intragastric pH and in the endocrine cells of the oxyntic mucosa by the following hypergastrinaemia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3792674&dopt=Abstract
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Scand J Gastroenterol. 1993 Jul;28(7):617-21.
Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study.
Valentini M, Bortoluzzi F, Cernigoi C, Toffoli G, Bertolissi E, Cannizzaro R, Sozzi M, Fornasarig M.
Division of Gastroenterology and Digestive Endoscopy, Regional Cancer Center, Aviano, Italy.
Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8362216&dopt=Abstract
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