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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short-term treatment.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate the relationship between CYP2C19 genotype and the effects of long-term omeprazole treatment.〈section xml:id="abs1-3"〉〈title type="main"〉Material and methods:A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods.〈section xml:id="abs1-4"〉〈title type="main"〉Results:In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long-term treatment (〉 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean ± s.e.) were both about threefold higher in the wild type/mutated (52.1 ± 7.6 p M and 7.3 ± 1.3 n M (n=19), respectively) compared to wild type/wild type (14.7 ± 0.9 p M and 2.5 ± 0.1 n M (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long-term treatment, both gastrin and chromogranin A were high (88 p M and 13.7 n M, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long-term treatment, compared with the corresponding wild type/wild type (n=49) group (147 ± 19 μg/L vs. 193 ± 12 μg/L, P=0.04).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusion:Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long-term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual’s capacity to metabolize omeprazole.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0878
    Keywords: Enterochromaffin-like cells ; Ultrastructure ; Hypertrophy ; Hypergastrinaemia ; Gastrin infusion ; Omeprazole ; Rat (Sprague Dawley) ; Syrian hamster ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present report describes the ultrastructure of the enterochromaffin-like (ECL) cells in the stomach of the rat, hamster and guinea pig, and the ultrastructural consequences of long-term hypergastrinaemia evoked either by continuous infusion of synthetic human (Leu15)-gastrin-17 for 4 weeks (rats) or by daily treatment with large doses of the antisecretory agent omeprazole for 2–10 weeks (rats, hamsters and guinea pigs). As a result, the ECL cells increased greatly in size (maximal effect after 2 weeks of omeprazole treatment, no further gain in size after 4 or 10 weeks). Also the endoplasmic reticulum and Golgi area were enlarged. The most conspicuous feature of the ECL cells is the cytoplasmic vesicles, which are of varying size and either devoid of a dense core or with a small, often eccentrically located dense core. The vesicles probably represent the main storage site of the secretory products of the ECL cell. In addition, the cytoplasm contains granules, which differ from the vesicles in that they possess a more or less electron-dense core, surrounded by a narrow halo. The size of the vesicles ranged from small to very large, while the granules were uniformly small. Many vesicles were seen to lie very close together, some displaying an irregular outline (vacuole-like vesicles), at times giving the impression that they were undergoing fusion. The profile size (median value) of the vesicles was unaffected by gastrin infusion for 4 weeks. However, there was a tendency to a relative increase in the number of very small vesicles. In contrast, the vesicles became larger during the omeprazole treatment. Also, the number of vesicles that seemed to be engaged in fusion increased after omeprazole treatment but not after gastrin infusion. The observations support the view that ECL cells are influenced by gastrin. The effects of gastrin infusion and of omeprazole treatment on ECL cell ultrastructure were not completely identical. It cannot be excluded that the omeprazole-evoked achlorhydria evokes effects unrelated to those of hypergastrinaemia on the ECL cells, or that endogenous gastrins may evoke effects that are in some ways distinct from those of synthetic human (Leu15)-gastrin-17. Alternatively, the additional effects seen after long-term omeprazole treatment may reflect simply the duration of the hypergastrinaemic stimulus.
    Type of Medium: Electronic Resource
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