[Circadian monitoring of intragastric pH in evaluation of efficiency of antisecretory therapy of duodenal ulcer] Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers. Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue. Rx drugs

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Klin Med (Mosk). 2002;80(2):54-6.
[Circadian monitoring of intragastric pH in evaluation of efficiency of antisecretory therapy of duodenal ulcer]

[Article in Russian]

Kolesnikova IIu, Beliaeva GS, Bordin DS.

Inhibitors of proton pump are thought "golden standard" in the treatment of ulcer. Usage of omeprasol generics in standard doses sometimes fail to adequately reduce acid production. In pain persistence in patients with duodenal ulcer receiving standard antisecretory therapy it is effective to control it with 24-h intragastric pH-metry which either indicate the necessity of dose correction or another cause of pain (concomitant affections as a rule). As shown by 24-h pH-metry, a new generic of omeprasol, omeprus, is close by effectiveness to the known drug omeaz.

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Cancer. 2002 Jan 15;94(2):323-30.
Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers.

Sanso GE, Domene HM, Garcia R, Pusiol E, de M, Roque M, Ring A, Perinetti H, Elsner B, Iorcansky S, Barontini M.

Centro de Investgaciones Endocrinologicas, Hospital de Ninos R. Gutierrez, Buenos Aires, Argentina.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident. METHODS: Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families. RESULTS: Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases. CONCLUSIONS: The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed.

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J Pharm Pharmacol. 2002 Mar;54(3):341-7.
Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue.

Hopkins AM, McDonnell C, Breslin NP, O'Morain CA, Baird AW.

Department of Pharmacology, University College Dublin, Belfield, Ireland.

Triple therapy using proton-pump inhibitors (PPIs) in combination with oral antibiotics for the treatment of Helicobacter pylori-associated gastritis has shown increased efficacy for reasons that are still poorly understood. Possible explanations include a direct antibacterial effect of the PPIs or a PPI-mediated increase in bacterial susceptibility to antibiotics. Using an in-vitro model of rat gastric mucosa, we examined fluxes of a radiolabelled marker molecule through the interepithelial tight junctions under normal conditions and under the influence of an acid secretagogue (50 microM histamine) and a PPI (100 microM omeprazole). Paracellular fluxes of the radiolabel (represented by calculation of apparent permeability coefficients) were linear over 2 h. Fluxes of the marker increased significantly after treatment with histamine followed by omeprazole, but were unaltered in paired preparations exposed to the same drugs given in reverse order. Enhancements in paracellular permeability were mirrored in separate experiments using a detergent (Triton X-100), a bile salt (deoxycholate) and an agent that disrupts the cytoskeleton (cytochalasin D) to interfere with tight junctional integrity. The results suggest that exposure of acid-secreting gastric mucosa to omeprazole widens the interepithelial spacing in a manner that may facilitate enhanced macromolecular transport. Increases in antibiotic delivery from the blood to the gastric lumen via such a mechanism may account for the greater eradication rates observed with PPI-based triple therapy in H. pylori-associated gastritis.

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