ABSTRACT
BACKGROUND: Nocturnal gastric acid breakthrough (NAB) is defined as nocturnal intragastric pH less than 4 for more than 1 h during proton pump inhibitor (PPI) administration. A bedtime dose of an H2 receptor antagonist (H2RA) inhibites NAB, but the efficacy of the H2RA decreases with continuous administration. We carried out the present study to investigate the effect of 14-day H2RA administration on NAB. METHODS: Ten male volunteers without Helicobacter pylori infection received four different 14-day regimens of rabeprazole and ranitidine (study a, morning dose of 20 mg rabeprazole; study b, morning dose of 20 mg rabeprazole with a single bedtime dose of 150 mg ranitidine only on the last day; study c, continuous 20 mg morning dose of rabeprazole and 150 mg at bedtime; study d, morning and evening doses of 10 mg rabeprazole). Ambulatory 24-h gastric pH monitoring was conducted on the last day of each regimen. RESULTS: NAB in studies a, b, c, and d was observed in 9, 1, 4, and 4 subjects, respectively, and the longest periods of nocturnal gastric pH at less than 4.0 were 102.5, 14.0, 37.5, and 52.5 min, respectively (study b vs study c, P<0.05). CONCLUSIONS: The continuous inhibitory effect of ranitidine combined with rabeprazole on nocturnal gastric acid secretion declined during 14-day-long administration in H. pylori-negative subjects. Split dosing of rabeprazole was more effective than the single morning dose for inhibiting nocturnal gastric acid secretion.
Subject(s)
Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Chronotherapy , Gastric Acid/metabolism , Helicobacter pylori/physiology , Ranitidine/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Cross-Over Studies , Drug Therapy, Combination , Humans , Male , Monitoring, Ambulatory , Omeprazole/analogs & derivatives , Rabeprazole , Reference ValuesABSTRACT
We investigated the frequency of BRAF mutations in human pancreatic cancer specimens to determine its role in the development of pancreatic cancer. Nine pancreatic cancer samples without a K-ras codon 12 mutation and 19 with a K-ras mutation were included in the study. Analyses of the BRAF sequence revealed mutations in exon 15 (V599E) in two cases, both of which also exhibited a K-ras codon 12 mutation. No BRAF mutation was found in cases without a K-ras mutation. The BRAF V599E mutation was not found to be a major mutation in pancreatic cancers that had no K-ras codon 12 mutation.
Subject(s)
Genes, ras/genetics , Mutation/genetics , Oncogene Proteins/genetics , Pancreatic Neoplasms/genetics , Adenocarcinoma/etiology , Adenocarcinoma/genetics , Adenocarcinoma, Mucinous/etiology , Adenocarcinoma, Mucinous/genetics , Aged , Aged, 80 and over , Carcinoma, Papillary/etiology , Carcinoma, Papillary/genetics , DNA Mutational Analysis , DNA Primers/chemistry , Female , Humans , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/etiology , Polymerase Chain Reaction , Proto-Oncogene Proteins B-raf , Survival Rate , Tumor Cells, CulturedABSTRACT
The location of calcitonin gene-related peptide (CGRP) receptors in the rat stomach has not been elucidated. It was recently reported that the CGRP receptor is formed when a calcitonin-receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 1 are co-expressed on the cell membrane. The aim of this study was to determine the location and the role of CGRP receptors in the rat gastric mucosa. Gene expressions of CRLR and RAMP1 were investigated by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. Immunohistochemical stainings for CGRP, somatostatin, gastrin, and chromogranin A were performed. Gastric endocrine cells were collected by counterflow-elutriation and their responses to CGRP were studied. CRLR and RAMP1 mRNA was expressed mainly in small gastric epithelial cells in the pyloric glands. The mRNA expression had a similar distribution to that of D cells. In cultured gastric endocrine cells, CGRP enhanced somatostatin production, while it inhibited the secretion of histamine and gastrin. Our results suggest that CGRP receptors are expressed in D cells in the rat gastric mucosa and control production and secretion of somatostatin.
