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BACKGROUND: Systematic assessments of the onset of symptom relief in the treatment of gastroesophageal reflux disease (GERD) are lacking. OBJECTIVE: This work evaluated the time interval until complete symptom relief from heartburn (including both daytime and nighttime heartburn) and acid regurgitation in patients with GERD or endoscopy-negative GERD (NERD) during the first 7 days of treatment with pantoprazole, nizatidine, or ranitidine. METHODS: This was a post hoc reanalysis of data from 2 previously published, multicenter, randomized, double-blind, active-controlled, parallel-group studies. Male and female patients aged >or=18 years with endoscopically proven GERD or NERD (Hetzel-Dent grade >or= [trial 1] or Savary-Miller grade 0 or 1 [trial 2]) were enrolled. Patients were required to have had reflux symptoms for the previous >or=3 months, with >or=1 symptom (ie, daytime heartburn, nighttime heartburn, or acid regurgitation) for >or=4 of the past 7 days in trial 1 or >or=1 symptom (ie, heartburn, acid eructation, or painful swallowing) of at least moderate intensity for the past 3 days in trial 2. The treatments were pantoprazole 20 mg once daily in both trials, nizatidine 150 mg BID in trial 1, or ranitidine 150 mg BID in trial 2. Presence and severity of symptoms were recorded on daily diary cards using a 4-point Likert-type scale. RESULTS: In total, 114 patients from trial 1 and 307 patients from trial 2 were evaluable for heartburn, and 58 patients from trial l and 271 patients from trial 2 were evaluable for acid regurgitation. In both studies, there were no significant differences in baseline characteristics between pantoprazole recipients and nizatidine or ranitidine recipients, with the exception of more men than women in trial 1 compared with trial 2 (P < 0.001). On day 2 of trial 1, 23 (39.0%) and 8 (14.5%) of pantoprazole and nizatidine recipients, respectively, experienced complete relief from heartburn (P < 0.01). The differences between groups remained statistically significant through day 7, when 28 (47.5%) and 8 (14.5%) of pantoprazole and nizatidine recipients had no heartburn (P < 0.001). There were no differences in control of acid regurgitation over 7 days with pantoprazole compared with nizatidine or ranitidine, except at days 2 and 4 of trial 1, when significantly more patients receiving pantoprazole experienced relief from acid regurgitation than those receiving nizatidine (day 2: 60.6% [n = 20] vs 20.0% [n = 5], P < 0.01; day 4: 48.5% [n =16] vs 24.0% [n = 6], P < 0.05). CONCLUSION: In this post hoc reanalysis of data from 2 previously published clinical trials, use of pantoprazole 20 mg once daily was associated with effective early relief from heartburn and acid regurgitation among these patients with GERD and NERD; relief occurred as fast as and, in some cases, even faster than that seen with nizatidine or ranitidine. [ABSTRACT FROM AUTHOR]

In lung fibroblasts, proliferation is inhibited by activation of EP2 prostanoid receptors which are known to couple to adenylyl cyclase. Beside the classic target of cAMP, protein kinase A (PKA), alternative cAMP effectors have been identified, among them Epac (exchange protein activated by cAMP). The present study aimed to illuminate transduction pathways mediating the anti-proliferative effects of EP2 receptors in lung fibroblasts. Proliferative activity of human lung fibroblasts was determined by measuring [3H]-thymidine incorporation. The selective EP2 receptor agonist butaprost inhibited [3H]-thymidine incorporation by 75%, an effect mimicked by forskolin, the phosphodiesterase inhibitor IBMX, the stable cAMP analogues dibutyryl-cAMP and bromo-cAMP, as well as by the Epac selective cAMP analogues 8-pCPT-2′- O-Me-cAMP and Sp-8-pCPT-2′- O-Me-cAMPS, whereas the PKA selective agonist 6-Bnz-cAMP was inactive. The PKA inhibitor Rp-8-Br-cAMPS inhibited butaprost-induced phosphorylation of CREB (cAMP response element-binding protein), but did not affect butaprost-induced inhibition of [3H]-thymidine incorporation. Partial knockdown of Epac1 by specific siRNA transfection resulted in a marked attenuation of the inhibitory potency of butaprost, whereas transfection of Epac2 siRNA or non-silencing siRNA did not affect the effectiveness of butaprost to inhibit [3H]-thymidine incorporation. In conclusion, Epac1 rather than the classic cAMP effector PKA is a crucial element in the signal transduction pathway mediating anti-proliferative effects of EP2 receptor activation. [ABSTRACT FROM AUTHOR]

Sufficient luminal distension is mandatory for small bowel imaging. However, patients often are unable to ingest volumes of currently applied oral contrast compounds. The aim of this study was to evaluate if administration of low doses of an oral contrast agent with high-osmolarity leads to sufficient and diagnostic bowel distension. Six healthy volunteers ingested at different occasions 150, 300 and 450 ml of a commercially available oral contrast agent (Banana Smoothie Readi-Cat, E-Z-EM; 194 mOsmol/l). Two-dimensional TrueFISP data sets were acquired in 5-min intervals up to 45 min after contrast ingestion. Small bowel distension was quantified using a visual five-grade ranking (5 = very good distension, 1 = collapsed bowel). Results were statistically compared using a Wilcoxon-Rank test. Ingestion of 450 ml and 300 ml resulted in a significantly better distension than 150 ml. The all-over average distension value for 450 ml amounted to 3.4 (300 ml: 3.0, 150 ml: 2.3) and diagnostic bowel distension could be found throughout the small intestine. Even 45 min after ingestion of 450 ml the jejunum and ileum could be reliably analyzed. Small bowel imaging with low doses of contrast leads to diagnostic distension values in healthy subjects when a high-osmolarity substance is applied. These findings may help to further refine small bowel MRI techniques, but need to be confirmed in patients with small bowel disorders. [ABSTRACT FROM AUTHOR]