BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. METHODS: Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) +/- EP1 antagonist. Significance was established using Student t test and P < 0.05. RESULTS: Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 +/- 0.88 to 4.43 +/- 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 +/- 0.70 vs. 4.43 +/- 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 +/- 0.01 to 1.97 +/- 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. CONCLUSIONS: In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.
Alprostadil ; Animals ; Baths ; Chloride Channels ; Constipation ; Contracts ; Dinoprostone ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Intestinal Secretions ; Intestine, Small ; Isotonic Solutions ; Mice ; Muscle Tonus ; Muscle, Smooth ; Muscles ; Pylorus ; Receptors, Prostaglandin E ; Receptors, Prostaglandin E, EP1 Subtype ; Lubiprostone

BACKGROUND/AIMS: Liver biopsy has traditionally been used for determining the degree of fibrosis, however there are several limitations. Endoscopic ultrasound (EUS) real-time elastography (RTE) is a novel technology that uses image enhancement to display differences in tissue compressibility. We sought to assess whether liver fibrosis index (LFI) can distinguish normal, fatty, and cirrhotic liver tissue. METHODS: A total of 50 patients undergoing EUS were prospectively enrolled. RTE of the liver was performed to synthesize the LFI in each patient. Univariate and multivariable analyses were performed. Chi-square and t-tests were performed for categorical and continuous variables, respectively. A p-value of <0.05 was considered significant. RESULTS: Abdominal imaging prior to endoscopic evaluation suggested normal tissue, fatty liver, and cirrhosis in 26, 16, and 8 patients, respectively. Patients with cirrhosis had significantly increased mean LFI compared to the fatty liver (3.2 vs. 1.7, p<0.001) and normal (3.2 vs. 0.8, p<0.001) groups. The fatty liver group showed significantly increased LFI compared to the normal group (3.8 vs. 1.4, p<0.001). Multivariable regression analysis suggested that LFI was an independent predictor of group features (p<0.001). CONCLUSIONS: LFI computed from RTE images significantly correlates with abdominal imaging and can distinguish normal, fatty, and cirrhotic-appearing livers; therefore, LFI may play an important role in patients with chronic liver disease.
Adipose Tissue ; Biopsy* ; Elasticity Imaging Techniques* ; Endosonography ; Fatty Liver ; Fibrosis ; Humans ; Image Enhancement ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Prospective Studies* ; Ultrasonography*

Background/Aims: Peroral endoscopic myotomy (POEM) has recently come to the forefront in the management of achalasia. We aimed to analyze the efficacy and safety of the use of electrocautery enhanced scissors (EES) for POEM. Methods: This retrospective cohort study prospectively collected the data of all adult patients (aged ≥18 years) with normal foregut anatomy who underwent POEM using EES. The patients’ baseline characteristics and procedure details (time, tunnel length, myotomy length, depth, and location) were recorded. The primary outcome was clinical success (3-month post-procedure Eckardt score of ≤3). The secondary outcomes were technical success and adverse events. A paired Student’s t-test was performed. Results: Fifteen patients were included in this study. The technical success rate of myotomy using EES was 100%. Fellows participated in the myotomy in all cases. The clinical success rate was 93.3% (14/15). The mean pre-Eckardt score was 5.4±2.5, while the mean post-Eckardt score was 1.3±1.3, which indicated a significant improvement (p≤0.0001). The most common treatment-related adverse events were post-procedure pain (4, 26.7%) and symptomatic reflux disease (4, 26.7%). Conclusions In the largest series to date on the use of EES in POEM, we demonstrated that this technique has both technical and clinical efficacy as well as an excellent safety profile.