Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway

Walter W Chan,Hiroshi Mashimo 대한소화기 기능성질환∙운동학회 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.3

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.

AIDS와 법 : 홍콩의 예

Chan Walter 대한에이즈예방협회 1998 레드리본 Vol.24 No.-

Differential role of endothelium in hawthorn fruit extract-induced relaxation of rat cerebral, coronary, carotid, and aorta

Chan, Hoi Yun,Chen, Zhen-Yu,Yao, Xiaoqiang,Lau, Chi-Wai,Zhang, ZeSeng,Ho, Walter Kwok Keung,Huang, Yu Kyung Hee Oriental Medicine Research Center 2002 Oriental pharmacy and experimental medicine Vol.2 No.2

The present study was aimed to examine the role of endothelium in the relaxant effect of hawthorn fruit extract of Crataegus pinnatifida in four different types of rat arteries, posterior cerebral communicating artery, right descending coronary artery, common carotid artery, and aorta. In $9,11-dideoxy-11{\alpha}$, $9{\alpha}-epoxy-methanoprostaglandin$ $F_{2{\alpha}}$ (U46619)-preconstricted arterial rings except for aorta, the extract produced endothelium-independent relaxations with similar potency. This relaxation was unaffected by pretreatment with $100\;{\mu}M\;N^G-nitro-L-arginine$ methylester (L-NAME, the nitric oxide synthase inhibitor), $3\;{\mu}M$ 1H-[l,2,4]oxadiazolo$[4,2-{\alpha}]$quinoxalin-1-one (ODQ, the guanylate cyclase inhibitor), or $10\;{\mu}M$ indomethacin (the cyclooxygenase inhibitor). Putative $K^+$ channel blockers (charybdotoxin plus apamin or glibenclamide) did not affect the extract-induced relaxation in cerebral or coronary artery rings. In contrast, in rat aortic rings the extract produced significantly smaller relaxant response in endothelium-denuded rings than that in endothelium-intact rings. Pretreatment with L-NAME or ODQ abolished the extractinduced endothelium-dependent aortic relaxation, whilst indomethacin $(3\;{\mu}M)$ had no effect. The present results indicate that hawthorn fruit extract possesses a vasorelaxing effect in cerebral, coronary and carotid arteries and this effect is independent of the presence of a functional endothelium. However, the extract-induced endothelium-dependent relaxation in rat aorta was mediated through endothelial nitric oxide and cyclic GMP-dependent mechanisms, suggesting that active components in the extract may act on endothelium to stimulate release of nitric oxide in large conduit arteries of the rats.

Determining the Safety and Effectiveness of Electrocautery Enhanced Scissors for Peroral Endoscopic Myotomy (with Video)

Kelly E. Hathorn,Walter W. Chan,Hiroyuki Aihara,Christopher C. Thompson 대한소화기내시경학회 2020 Clinical Endoscopy Vol.53 No.4

Background/Aims: Peroral endoscopic myotomy (POEM) has recently come to the forefront in the management of achalasia. Weaimed 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 foregutanatomy 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 Eckardtscore 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 participatedin 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 meanpost-Eckardt score was 1.3±1.3, which indicated a significant improvement (p≤0.0001). The most common treatment-related adverseevents 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 andclinical efficacy as well as an excellent safety profile.

A Prospective Blinded Study of Endoscopic Ultrasound Elastography in Liver Disease: Towards a Virtual Biopsy

Allison R. Schulman,Ming V. Lin,Anna Rutherford,Walter W. Chan,Marvin Ryou 대한소화기내시경학회 2018 Clinical Endoscopy Vol.51 No.2

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.

Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis

( Lawrence F Borges ),( Vikrant Jagadeesan ),( Hilary Goldberg ),( Sravanya Gavini ),( Wai-kit Lo ),( Robert Burakoff ),( Natan Feldman ),( Walter W Chan ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.3

Background/Aims Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in prelung transplant IPF patients. Methods This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes. Results Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380). Conclusion Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients. (J Neurogastroenterol Motil 2018;24:395-402)