Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice.

BACKGROUND: Sphingolipids play a very important role in cell membrane formation, signal transduction and plasma lipoprotein metabolism. The first rate-limiting step in the sphingolipid biosynthetic pathway is catalyzed by serine palmitoyltransferase (SPT), and myriocin is a potent and specific inhibitor of SPT. We investigated the impact of SPT inhibition on cholesterol gallstone formation in C57BL/6J mice. METHODS: Three groups of eight-week-old C57BL/6J mice were utilized. Each group consisted of 20 mice; group A, B, and C were fed normal chow, lithogenic diet with phosphate buffered saline, and lithogenic diet with myriocin (0.3 mg/kg), respectively, for 6 weeks. The ceramide levels in both serum and bile were assessed by high performance liquid chromatography analysis. Protein expression of ERK, JNK and p38 in the extracted gallbladder were determined by Western-blot analysis. RESULTS: Myriocin treatment caused a significant decrease in the rate of cholesterol gallstone formation. The lithogenic diet mice (group B) showed the highest ceramide activities in both the serum and bile among all the tested groups and there was significant suppression of the ceramide levels in both the serum and bile of the myriocin-treated mice (group C, p < 0.05). Phosphorylation of p38 in the gallbladder was increased in the lithogenic-diet mice and the expression of phosphorylated p38 was significantly suppressed in the myriocin treated mice. CONCLUSIONS: SPT inhibition by myriocin suppressed gallstone formation and the levels of ceramide in both the serum and bile. p38 in the cellular signaling pathways might be associated with cholesterol gallstone formation.

[Critical reappraisal of cholecystectomy in patients with asymptomatic gallstones for early diagnosis and removal of dysplasia and cancer].

BACKGROUND/AIMS: It has been known that chronic trauma and inflammation of gallbladder (GB) mucosa by gallstones (GS) can induce epithelial dysplasia, carcinoma in situ, and invasive cancer. This study was designed to investigate the usefulness of cholecystectomy in patients with asymptomatic GS for the early diagnosis and removal of dysplasia or cancer. METHODS: From January 2004 to July 2008, the clinical records of 703 cases with GS who underwent cholecystectomy at Korea University Guro Hospital were reviewed, and the prevalence of dysplasia and cancer was analyzed. RESULTS: In symptomatic GS (542 cases) group, low grade dysplasia was found in 4 cases (0.74%) and high grade dysplasia in 1 case (0.18%). In asymptomatic GS (161 cases) group, low grade dysplasia was found in 4 cases (2.48%) and cancer in 2 cases (1.24%) (p=0.012 vs. symptomatic cases). Dysplasias in symptomatic GS group were not associated with polyps, but dysplasias and cancers in asymptomatic GS group were associated. Patients with asymptomatic GS and polyps were analyzed according to the size of polyps. In those (12 cases) with larger polyps (> or 1 cm), low grade dysplasia was found in 2 cases and cancer in 2 cases. And in those (12 cases) with smaller polyps (<1 cm), low grade dysplasia was found in 2 cases. CONCLUSIONS: Extending indication of prophylactic cholecystectomy in patients with asymptomatic GS without polyp to prevent GB dysplasia or cancer beyond the existing indication does not seem to be justifiable in Korea. However, further studies are needed in patients with asymptomatic GS and polyp of any size.

Cellulase production from Pseudoalteromonas sp. NO3 isolated from the sea squirt Halocynthia rorentzi.

Pseudoalteromonas sp. NO3 was isolated from the hemolymph of diseased sea squirts (Halocynthia rorentzi) with symptoms of soft tunic syndrome. The strain was found to produce an extracellular cellulase (CelY) that consisted of a 1,476 bp open reading frame encoding 491 amino acid residues with an approximate molecular mass of 52 kDa. Homologies of the deduced amino acid sequence of celY with the products of the celA, celX, celG and cel5Z genes were 92.6, 93.3, 92.6, and 59.1%, respectively. Additionally, CelY had 50-80% remnant catalytic activity at temperatures of 10-20 degrees C. Highest carboxymethyl cellulose (CMC) hydrolysis was observed at pH 8.0 and 40 degrees C. CMC activity was determined by zymogram active staining and different degraded product profiles for CelY were obtained when cellotetraose, cellopentaose, and CMC were used as substrates. This study identified a transglycosylation activity in CelY that allows the enzyme to digest G4 to G2 and G3 without the production of G1.

[A prospective multicenter study on the prevalence and symptoms of erosive reflux esophagitis in secondary and tertiary hospitals in Korea].

BACKGROUND/AIMS: Recent studies suggest that the prevalence of erosive esophagitis (EE) is increasing in Asia. The aims of this study were to determine the prevalence of EE among outpatients visiting gastroenterology clinics of secondary and tertiary hospitals in Korea, and to analyze their symptoms. METHODS: From May to July 2003, outpatients undergoing their first upper gastrointestinal endoscopies after visiting gastroenterology clinics in secondary and tertiary hospitals in Korea were enrolled. Prevalence of EE was calculated from their endoscopic findings, and symptoms were analyzed from the validated symptom questionnaire. RESULTS: Among 4,275 cases from 24 hospitals, 506 (11.8%) had EE. Among 836 cases with predominantly typical GERD symptoms, EE was diagnosed in 140 (16.7%). Among 530 cases having predominantly typical GERD symptoms with a frequency of at least twice a week or with a significant impact on their daily lives, EE was found in 104 (19.6%). The prevalence of EE was positively associated with males irrespective of age, old aged (> or =65 years) females, predominantly typical GERD symptoms at least twice a week, and the numbers of typical GERD symptoms. The severity of GERD symptoms did not affect the prevalence of EE. The most common typical and atypical GERD symptoms in cases with EE were regurgitation and epigastric soreness, respectively. CONCLUSIONS: The prevalence of EE among outpatients visiting gastroenterology clinics in Korea was 11.8%. Independent factors associated with increased prevalence of EE were males irrespective of age, old aged (> or =65 years) females, number of typical GERD symptoms, and frequent typical GERD symptoms.

[Prevalence of pancreatic cancer in diabetics and clinical characteristics of diabetes-associated with pancreatic cancer--comparison between diabetes with and without pancreatic cancer].

BACKGROUND/AIMS: In Korea, the prevalence of pancreatic cancer (PC) in general population has been reported as 7 in 100,000. However, that in diabetes mellitus (DM) has not been elucidated yet. This study was designed to estimate the prevalence of PC among DM patients, and characterize and compare the patients with DM with and without PC. METHODS: 5,082 patients (4,890 DM without PC, 78 PC with DM, and 114 PC without DM) were enrolled from Korea University Guro Hospital during a period of 4 years between January 2004 and January 2008. RESULTS: The prevalence of PC in DM patients was 1.6% and that of DM in PC patients was 40.6%. No significant differences in the clinical characteristics except HbAIc and ALP were observed between PC patients with DM and without DM. Among 78 PC patients with DM, DM was diagnosed in 19 (29.4%) and 29 (37.1%) patients concomitantly or within 2 years prior to the diagnosis of PC, respectively. Among the cases with recent onset DM (less than 2 years duration), the disease duration of DM before the diagnosis of PC was less than 1 year in 14 patients (17.9%) and 1 to 2 years in 15 patients (19.2%). DM patients with PC were found to have significantly higher ALT, total bilirubin, and ALP levels than in DM patients without PC. CONCLUSIONS: The prevalence of PC in DM patients was 1.6% and was higher than in the general population. Recent onset DM was frequent in PC patients (less than 2 years duration). We recommend close follow-up for at least 2 years in new-onset diabetes.