Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito.

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides--adonioside A (1) and adonioside B (6)--as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3).

Neolignans from the fruits of Magnolia obovata and their inhibition effect on NO production in LPS-induced RAW 264.7 cells.

Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2-hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2), isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated from the fruits of Magnolia obovata using silica gel and ODS column chromatography. From the results of spectroscopic data including EIMS, IR, 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were determined. All isolated compounds were evaluated for inhibition activity on nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7, and 9 showed significant activity with IC50 values of 15.8 ± 0.3, 3.3 ± 1.2, 14.1 ± 0.9, 6.2 ± 1.2, 14.8 ± 2.3, 14.2 ± 1.2, and 14.8 ± 3.2 µM, respectively, without any visible toxic effect.

A new phenanthrene derivative and two diarylheptanoids from the roots of Brassica rapa ssp. campestris inhibit the growth of cancer cell lines and LDL-oxidation.

Brassica rapa ssp. campestris (Brassicaceae) is a conical, deep purple, edible root vegetable commonly known as a turnip. We initiated phytochemical and pharmacological studies to search for biological active compounds from the roots of B. rapa ssp. campestris. We isolated a novel phenanthrene derivative, 6-methoxy-1-[10-methoxy-7-(3-methylbut-2-enyl)phenanthren-3-yl]undecane-2,4-dione, named brassicaphenanthrene A (3) along with two known diarylheptanoid compounds, 6-paradol (1) and trans-6-shogaol (2), through the repeated silica gel (SiO2), octadecyl silica gel, and Sephadex LH-20 column chromatography. The chemical structures of the compounds were determined by spectroscopic data analyses including nuclear magnetic resonance, mass spectrometry, ultraviolet spectroscopy, and infra-red spectroscopy. All compounds exhibited high inhibitory activity against the growth of human cancer lines, HCT-116, MCF-7, and HeLa, with IC50 values ranging from 15.0 to 35.0 µM and against LDL-oxidation with IC50 values ranging from 2.9 to 7.1 µM.

Expression of MUC5AC and Trefoil Peptide 1 (TFF1) in the Subtypes of Intestinal Metaplasia.

BACKGROUND/AIMS: Alterations of the expression pattern of mucins and trefoil peptides have been described in gastric adenocarcinomas and in their precursor lesions. The aim of this study was to determine the progression patterns of intestinal metaplasia (IM) subtypes by analyzing the expression patterns of TFF1 and MUC5AC in different subtypes of IM of the stomach. METHODS: Endoscopic gastric biopsies of the antrum and body were obtained from patients with dyspepsia and endoscopic IM. Alcian blue/periodic acid-Schiff staining and the high iron diamine technique were used to classify the subtypes of IM. Immunoreactivity for MUC5AC and TFF1 was estimated in different types of IM. RESULTS: IM was detected in 128 samples from 80 patients; type I was found in 48 samples, type II was found in 37 samples, and type III was found in 43 samples. There was a gradual decrease in MUC5AC and TFF1 expression during the progression of IM from type I to type III via the type II intermediate. CONCLUSIONS: This downregulation of MUC5AC and TFF1 expression may challenge the sequential progression of IM from type I to type III via the type II intermediate, and it might be associated with gastric carcinogenesis.

Increased incidence of gastric cancer in renal transplant recipients.

OBJECTIVE: The risk of malignancy after transplantation is regarded to be higher than in the general population. The aim of this study was to evaluate the frequency of gastric cancer in renal transplant recipients. METHODS: A total of 820 renal transplantation recipients were invited for gastric cancer screening. Frequencies of gastric cancer in this cohort and in 10,080 asymptomatic subjects were compared. Cancer specimens were examined for Epstein-Barr virus by in situ hybridization. RESULTS: A total of 509 recipients (mean age, 48.1 ± 10.7 y; men, 56.8%) participated. Fifteen (2.9%) and 10 (0.1%) cases of adenocarcinoma were identified among recipients and controls, respectively (P<0.001; odds ratio, 30.58). Early gastric cancer was detected in 9 of the 15 recipients, and 4 of the 9 were treated by endoscopic resection. Recipient age was found to be a significant factor of gastric cancer development. In cancer tissues, Epstein-Barr virus was detected in 5 (33.3%) renal recipients and in 1 (10%) of the controls, respectively. CONCLUSIONS: The frequency of gastric cancer was found to be higher in renal recipients than in controls. Gastric cancer screening should be considered after transplantation, because it would provide cure by minimally invasive treatment.

Long-term prognosis of an endoscopically treated rectal neuroendocrine tumor: 10-year experience in a single institution.

BACKGROUND AND AIM: The endoscopic techniques for treating a small rectal neuroendocrine tumor (NET) are performed in most large centers; however, the endoscopic management of this condition is not well established. This study was designed to determine the long-term prognosis of endoscopically resected NET. METHODS: We prospectively studied patients with endoscopically treated rectal NET in Seoul St Mary's hospital, between January 2000 and June 2010. The long-term outcomes were analyzed in association with the pathological complete resection and resection procedures. RESULTS: Seventy-seven patients (48 men and 29 women; mean age, 52.3 years; range, 23-77 years) were included. The average NET size was 7.0±2.8 mm (range, 3-16 mm). There was no procedure-related complication. En-bloc removal was achieved for all lesions, and the rate of histological complete resection was 75.3% (58/77). Histological complete resection rates were 71.4% (10/14) by conventional endoscopic mucosal resection (EMR), 74.1% (43/58) by a two-channel EMR, and 100.0% (5/5) by endoscopic submucosal dissection (ESD). Among six patients with incomplete histological resection, two underwent additional EMR, two underwent transanal endoscopic microsurgery, and two underwent low anterior section with lymph node dissection. The remaining 13 patients with 'possible' remnant NET underwent regular endoscopic surveillance without additional resection. In the latter group, only one patient had local recurrence, detected on regular colonoscopic surveillance, after 56 months and was treated with additional EMR. All of the patients are alive and 98.7% (76/77) of the patients are free from disease during the follow-up periods. CONCLUSION: Endoscopic resection is a safe and effective modality and may potentially be used for the treatment of NETs smaller than 15 mm in diameter, those confined to the submucosal layer, and those without metastasis. Local treatment was believed to be curative in cases with complete histological resection. In addition, this treatment may have an excellent prognosis in patients with 'possible' remnant NET.

Bioactive 3,4-seco-Triterpenoids from the Fruits of Acanthopanax sessiliflorus.

Eight new 3,4-seco-lupane triterpenes and glycosides, acanthosessiligenins I and II (1, 3) and acanthosessiliosides A-F (2, 4-8), as well as six known 3,4-seco-lupane triterpenes (9-14) were isolated from an ethanolic extract of Acanthopanax sessiliflorus fruits. The chemical structures of 1-8 were determined by spectroscopic data interpretation. All isolated compounds were tested for their cytotoxicity against six human cancer cell lines and their ability to inhibit LPS-induced nitric oxide production in RAW 264.7 macrophages.

Performance and cost of disposable biopsy forceps in upper gastrointestinal endoscopy: comparison with reusable biopsy forceps.

BACKGROUND/AIMS: It is believed that disposable biopsy forceps are more costly than reusable biopsy forceps. In this study, we evaluated performance and cost of disposable forceps versus reusable forceps in esophagogastroduodenoscopic biopsy. METHODS: Between October 2009 and July 2010, we enrolled 200 patients undergoing esophagogastroduodenoscopic biopsy at Seoul St. Mary's Hospital. Biopsies were performed with 100 disposable or 5 reusable forceps by random assignment. Seventy-five additional patients were studied to estimate durability of reusable forceps. The assisting nurses estimated the performance of the forceps. The evaluation of costs included purchase prices and reprocessing costs. The adequacy of the sample was estimated according to the diameter of the obtained tissue. RESULTS: Performance of disposable forceps was estimated as excellent in 97.0%, good in 2.0% and adequate in 1.0%. Reusable forceps were estimated as excellent in 36.0%, good in 36.0%, adequate in 25.1% and inadequate in 2.9%. The performance of reusable forceps declined with the number of uses. The reprocessing cost of reusable forceps for one biopsy session was calculated as ₩8,021. The adequacy of the sample was excellent for both forceps. CONCLUSIONS: Disposable forceps showed excellent performance. Considering the reprocessing costs of reusable forceps, usage of disposable forceps with a low price should be considered.

Maximizing field-effect mobility and solid-state luminescence in organic semiconductors.

Conductive and emissive: organic transistors made from a simple styrylanthracene derivative have high charge mobility and high luminescence quantum yields. These properties are attributed to the lack of singlet fission, and challenge the idea that the efficient π interactions required for high mobility always lead to quenching of emission. The transistors emit blue electroluminescence and are stable during operation and storage.

The effect of exenatide and erythromycin on postprandial symptoms and their relation to gastric functions.

BACKGROUND: The relationship between abnormal gastric motor function and postprandial abdominal symptoms has not been fully clarified. The aim of the study was to investigate this relationship in response to mediators that affect gastric function. METHODS: Ten healthy volunteers participated in a 3-way cross-over study of treatment with placebo, exenatide and erythromycin. The studies were performed at 1-week intervals. Each subject underwent 3-dimensional single photon emission computed tomography to measure fasting and postprandial gastric volumes. A combined nutrient drink test and cutaneous electrogastrography (EGG) were performed on the next day. RESULTS: Erythromycin reduced postprandial symptoms compared with placebo. The postprandial gastric volume after exenatide was greater than after placebo and erythromycin treatment. Exenatide did not aggravate postprandial symptoms compared with placebo. The ratio of postprandial over fasting gastric volume was inversely correlated with the total postprandial symptom score after placebo, exenatide and erythromycin treatment. The postprandial symptom score of the normal EGG group was significantly lower than that of the abnormal group, considering overall treatments. CONCLUSIONS: Erythromycin reduced postprandial symptoms, whereas exenatide did not aggravate postprandial symptoms, possibly due to its enhancement of gastric accommodation. An abnormal EGG rhythm was associated with postprandial symptoms.

Endoscopic submucosal dissection of gastric neoplasia involving the pyloric channel by retroflexion in the duodenum.

BACKGROUND: Tumors involving the pyloric channel have been considered as difficult lesions for successful endoscopic resection. We studied the feasibility of endoscopic submucosal dissection (ESD) using retroflexion in the duodenum to resect the gastric neoplasia involving the pyloric channel. AIM: To compare the treatment outcomes of a new ESD technique using retroflexion to those without retroflexion in the duodenum. METHODS: Twenty-four cases of gastric neoplasia involving the pyloric channel were resected by ESD. In 14 cases, ESDs were performed from both the antrum and duodenal bulb using retroflexion (retroflexion group). In ten cases, ESDs were performed conventionally only from the side of the antrum (conventional group). We compared the outcomes between the two methods. RESULTS: There was no complication regarding retroflexion in the duodenum. In the retroflexion group, the en bloc and complete resection rate was 100%, respectively. The rate of complete resection was significantly higher in the retroflexion group than in the conventional group (P = 0.01). In the conventional group, three patients with early gastric cancer underwent additional subtotal gastrectomy for positive lateral margin, and one patient with perforation was treated additionally by surgical repair. In the retroflexion group, microperforation and pyloric channel stenosis occurred in one patient, which resolved with conservative treatment. CONCLUSIONS: Tumors involving the pyloric channel could be successfully resected by ESD using retroflexion in the duodenum without severe complication. This technique appears to be a feasible and effective method for the treatment of tumors involving the pyloric channel.

Prospective assessment of risk of bacteremia following colorectal stent placement.

BACKGROUND: Colorectal stent insertion is an invasive endoscopic procedure. However, there are no reports regarding the incidence of bacteremia with colorectal stent. OBJECTIVE: This study was to evaluate the risk of bacteremia and infectious complications after stent insertion for colorectal obstruction. METHODS: Patients who underwent colorectal stent insertion were enrolled consecutively. Blood cultures were obtained before colorectal stent insertion and at 30 min after the procedure. Patients were monitored for 48 h after colorectal stent insertion to detect the development of infectious complications. Procedural data collected included location of obstruction, degree of bowel preparation, obstructive symptoms, and the time required for the procedure. RESULTS: Of 64 patients undergoing colorectal stent, four (6.3%) had a positive post-stent blood culture. All patients, including those with positive cultures, remained asymptomatic during the 48 h after the procedure. Site of obstruction, degree of bowel preparation, age, and underlying disease were not different between the two groups. Development of bacteremia was associated with long procedure time (p < 0.05). CONCLUSIONS: Colorectal stent insertion does not induce significant bacteremia in patients with colorectal obstruction. These findings suggest that the routine use of prophylactic antibiotics may not be necessary in colorectal stent insertion.

Clinical outcome of self-expandable metal stent placement in the management of malignant proximal colon obstruction.

BACKGROUND/AIMS: There are limited data regarding the clinical outcomes of self-expandable metal stents in the treatment of proximal colon obstruction. We compared the clinical outcomes of stent placement in patients with malignant proximal to distal colon obstructions. METHODS: We reviewed medical records from 37 consecutive patients from three institutions (19 men; mean age, 72 years) who underwent endoscopic stent placement at a malignant obstruction of the proximal colon. We also examined the records from 99 patients (50 men; mean age, 65 years) who underwent endoscopic stent placement for a distal colon obstruction. Technical success, clinical improvements, complications and stent patency were compared between treatments. RESULTS: The technical success rate tended to be lower in stents inserted to treat proximal colon obstructions than in those used to treat distal colon obstructions (86% vs 97%, p=0.06). Clinical improvement was achieved in 78% of patients (29/37) with proximal colonic stenting and in 91% of patients (90/99) with distal colonic stenting (p=0.08). Complications (24% vs 27%), stent migration (8% vs 8%) and stent reocclusion rates (11% vs 17%) did not differ significantly between groups. Two cases of bowel perforation related to stenting (5%) occurred in patients with proximal colonic stenting. CONCLUSIONS: The technical success and clinical improvement associated with self-expandable metal stents used to treat proximal colon obstruction tend to be lower than cases of distal colon obstruction. Technical failure is an important cause of poor clinical improvement in patients with proximal colon stenting. Complication rates and stent patency appear to be similar in both groups.

Functional Gastrointestinal Disorders Diagnosed by Rome III Questionnaire in Korea.

BACKGROUND/AIMS: Rome criteria classifying functional gastrointestinal disorder (FGID) were updated. The aims of this study were to assess the spectra of FGID and to evaluate the applicability of Rome III criteria in Korea. METHODS: New patients who visited 2 primary clinics and 2 tertiary care hospitals were consecutively invited to complete questionnaires. These consisted of questionnaires for FGID based on Rome III criteria and symptom checklist-90-revised for somatization, depression and anxiety. RESULTS: A total of 786 patients was participated. Among them, FGID was observed in 49.7%. In the patients with FGID, functional dyspepsia was most common (46.0%) followed by irritable bowel syndrome (IBS, 40.2%). Functional dyspepsia was most common both in the primary care clinics and tertiary care hospitals. Postprandial distress syndrome was the most common subtype and the frequency of epigastric pain syndrome was low. There were few responders for constipation as Bristol types 1 and 2 and for diarrhea as types 6 and 7 in subtype classification using the Bristol Stool Form Scale. Thereby, unspecified IBS defined by stool form was unexpectedly common in 43.9% of IBS, whereas unspedified IBS defined by Rome III definition was 5.1%. Patients with overlap FGIDs had higher score of anxiety, depression or somatization. CONCLUSIONS: FGIDs were common both in primary care clinics and tertiary care hospitals of Korea. Overlap FGIDs is still common by Rome III criteria, which may limits its wide application.

Gastric fundic gland polyps and their relationship to colorectal neoplasia in Koreans: a 16-year retrospective study.

BACKGROUND/AIMS: There is an ongoing debate on the relationship between gastric fundic gland polyps and increased incidence of colorectal neoplasia in Caucasians. However, there was no report on the relationship between gastric fundic gland polyp and colorectal neoplasia in Korea. The aim of this study was to identify the characteristics of gastric fundic gland polyps and whether a relationship exists between fundic gland polyps and colorectal neoplasia in Korean population. METHODS: Persons who underwent an esophagogastroduodenoscopy and colonoscopy from 1992 to 2007 at the Health Promotion Center of Incheon St. Mary's Hospital, The Catholic University of Korea were reviewed retrospectively. The relationship between gastric fundic gland polyps and colorectal neoplasia were analyzed. RESULTS: Among 22,451 subjects, fundic gland polyps were found in 328 subjects (1.5%). Fundic gland polyps were more common in women than in men (odds ratio of 6.25; 95% CI of 4.68-8.34). The odds ratios for colorectal neoplasia in all subjects with gastric fundic gland polyps were 0.56 (95% CI of 0.33-0.95) and men who were 50 years of age or older had an odds ratio of 2.81 (95% CI of 1.03-7.66) as compared to the control group. However, age and sex-adjusted odds ratios for all gastric fundic gland polyps were 0.73 (95% CI of 0.42-1.26), for men 1.78 (95% CI of 0.80-3.98), and for women 0.37 (95% CI of 0.16-0.87). CONCLUSIONS: Surveillance colonoscopy in patients with fundic gland polyps can be performed in the same manner as general population in Korea.

[Steroid responsive pancreatic mass-forming type 2 autoimmune pancreatitis].

Autoimmune pancreatitis (AIP) has two distinct subsets. Type 1 AIP or lymphoplasmacytic sclerosing pancreatitis is systemic disease with the elevation in serum levels of the IgG4. Type 2 AIP, also called duct-centric pancreatitis, features granulocyte epithelial lesions with duct obstruction in the pancreas without systemic involvement. Here, we report a case of type 2 AIP diagnosed by pathology, which is the first report in Korea. The case is a 56-year-old woman who presented with anorexia and vomiting. Computed tomography revealed mass-like lesion in the pancreatic head and the compression of the distal common bile duct and the head portion of the main pancreatic duct. Serum levels of the IgG4 were normal. Histologic examination revealed a dense neutrophil infiltration in the pancreatic parenchyme associated with extensive fibrosis, thereby confirming the diagnosis of type 2 AIP. The abnormalities in the clinical, laboratory, and radiological findings improved after oral steroid treatment.

Anxiety, depression and quality of life in patients with irritable bowel syndrome.

BACKGROUND/AIMS: There have been few Asian studies regarding anxiety and depression associated with irritable bowel syndrome (IBS). The aim of this study was to evaluate the frequency and importance of anxiety and depression in Korean patients with IBS. METHODS: A total of 124 IBS patients and 91 healthy subjects were enrolled consecutively. All participants were asked to complete self-administered questionnaires: one addressing symptom severity, the Short Form 36, and the Hospital Anxiety and Depression Scale (HADS). The patients were also asked to complete the IBS-specifi c quality of life (IBS-QOL) questionnaire. RESULTS: Anxiety and depression were observed in 38.6% and 38.6% of IBS patients, respectively, and in 24.2% and 16.5% of healthy subjects, respectively (p<0.05 for both). The mean HADS scores for anxiety and depression in IBS patients were 6.8±4.5 and 7.1±4.4, respectively. Both anxiety and depression were associated with self-reported symptom severity (p<0.012 and p<0.001, respectively). As determined by multivariate analysis, symptom severity was the most important factor in the prediction of anxiety and depression. Self-reported symptom severity and depression were clearly and independently associated with the overall IBS-QOL score. CONCLUSIONS: Anxiety and depression were frequently observed in Korean IBS patients and were related to the severity of their symptoms and the impairment of the patient's QOL. Our data suggest that assessing anxiety and depression is important when evaluating IBS patients.

Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells.

For gastric cancers, the antineoplastic activity of cannabinoids has been investigated in only a few reports and knowledge regarding the mechanisms involved is limited. We have reported previously that treatment of gastric cancer cells with a cannabinoid agonist significantly decreased cell proliferation and induced apoptosis. Here, we evaluated the effects of cannabinoids on various cellular mediators involved in cell cycle arrest in gastric cancer cells. AGS and MKN-1 cell lines were used as human gastric cancer cells and WIN 55,212-2 as a cannabinoid agonist. Cell cycles were analyzed by flow cytometry and western blotting. Treatment with WIN 55,212-2 arrested the cell cycle in the G0/G1 phase. WIN 55,212-2 also upregulated phospho-ERK1/2, induced Kip1/p27 and Cip1/WAF1/p21 expression, decreased cyclin D1 and cyclin E expression, decreased Cdk 2, Cdk 4, and Cdk 6 expression levels, and decreased phospho-Rb and E2F-1 expression. ERK inhibitor decreased the proportion of G0/G1 phase which was induced by WIN 55,212-2. Inhibition of pAKT led to cell cycle arrest in gastric cancer cells. Cell cycle arrest preceded apoptotic response. Thus, this cannabinoid agonist can reduce gastric cancer cell proliferation via G1 phase cell cycle arrest, which is mediated via activation of the MAPK pathway and inhibition of pAKT.

Successful control of peristomal infection by introducer-type percutaneous endoscopic gastrostomy: a retrospective historical control study.

BACKGROUND: The techniques of percutaneous endoscopic gastrostomy are classified as the pull and introducer methods. Peristomal infection is the most common procedure-related complication in the pull method. OBJECTIVES: The objective of this study was to compare procedure-related complications between the two methods and to assess the outcome of long-term use of the introducer method. METHODS: Between January 1999 and November 2009, 116 patients received percutaneous endoscopic gastrostomy at Seoul St. Mary's Hospital in Korea. Before June 2006, the pull method was used for all patients; since then, every patient had been treated using the introducer method. We compared outcomes and complications within 180 days of gastrostomy placement for the two methods. RESULTS: The pull method was performed on 63 patients and the introducer method on 53 patients. The occurrence of peristomal infection within 30 days was significantly lower in the introducer method group than in the pull method group (1.9% vs. 36.5%, P = 0.001). Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the major organisms isolated from the peristomal infection. The requirement for catheter reinsertion because of displacement, obstruction, or damage to the catheter between 30 and 180 days was significantly higher in the introducer method group than in the pull method group (40.5% vs. 0%, P = 0.001). CONCLUSIONS: Our results suggest the superiority of the introducer method in terms of infection control. However, the balloon-type catheter is associated with problems such as balloon insufficiency in long-term use.