Peroxisome proliferator-activated receptor gamma ligands exert antineoplastic effects in hepatocellular carcinoma cells / 대한내과학회지

BACKGROUND/AIMS: Thiazolidinediones, which are synthetic insulin sensitizers, are known activators of peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma ligands, including endogenous 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), are thought to elicit antineoplastic effects in various cancer cells. In this study, the antineoplastic effects of PPARgamma ligands against hepatocellular carcinoma (HCC) cells were investigated. METHODS: HepG2, Hep3B, and PLC/PRF5 cells were cultured with troglitazone (TGZ), pioglitazone (PGZ), rosiglitazone (RGZ), or 15d-PGJ2 at concentrations of 20-100 micrometer. Cell viability, cell cycle arrest, apoptosis, and caspase activity were measured using the MTT assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and colorimetric assays, respectively. The effects of various caspase inhibitors were also measured using a cell death detection ELISA. RESULTS: All three cell lines expressed the PPARgamma gene. TGZ and 15d-PGJ2 strongly inhibited growth in HepG2, Hep3B, and PLC/PRF5 cells. In contrast, PGZ and RGZ showed a much weaker effect in all cell lines. In terms of cell cycle arrest and apoptosis, TGZ induced G0/G1 arrest in HepG2 cells and increased the apoptotic fraction in Hep3B and PLC/PRF5 cells. In contrast, 15d-PGJ2 induced apoptosis only in HepG2 and Hep3B cells. TGZ and 15d-PGJ2 increased caspase-3 activity significantly and increased caspase-9 activity slightly. TGZ- and 15d-PGJ2-induced apoptoses were inhibited by a pancaspase inhibitor (Z-VAD-FMK) and a caspase-3 specific inhibitor (Z-DEVD-FMK) in a dose-dependent manner. CONCLUSIONS: TGZ and 15d-PGJ2 elicit antineoplastic effects in various HCC cells via caspase-dependent apoptotic induction. Their differential effects on similar cell types suggest that another antineoplastic mechanism, most likely a PPARgamma-independent pathway, is involved.

Comparison of Real-Time Quantitative PCR with Northern Hybridization for Quantification of CgCDR1 and CgCDR2 Gene Expression in Candida glabrata / 대한의진균학회지

BACKGROUND: One of main mechanisms responsible for acquired azole resistance of Candida glabrata is the increased drug efflux mediated ABS transporters, which are encoded by CgCDR1 and CgCDR2 genes. OBJECTIVES: We compared real-time reverse transcriptase PCR (RT-PCR) with northern hybridization for quantitative analysis of CgCDR1 and CgCDR2 expression in bloodstream isolates of C. glabrata. METHODS: Nineteen blood isolates of C. glabrata were selected, including nine fluconazole susceptible (MIC < or =8 microgram/ml), nine susceptible dose-dependent (S-DD, MIC 16~32 microgram/ml), and one resistant (MIC 128 microgram/ml), isolates. The expression of CgCDR1 and CgCDR2 was quantified using real-time RT-PCR with ROTOR Gene 3000 (Corbettet research, Austria). The results were compared with northern hybridization with sequence-specific probes. RESULTS: Correlation of quantification results between real-time RT-PCR and northern hybridization yielded correlation coefficients of 0.92 for CgCDR1 and 0.82 for CgCDR2 gene. By both methods, no significant differences were observed in the levels of expression of CgCDR1 and CgCDR2 between fluconazole-susceptible isolates and S-DD isolates. In contrast, a strain with high fluconazole resistance (MIC 128 microgram/ml) revealed a greater abundance of CgCDR1 by both methods, compared to the other isolates. Conclusion: This study show that real-time PCR method for C. glabrata RNA quantification correlates well with traditional northern hybridization and can be a valuable alternative to northern hybridization for rapid quantification of CgCDR1 and CgCDR2 genes in clinical isolates of C. glabrata.

Extrahepatic Biliary Schwannomas: A Case Report

Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature.

The Role of Smoking as a Risk Factor in Inflammatory Bowel Diseases: Single Center Study in Korea / 대한소화기학회지

BACKGROUND/AIMS: Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study. METHODS: Prevalence of smoking at the time of IBD diagnosis were compared between CD and UC patients in Kyung-Hee Medical Center with healthy general population at age-, gender-, and time period-adjusted rates. We investigated the smoking status of IBD patients at the time of diagnosis by telephone interview. There were 178 IBD patients (98 UC patients and 80 CD patients) between January 1995 and December 2004. RESULTS: The male to female ratio in CD and UC were 2:1 and 1:1.4, respectively. The onset of age was 28.2 years and 38.8 years, respectively. The prevalence of smoking was significantly lower in CD and UC patients than in the general population (CD; odds ratio 0.21, 95% confidence interval 0.12-0.41, p<0.001, UC; odds ratio 0.06, 95% confidence interval 0.03-0.14, p<0.001). After statistical adjustment for gender and age at the diagnosis of IBD, the odds ratio of a current smoker diagnosed as UC was 73% lower than that of CD (adjusted odds ratio 0.27, 95% confidence interval 0.12-0.59, p<0.001). In contrast, being a former smoker showed a risk of approximate 1.27-fold higher likelihood of having UC diagnosis (adjusted odds ratio 1.27, confidence interval 0.41-3.95, p=0.68). CONCLUSIONS: Cigarette smoking is protective against developing UC at any age, but is not associated with the development of CD in Korean population. Former smoking is not the high risk factor in developing UC.

A Comparison of the Effect of High-dose Oral and Intravenous Proton Pump Inhibitor on the Prevention of Rebleeding after Endoscopic Treatment of Bleeding Peptic Ulcers / 대한소화기내시경학회지

BACKGROUND/AIMS: The use of proton pump inhibitor (PPI) prevents rebleeding by elevating the intragastric pH in patients with bleeding peptic ulcers after hemostasis has been achieved. We assessed if high-dose oral pantoprazole is as effective as high-dose intravenous pantoprazole for their ability to prevent rebleeding after having achieved initial hemostasis in patients with active bleeding or nonbleeding visible vessels. METHODS: Thirty eight patients with bleeding peptic ulcers who had achieved initial hemostasis were enrolled in this randomized controlled trial. In the high-dose oral pantoprazole group (n=19), 40 mg of pantoprazole was given orally twice daily for 5 days. In the high-dose intravenous pantoprazole group (n=19), an 80 mg intravenous bolus of pantoprazole was given; this was followed by 8 mg/hour of continuous infusion daily for 3 days. Thereafter, 40 mg of pantoprazole was given orally once daily for 8 weeks. RESULTS: The two groups were similar with respect to all the background variables. Rebleeding occurred in 2 patients (10.5%) in the intravenous group and in 1 patient in the oral group (5.3%) by day 30 after enrollment (p=1.000). There was no significant difference in terms of the number of therapeutic endoscopic sessions (1 vs. 1.13+/-0.52), the surgery (0% vs. 0%), the bleeding related mortality (0% vs. 0%), and the mean number of units of transfused blood. CONCLUSIONS: The high-dose oral pantoprazole is as effective as an intravenous administration in reducing rebleeding episodes in patients with bleeding peptic ulcers after successful endoscopic therapy.

A Pure Case of Gastric Carcinoid Tumor Presented with Intestinal Pseudoobstruction / 대한소화기내시경학회지

Clinical significance and prevalence of gastric carcinoid tumor are considerably rising. This is reflective of both their increased identification, with the widespread availability of upper gastrointestinal endoscopy, as well as the development of immunohistochemical study. The improvements in survival rates of gastric carcinoid tumor indicate an ability to develop optimal therapeutic strategies and regimens. Usually, the recommended treatment is surgical or endoscopic excision of the tumor. We experienced a case of intestinal pseudoobstruction combined with gastric carcinoid tumors in a 45 year-old man. He was successfully treated with endoscopic polypectomy.

A Case of Metformin-associated Lactic Acidosis / 대한신장학회잡지

A 76-year-old female admitted with nausea, anorexia, vague abdominal pain, and malaise. Her past medical history included an 15-year history of type 2 diabetes mellitus and hypertension. She had been taking metformin, glipizid, and amlodipine for past 2 years. One week previously, she underwent gastroscopy to evaluate epigastic pain, and she was diagnosed Helicobacter pylori positive duodenal ulcer, for which she was treated with amoxicillin, clarithromycin, and omeprazole. At admission, laboratory test revealed lactic acidosis (pH 7.23, bicarbonate 8.3 mEq/L, and lactate 5.51 mmol/L) and acute renal failure with a serum creatinine of 7.4 mg/dL. We diagnosed meformin-associated lactic acidosis and the patient made a complete recovery following therapy with bicarbonate-based hemodialysis and supportive care. It is the first report of metformin-associated lactic acidosis in Korea.

Etiology and Clinical Consequence of Spontaneous Acute Exacerbation of Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: Acute exacerbation (AE) of chronic hepatitis B (CHB) can occur spontaneously, and may be followed by HBeAg clearance. HBeAg seroconversion often coincides with the normalization of liver biochemical tests and clinical remission. The purpose of this study was to identify the etiology and the clinical consequence of severe AE in Korean patients with CHB. METHODS: The medical records of CHB patients with severe AE (defined by the sudden increase of ALT above 400 IU/L) who were admitted to Kyung Hee University Hospital between January 1992 and December 2001, were reviewed retrospectively. Forty-four patients were included in the severe AE group. RESULTS: The most common etiology of severe AE was spontaneous exacerbation (77%). Drugs (16%), alcohol (5%), and HCV coinfection (2%) were suspected of causing AE in the remaining patients. HBeAg seroconversion at 12, 18, and 24 months following severe spontaneous AE was 18.5%, 40.7%, and 48.1%, respectively. These were significantly higher compared to CHB patients without AE (4.3%, 4.3%, and 10.9%, respectively). Seroconversion within 3 months, however, occurred in only 15% of CHB patients with AE. There was a tendency to progress to liver cirrhosis more frequently in the patients with AE as compared to the patients without AE (17.6% vs. 5.5%, P<0.08). CONCLUSIONS: Severe AE in patients with CHB is mainly caused by spontaneous exacerbation. Although HBeAg seroconversion occurs frequently in these patients, the rates are relatively low compared to those reported in other countries and early seroconversion is expected only in a small proportion. Further studies will be warranted to determine the efficacy of the early use of antiviral agents at the time of AE.

Relationship between Esophageal Lesions Observed by Endoscopy and Nasogastric Intubation: A Study of 185 Cases of Percutaneous Endoscopic Gastrostomy / 대한소화기학회지

BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy (PEG) is a method widely used for long-term enteral nutrition in dysphagia. Mostly, it is preceded by nasogastric intubation (NI) for short-term enteral nutrition; endoscopic findings associated with NI are encountered during PEG. The purpose of this study was to discuss such findings and to delineate a relationship between these findings, especially esophageal lesions and the duration of NI. METHODS: This study involved 185 individuals who had undergone PEG at Kyung Hee Medical Center from January 1999 to May 2002. The medical records were examined retrospectively. RESULTS: The dysfunction of the CNS comprised 98.4% of the causes of dysphagia. The duration of NI was 15.2 weeks on average, with median value of 8.7 weeks, indicating that PEG was performed relatively soon. Endoscopic findings revealed esophagitis in 63 cases, esophageal ulcers in 27 and active bleedings in another 10. The incidence of esophageal lesions was shown to be higher in subjects with duration of NI under 12 weeks than in those with duration over 12 weeks (p=0.032). CONCLUSIONS: PEG was carried out in many cases during the early stages of dysphagia, and NI-associated esophageal lesions appeared to be more prevalent within 12 weeks of NI duration. These results may be of help in deciding the timing of PEG.