The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

Background@#Benzo(a)pyrene (BaP) is a carcinogenic compound in contaminated foodstuffs.The effect of oral intake of the environmental carcinogen BaP under low doses and frequent exposure on a digestive system has not been thoroughly verified. @*Methods@#In this regard, this study was conducted to prove the toxicity effects of BaP on the stomach and colon tissue after exposure to C57BL/6 mouse (3 and 6 µg/kg) following daily oral administration for 60 days. This study investigated acute gastric mucosal injury, severe gastric edema, cell infiltration, and mononuclear cells, multifocal cells, and tumoral inflammatory cells. @*Results@#The results of ELISA showed that the expression of serum interleukin (IL)-6 and tumor necrosis factor-α in the BaP exposure group were significantly increased, and a high level of DNA adduct distribution in their stomach and colon. Moreover, this study has confirmed the expression of early carcinogenesis markers: nuclear factor (NF)-κB, p53, IL-6, superoxide dismutase 1 (SOD1), mucin (MUC1 and MUC2), and β-catenin in the stomach and colon, and showed that there was a significant increase in IL-6, NF-κB, SOD1, β-catenin, and MUC1 (P< 0.05). At the same time, there was a significant decrease in MUC2 and p53 (P < 0.05). Thus, even in low doses, oral intake of BaP can induce DNA damage, increasing the potential risk of gastrointestinal cancer. @*Conclusion@#This study will provide a scientific basis for researching environmental contaminated food and intestinal health following daily oral administration of BaP.

Potential Moracin M Prodrugs Strongly Attenuate Airway Inflammation In Vivo

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPSinduced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

A study on the ecosystem of welfare technology using social economy: a case study of dental clinics in health welfare social cooperative / 대한구강보건학회지

OBJECTIVES: In this study, we strived to determine the possibility of socioeconomic welfare in oral healthcare by analyzing the National Health Insurance (NHI) coverage rate. To date, efforts to realize the “social economy” of healthcare are active. While oral disease is common and chronic among Koreans, the rate of NHI coverage of dental clinics is substantially lower than that of the medical clinics. METHODS: We defined the NHI coverage of dental clinics as a proxy for “social skills” to improve oral health problems. The data were collected through a comparative analysis of the NHI coverage of dental clinics and that of non-dental clinics, in health welfare social cooperatives. RESULTS: The NHI coverage rate of the dental clinics in health welfare social cooperatives ranged from 0.97 to 2.62 times that of the non-dental clinics in health welfare social cooperatives. CONCLUSIONS: In conclusion, responsible management is recommended for making health welfare social cooperatives meaningful as a social economy.

Can a dual-energy computed tomography predict unsuitable stone components for extracorporeal shock wave lithotripsy?

PURPOSE: To assess the potential of dual-energy computed tomography (DECT) to identify urinary stone components, particularly uric acid and calcium oxalate monohydrate, which are unsuitable for extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: This clinical study included 246 patients who underwent removal of urinary stones and an analysis of stone components between November 2009 and August 2013. All patients received preoperative DECT using two energy values (80 kVp and 140 kVp). Hounsfield units (HU) were measured and matched to the stone component. RESULTS: Significant differences in HU values were observed between uric acid and nonuric acid stones at the 80 and 140 kVp energy values (p or =90%, calcium oxalate dihydrate group: monohydrate<90%). Significant differences in HU values were detected between the two groups at both energy values (p<0.001). CONCLUSIONS: DECT improved the characterization of urinary stone components and was a useful method for identifying uric acid and calcium oxalate monohydrate stones, which are unsuitable for ESWL.

Prediction of Nuclear Targeting Proteins with Nuclear Localization Signals in Staphylococcus aureus and Nuclear Targeting of beta-lactamase in Host Cells

Nuclear targeting of bacterial proteins in host cells and subsequent interaction with nuclear molecules are an emerging pathogenic mechanism of bacteria. In this study, we predicted the nuclear targeting proteins with nuclear localization signals (NLSs) in Staphylococcus aureus using bioinformatic analysis. A total of 51 proteins of S. aureus, comprising of 24 functional and 27 hypothetical proteins, were predicted to carry putative NLSs. Among them, beta-lactamase and MsrR proteins with the putative NLSs were selected to determine the nuclear targeting in host cells. Fusion proteins of BlaZ-green fluorescent protein (GFP) were evenly distributed in the nuclei of host cells and subsequently induced host cell death. However, fusion proteins of MsrR-GFP were not localized in the nuclei of host cells In conclusion, screening of nuclear targeting proteins with NLSs and determination of their pathology in host cells may open up the new field of S. aureus pathogenesis.

Effect of Low-Dose Triple Therapy Using Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug for Overactive Bladder Symptoms in Patients With Bladder Pain Syndrome / 대한배뇨장애요실금학회지

PURPOSE: Patients with bladder pain syndrome/interstitial cystitis (BPS/IC) can have pain as a main symptom and overactive bladder (OAB) symptoms that are directly or indirectly related to a major mechanism that causes pain. The primary purpose of this study is firstly to identify the prevalence rate of OAB symptoms in patients with BPS/IC, secondly to identify changes in OAB symptoms after low-dose triple therapy, and thirdly to build a theoretical foundation to improve quality of life for patients. METHODS: Patients who met the inclusion criteria of BPS/IC through basic tests including the O'Leary-Sant symptom index, overactive bladder symptom score (OABSS), and visual analog scale (VAS) were identified. Treatment-based changes in OAB symptoms were identified using the IC Symptom Index and IC Problem Index (ICSI/ICPI), OABSS, and VAS before, and 4 and 12 weeks after low-dose triple therapy. RESULTS: The patients consisted of 3 men and 20 women, and their mean age was 61.9 years (41.0-83.2 years). Comparing values before treatment, and 4 and 12 weeks after treatment (baseline vs. 4 weeks to baseline vs. 12 weeks), the rates of improvement were as follows: ICSI, 44.2% to 63.7%; ICPI, 46.9% to 59.4%; OABSS, 34.3% to 58.2%; and VAS, 53.6% to 75.0%, which showed statistically significant differences (P0.05). CONCLUSIONS: Low-dose triple therapy in BPS/IC results in a clear decrease in OAB symptoms in the first 4 weeks after treatment, and additional treatment for 8 weeks had a partial effect with varied statistical significances depending on the questionnaires.

Prevalence and associated factors of nonalcoholic fatty liver disease in the health screen examinees / 대한내과학회지

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a kind of most common hepatic disease having wide pathologic spectrum and has been increasingly recognized as an important disorder because it may progress to end stage of liver disease. In spite of several foreign reports about clinical aspects of NAFLD, there are not enough reports analyzing large group for long times in Korea. We have examined the prevalence and associatd factors for NAFLD in health screen examinees from January 1997 to June 2003. METHODS: The results of 29,781 health screen examinees were analyzed retrospectively. Prevalence of alcoholic and nonalcoholic fatty liver was computed and associating factors were analyzed statistically. RESULTS: Overall prevalence of NAFLD was 18.6% and higher in the groups of age over 50 years. NAFLD was more preponderant in male. Age, body mass index, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, and abnormal serum low density lipoprotein, high density lipoprotein, ALT level were independently associated factors with presence of NAFLD in logistic regression analysis. CONCLUSIONS: The prevalence of NAFLD and tendency of associated factors were similar to Western world. To prevent development of this common hepatic disorder which may results in end stage liver disease, prevention and control of obesity, diabetes, hyperlipidemia must be important.

A Case of Triple Cancers of the Esophagus, Stomach and Duodenum / 대한소화기내시경학회지

Multiple primary cancer is defined as the multiple occurrence of malignant neoplasm in the same individual. The incidence of multiple primary cancer is 0.26~1.43% in Korea, but this malady is increasing due to development of diagnostic modalities, the treatment of cancer and the recording of accurate cancer statistics. The most common site of multiple primary cancer in Korea is the stomach, colon, breast, cervix, liver and lung. We report here on a case of triple cancer that was located at the middle esophagus, stomach and duodenum in 75 year-old man.

Abnormal Electron Microscopic Findings of Nonalcoholic Steatohepatitis and Related Factors / 대한소화기학회지

BACKGROUND/AIMS: In spite of increasing interests about nonalcoholic steatohepatitis (NASH), there are few reports about the ultrastructure of hepatocyte in this disease. The aim of this study was to clarify abnormal electron microscopic (EM) findings and related factors in NASH. METHODS: Total of fourteen patients who underwent liver biopsy due to steatohepatitis were included. Precise personal history was taken and variable blood tests such as liver function test, lipid profile, and serum iron study were done. Pathologic examination with light and electron microscopy was done by single pathologist. RESULTS: Eleven men and three women were included and mean age was 33.7+/-12.8 years. Nine patients drinking less than 40 g/week was grouped as "NASH group" and other 5 patients drinking more than 40 g/week and body mass index less than 25 was grouped as "ASH (Alcoholic Steatohepatitis) group". Polymorphism of mitochondria such as megamitochondria or loss of cristae was major abnormal EM findings and was more common in "NASH group" than "ASH group" (p=0.027). There was no significant clinical or pathological factors related with the presence of these abnormal EM findings. CONCLUSIONS: Polymorphism of mitochondria is major abnormal EM finding of steatohepatitis and is more common in NASH than ASH. And there is no significant clinical or pathological factors which could predict the presence of these abnormal EM findings.

Efficacy of Hepatic Arterial Infusion Therapy for Advanced Hepatocellular Carcinoma Using 5-Fluorouracil, Epirubicin and Mitomycin-C / 대한소화기학회지

BACKGROUND/AIMS: Prognosis of advanced hepatocellular carcinoma (HCC) treated by conventional therapies has been considered to be poor. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using FEM (5-fluorouracil, epirubicin, mitomycin-C) regimen for advanced HCC. METHODS: Eighteen patients received repeated HAIT using an implanted drug delivery system. Of the 18 patients, 8 patients had HCC with portal vein tumor thrombosis, 9 patients had recurrent HCC after transarterial chemoembolization (TACE) and 1 patient after surgical resection. The patients received 5-fluorouracil (330 mg/m2, every week), epirubicin (30 mg/m2, every 4 weeks) and mitomycin-C (2.7 mg/m2, every 2 weeks). RESULTS: Mean age was 51 years. The response rate (complete response+partial response) by tumor size on abdominal CT was 38.9%. Survival ranged from 2 to 24 months and the median survival time was 8 months. The cumulative survival rate of responders group was significantly higher than non-responders group (p=0.0385). The mean levels of serum alpha-FP and PIVKA-II in responders group decreased after HAIT (3,179 ng/mL and 2,850 ng/mL) than before (11,218 ng/mL and 4,396 ng/mL), but not significantly. Chemotherapy-related side effects were nausea, vomiting and alopecia. Three patients had catheter-related complications. One patient developed gastric ulcer. CONCLUSIONS: HAIT using FEM regimen is a useful therapeutic option for patients with advanced HCC with portal vein tumor thrombosis or ineffective response to other therapies.

Antioxidant Status in Nonalcoholic Steatohepatitis / 대한간학회지

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is chronic liver disease that can potentially progress to end stage liver disease. Oxidative stress to the vulnerable fatty liver has been reported as a key mechanism in development of NASH. Several antioxidant pathways have been identified, but reports that involved quantitative analysis of each antioxidant systems are rare, and these reports have shown various results. So, we investigated antioxidant status and the degree of oxidative stress by measuring several antioxidant enzymes, the total antioxidant status (TAS), and the metabolites of superoxide in NASH patients. METHODS: Nineteen NASH patients who were confirmed by liver biopsy and fifteen controls were involved in this study. The levels of body mass index (BMI), AST, ALT, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, TAS, hydrogen peroxide (H2O2), and malondialdehyde (MDA) were compared between both groups. The relationship between the histologic severity and the levels of each antioxidants were analyzed in the NASH group. RESULTS: The activities of SOD and catalase were lower in the NASH group. The concentrations of TAS and H2O2 were higher in NASH group. The level of GPx and MDA showed no significant differences between both groups. There were no significant relationships between the above variables and the pathological severity. CONCLUSIONS: The disturbed metabolism of superoxide due to the decreased activities of SOD and catalase seem to be important in the pathogenesis of NASH. Further investigations about the nonenzymatic secondary antioxidant mechanism are necessary because the TAS was higher for the NASH group. The lack of difference between both groups for the concentration of MDA indicates that mechanisms other than lipid peroxidation also may be important in the pathogenesis of NASH.

The Efficacy of Hepatic Arterial Infusion Therapy for Advanced Hepatocellular Carcinoma according to Extrahepatic Collateral Feeding Vessels / 대한간학회지

BACKGROUND/AIMS: Despite the poor response rate of 20-30%, hepatic arterial infusion therapy (HAIT) has been often tried for advanced hepatocellular carcinoma with portal vein tumor thrombosis or ineffective response to other treatments. The factors that predict treatment response to HAIT remain unclear. This study ascertained the response rate to HAIT based on the existence of extrahepatic collateral feeding vessels or anatomical variants. METHODS: Forty one patients received repeated HAIT using an implanted drug delivery system. Of the 41 patients, 18 patients were treated with 5-FU, epirubicin and mytomycin-C; 17 patients were treated with 5-FU and cisplatin; and 6 patients were treated with 5-FU, cisplatin and leucovorin. The patients were divided into two groups according to the existence of extrahepatic collateral feeding vessels or anatomical variants. RESULTS: Of the 41 patients, 10 patients (24.4%) showed a complete response (CR) or partial response (PR). Of 41 patients, 22 patients (group A) did not have extrahepatic collateral feeding vessel or an anatomical variant, but 19 patients (group B) did. In group A, 10 patients (45.5%) had a treatment response (CR+PR). However, only one patient (5.3%) had a treatment response (CR+PR) in group B. The response rate in group A was significantly higher than that in group B (45.5 vs. 5.3%; P=0.005). The median survival of group A was significantly longer than that of group B (10.8 vs 3.4 months, P=0.031). CONCLUSIONS: Hepatic arterial infusion therapy may be useful therapeutic option for patients with advanced HCC, especially in those that do not have extrahepatic collateral feeding vessel or anatomical variant.

Factors Associated or Related to with Pathological Severity of Nonalcoholic Fatty Liver Disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been more and more often regarded as a serious disorder, because nonalcoholic steatohepatitis (NASH), a part of NAFLD, may progress to the end stage of liver disease. Though an advanced age, obesity, diabetes mellitus (DM) etc. being not infrequent conditions in Korea, are known to exacerbate the severity of this disease, there are only a few Korean reports on this subject. The purpose of this study is to identify possible factors that might add up to the pathological severity of this disorder in Korean patients. METHODS: Of 60 patients with steatosis found at liver biopsy, 43 NAFLD patients were reviewed retrospectively after exclusion of other liver diseases. RESULTS: The cases of steatosis were mild, moderate, and severe in 9, 10, and 24 patients, respectively. The degree of necroinflammatory activity was mild, moderate, and severe in 33, 9, and 1 patients, respectively. There were no established factors directly related to these classes. As to fibrosis, the cases were classified as none, mild, moderate, severe, and cirrhotic in 9, 11, 16, 7, and 0 patients, respectively. The stage of fibrosis correlated with the age (p< 0.001), BMI (body mass index) (p=0.032), and the platelet count (p=0.009), but the presence of NASH was associated only with BMI (p=0.002) and obesity (p=0.001). CONCLUSION: It seems that there are no factors that are directly related to the degree of steatosis or necroinflammatory activity. BMI seems to be a unique factor directly related to both the severity of fibrosis and the presence of NASH. The age and the platelet count are factors that are directly related to the degree of fibrosis but not to the presence of NASH.

A case of primary hepatic angiosarcoma: Report of a case and review of previous Korean cases / 대한내과학회지

Primary hepatic angiosarcoma, which is malignant tumor originated from endothelial cell of vessel, is rare condition and is found at only one of fifty thousand autopsy cases. Six cases of hepatic angiosarcoma have been reported in Korea. Two of them were thought as be metastasized from spleen and other four were primary. In spite of foreign reports that lung and spleen is frequent metastatic sites of this tumor, metastatic case had not been reported in Korea yet. So we report a case of primary hepatic angiosarcoma presenting as hemoptysis and metastasized to lung and spleen with review of previously reported cases.

The Difference in Success Rate of Endoscopic Stent Insertion with or without Fluoroscopic Guidance / 대한소화기내시경학회지

BACKGROUND/AIMS: Sometimes, the endoscopic stent insertion may be done without fluoroscopic guidance. This study was performed to evaluate the difference in success rate of endoscopic stent insertion with or without fluroscopic guidance. A total of hundred and sixty three patients with upper gastrointestinal obstruction were included. METHODS: The group I comprised 82 patients in which the stent insertion was done without fluoroscopy. The group II included 81 patients in which stent was inserted under the fluoroscopy. RESULTS: The locations of obstruction are at esophagus and cardia (group I /group II, 44/40 patients), at pylorus and duodenum (15/34 patients) and at post-operative stenosis of gastro-jejunal anastomosis (23/7 patients). The statistical difference of success rate were not found between the two groups [79/82 (96.3%) in group I, 80/81 (98.2%) in group II, p=0.620]. Among group I, three patients (3.7%) were failed due to incomplete guidewire insertion. These patients were the two cases of jejunal stenosis of esophago-jejunal anastomosis and one case of duodenal obstruction with carcinomatosis peritonei. However, in these cases, the stents were successfully inserted under the fluoroscopic guidance. CONCLUSION: The success rate of the endoscopic stent insertion with or without the fluoroscopic guidance is not different. But in cases of inaccurate guidewire insertion, especially in patients with pyloric obstruction, the endoscopic stent insertion under the fluoroscopic guidance may be more safe and successful.

A Case of Primary Small Cell Carcinoma in the Common Bile Duct / 대한소화기학회지

Extrapulmonary primary small cell carcinoma comprises approximately 4% of all small cell carcinoma. In the common bile duct, small cell carcinomas are extremely rare. We experienced a 60-year-old woman with small cell carcinoma arising in the common bile duct. Abdominal CT scan revealed an intraluminal mass in the proximal common bile duct and multiple lymphadenopathies. Microscopic examination of the tumor revealed proliferation of small monotonous anaplastic cells, which were characterized with hyperchromatic nuclei, high nuclear to cytoplasmic ratio, and frequent mitosis. By immunohistochemical stain, the tumor cells were strongly positive for chromogranin, synaptophysin, and CD56. We report this case with a review of literatures.

Esophageal Mucosal Desquamation with Hemorrhage in Bullous Pemphigoid: A Case Report / 대한소화기학회지

Bullous pemphigoid is a subepidermal blistering skin disease, usually occurred in the elderly. It is an autoimmune disease associated with circulating autoantibodies directed against structural components of hemodesmosome. Rarely, it can involve the esophagus, which can be complicated by upper gastrointestinal hemorrhage. We report a case of bullous pemphigoid with esophageal mucosal desquamation and hemorrhage in patient with chronic renal failure.

Efficacy of Hepatic Arterial Infusion Therapy for Advanced Hepatocellular Carcinoma Using 5-fluorouracil and Cisplatin / 대한간학회지

BACKGROUND/AIMS: There has been no standard treatment for advanced hepatocellular carcinoma (HCC) until now. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using 5-fluorouracil (5-FU) and cisplatin (CDDP) for advanced HCC. METHODS: Twenty patients received repeated HAIT using an implanted drug delivery system. Of the 20 patients, eight patients had HCC with portal vein tumor thrombosis (PVTT), eleven patients had residual tumor despite transcatheter arterial chemoembolization (TACE) or percutaneous ethanol injection therapy (PEIT), and one patient had multiple recurrent HCC nodules after surgical resection. The patients were repeatedly treated with an arterial infusion of 5-FU (250 mg/5 hours on day 1-5) and CDDP (10 mg/1 hour on day 1-5) via the drug delivery system at three weekly intervals. RESULTS: Of the 20 patients, three patients were excluded from the study due to death within the first 1 week of treatment or during follow-up before evaluation. The response rate according to tumor size on abdominal CT was 29.4% (5 patients). One of the five patients showed a complete response (CR, 5.9%), three patients showed partial responses (PR, 17.6%), and one patient showed a minor response (MR, 5.9%). Chemotherapy- related side effect, such as grade I-II nausea (n=2), grade II vomiting (n=1), fever (n=1), drug eruption (n=1) and catheter-related complication such as dislodgement of the catheter (n=2), occurred in six patients. CONCLUSIONS: HAIT using the FP regimen is another option for patients having advanced HCC with PVTT or for patients showing an ineffective response to other therapies.

Gastric metaplasia and Helicobacter pylori infection of duodenal mucosa in duodenal ulcer / 대한내과학회지

BACKGROUND: The roles of gastric metaplasia and Helicobacter pylori (H. pylori) infection of duodenal mucosa in the pathogenesis of duodenal ulcer has been emphasized. Though there are a few reports which compared degree of these two risk factors between the duodenal ulcer and control groups, the reports which compared ulcer site with nonulcer site within ulcer group are rare. The aim of this study was to compare the frequencies of gastric metaplasia and H. pylori infection between both sites within ulcer group, as well as between both groups. METHODS: The active duodenal ulcer patients group (n=30) and control group (n=31) were selected. The frequency of gastric metaplasia and H. pylori infection were compared among the ulcer sites, the nonulcer sites of ulcer patients, and the intact duodenal mucosa of controls. RESULTS: The frequencies of gastric metaplasia and H. pylori infection were higher at ulcer sites than nonulcer sites within ulcer group, however, there were no differences between the nonulcer sites of ulcer group and control group. Positivities of H. pylori infection at metaplastic area were not different at 3 compared sites. CONCLUSION: It seems that duodenal ulcer develop more frequently at area of gastric metaplasia infected by H. pylori. However, further evaulation about the pathogenesis of duodenal ulcer is necessary because there are lots of duodenal ulcer cases which are not accompanied by gastric metaplasia.

A Case of Duodenal Perforation during Endoscopic Hemostasis in EST Site Bleeding / 대한소화기내시경학회지

The endoscopic retrograde cholangiopancreatography (ERCP) has become a commonly performed endoscopic procedure in biliary pathology. ERCP is a relatively safe procedure. however, there are chance of potentially severe complications; pancreatitis, hemorrhage, infection, and perforation. Duodenal perforation, uncommon but severe complication of ERCP, occurred in less than 1% of most series. According to the related mechanism, anatomical location, and the severity of injury, three to four distinct types of perforations have been described. We experienced the barotrauma associated duodenal perforation during endoscopic hemostasis in patient with EST site bleeding. This duodenal perforation was related with excessive air inflation to maintain the patency of a lumen. Endoscopists performing ERCP should bear in mind that continued air inflation may lead to duodenal perforation.