Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats.

In this study, the hepatic expression of cytochrome P450 (CYP) enzymes, including CYP1A1/2, 2B1, 2C11, 2E1, 3A1/2, and 4A, was investigated in 5-week-old (insulinresistant state) and 11-week-old (diabetic) Zucker diabetic fatty (ZDF) rats. Serum glucose and glycated hemoglobin levels were increased in 11-week-old ZDF rats, but not in 5-weekold ZDF rats. Hyperinsulinemia was observed in both age groups. The microsomal protein, total CYP, CYP reductase, CYP1A1/2, and CYP3A1 levels did not differ between 5- and 11-week-old ZDF rats and their respective control rats, while CYP4A was up-regulated in both groups. Hepatic levels of cytochrome b5, CYP2B1, CYP2C11, CYP2E1, and CYP3A2 were decreased in 5-week-old ZDF rats, but not in 11-week-old ZDF rats. Similarly, pentoxyresorufin O-depentylase, testosterone 2α- and 16α-hydroxylase, chlorzoxazone 6- hydroxylase, and midazolam 1'- and 4-hydroxylase activities were decreased only in 5-weekold ZDF rats. Based on these results, the 5-week-old ZDF rats exhibited down-regulation of the major CYP enzymes. These results suggest that hepatic expression of CYP enzymes may be dysregulated during development in ZDF rats. With the exception of CYP2B1 and CYP4A, the hepatic levels and activities of CYP were comparable between 11-week-old ZDF and control rats, suggesting that xenobiotic metabolism is normally regulated in the early diabetic state.

Evaluation of the total oxidant scavenging capacity of saponins isolated from Platycodon grandiflorum.

The antioxidant activity of saponins isolated from Platycodon grandiflorum (PG; Balloon flower) was determined using the total oxidant-scavenging capacity (TOSC) assay. Platycodigenin, polygalacic acid, platycodin D, platycoside E and deapioplatycoside E were isolated and their structures were characterised based on their physical and spectral properties and by comparison of these results with similar data in the literature. Platycodin D showed the greatest TOSC value against peroxyl radicals, followed (in decreasing order) by polygalacic acid, platycodigenin, deapioplatycosides E and platycoside E. Although the TOSC value of the saponins against peroxyl radicals was less than that of glutathione (GSH) and Trolox used as positive controls. However, TOSC value of platycodigenin, deapioplatycoside E, platycodin D or platycoside E against peroxynitrite was 2.35-, 1.27-, 1.02- or 0.75-fold of GSH, respectively, while polygalacic acid exhibited no scavenging capacity of peroxynitrites. These results suggest importance of the presence of hydroxyl group at carbon 24 in platycodigenin in peroxynitrite scavenging. As the number of attached sugar residues in the saponin glycosides is increased, the scavenging capacity of peroxyl radical, but not peroxynitrite was significantly decreased. These results showed that PG saponins have potent antioxidant activities, which is different according to the structure of aglycones and the number of attached sugar residues.

Influencing factors for cure of clonorchiasis by praziquantel therapy: infection burden and CYP3A5 gene polymorphism.

Chemotherapy of clonorchiasis with praziquantel (PZQ) is effective but about 15% of treated cases have been reported uncured. The present study investigated correlation of single nucleotide polymorphisms (SNPs) of the cytochrome P450 gene, CYP3A5 and cure of clonorchiasis. A total of 346 egg passing residents were subjected and treated by 3 doses of 25 mg/kg PZQ. Reexamination recognized 33 (9.5%) uncured and 313 cured. Numbers of eggs per gram of feces (EPGs) before treatment were significantly lower in the cured group than in the uncured group (2,011.2±3,600.0 vs 4,998.5±7,012.0, P<0.001). DNAs of the subjects were screened for SNPs at 7 locations of CYP3A5 using PCR. In the uncured group, the SNP frequencies at g.-20555G>A and g.27526C>T of CYP3A5 were 15.2% and 9.1% while those were 3.8% and 1.0%, respectively, in the cured group. The cure rate was significantly lower in the cases with SNP at g.27526C>T and EPGs≥1,000. In conclusion, EPGs and SNPs of CYP3A5 are factors which influence cure of clonorchiasis by PZQ therapy. It is strongly suggested to recommend 2-day medication for individuals with high EPGs≥1,000.

Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut-off value in the screening population. METHODS: A consecutive 515 patients undergoing a routine health check-up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, (13)C-urea breath test, and serology) were positive. A stool antigen test (EZ-STEP H. pylori) was performed for the detection of H. pylori. The optimal cut-off value was determined by the receiver-operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the (13)C-urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6-95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. CONCLUSIONS: The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.

Visceral obesity and insulin resistance as risk factors for colorectal adenoma: a cross-sectional, case-control study.

OBJECTIVES: Colorectal adenoma is known to be associated with obesity, but the association between colorectal adenoma and visceral adipose tissue (VAT) area measured by abdominal computed tomography (CT) has not been documented clearly. In addition, the relationship between insulin resistance and colorectal adenomas, which underlies the mechanism that links obesity and colorectal adenoma, has not been studied extensively. The aim of this study was to examine VAT area and insulin resistance as risk factors of colorectal adenoma. METHODS: A cross-sectional, case-control study was conducted in Koreans that presented for health check-ups. Subjects underwent various laboratory tests, abdominal CT, and colonoscopy. VAT, subcutaneous adipose tissue (SAT), and homeostatic metabolic assessment (HOMA) index were evaluated as potential risk factors of colorectal adenoma in 2,244 age- and sex-matched subjects. RESULTS: According to univariate analysis, the prevalences of smoking, hypertension, metabolic syndrome, and family history of colorectal cancer were higher in the adenoma group than in the normal control group. In addition, body mass index, waist circumference, triglyceride, high-density lipoprotein cholesterol, and VAT and SAT areas were significantly different in the two groups. According to the multivariate analysis adjusted for multiple confounders, VAT area was independently associated with the risk of colorectal adenoma (odds ratio (OR)=3.09, 95% confidence interval (CI): 2.19-4.36, highest quintile vs. lowest quintile). Mean HOMA index was higher in the adenoma group than in the control group (OR=1.99, 95% CI: 1.35-2.92, highest vs. lowest quintile). CONCLUSIONS: Visceral obesity was found to be an independent risk factor of colorectal adenoma, and insulin resistance was associated with the presence of colorectal adenoma.

Clinical spectrum of reflux esophagitis among 25,536 Koreans who underwent a health check-up: a nationwide multicenter prospective, endoscopy-based study.

BACKGROUND: Gastroesophageal reflux is a commonly encountered condition, but detailed data on reflux symptoms in Asian countries are lacking. GOALS: To evaluate the prevalence and to document the clinical spectrum of endoscopic reflux esophagitis (RE). STUDY: A total 25,536 subjects underwent an upper gastrointestinal endoscopic examination as part of a health check, and completed a gastroesophageal reflux questionnaire. Endoscopic findings classified according to the Los Angeles (LA) classification and the data from gastroesophageal reflux questionnaire were analyzed. RESULTS: On the basis of endoscopic findings, 2019 subjects (7.91%) were found to have RE: 5.87% in LA-A; 1.84% in LA-B; 0.18% in LA-C; and 0.02% in LA-D. Heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough, and epigastric soreness were found to be associated with RE (P<0.05). Heartburn, acid regurgitation, and epigastric soreness were more frequent in LA-B than in LA-A (P<0.05). Epigastric soreness was most bothersome in LA-A and LA-B, and acid regurgitation was most bothersome in LA-C and LA-D (P<0.01). Heartburn, hoarseness, and globus sensation were more frequent in men with RE, and acid regurgitation was most common in women. CONCLUSIONS: The prevalence of RE was found to be 7.91% in Korea, and the profiles of reflux symptoms were found to depend on grade of RE and sex.

[Nonalcoholic fatty liver disease as a risk factor of cardiovascular disease: relation of non-alcoholic fatty liver disease to carotid atherosclerosis].

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is closely associated with abdominal obesity, dyslipidemia, hypertension, and Type 2 diabetes, which are all features of the metabolic syndrome. The aim of the present study was to elucidate whether NAFLD is associated with carotid atherosclerosis. METHODS: The study population comprised 659 subjects without hepatitis B and C infections and who did not consume alcohol. Fatty infiltrations of liver were detected by abdominal ultrasonography, and intima-media thickness (IMT) and plaque prevalence were estimated by carotid ultrasonography. RESULTS: The mean values of systolic and diastolic pressures, body mass index (BMI), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, fasting glucose, fasting insulin, homeostasis model of assessment (HOMA) index, hemoglobin A1c, and plasminogen activator inhibitor-1 differed significantly between patients with NAFLD (n=314) and normal controls (n=345). The carotid IMT was 0.817+/-0.212 (mean+/-SD) mm in patients with NAFLD and 0.757+/-0.198 mm in normal controls (p<0.001). The prevalence of carotid plaques was higher in patients with NAFLD (26.4%) than in normal controls (15.9%) (p<0.001). This association persisted significantly after adjusting for age, sex, BMI, HOMA index and individual factors of metabolic syndrome by multiple logistic regression analysis. CONCLUSIONS: Patients with NAFLD are at a high risk of carotid atherosclerosis regardless of metabolic syndrome and classical cardiovascular risk factors. Therefore, the detection of NAFLD should alert to the existence of an increased cardiovascular risk. Moreover, NAFLD might be an independent risk factor for cardiovascular disease.

Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography.

BACKGROUND AND AIM: The purpose of this study was to evaluate extracolonic findings that could be encountered with computed tomography colonography (CTC) using intravenous (IV) contrast material in an asymptomatic screening population. METHODS: Intravenous contrast medium-enhanced CTC was performed in 2230 asymptomatic adults (mean age, 57.5 years). Axial images were prospectively examined for extracolonic lesions. These findings were classified into three categories: potentially important findings, likely unimportant findings, and clinically unimportant findings. Potentially important extracolonic findings were defined as those which required immediate further diagnostic studies and treatment. Clinical and radiologic follow up, missed lesions and clinical outcomes were assessed using medical records (mean duration of follow up, 1.6 years). RESULTS: A total of 115 new potentially important findings in 5.2% of subjects (115/2230) were found. Subsequent medical or surgical intervention was performed in 2.0% (45/2230). New extracolonic cancer was detected in 0.5% (12/2230), and the majority of them (83.3%) were not metastasized. Computed tomography colonography missed eight potentially important extracolonic findings in eight subjects (0.4%, 8/2230): 0.8-cm early-stage prostatic cancer, six adrenal mass and one intraductal papillary mucinous tumor. There were no severe life-threatening complications related to contrast medium. CONCLUSION: Intravenous contrast-enhanced CTC could safely detect asymptomatic early-stage extracolonic malignant diseases without an unreasonable number of additional work-ups, thus reducing their morbidity or mortality.

Features of Gastric Neoplasm Detected during the Screening Examination.

BACKGROUND/AIMS: Gastric cancer is the leading malignancy in Korea and early detection through the health screening seems to be important. The aims of this study were to investigate the features of gastric neoplasms detected during screening, and to figure out the risk factors of these lesions. METHODS: From October 2003 to September 2005, subjects who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-up were included in the study. The program included a questionnaire and tests including anti-Helicobacter pylori (H. pylori) antibody, esophagogastroduodenoscopy or double contrast upper gastrointestinal study. To figure out the risk factors, an age and gender-matched, four-fold sized control group was selected from the subjects. RESULTS: Of 25, 432 subjects, 122 cases of gastric neoplasms were detected including 61 adenocarcinoma (45 early gastric cancers), 53 adenoma, 7 mucosa-associated lymphoid tissue lymphoma, and one metastatic cancer. There was no significant statistical difference in basal characteristics of the subjects between gastric adenocarcinoma and adenoma. When comparing with the control group those without gastric neoplasms, smoking history, family history of stomach cancer, and H. pylori seropositivity were found to be significant risk factors for gastric neoplasms. Metabolic syndrome was more prevalent in adenoma than in the control (p<0.05). CONCLUSIONS: The health screening may be beneficial in early detection of gastric cancer. In addition, metabolic syndrome might be related with gastric adenoma.