Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages.

Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1ß in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.

Significance of palliative gastrojejunostomy for unresectable pancreatic head carcinoma.

BACKGROUND/AIMS: When diagnosed, most patients with pancreatic head cancer are defined as having an unresectable tumor, and thus appropriate relief of main symptoms, such as, obstructive jaundice, duodenal obstruction, and pain, is the major concern. However, debate continues concerning the efficacy of gastrojejunostomy at preventing duodenal obstruction. In this study, we evaluated the effects of palliative gastrojejunostomy on the quality of life of patients with unresectable pancreatic head cancer. METHODOLOGY: Between January 2000 and December 2004, of 61 patients with unresectable pancreatic head cancer, 46 underwent palliative surgery; 24 patients underwent biliary bypass with gastrojejunostomy (Group I) and 22 patients underwent biliary bypass only (Group II). Frequencies of nausea and vomiting, serum protein and albumin levels, oral intake, and other metrics were carefully monitored. RESULTS: No significant differences in age, sex, TNM stage, and preoperative symptoms were evident between the two groups. Incidences of nausea and vomiting were similar preoperatively (Group I, 45.8%; Group II, 40.9%, P=0.736), but were significantly different at 3 months postoperatively (Group I, 25.0%; Group II, 68.2%, P=0.003). Preoperative serum protein and albumin levels were similar in the two groups (Group I: 6.6g/dL, 3.5g/dL; Group II: 6.4g/dL, 3.4g/dL, respectively, P-0.223, 0.472), but at 3 months postoperatively, serum protein and albumin levels were significantly different (Group I: 5.9g/dL, 3.1g/dL; Group II: 5.2g/dL, 2.6g/dL, respectively, P=0.010, 0.047). CONCLUSIONS: Our data suggest that palliative gastrojejunostomy in patients with unresectable pancreatic head cancer reduces symptoms related to duodenal obstruction and contributes to quality of life.

Factors affecting the technical difficulty of colonoscopy.

BACKGROUND/AIMS: Colonoscopy is a standard diagnostic tool for screening and surveillance of diseases affecting the colon. Colonoscopy may be painful for patients and difficult for the endoscopist. The aim of this study was to identify the factors affecting the technical difficulty of a colonoscopic examination and to predict potential difficult patients who will undergo colonoscopy. METHODOLOGY: A total of 646 outpatients were consecutively included in this study. Patient's age and gender, body mass index (BMI), prior surgical history, and the duration and symptoms of irritable bowel syndrome (IBS) were recorded before the procedure. The quality of bowel preparation, the difficulty of examination reported by the colonoscopist, the degree of patient pain, the degree of pain as reported by an observer, cecal intubation time andcolonoscopic findings were assessed after the procedure. RESULTS: We evaluated the difficulty of colonoscopy by cecal intubation time. Advanced age (>50 years), female gender, low BMI (< or = 23 Kg/m2), poor bowel preparation, prior surgical history, patient pain and the presence of IBS were associated with prolonged cecal intubation time. A multivariate logistic regression analysis demonstrated that advanced age, female gender, low BMI, poor bowel preparation and patient pain were independent factors related to prolonged cecal intubation time. CONCLUSIONS: In patients with advanced age, female gender and low BMI, information that colonoscopy may be difficult and painful should be provided. If a colonoscopy is not absolutely indicated, barium enema or CT colonography may be performed as alternative diagnostic modalities.

Factors affecting the serum levels of adipokines in Korean male patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Adipokines are associated with various metabolic disorders including insulin resistance, obesity, and dyslipidemia. Metabolic disorders have also been reported to be associated with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the relationship between the serum adipokine levels and the degrees of hepatic fat infiltration in NAFLD. This study also attempted to determine the independent factors influencing the serum adipokine levels in NAFLD. METHODOLOGY: Sixty-five Korean male patients were enrolled in this study. The degree of hepatic fat infiltration was classified into the following three groups according to the ultrasonographic findings: Group I, normal liver; Group II, mild fatty liver; and Group III, moderate to severe fatty liver. The anthropometric parameters, fasting serum adipokine levels including leptin, adiponectin and resistin were measured in all subjects. The level of insulin resistance was estimated using the HOMA-IR. RESULTS: The serum leptin levels increased with increasing degree of hepatic fat infiltration (mean +/- SD: Group I, 2.052 +/- 1.071; Group II, 2.879 +/- 1.016; and Group III, 4.457 +/- 1.965 ng/mL, P < 0.001). However, the serum adiponectin and resistin levels were similar. The fasting serum insulin level was only a related factor for the changes in the serum leptin levels (P = 0.004). There were no related factors for the change in the serum adiponectin and resistin levels. CONCLUSIONS: This study suggests an indirect role for leptin in the pathogenesis of NAFLD by inducing insulin resistance, resulting in increased fasting serum insulin level.

The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has been associated with metabolic disorders, including central obesity, dyslipidema, hypertension, and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of NAFLD. The aim of this study was to identify the relative contribution of the metabolic syndrome, obesity, and insulin resistance to alanine aminotransferase (ALT) activity in NAFLD. A total of 3091 subjects diagnosed with fatty liver by ultrasonography were enrolled. All components of metabolic syndrome criteria, anthropometric parameters, fasting insulin levels, high-sensitivity C-reactive protein (hs-CRP) as an inflammation marker, and ALT were measured in each subject. Homeostasis model assessment--insulin resistance (HOMA-IR) as a measure of insulin resistance and body mass index (BMI) as a measure of obesity were calculated. The prevalence of increased ALT levels (>40 IU/L) was 26.7%. Increased ALT activity was significantly associated with the following characteristics: male sex, young age, increased triglycerides, fasting glucose, fasting insulin, HOMA-IR, hs-CRP, waist circumference, BMI and diastolic blood pressure, and decreased high-density lipoprotein cholesterol (HDL-C). According to the increase in the number of metabolic syndrome components, BMI, HOMA-IR, and hs-CRP, the prevalence and odds ratio for having increased ALT activity were significantly increased. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose were strongly associated with increased ALT activity. In conclusion, a number of metabolic syndrome components, obesity, insulin resistance, and hs-CRP, are strong predictors of increased ALT activity in NAFLD. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose are metabolic syndrome components that contributed to increased ALT activity.

[Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication].

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.

[Is gastric cancer a new indication for surveillance colonoscopy? Colon cancer is increased in gastric cancer patients].

BACKGROUND/AIMS: It has been reported that the risk of gastric polyp is increased in various colonic polyposis syndromes or in series of patients with sporadic colonic polyps. However, there are only a few large case controlled studies of colon cancer incidence in gastric cancer patients who underwent colonoscopy. The aims of this study were to determine the incidence of colorectal neoplasm and to evaluate the necessity of colonoscopic surveillance in patients with gastric cancer. METHODS: We performed colonoscopy in 105 patients with gastric cancer who agreed to undergo colonoscopy before or after 6 months from gastric resection between January 2002 and December 2004 in Kangbuk Samsung hospital. As a control group, 269 consecutive, age and sex matched patients without gastric neoplasm on gastroscopy who underwent colonoscopy within 6 months for the evaluation of various gastrointestinal symptoms during the year 2004 were included. Endoscopic reports and pathological results were reviewed retrospectively. RESULTS: In the patient group, adenomatous polyps were diagnosed in 24/105 patients (22.9%) and colorectal adenocarcinoma in 10/105 patients (9.5%). In the control group, adenomatous polyps were diagnosed in 78/269 patients (29.0%) and colorectal adenocarcinoma in 2/269 patients (0.7%). The incidence of colorectal adenocarcinoma between the patient group and control group showed significant differences (odds ratio 11.04, p=0.003). CONCLUSIONS: The risk of colorectal adenocarcinoma increases significantly in patients with gastric cancer. We suggest that the patients with gastric cancer might carry a high risk for colorectal cancer whom require surveillance colonoscopy.

[The relationship between serum adiponectin level and serum alanine aminotransferase elevation in Korean male with nonalcoholic fatty liver disease].

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) comprises a large part of chronic liver diseases. Recently it was reported that adipokines are closely associated with the common risk factors for NAFLD, such as obesity, diabetes, dyslipidemia, and insulin resistance. We aimed to evaluate the changes in serum adiponectin, resistin and leptin concentrations related to alanine aminotransferase (ALT) elevations in Korean men with NAFLD. METHODS: We studies 38 men who were diagnosed with fatty liver by abdominal ultrasonography. None had a history of excessive alcohol consumption, autoimmune hepatitis, inherited or metabolic liver disease or viral hepatitis. The subjects were divided into two groups. One group had normal levels of ALT (n=28) and the other had increased ALT (n=10). We compared anthropometrical parameters, biochemical items and serum adipokine levels between these two groups. RESULTS: Serum adiponectin levels were lower in the increased ALT group than in the normal ALT group (3.89 +/- 1.77 vs 7.01 +/- 2.54 microgram/dL, P=0.001). But there were no significant differences in serum leptin and resistin levels between two groups (4.02 +/- 2.04 vs 3.26 +/- 1.41 ng/mL, p=0.245, 80.14 +/- 14.8 vs 80.5 +/- 11.34 ng/mL, P=0.937, respectively). Multiple linear regression analyses demonstrated that the serum adiponectin level is inversely correlated with serum ALT level and that the serum aspartate aminotransferase (AST) level is positively correlated with the serum ALT level. CONCLUSIONS: Our study shows that hypoadiponectinemia is associated with an ALT elevation in patients with NAFLD. Adiponectin may play an indirect role in the development of NAFLD.

Abdominal obesity is an independent risk factor for erosive esophagitis in a Korean population.

BACKGROUND: The relationship between obesity and gastroesophageal reflux disease (GERD) is controversial. The aim of the present study was to investigate the potential roles of body mass index (BMI) and waist circumference on GERD in a Korean population. METHODS: A total of 2457 subjects who visited the Kangbuk Samsung Hospital medical screening center for esophagogastroduodenoscopy from September 2004 to April 2005 were enrolled. All participants were given a questionnaire to determine reflux symptoms. Abdominal obesity was defined as a waist circumference > or =80 cm in women and > or =90 cm in men. RESULTS: The proportion of subjects in each BMI group was 68.9%, 28.7% and 2.4% for BMI <25, 25-30 and >30, respectively. The prevalence of abdominal obesity was 24.2%. The prevalence of reflux symptoms was 8.2%. Neither BMI nor abdominal obesity was significantly associated with reflux symptoms after adjustment. The prevalence of erosive esophagitis was 6.6%. There was a clear dose-response relationship between prevalence of erosive esophagitis and BMI (5.6%, 8.1% and 15.5% for BMI <25, 25-30 and >30, respectively, P = 0.002). Abdominal obesity was also associated with erosive esophagitis (odds ratio, 2.3; 95% confidence interval, 1.6-3.1). However, only the association between abdominal obesity and erosive esophagitis remained strong after adjustments. CONCLUSIONS: Abdominal obesity rather than BMI is an independent risk factor for erosive esophagitis in the Korean population.

Eosinophilic peritonitis in a patient with continuous ambulatory peritoneal dialysis (CAPD).

Eosinophilic peritonitis is defined as when there are more than 100 eosinophils present per milliliter of peritoneal effluent, of which eosinophils constitute more than 10% of its total WBC count. Most cases occur within the first 4 weeks of peritoneal catheter insertion and they usually have a benign and self-limited course. We report a patient of eosinophilic peritonitis that was successfully resolved without special treatment. An 84-year-old man with end stage renal disease secondary to diabetic nephropathy was admitted for dyspnea and poor oral intake. Allergic history was negative. and physical examination was unremarkable. Complete blood count showed a hemoglobin level of 11.1 g/dL, WBC count was 24,500/mm3 (neutrophil, 93%; lymphocyte, 5%; monocyte, 2%), platelet count was 216,000/mm3, serum BUN was 143 mg/dL, Cr was 5.7 mg/dL and albumin was 3.5 g/dL. Creatinine clearance was 5.4 mL/min. Three weeks after peritoneal catheter insertion, he was started on peritoneal dialysis with a 6-hour exchange of 2L 1.5% peritoneal dialysate. After nine days, he developed turbid peritoneal effluents with fever (38.4 degrees C), abdominal pain and tenderness. Dialysate WBC count was 180/mm3 (neutrophil, 20%; lymphocyte, 4%; eosinophil, 76% [eosinophil count: 136/mm3]). Cultures of peritoneal fluid showed no growth of aerobic or anaerobic bacteria, or of fungus. Continuous ambulatory peritoneal dialysis (CAPD) was commenced, and he was started on intraperitoneal ceftazidime (1.0 g/day) and cefazolin (1.0 g/day). After two weeksr, the dialysate had cleared up and clinical symptoms were improved. Dialysate WBC count decreased to 8/mm3 and eosinophils were not detected in peritoneal fluid. There was no recurrence of eosinophilic peritonitis on follow-up evaluation, but he died of sepsis and pneumonia fifteen weeks after admission.