Immunostimulatory activity of the aqueous extract from the leaves of Sambucus racemosa subsp. pendula through TLR4­dependent JNK activation in RAW264.7 cells.

Sambucus racemosa subsp. pendula (SRP) is an endemic plant of Korea, exclusively found on Ulleungdo Island. SRP is widely used as both a traditional medicine and food source. However, there is a lack of research on the pharmacological activities of SRP. Therefore, the present study aimed to explore the potential use of SRP leaves (SRPL) as a natural immunostimulant by analyzing its macrophage activation properties and the underlying mechanisms of action. Among the various extraction conditions, SRPL (AE20-SRPL) extracted with 100% distilled water at 20˚C induced the highest nitric oxide (NO) production in RAW264.7 cells. Thus, the further studies were performed using AE20-SRPL. AE20-SRPL increased the production of immunostimulatory factors such as NO, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1ß and TNF-α and phagocytosis in a dose-dependent manner in RAW264.7 cells without exhibiting cytotoxicity. Among Toll-like receptor (TLR)2 and TLR4, inhibition of TLR4 significantly reduced AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Furthermore, in RAW264.7 cells, inhibition of JNK, one of the components of MAPK signaling along with ERK1/2 and p38, attenuated the AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis. Additionally, AE20-SRPL induced the phosphorylation of JNK and inhibition of TLR4 reduced AE20-SRPL-mediated JNK phosphorylation. These results suggested that AE20-SRPL may enhance the production of immunostimulatory factors and phagocytosis through TLR4-dependent activation of JNK in macrophages. Although the present study is limited to in vitro research using a cell model, AE20-SRPL demonstrated potential as a natural material capable of inducing macrophage activation for immune enhancement.

Higher prevalence of obesity in gastric cardia adenocarcinoma compared to gastric non-cardia adenocarcinoma.

BACKGROUND AND AIMS: Obesity is one of the main risk factors for gastric cardia adenocarcinoma (GCA) in the West. Also, recent studies have suggested that GCA is distinct from distal stomach tumor, with differing risk factors, tumor characteristics, and biological behavior. The objective of our research was to evaluate the relationship between obesity and GCA compared to non-cardia adenocarcinoma. MATERIALS AND METHODS: A total of 298 patients who were diagnosed with gastric adenocarcinoma and underwent surgery at Seoul National University Bundang Hospital were evaluated. Ninety-one cases were GCA, and 207 cases were non-cardiac adenocarcinoma. Obesity was estimated by body mass index (BMI, kg/m(2)). The degree of obesity was determined by using BMI <18.5, 18.5-23.9, 24-27.9, and ≥ 28 (kg/m(2)) as the cut-off points for underweight, normal weight, overweight, and obese, respectively. Association with obesity was estimated by odds ratio (OR) and 95% confidence interval (CI). RESULTS: Obesity was more prevalent in patients with GCA at the time of diagnosis for gastric cancer. Among obese persons with a BMI of 28 kg/m(2) or higher, the OR was 3.937 (95% CI, 1.492-10.389; p = 0.006) for GCA compared to non-cardia adenocarcinoma. For overweight individuals, the OR was 2.194 (95% CI, 1.118-4.305; p = 0.022). Multivariate analysis of age, Helicobacter pylori infection, smoking, stage, and BMI with logistic regression was performed. BMI was an independent risk factor for GCA (OR, 1.123; 95% CI, 1.037-1.217; p = 0.004). CONCLUSION: Obesity was more prevalent in patients with GCA compared to that in patients with gastric non-cardia adenocarcinoma. Also, BMI was an independent risk factor for GCA.

Chronic hepatitis B, non-Hodgkin's lymphoma, and effect of prophylactic antiviral therapy.

BACKGROUND: Hepatitis B virus (HBV) infection can be associated with non-Hodgkin's lymphoma (NHL), and prophylactic antiviral therapy is recommended for NHL patients with chronic HBV infection who are receiving anticancer chemotherapy. OBJECTIVES: The aims of this study were to investigate the association between HBV infection and NHL, and to evaluate the application rate and the effect of prophylactic antiviral therapy for HBV-infected NHL patients. STUDY DESIGN: A retrospective, case-control study was performed. RESULTS: The prevalence of hepatitis B surface antigen in 344 patients who were consecutively diagnosed with NHL from May 2003 to October 2009 (44 of 344; 12.8%) was significantly higher than that of 688 age- and sex-matched health-check examinees (24 of 688; 3.5%) (adjusted odds ratio, 4.08; 95% confidence interval, 2.44-6.85). T cell type NHL, as well as B cell type, showed a significant association with HBV carrier rate. Among 32 NHL patients who received anticancer chemotherapy, 30 patients (93.8%) received prophylactic antiviral therapy, primarily lamivudine. However, HBV DNA monitoring during antiviral therapy was frequently omitted in hemato-oncology clinics. While there was no occurrence of hepatitis flare during antiviral therapy, withdrawal hepatitis after discontinuation of antiviral drug occurred frequently (60%). CONCLUSION: HBV may play a significant role in development of NHL, which prompts further study on the lymphomagenic mechanism of HBV infection. Prophylactic antiviral therapy was administered during chemotherapy to almost all of the NHL patients with HBV infection; however, further investigation should be conducted for determination of optimal duration and monitoring of antiviral therapy.

Learning curves for colonoscopy: a prospective evaluation of gastroenterology fellows at a single center.

BACKGROUND/AIMS: Colonoscopy training programs and the minimal experience with colonoscopy required to be considered technically competent are not well established. The aim of this study was to determine the colonoscopy learning curves and factors associated with this difficult procedure at a single center. METHODS: A total of 3,243 colonoscopies were performed by 12 first-year gastroenterology fellows, and various clinical factors were assessed prospectively for 22 months. Acquisition of competence (success rate) was evaluated based on two objective criteria: (i) the adjusted completion rate (>90%) and (ii) cecal intubation time (<20 minutes). RESULTS: The overall success rate in reaching the cecum in less than 20 minutes was 72.8%. The cecal intubation time was 9.34+/-4.13 minutes (mean+/-SD). Trainees' skill at performing cecal intubation in <20 minutes reached the requisite standard of competence after 200 procedures. Cecal intubation time decreased significantly from 11.3 to 9.4 minutes after 100 procedures and improved continuously thereafter. Female patients and advanced patient age (over 60 years) were associated with prolonged cecal intubation time (>20 minutes). Surgery of the uterus and ovaries was significantly correlated with delayed cecal intubation time, but not after sufficient colonoscopy experience. CONCLUSIONS: The minimum number of procedures to reach technical competence was 200. The cecal intubation time was longer in female and older patients.

Validation of diagnostic tests for Helicobacter pylori with regard to grade of atrophic gastritis and/or intestinal metaplasia.

BACKGROUND AND AIMS: To evaluate the validity of the biopsy-based tests (histology, culture, and urease test) and serology in detecting current Helicobacter pylori infection against a background of atrophic gastritis (AG) or intestinal metaplasia (IM). METHODS: Helicobacter pylori infection was diagnosed in 651 subjects, using the predefined gold standard for H. pylori tests. The sensitivity, specificity, and positive and negative predictive values of culture, CLOtest, histology (Giemsa stain), and serology were calculated with regard to the histological grade of AG and IM. The level of serum pepsinogen (PG) I and II was also measured as a marker for the presence of AG. RESULTS: In the study population (n = 651), sensitivity and specificity, respectively, were as follows: culture, 56.2 and 100%; histology, 93.0 and 94.0%; CLOtest, 80.4 and 96.7%; serology, 96.0 and 67.5%. If the analysis is limited to those without AG or IM (n = 158) or to those younger than 40 years (n = 69), all tests, except for culture, had a sensitivity and specificity >90%. The sensitivity of CLOtest and the specificity of serology markedly decreased with progression of AG and IM, and serology was less specific in the presence of AG, as determined by a PG I/II ratio < or =4.1 (specificity, 83.7% vs 40.7% in PG I/II >4.1 and < or =4.1, respectively). CONCLUSIONS: Any one of biopsy-based tests or serology was found to be excellent for identifying current H. pylori infection among individuals without AG or IM and/or younger patients (<40 years). However, a combination of at least two tests is necessary in the clinical setting of AG or IM.

Hepatitis a in Korea: epidemiological shift and call for vaccine strategy.

OBJECTIVE: The number of adult hepatitis A cases has progressively been increasing during the last several years in Korea. The aim of the present study was to describe the recent clinical features of hepatitis A and the seroprevalence of hepatitis A virus (HAV), and to discuss HAV vaccine strategy in Korea. METHODS: Retrospective analysis of clinical characteristics of hepatitis A from 109 patients consecutively enrolled at a community hospital between 2003 and 2006 as well as cross-sectional study of seroprevalence of HAV from 307 patients of hospital population group during the same period were performed. RESULTS: Most hepatitis A cases were young adults in their twenties or thirties, and the severity of the disease was related to the age of patients. The seroprevalence of HAV was 62%, which was dependent on the age of patients. HAV seroepidemiology in Korea is rapidly changing and a growing number of young adults are susceptible to HAV infection. CONCLUSIONS: The clinical features and the epidemiological shift of HAV urge Korea, as well as other countries which are experiencing similar issues, to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults.

[Recent etiology and clinical features of acute viral hepatitis in a single center of Korea].

BACKGROUND AND AIMS: The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea. METHODS: We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E. RESULTS: The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1+/-4.38, 38.7+/-11.72, 45.3+/-17.62 and 32.4+/-6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area. CONCLUSIONS: The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future.

[The prevalence of peripheral iron overload and the presence of HFE gene (H63D) mutation among the Korean patients with nonalcoholic fatty liver disease].

BACKGROUNDS/AIMS: There are controversies on the role of iron overload in the mechanism of liver injury in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of peripheral iron overload, and to study the presence of HFE mutations (C282Y, H63D, S65C) in a cohort of Korean NAFLD patients. METHODS: 255 patients with NAFLD were included. The patients had been diagnosed as having NAFLD by the criteria of elevated aminotransferase levels, compatible ultrasonographic findings and exclusion of other etiologies. Blood samples were tested for chemistry, iron profile, and mutational analysis for HFE gene (C282Y, H63D, S65C). RESULTS: Of the 255 NAFLD patients, the prevalence of peripheral iron overload was 19.2% according to the cutoff level of transferrin saturation (TS) > 45%, and 3.9% of NAFLD patients were having hyperferritinemia over 400 ng/mL. Hyperferritinemia was significantly associated with elevated serum levels of fasting glucose, AST and TS. We found the presence of H63D mutation, either heterozygote or homozygote, among the NAFLD patients with peripheral iron overload. CONCLUSIONS: The prevalence of peripheral iron overload in the Korean NAFLD patients was not rare, and the presence of H63D mutation among NALFD patients was identified. Further studies on the significance of iron overload or HFE mutation in the pathogenesis of NAFLD are needed.