Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

Development and evaluation of the Korean Health Literacy Instrument.

The purpose of this study is to develop and validate the Korean Health Literacy Instrument, which measures the capacity to understand and use health-related information and make informed health decisions in Korean adults. In Phase 1, 33 initial items were generated to measure functional, interactive, and critical health literacy with prose, document, and numeracy tasks. These items included content from health promotion, disease management, and health navigation contexts. Content validity assessment was conducted by an expert panel, and 11 items were excluded. In Phase 2, the 22 remaining items were administered to a convenience sample of 292 adults from community and clinical settings. Exploratory factor and item difficulty and discrimination analyses were conducted and four items with low discrimination were deleted. In Phase 3, the remaining 18 items were administered to a convenience sample of 315 adults 40-64 years of age from community and clinical settings. A confirmatory factor analysis was performed to test the construct validity of the instrument. The Korean Health Literacy Instrument has a range of 0 to 18. The mean score in our validation study was 11.98. The instrument exhibited an internal consistency reliability coefficient of 0.82, and a test-retest reliability of 0.89. The instrument is suitable for screening individuals who have limited health literacy skills. Future studies are needed to further define the psychometric properties and predictive validity of the Korean Health Literacy Instrument.

Risk of gastric cancer is associated with PRKAA1 gene polymorphisms in Koreans.

AIM: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer. METHODS: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method. RESULTS: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. CONCLUSION: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.

Activation of TOPK by lipopolysaccharide promotes induction of inducible nitric oxide synthase through NF-κB activity in leukemia cells.

T-LAK cell-originated protein kinase (TOPK) is known to be involved in tumorigenesis or cancer progression. However, the role of TOPK in inflammatory response remains elusive. Here we show that TOPK positively regulates inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in response to lipopolysaccharide (LPS). In TOPK-depleted cells, the iNOS expression was shown to be greatly abolished. Also, we revealed that LPS treatment augmented the expression and activity of TOPK, the interaction of TOPK with IκBα, and promoted TOPK kinase activity against IκBα. Moreover, NF-κB or iNOS promoter-driven transcriptional activity in response to LPS was markedly reduced by knocking down of TOPK or deletion of NF-κB sites. On the other hand, endogenous TOPK level was expressed very lowly in bone marrow-derived macrophage (BMDM) prepared from Toll-like receptor 4 (TLR4) knockout mice, compared to BMDM from wild type (WT) mice. Collectively, these findings demonstrate that TOPK upregulates iNOS gene expression in T cell leukemia Jurkat cells or macrophage leukemic Raw 264.7 cells via NF-κB activation in response to LPS, and might act as a critical effector in LPS/TLR4-mediated signaling cascade, suggesting a possible role of TOPK in inflammatory response or inflammation-related diseases.

The association of baseline adipocytokine levels with glycemic progression in nondiabetic Korean adults in 4 years of follow-up.

AIMS: Low-grade inflammation and lipotoxicity contribute to insulin resistance and islet secretory dysfunction that lead to insulin deficiency. We analyzed the associations of several adipocytokines measured at baseline with glycemic progression in non-diabetic Korean subjects after a 4-year follow-up. METHODS: In 479 non-diabetic Korean subjects who underwent medical screening in 2003, serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, retinol-binding protein (RBP)-4, monocyte chemoattractant protein (MCP)-1, visfatin and fatty acid-binding protein (FABP)-4 were measured at baseline. After 4 years, changes in glycemia were assessed. RESULTS: Among the subjects, 79.2% maintained their baseline glycemic status, 14.6% progressed to worse glycemic status (impaired fasting glucose (IFG) to diabetes, normoglycemia to IFG or normoglycemia to diabetes) and 5.8% regressed to normoglycemia after 4 years. Baseline TNF-α and FABP4 showed the highest values in the progression group. In the logistic regression analyses with glycemic progression as the dependent variable and TNF-α and FABP4 as independent variables in separate models, TNF-α and FABP4 individually predicted glycemic progression after adjustment for confounding variables. When both adipocytokines were included in the same model, only FABP4 significantly predicted glycemic progression after 4 years. CONCLUSIONS: TNF-α and FABP4 were significant predictors for glycemic progression in 4 years, with FABP4 being the stronger predictor.

High prevalence of both anti-insulin and anti-insulin receptor antibodies in Korean patients with insulin autoimmune syndrome.

We performed a retrospective pooled analysis of 28 patients who had been diagnosed with insulin autoimmune syndrome and evaluated the prevalence of anti-insulin receptor antibodies. Dual positivity for anti-insulin and anti-insulin receptor antibodies was common (53.8%). However, these patients had a similar phenotype compared with insulin receptor antibody-negative patients.

Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes.

BACKGROUND: Recent studies indicate postprandial triglyceride (TG) had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG. METHODS: In a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539) and impaired fasting glucose (IFG, group II, n=100) after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein). RESULTS: Fasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001) in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide) in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D. CONCLUSION: Postprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet.