Yangho Kim

Evaluation of estrogenicity of major heavy metals

We have employed an estrogen receptor dependent transcriptional expression assay and E-Screen assay systems to evaluate the estrogenicity of various heavy metals and their species. Using the former, the following estrogenicity ranking was measured: bis(tri-n-butyltin)>cadmium chloride>antimony chloride>barium chloride=chromium chloride>lithium hydroxide>sodium selenate=lead acetate>stannous chloride. Using the latter, the following estrogenicity ranking was measured: bis(tri-n-butyltin)>cadmium chloride>antimony chloride>lithium hydroxide>barium chloride>sodium selenate>chromium chloride. Especially, bis(tri-n-butyltin), cadmium chloride, antimony chloride, lithium hydroxide, barium chloride, and chromium chloride showed estrogenicity in both assay systems. Recent studies suggesting that bis(tri-n-butyltin), cadmium chloride, and lithium hydroxide have estrogenicities are compatible with the present findings. Furthermore, our studies are the first to suggest that antimony, barium, chromium may be estrogenic. A range of estrogenicity was observed for different species of the same heavy metal. The results demonstrate that an estrogen receptor dependent transcriptional expression assay and the E-Screen assay systems could serve as a useful method to assess the estrogenicity of heavy metals.

Association of serum ferritin with metabolic syndrome and diabetes mellitus in the South Korean general population according to the Korean National Health and Nutrition Examination Survey 2008.

We examined the association of serum ferritin levels with metabolic syndrome (MS) and diabetes mellitus in a representative sample of the adult South Korean population using data from the 2008 Korean National Health and Nutrition Examination Survey. We conducted a cross-sectional study of 6311 adults older than 20 years who participated in the 2008 Korean National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least 3 of the following: elevated blood pressure, low high-density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Diabetes mellitus was defined as fasting glucose of at least 126 mg/dL. Insulin resistance was determined using the homeostasis model assessment estimate of insulin resistance. In a representative sample of the adult Korean population, MS was more prevalent in the highest quartile compared with the lowest quartile of serum ferritin concentrations in women following adjustments for age, education, smoking, alcohol intake, body mass index, aspartate aminotransferase, and alanine aminotransferase. Diabetes mellitus was more prevalent in the highest quartile compared with the lowest quartile of serum ferritin concentrations in premenopausal women and men. The geometric means of fasting insulin and insulin resistance determined using the homeostasis model assessment of insulin resistance in the fourth serum ferritin quartiles of postmenopausal women and men were significantly higher compared with those in the first quartile of the respective groups. The present study demonstrates that elevated serum ferritin concentrations are associated with an increased risk of MS and diabetes mellitus in a representative sample of the adult South Korean population.

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders

OBJECTIVES The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. METHODS A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. RESULTS Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. CONCLUSIONS The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.

Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis.

We examined whole blood (MnB), plasma (MnP) and urinary Mn (MnU) concentrations in 33 cirrhotics and 11 healthy controls to clarify: (1) whether, in chronic liver diseases, MnB or MnP reflects pallidal signal intensities in magnetic resonance imaging (MRI); and (2) which factors in chronic liver diseases correlate with pallidal signal intensities in T1-weighted MRI. Increased signal intensity in the pallidum was observed in 27 (81.8%) of 33 patients with liver cirrhosis in T1-weighted MRI. There was a significant correlation between MnB and pallidal index (PI) (gamma = 0.559, P < 0.01) in the patients. However, no significant correlation was observed between MnP and PI (gamma = 0.353, P > 0.05). According to a multiple linear regression, MnB reflected the signal intensities of T1-weighted MRI better than MnP or MnU. Child/Pugh score and total bilirubin level also correlated with PI. However, the hemoglobin level did not correlate with PI significantly.

Inappropriate Survey Design Analysis of the Korean National Health and Nutrition Examination Survey May Produce Biased Results

Objectives The inherent nature of the Korean National Health and Nutrition Examination Survey (KNHANES) design requires special analysis by incorporating sample weights, stratification, and clustering not used in ordinary statistical procedures. Methods This study investigated the proportion of research papers that have used an appropriate statistical methodology out of the research papers analyzing the KNHANES cited in the PubMed online system from 2007 to 2012. We also compared differences in mean and regression estimates between the ordinary statistical data analyses without sampling weight and design-based data analyses using the KNHANES 2008 to 2010. Results Of the 247 research articles cited in PubMed, only 19.8% of all articles used survey design analysis, compared with 80.2% of articles that used ordinary statistical analysis, treating KNHANES data as if it were collected using a simple random sampling method. Means and standard errors differed between the ordinary statistical data analyses and design-based analyses, and the standard errors in the design-based analyses tended to be larger than those in the ordinary statistical data analyses. Conclusions Ignoring complex survey design can result in biased estimates and overstated significance levels. Sample weights, stratification, and clustering of the design must be incorporated into analyses to ensure the development of appropriate estimates and standard errors of these estimates.

Prenatal bisphenol A and birth outcomes: MOCEH (Mothers and Children's Environmental Health) study.

Bisphenol A (BPA) is used primarily in the production of polycarbonate plastics and epoxy resins. Widespread exposure to BPA has created a great deal of concern regarding its potential adverse effects on human health. This study examined the relationship between prenatal BPA exposure and birth outcomes, including birth weight, birth length, and ponderal index considering gender difference. A multi-center birth cohort study, Mothers and Childrens Environmental Health (MOCEH) has been established in Korea since 2006. Study subjects are 757 pregnant women from the original cohort, who had their urinary BPA level measured during the third trimester, as well as information on birth outcome, prior medical history, psychosocial status, health behavior, environmental exposure as well as socio-demographic characteristics. Regression analysis was performed to assess the effect of BPA on birth outcome. The geometric mean concentration of BPA in pregnant women was 1.29 μg/L (1.87 μg/g creatinine) during late pregnancy. Urinary BPA concentrations were shown to be higher in women with a higher income level. Univariate regression analysis revealed a significant association between BPA levels and birth weight. In adjusted analysis, the second tertile of maternal BPA exposure exhibited an increase in birth weight, relative to the first tertile (p=0.04). These relationships were more pronounced in male neonates. Also, prenatal exposure to BPA was associated with an increase of ponderal index in total, and especially female neonates. This study shows that the association of prenatal exposure to BPA with anthropometric measures, such as birth weight and birth length, differed by gender. Further study is required to more fully elaborate this relationship between prenatal BPA exposure and birth outcome.

Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data.

INTRODUCTION The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. METHODS This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. RESULTS In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium and mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m² (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m² (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. DISCUSSION In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 μg/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.

A case of generalized argyria after ingestion of colloidal silver solution

A 58-year-old woman was referred to our hospital due to progressive skin darkening, which began 5 months previously. The patient had strikingly diffuse blue-gray discoloration of the skin, most prominent in sun-exposed areas, especially her face and hands. The oral mucosa, tongue, gums, eye conjunctiva, ears, nail beds, and trunk were also involved. Bluish-gray discoloration of all nails was aggravated by cold weather. She had ingested 1 L of colloidal silver solution daily for approximately 16 months as a traditional remedy. Her serum silver concentration was 381 ng/ml which was a very high (reference level: <15 ng/ml). Light microscopic examination of a punch biopsy specimen from her nose revealed fine, minute, round, and brown-black granules deposited in the basement membrane of hair follicular epithelium. Scanning electron microscopic examination showed electron-dense granules deposited in the intercellular space of sweat glands. Energy disperse X-ray spectrometry analysis demonstrated peaks for silver and sulfur in the dense black deposits. The ingestion of colloidal silver appears to be an increasing practice among patients using alternative health practices. All silver-containing products including colloidal silver should be labeled with a clear warning to prevent argyria, especially in alternative health practices.

Iron deficiency increases blood manganese level in the Korean general population according to KNHANES 2008.

INTRODUCTION We present data from Korean National Health and Nutritional Examination Survey (KNHANES) 2008 on the distribution of blood manganese (Mn) levels and their associations with iron deficiency in a representative sample of the adult Korean population. METHODS This study was based on data obtained in KNHANES 2008, which was conducted for three years (2007-2009) using a rolling sampling design that involves a complex, stratified, multistage, probability-cluster survey of a representative sample of the noninstitutionalized civilian population in South Korea. RESULTS Geometric means (GMs) of blood Mn in the low serum ferritin group in women, men, and all participants were significantly higher than in the normal group. GMs of blood Mn in the low-normal serum ferritin groups in women and all participants were significantly higher than in the normal group. In addition, multiple regression analysis after controlling for covariates including gender, age, regional area, education level, and smoking and drinking status showed that blood Mn was significantly higher in the low ferritin group in women, men, and all participants compared with the normal group, whereas blood Mn was significantly higher in the low-normal ferritin group only in women and all participants. DISCUSSION The present study shows that iron deficiency increases blood Mn level in the general population. To the best of our knowledge, the present study is the first to show an association between blood Mn level and ferritin level in a representative sample of the adult population such as that evaluated in KNHANES.

Prenatal lead and cadmium co-exposure and infant neurodevelopment at 6 months of age: The Mothers and Children's Environmental Health (MOCEH) study

BACKGROUND This study aimed to explore the developmental effects of prenatal exposure to Pb and Cd on infant cognitive development at 6 months of age. METHODS Between 2006 and 2010, the blood levels of Pb and Cd were measured in 884 mothers during their early and late pregnancy. The mental (MDI) and psychomotor (PDI) development index scores of the infants were assessed using the Bayley Scales of Infant Development. The development index scores were adjusted for birth weight, maternal age, maternal education level, family income, breastfeeding status, and residential area. RESULTS The geometric mean of the maternal blood concentration was 1.36μg/dL (10th percentile=0.83; 90th percentile=2.13; range=0.26-9.10) for Pb and 1.42μg/L (10th percentile=1.01; 90th percentile=2.16; range=0.03-9.87) for Cd during the early pregnancy period and 1.27μg/dL (10th percentile=0.77; 90th percentile=2.10; range=0.12-4.28) for Pb and 1.52μg/L for Cd (10 percentile=1.07; 90th percentile=2.10; range=0.43-3.73) during the late pregnancy period. The prenatal Pb and Cd concentrations during the early pregnancy period showed no association with the adjusted MDI or PDI scores. The antagonistic interaction between the prenatal Pb and Cd levels during the early pregnancy period had a significant effect on the MDI score (B=-4.64, 95% CI=-8.17 to -1.12, p=0.01), but the effect of this interaction did not reach statistical significance for the PDI score (B=-3.69, 95% CI=-7.94 to 0.56, p=0.09). The Pb levels during the late pregnancy period were inversely associated with the MDI score (B=-1.94, 95% CI=-3.60 to -0.29, p=0.02) but not with the PDI score (B=-1.69, 95% CI=-3.65 to 0.27, p=0.09). The prenatal Cd levels during the late pregnancy period showed no association with the MDI or PDI score. However, the MDI score (B=-3.20, 95% CI=-5.35 to -1.06, p<0.01) and the PDI score (B=-2.86, 95% CI=-5.55 to -0.16, p=0.04) of infants with Cd levels >1.51μg/L were significantly associated with the Pb level, whereas there were no such associations for infants with Cd levels <1.51μg/L. These results suggest that there is a synergistic effect modification between Pb and Cd during the late pregnancy period. CONCLUSIONS These findings suggest that there is dose-dependent interaction between prenatal exposure to Pb and prenatal exposure to Cd. The results further demonstrate the biological complexities of examining the neurodevelopmental effects of co-exposure to multiple toxicants.