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Background Nonhuman primates (NHPs) are superior model for ocular research due to its morphological and physiological similarities with humans. Thus, the effect of four different anesthetic combinations [ketamine (10 mg/kg), ketamine + xylazine (7 + 0.6 mg/kg), zoletil (4 mg/kg), and zoletil + xylazine (4 + 0.2 mg/kg)] on intraocular pressure (IOP) was determined in cynomolgus monkeys. Results The administration of ketamine + xylazine or zoletil + xylazine resulted in lower IOP compared to ketamine or zoletil alone. Moreover, the IOP in male monkeys was higher than in females. The difference between the right and left eye was not found. Conclusions Anesthetics affected the IOP, and gender differences should be considered when measuring the IOP of nonhuman primates (NHPs).

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 – as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 μg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.

Recently, some researchers have demonstrated that inhaled zinc oxide nanoparticles (ZnONPs) induce an acute systemic inflammatory response in workers. Considering nonhuman primates are preferably considered an animal model for translational research due to their proven similarity with humans in terms of genetics and physiology, we intratracheally instilled ZnONPs to cynomolgus monkey for 14 days and identified the toxic mechanism and bioaccumulation. ZnONPs were rapidly ionized or aggregated in a simulated pulmonary fluid, and they attracted neutrophils to the lungs and increased the pulmonary level of inflammatory mediators. Additionally, thickened alveolar walls, fibrin clots, and hemorrhages were observed in the lungs of the monkeys instilled with the higher dose accompanied by cell debris in the alveolar ducts and alveoli. Dark-field microscopy images revealed translocation of ZnONPs into other tissues accompanied by an increase in the relative weight of livers to body weight. In addition, when instilled at the higher dose, the albumin/globulin ratio notably decreased compared to the control, whereas the C-reactive protein (CRP) level was significantly elevated. ZnONPs also clearly induced apoptotic cell death in a 24 h exposure to alveolar macrophages. Taken together, part of inhaled ZnONPs may be ionized in the lung, resulting in acute toxic effects, including cell death and tissue damage, and the rest may move to other tissues in the form of particles, causing a systemic inflammatory response. Based on the proven evidence among workers, we also suggest that the CRP level can be recommended as a biomarker for ZnONPs-induced adverse health effects.

High-dose radiation-induced tissue damage is a major limiting factor in the medical application of nuclear technology. Herein, we tested 28-day repeated-dose toxicity of KMRC011, an agonist of toll-like receptor (TLR) 5, which is being developed as a medical countermeasure for radiation, using cynomolgus monkeys. KMRC011 (0.01, 0.02 or 0.04 mg/kg/day) was intramuscularly injected once daily for 4 weeks, and each two monkeys in both control and 0.04 mg/kg/day group were observed for an additional 2-week recovery period. There were no dose-related toxicological changes in mortality, clinical observations, body weight, food consumption, ophthalmological findings, electrocardiographs, coagulation, serum chemistry, organ weights, or urinalysis and urine chemistry. Although treatment-related changes, such as increased white blood cells, increased absolute and relative neutrophils, decreased relative lymphocytes and inflammatory lesions, were noted in the maximum dose group, these findings were not observed after the 2-week recovery period. Further, we considered that the kidneys and heart may be target organs of TLR5 agonists, as well as the spleen, and that autophagic signals can be triggered in tissue damage and the repair process. Importantly, accumulation of p62 protein, an indicator of autophagy, and a decrease of caveolin-1 protein, a regulator of TLR5 protein half-life, were found in both tissues from the highest dose group. Therefore, we conclude that the no-observed-adverse-effect level for KMRC011 may be greater than 0.04 mg/kg/day in male and female monkeys. Additionally, we propose that further studies are needed to identify the molecular signals, which are related to KMRC011-induced adverse effects.

To assess the relevance of previous epidemiologic studies on bisphosphonate-related osteonecrosis of the jaw (BRONJ), we first conducted a systematic review of large population-based observational studies and evaluated the validity of claims-based algorithms for the identification of BRONJ. Studies containing primary observational epidemiologic data regarding bisphosphonate (BP) exposure and outcomes of osteonecrosis of the jaw were systematically reviewed. Using surrogates for identifying potential BRONJ cases from a population-based hospital registry, validation was performed through medical chart review. Positive predictive value (PPV) was estimated for each diagnostic code and for the overall algorithm utilized. Various strategies to increase PPV were also performed. Seventeen studies were systematically reviewed and presented with variations in study quality as well as inconsistent findings. Moreover, there was a high level of methodological heterogeneity. A total of 1920 patients were identified through the ICD-10 algorithm with potential BRONJ, although only 109 cases were confirmed, corresponding to an overall PPV of 5.68% (95% confidence interval [CI] 4.68-6.81). Only K10.2 (inflammatory conditions of the jaw) exhibited a relatively high PPV of 26.18%, which increased to 74.47% after confinement to BP users. Other strategies to increase PPV value were not effective. Our findings showed that the overall PPV for BRONJ identification was very low, indicating low validity of the current algorithm and possible overestimation of ONJ occurrence. There is an urgent need to develop more reliable and specific operational definitions for the identification of BRONJ cases in large population databases. © 2016 American Society for Bone and Mineral Research.

Background: Vitamin D is effective in prevention of osteoporosis. Lower than recommended intake of vitamin D leads to an increased risk of cancer, hypertension, cardiovascular disease, diabetes mellitus, and autoimmune disease. We aimed to evaluate the relationship between serum vitamin D levels and metabolic syndrome in Korean elderly people. Methods: In this cross-sectional study, we assessed 1,515 participants aged ≥65 years from Korean National Health and Nutritional Examination Survey 2012. We excluded patients with chronic renal and hepatic failure along with those who were bed-ridden for more than 15 days. In total, 1,264 individuals were enrolled. Results: We observed that higher levels of vitamin D were associated with lower prevalence of metabolic syndrome (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.154–0.709; P=0.004). The adjusted OR for triglyceride concentration in individuals with optimum vitamin D intake was 0.41 (95% CI, 0.18–0.92; P=0.029). Conclusion: These findings indicate that levels of vitamin D are significantly associated with the prevalence of metabolic syndrome and triglyceride concentration in the Korean elderly people.

Background: This study aimed to evaluate the association between smoking and bone mineral density in Korean men. Methods: We assessed the data for 2,821 participants aged ≥19 years, obtained from the Korean National Health and Nutritional Examination Survey 2010. We compared the bone mineral density values taking into account life style-related factors and examined the relationship between smoking and bone mineral density. To investigate the impact of smoking on bone mineral density, a logistic regression analysis was conducted. Results: Bone mineral density values for the femur neck in former smokers were significantly lower than that in never smokers (P

prevalence of chronic kidney disease was analyzed based on the quartiles. Results: The results showed a positive correlation between an increasing tendency of the odds ratio (OR) for the prevalence rate of chronic kidney disease (95% confidence interval) and an increase in the TG/HDL-C ratio in an unadjusted model for Korean adults (P for trend

Background: There is little research regarding whether working as a physician affects cancer risk. Moreover, there is no research on cancer prevalence among physicians in Korea. This study utilized the Korea National Cancer Incidence Database to determine whether the prevalence of cancer among physicians differs from the prevalence of cancer within the general population. Methods: We analyzed the medical records of a representative sample of 382 doctors who underwent a health examination between 2010 and 2013 at a health examination center in a Ewha Womans University Medical Center. Cancer incidence was measured as cases that were eventually diagnosed as cancer according to a biopsy. Results: We collected medical records from 382 physicians (mean age, 51.9±8.1 years) and calculated the standardized prevalence ratios compared to the general population. Thirty physicians (9 male and 21 female) were identified as having cancer. Physicians had a significantly higher prevalence of cancer compared to the general population. Cancer prevalence in male physicians was found to be 2.47 times higher than the prevalence expected within the general population (P=0.006). Among female physicians, cancer prevalence was 3.94 times higher than that in the general population (P

In this study, we aimed to identify a toxic mechanism and the potential health effects of ambient dusts in an underground subway station. At 24 h exposure to human bronchial epithelial (BEAS-2B) cells (0, 2.5, 10, and 40 μg/mL), dusts located within autophagosome-like vacuoles, whereas a series of autophagic processes appeared to be blocked. The volume, potential and activity of mitochondria decreased in consistent with a condensed configuration, and the percentage of late apoptotic cells increased accompanying S phase arrest. While production of reactive oxygen species, expression of ferritin (heavy chain) protein, secretion of IL-6, IL-8 and matrix metalloproteinases, and the released LDH level notably increased in dust-treated cells (40 μg/mL), intracellular calcium level decreased. At day 14 after a single instillation to mice (0, 12.5, 50, and 200 μg/head), the total number of cells increased in the lungs of dust-treated mice with no significant change in cell composition. The pulmonary levels of TGF-β, GM-CSF, IL-12 and IL-13 clearly increased following exposure to dusts, whereas that of CXCL-1 was dose-dependently inhibited. Additionally, the population of cytotoxic T cells in T lymphocytes in the spleen increased relative to that of helper T cells, and the levels of IgA and IgM in the bloodstream were significantly reduced in the dust-treated mice. Subsequently, to improve the possibility of extrapolating our findings to humans, we repeatedly instilled dusts (1 time/week, 4 weeks, 0.25 and 1.0 mg/head) to monkeys. The total number of cells, the relative portion of neutrophils, the level of TNF-α significantly increased in the lungs of dust-treated monkeys, and the expression of cytochrome C was enhanced in the lung tissues. Meanwhile, the pulmonary level of MIP-α was clearly reduced, and the expression of caveolin-1 was inhibited in the lung tissues. More importantly, inflammatory lesions, such as granuloma, were seen in both mice and monkeys instilled with dusts. Taken together, we conclude that dusts may impair the host's immune function against foreign bodies by inhibiting the capacity for production of antibodies. In addition, iron metabolism may be closely associated with dust-induced cell death and inflammatory response.

Aim The main purposes of the study were (i) to evaluate serum vitamin D concentration in the forms of 25(OH)D2 , 25(OH)D3 and total 25(OH)D in Korean postmenopausal women using the LC-MS/MS method, which offers increased sensitivity and selectivity; (ii) to determine the relationship between the bone turnover marker, parathyroid hormone (PTH) and 25(OH)D3 , total 25(OH)D separately; and (iii) to determine the factors that may be associated with vitamin D deficiency using body composition analysis and laboratory blood tests. Method A total of 200 postmenopausal women were recruited from November 2012 to March 2014. To control for seasonal ultraviolet exposure time differences in serum 25(OH)D, laboratory tests were performed only from November to March when vitamin D is not synthesized. Independent relationships between 25(OH)D3 , total 25(OH)D and other variables were assessed by multiple regression analysis. Results The mean serum 25(OH)D2 , 25(OH)D3 and total 25(OH)D levels were 0.51 (±0.44) ng/mL, 14.23 (±7.05) ng/mL and 14.69 (±7.13) ng/mL, respectively. Both 25(OH)D3 and total 25(OH)D were positively correlated with erythrocyte sedimentation rate (ESR), Apo A-I and C-terminal cross-linked telopeptides of type I collagen in Korean postmenopausal women. Both serum 25(OH)D3 and total 25(OH)D were negatively correlated with alkaline phosphatase , PTH and percent body fat. However, osteocalcin showed a negative correlation (r = -0.451; P = 0.041) with only 25(OH)D3 and not with total 25(OH)D (r = -0.417; P = 0.064). Conclusion Both 25(OH)D3 and total 25(OH)D were negatively correlated with PTH, a bone formation marker (alkaline phosphatase) and percent body fat. Both 25(OH)D3 and total 25(OH)D were positively correlated with a bone resorption marker (C-terminal cross-linked telopeptides of type I collagen), ESR and Apo A-I after multiple regression analysis.

Despite the previous studies showing the relationship between microalbuminuria and insulin resistance, longitudinal effect of insulin resistance on development of microalbuminuria is not clearly identified in non-diabetic population.One thousand six hundred three non-diabetic Korean men without microalbuminuria in 2005 had been followed up for the development of microalbuminuria until 2010. Microalbuminuria was evaluated by urine-albumin creatinine ration, and insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Cox proportional hazards model was used to estimate the risk for microalbuminuria according to the tertile of HOMA-IR.During 5465.8 person-y of average follow-up, microalbuminuria developed in 76 (4.7%) participants. Incidence of microalbuminuria increased in proportion to the level of HOMA-IR (tertile 1: 3.0%, tertile 2: 4.1%, tertile 3: 7.1%, P0.001). When the 1st tertile of HOMA-IR was set as reference, hazard ratios and 95% confidence interval were 1.15 (0.56-2.35) and 2.07 (1.05-4.09) for those in the 2nd and 3rd tertiles of HOMA-IR, even after adjusting multiple covariates, respectively (P for linear trend=0.054).Increased insulin resistance was a predictor of microalbuminuria in Korean men.

Aims There have been several studies on the association between metabolic syndrome (MetS) and microalbuminuria. However, none has examined whether MetS is associated with the prospective development of microalbuminuria. Accordingly, we performed a prospective study to evaluate the longitudinal effects of baseline number of MetS traits on the development of microalbuminuria in Korean men. Methods 1649 Korean men without microalbuminuria in 2005 were included and followed prospectively until 2010 with the endpoint being the development of microalbuminuria. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Microalbuminuria was evaluated by urine albumin creatinine ratio (UACR). Risk estimations for development of microalbuminuria were analyzed according to the number of MetS traits using multivariate adjusted Cox proportional hazards model. Results During 5611.8 person-years of follow-up (median 3.40 ± 1.46 years), microalbuminuria developed in 91 (5.5%) participants between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% confidence interval) for development of microalbuminuria comparing 1, 2 and 3–5 MetS traits vs 0 were 2.57 (0.97–6.82), 2.94 (1.09–7.98) and 3.85 (1.37–10.86), respectively. Conclusions The number of MetS traits independently associated with the future development of microalbuminuria during the 5-year follow-up period, and MetS per se was an independent risk factor for microalbuminuria.

Considering that cigarette smoke condensate (CSC) is primarily absorbed through the alveoli in the lungs, herein, we used a mouse alveolar macrophage cell line (MH-S cells). After 24 h exposure, CSC decreased dose-dependently cell viability accompanying an increase in intracellular ROS and NO level. CSC structurally or functionally damaged organelles including mitochondria, ER and lysosome and enhanced the expression of proteins related to apoptosis, ER stress and DNA damage accompanying an elevated proportion of annexin V-bound cells. Meanwhile, the expression of certain proteins related to mitochondrial dynamics (OPA1 and DRP1) and autophagy (ATG5) did not overall show significant dose-dependent change in cells exposed to CSC. More importantly, conversion of LC3-I to LC3B-II, a representative marker for autophagy, was also unclear. Considering that intracellular organelles work together in harmony to perform defense mechanism against foreign bodies, we investigated changes in immune response following CSC exposure. The level of IFN-γ and MIP-1α was elevated in CSC-exposed cells, whereas the MCP-1α level decreased. The expression of chemokine receptors (CD195 and CXCR2) and an adhesion molecule (CD54) increased by CSC treatment, the expression of certain antigen presentation-related proteins (MHC class II, CD40, and CD80) were also enhanced. Meanwhile, the expression of CD86, a co-stimulatory molecule for antigen presentation, dose-dependently decreased. In conclusion, we suggest that CSC may induce apoptotic cell death and disturbance in host defense mechanisms by impairing function of cellular components.

Graduate School of Education, Seoul National University,Seoul, KoreaOBJECTIVES: This study investigated the associationbetween bone mineral density (BMD) and periodontitisin a representative sample of Korean adults.MATERIAL AND METHODS: Of 36 188 individuals whoparticipated in the Korea National Health and NutritionExamination Survey in 2008, 2009, and 2010, 9977participants aged ≥40 years were included in this cross-sectional study. The associations of BMD of lumbarspine, total femur, and femoral neck with periodontitiswere investigated using logistic regression analysis.Additionally, dose–response relationships with BMDdivided into quintiles and the association between oste-oporosis and periodontitis were investigated.RESULTS: With the set of Community PeriodontalIndex (CPI) ≥ 3 as a dependent variable, logistic regres-sion analysis revealed that a decrease of BMD was sig-nificantly associated with higher odds of periodontitis[range of adjusted odds ratios (AORs); 1.15–1.20,P < 0.001 for all BMD sites]. Similarly, these associa-tions were also found in the CPI 4 model. With regardto dose–response relations, the lower the BMD quintile,the higher the AORs appeared with statistical signifi-cance in the CPI ≥ 3 model. (P for trend < 0.001) Partic-ipants with osteoporosis had 2.26 and 1.91 times higherodds for CPI ≥ 3 and CPI 4, respectively, than thosewith normal BMD, indicating a significant associationbetween the two diseases.CONCLUSIONS: Our results suggest that BMD issignificantly associated with periodontitis.Oral Diseases (2014) 20, 609–615Keywords: osteoporosis; periodontitis; bone mineral density;osteopenia; National Health and Nutrition Examination Survey;Community Periodontal Index

Background Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. Conclusion A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Objective Cardiovascular disease risk increases after menopause, which may be related to insulin resistance, and arterial stiffness is a significant predictor of atherosclerosis. We investigated the relationships among insulin resistance, adiponectin, and arterial stiffness in normoglycemic normotensive postmenopausal women. Methods From 9,555 participants who had routine health checkups, 455 normoglycemic normotensive postmenopausal women were enrolled. Serum concentrations of glucose, total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness. Results The women were stratified into three groups according to their HOMA-IR values, and comparisons were made among the three groups. There were significant differences in metabolic parameters between the groups. The mean age, body mass index, waist circumference, fasting plasma glucose, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), aortic PWV, and peripheral PWV increased sequentially with the degree of insulin resistance. Meanwhile, HDL-C and adiponectin levels decreased with the worsening of insulin resistance. Age, body mass index, fasting plasma glucose, TG, insulin, SBP, HOMA-IR, aortic PWV, and peripheral PWV were significantly higher in women with central obesity, and HDL-C and adiponectin were significantly lower in women with central obesity. Aortic PWV and peripheral PWV were significantly correlated with age, waist circumference, total cholesterol, SBP, DBP, insulin, and HOMA-IR, but adiponectin was not associated with PWV. The results of multiple regression analysis indicated that SBP, DBP, and insulin resistance were independently correlated with PWV. Conclusions Insulin resistance was independently associated with PWV in normoglycemic normotensive postmenopausal women.

Background: Several reports have raised the possibility that newly addressed lipid measures might be superior to the traditional ones for cardiovascular risk prediction. However, data on the associations between these lipid measures with metabolic syndrome (MetS) is limited. Methods and Results: A cross-sectional study of participants in routine health examinations was performed. The associations between lipid measure variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, LDL-C/HDL-C, TG/HDL-C ratio and non-HDL-C) and MetS, insulin resistance (IR) by homeostatic model assessment (HOMA) and adiponectin were analyzed in 6,546 participants (3,820 men; mean age 46.0±9.2 years in men, 44.6±9.5 years in women). In multivariable adjusted regression analysis, the 3 lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C showed significant association with the number of MetS components, HOMA and log adiponectin level in both men and women without MetS (P

The aims of this study were to determine (1) whether the urinary mid pregnancy and placental delivery oxidative stress levels are related to the intrauterine condition and (2) whether long-lasting adverse oxidative stress is related to the birth size. We investigated pregnant women when they were at 24-28 weeks of pregnancy from October 2001 to May 2003 and at their delivery. Samples were obtained at each investigation time. Other information of mothers and their birth records were tracked from medical charts at Ewha Womans University Hospital in Seoul, South Korea. We quantified mid pregnancy oxidative stress by measuring urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 272 subjects. Intrauterine oxidative stress at delivery was measured by placental levels of 8-OHdG and MDA in 54 and 38 subjects, respectively. To identify the correlated intrauterine oxidative stress conditions, we evaluated kappa statistics and Pearson's correlations between maternal and placental oxidative stress. The relationships between intrauterine oxidative stress and birth sizes were examined by a general linear model. The levels of oxidative stress were divided to two groups based on their 75th percentile values. There was no correlation between urinary mid pregnancy and placental delivery oxidative stress levels for both MDA (kappa index=0.32, r=0.21) and 8-OHdG (kappa index=-0.13, r=-0.11). Both the urinary mid pregnancy and delivery 8-OHdG levels were significantly related to birth size. The birth size was largest in the 8-OHdG group. In addition, birth size was worse in the group with both high urinary mid pregnancy and placental oxidative stress than in any other combinations of low and high groups of urinary mid pregnancy and placental delivery oxidative stress. This evidence for a weak correlation between urinary mid pregnancy and placental delivery oxidative stress levels and its interactive effects on birth size suggest that the period from the middle to the end of pregnancy is critical window to intrauterine growth and also represents a modifiable period of the intrauterine condition. Therefore, applying interventions to pregnant women with high oxidative stress levels at midterm could contribute to increasing birth sizes.

We aimed to assess how metabolic profiles, surrogate markers of insulin resistance, and subclinical atherosclerosis are interrelated in subjects with impaired fasting glucose (IFG) and investigate whether the diagnosis of metabolic syndrome (MetS) further increases the risk of cardiovascular disease among subjects already at risk. We analyzed 1739 Korean subjects with IFG. The parameters of MetS, plasma adiponectin level, and pulse wave velocity (PWV) were assessed. Subjects with MetS had unfavorable metabolic parameters, lower adiponectin level, and higher peripheral PWV compared to those without MetS. Adiponectin correlated with fasting glucose, waist circumference, triglyceride, HDL-cholesterol, BMI, HOMA-IR, and the number of MetS components. In addition to blood pressure, peripheral PWV was associated with triglyceride, waist circumference, and the number of MetS components while aortic PWV correlated positively with fasting plasma glucose. Multiple linear regression analysis revealed that adiponectin correlated with HDL-cholesterol, HOMA-IR, fasting glucose, waist circumference, and triglyceride, peripheral PWV with blood pressure, body mass index, waist circumference, and the number of MetS components, and aortic PWV with fasting plasma glucose. In subjects with IFG, concurrent MetS increases PWV and has an unfavorable effect on cardiovascular risks, and these risks were further increased by additional MetS components.

As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well-known risk factors for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. The WC, BMI, and serum adiponectin were measured in 4459 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high-density lipoprotein (HDL) cholesterol (P < .001). After adjusting for age, BMI, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in women but not men. The combined effects of WC and adiponectin on diabetes progressively increased; however, the interaction of these 2 variables was not statistically significant. The combined effect of BMI and adiponectin on diabetes showed similar results. These results suggest that adiponectin was associated with diabetes. The association was independent of BMI and WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC and BMI on diabetes.

Pregnancy is associated with increased susceptibility to oxidative stress. Deficiencies in antioxidants during pregnancy and placental oxidant-antioxidant imbalance may impair the development of the fetoplacental unit or the eventual offspring. In order to elucidate the association of prenatal status of vitamin C with the oxidative stress and apoptotic activity in normal full-term placentas, we evaluated the content of placental lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and the trophoblast apoptotic index in normal-term human pregnancies. Tissue samples of placentas obtained from 80 normal-term pregnancies were categorized into 40 cases with a lower level of prenatal vitamin C (8.997 microg/ml) and 40 cases with a higher level of prenatal vitamin C (or =11.734 microg/ml). We evaluated the placental LOX-1 content and the trophoblast apoptotic index with Western blot analysis and immunohistochemistry, and then determined their correlation with the prenatal status of vitamin C. We confirmed that the trophoblast expression for the endothelial scavenger receptor LOX-1 and the apoptotic activity were significantly lower in the group with a higher prenatal level of vitamin C, indicating that placental oxidative stress and the apoptotic index were associated with the maternal status of vitamin C. We therefore postulate that the maternal status of antioxidant vitamins during pregnancy can affect fetal development.

Background Insulin resistance (IR) reduces reactivity of the target organ to blood insulin. Researchers have attempted to evaluate IR using various serum lipid concentration ratios. We aimed to determine the most strongly IR-predictive lipid profile ratios for each sex by studying associations between lipid concentration ratios and IR using data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1) 2010. Methods Overall, 8958 individuals participated in health interview and examination surveys. Among them, 1910 individuals who completed physical examinations and 8-h fasting blood tests and were older than 20 years of age were enrolled (929 men and 981 women). The lipid-ratio-related study outcomes were the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglyceride (TG)/HDL-C, and non-HDL-C (LDL-C + TG/5)/HDL-C ratios. We divided subjects into 4 groups according to lipid profile ratio quartiles for a comparison of homeostasis model assessment (HOMA)-IR values. Regression analyses were performed after adjusting for the confounding factors of age, body mass index, and diabetes mellitus history. Results HOMA-IR values tended to increase significantly along with LDL-C/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios in both sexes. In men, multiple linear regression analyses showed that after adjusting for confounding factors, a significant positive association remained only with the LDL-C/HDL-C ratio (p = 0.0238, R2 = 0.3605, root mean squared error [MSE] =0.3512). In women, multiple linear regression analyses showed that after adjusting for confounding factors, significant positive associations remained with the LDL-C/HDL-C (p

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD). DESIGN: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group. SETTINGS: University medical centers and community geriatric hospitals in Korea. PARTICIPANTS: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health. INTERVENTION: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo. MEASUREMENTS: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale. RESULTS: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity. CONCLUSIONS: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Human N-acetylglucosaminyltransferase-III (GnT-III) has not been hitherto purified from either tissue or cell line. Although rat GnT-III has been purified from rat kidney tissue, the procedure involves laborious and complex steps. We have developed a simplified procedure based on a QAE (diethyl[2-hydroxypropyl]aminoethyl)-Sepharose and an immunoaffinity chromatography technique. The immunoaffinity chromatography utilized a monoclonal antibody to human aglycosyl recombinant N-acetylglucosaminyltransferase-III. With the new procedure, human N-acetylglucosaminyltransferase-III was purified from hepatocellular carcinoma tissues with an increase in the specific enzyme activity of 378-fold.

ISIS 481464 is a constrained ethyl (cEt) modified phosphorothioate antisense oligonucleotide (ASO) targeting signal transducer and activator of transcription 3 (STAT3) studied in mice and monkey to support oncology clinical trials. Six-week toxicology studies were performed in mice and cynomolgus monkey (up to 70 and 30 mg/kg/week respectively). Reduction in STAT3 protein up to 90% of control was observed in monkey. Cynomolgus monkey was considered the most relevant species to human with respect to pharmacokinetic properties, but mice are useful in their relative sensitivity to the potential proinflammatory and hepatic effects of oligonucleotides. In monkeys, there was no impact on organ function at doses up to 30 mg/kg/week for 6 weeks. Minimal to slight proximal tubular epithelial cell degeneration and regeneration within the kidney was observed, which had no impact on renal function and showed reversibility at the end of the treatment-free period. Additionally, mild and transient activated partial thromboplastin time elevations and mild increases in complement Bb were observed at the higher doses by intravenous dosing only. In mice, the alterations at 70 mg/kg/week included spleen weight increase up to 1.4-fold relative to control, increases in alanine aminotransferase and aspartate aminotransferase up to 1.8-fold over control, interleukin-10 increases up to 3.7-fold, and monocyte chemoattractant protein-1 increase up to 1.9-fold over control. No significant clinical pathology or histopathology changes were seen in mice at 20 mg/kg/week or less. The toxicity profile of ISIS 481464 is consistent with effects observed with phosphorothioate ASOs containing 2'-O-methoxyethylribose modifications instead of cEt.

Background The sodium intake of Koreans was higher than that recommended by the World Health Organization. Urinary sodium, which is correlated with sodium intake, can be easily calculated by the Tanaka's equation. This study aimed to evaluate the association between urinary sodium and metabolic syndrome in Korean adults using the 2010-2011 Korean National Health and Nutrition Examination Survey (KNHANES). Methods A total of 5,870 participants from the 2010-2011 KNHANES were included in this study. Twenty-four hour urinary sodium was calculated by the Tanaka's equation using spot urine. Participants were divided into tertiles based on urinary sodium levels. The association between urinary sodium and metabolic syndrome was analyzed using multivariate logistic regression analysis. Results The odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome for the 2nd and 3rd tertile of urinary sodium levels was 1.51 (1.16-1.97) and 1.56 (1.23-1.97) compared to the lowest tertile of urinary sodium in men. The ORs and 95% CIs of metabolic syndrome in women were 1.20 (0.95-1.51) for the 2nd tertile and 2.16 (1.68-2.78) for the 3rd tertile. These associations remained statistically significant, even after adjusting for multiple covariates such as age, education, regular exercise, smoking, and alcohol consumption. Conclusion These findings indicate that urinary sodium is significantly associated with metabolic syndrome in Korean adults.

Mounting evidence suggests that not all obese subjects are at increased cardiovascular risk. However, the relationship between the metabolically healthy obese (MHO) phenotype and cardiovascular diseases (CVDs) or stroke remains unclear. Therefore, we retrospectively investigated the prevalence of CVDs or stroke according to metabolic health with obese.We studied 3695 subjects (40-85 years) from the Fifth Korean National Health and Nutrition Examination Survey. Participants were divided into 2 groups and 6 subgroups based on the body mass index (BMI) and metabolic syndrome (MetS) components: healthy (exhibiting none of the 5 MetS components) with the followings: healthy-normal weight (BMI < 23 kg/m), healthy-overweight (BMI = 23-24.9 kg/m), and healthy-obese (BMI ≥ 25 kg/m); and unhealthy (exhibiting 2 or more MetS components) with the followings: unhealthy-normal weight, unhealthy-overweight, and unhealthy-obese.In the healthy group (n = 1726), there were 76 CVDs or stroke patients (4.4%), whereas in the unhealthy group (n = 1969), there were 170 (8.6%). The prevalence was significantly different between the 2 groups (P < 0.001). However, the prevalence was not significantly different among healthy subgroups (P = 0.4072). The prevalence in unhealthy subgroups also demonstrated no statistically significant difference (P = 0.3798).We suggest that the prevalence of CVDs or stroke is different between metabolically healthy and unhealthy phenotype. Furthermore, MHO did not reveal higher CVDs or stroke prevalence rather than metabolically healthy other groups. Additional cohort studies are needed to explain causality between CVDs or stroke incidence and subjects exhibiting the MHO phenotype.

A strategy to produce sufficient anticoagulant properties with reduced risk of bleeding may be possible through inhibition of factor XI (FXI), a component of the intrinsic coagulation cascade. The objective of this work was to determine the safety profile of ISIS 416858, a 2′-methoxyethoxy (2′-MOE) antisense oligonucleotide inhibitor of FXI, with focus on assessment of bleeding risk. Cynomolgus monkeys administered ISIS 416858 (4, 8, 12, and 40 mg/kg/wk, subcutaneous) for up to 13 weeks produced a dose-dependent reduction in FXI (mRNA in liver and plasma activity) and a concomitant increase in activated partial thromboplastin time (APTT). ISIS 416858 (20 or 40 mg/kg/wk) reduced plasma FXI activity by 80% at 4 weeks of treatment that resulted in a 33% increase in APTT by 13 weeks with no effects on PT, platelets, or increased bleeding following partial tail amputation or gum and skin laceration. The dose-dependent presence of basophilic granules in multiple tissues in ISIS 416858–treated animals was an expected histologic change for a 2′-MOE antisense oligonucleotide, and no toxicity was attributed to hepatic FXI reduction. Basophilic granules reflect cellular drug uptake and subsequent visualization on hematoxylin staining. These results suggest that ISIS 416858 has an acceptable preclinical safety profile and is a promising clinical candidate to treat thrombotic disease.

This study examines the relationship between adherence to different dietary patterns and the presence of metabolic syndrome and its components among Korean adults. The sample consisted of 406 Korean adults aged 22 to 78 years recruited from hospitals. Metabolic syndrome was defined according to the criteria issued by the Adult Treatment Panel III, with the exception of central obesity, which was defined according to the Asian-Pacific criteria. Dietary information was obtained by means of a 24-hour recall and a 3-day food record, and factor analysis was used to define dietary patterns. Factor analysis identified 4 major dietary patterns, which explained 28.8% of the total variance, based on the percentage of total daily energy intake from each food group: Korean traditional, alcohol and meats, sweets and fast foods, and fruit and dairy. After controlling for all potential confounders, we found that the Korean traditional dietary pattern was not associated with individual components of the metabolic syndrome but was significantly associated with increased odds of having metabolic syndrome. The fruit and dairy pattern was significantly associated with decreased odds of impaired blood glucose, hypertriglyceridemia, and metabolic syndrome. Our findings suggest that the fruit and dairy pattern is associated with reduced risk of having metabolic syndrome.

A B-cell activating factor of the tumor necrosis factor (TNF) family (BAFF) is an essential B-cell survival factor. Myasthenia gravis (MG) is one of the most typical antibody-mediated autoimmune disorders. To test whether serum BAFF levels are increased in MG patients, we compared the serum BAFF levels of 40 MG patients with those of 30 healthy controls. Serum BAFF levels of MG group were significantly higher than those of healthy group. These results suggested that the BAFF might play a role in the immunopathogenesis of MG and further study on B-cell and T-cell activation may be needed.

Serum asialoglycoproteins (desialylated glycoproteins) concentration was reported to be elevated in patients with hepatic disease as compared with that of normal subjects. In this study, we measured serum asialo-alpha(1) acid glycoprotein (AsAGP) level by a solid-phase sandwich assay in which monoclonal antibody (mAb) to alpha(1)-acid glycoprotein and galactose-binding lectin, ricinus communis (RCA), have been employed as capture protein and probe protein, respectively. The mAb-RCA sandwich assay was sensitive (0.02 μg/ml) and specific for AsAGP. We have determined AsAGP concentration of 869 serum specimens and analyzed the results using l.38 and 2.24 μg/ml (AsAGP) as cut-off values, respectively. AsAGP level was 0.80+/-0.29 μg/ml (mean+/-S.D.) with 97 normal serum specimens and elevated primarily in patients with liver cirrhosis (LC) or hepatocellular carcinoma (HCC). Using 1.38 μg/ml as a cutoff, 4/97 normal subjects, 11/39 acute hepatitis and 26/159 non-hepatic disease exhibited a slight elevation, whereas, AsAGP level was significantly elevated in 182/230 LC and 63/72 HCC. Meanwhile, a cutoff of 2.24 μg/ml allowed significant differentiation of LC or HCC from chronic hepatitis. Serum AsAGP level appeared to increase progressively with increasing severity of liver disease in cirrhotic patients. Thus, serum AsAGP concentration, as measured by the new mAb-RCA sandwich assay, may be a useful differential marker as a diagnostic aid for LC or HCC.

Background Lung age, calculated from sex, forced expiratory volume in one second (FEV1), and height, was developed to illustrate premature changes to the lungs and could be used to motivate smoking cessation. However, this method has not been tested in association with smoking in Korea. The purpose of this study was to investigate the association of lung age with smoking and other factors in Korean males. Methods We reviewed the records of 1,100 healthy men who visited a health promotion center at Ewha Womans University Medical Center from January 2008 to June 2009. Lung age was calculated from FEV1 and normal predictive values of spirometry according to age in the Korean population. The difference between lung age and chronological age was evaluated in relation to smoking status, weight, body mass index, waist, muscle mass, fat mass, and exercise. Results The age difference was significantly higher in current smokers than in non-smokers (12.47 ± 19.90 vs. 7.30 ± 19.52, P < 0.001). Additionally, the age difference was positively correlated with life time pack-year (β = 0.223; P < 0.001) and fat mass (β = 0.462; P < 0.001). Lung age increased 1 year for 4.48 pack-year increase or for 2.16% increase in fat mass. Conclusion We found a significant relationship between lung age and both smoking status and fat mass in healthy Korean males. Lung age may be a useful tool for motivating cessation of cigarette smoking and management of risk factors related to obesity.

The goal of this study was to evaluate the association between gallbladder (GB) polyps and metabolic syndrome. A total of 5,685 healthy subjects were included, and 485 of these subjects had GB polyps and 744 had metabolic syndrome. In this study, metabolic syndrome was diagnosed according to standards suggested by the AHA/NHLBI ATP III 2005, and abdominal obesity (≥ 90 cm in men and ≥ 85 cm in women for Korean) was diagnosed according to standards set forth by the Korean Society for Study of Obesity. Biphasic logistic regression adjusted for age and gender was used to evaluate the association between metabolic syndrome and GB polyps. Subjects who were male (OR, 1.493; 95% CI, 1.11-2.00) and hepatitis B suface Ag (HBsAg) positive (OR, 1.591; 95% CI, 1.06-2.38) were significantly more likely to have GB polyps. The metabolic syndrome group had a higher risk of GB polyps (OR, 1.315; 95% CI, 1.01-1.69) than the group without metabolic syndrome. In conclusion, subjects who were HBsAg positive and male appear to be associated with the risk of GB polyps. The presence of metabolic syndrome also appears to be associated with the risk of GB polyps in Koreans.

Background Typical symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation. Extraesophageal (EE) symptoms such as cough and throat clearing are less commonly associated with GERD but represent a common presenting symptom for reflux testing. Proximal extent of refluxate into the larynx or even the lungs is proposed as a potential mechanism for EE symptoms. Aim We tested the hypothesis that EE symptoms are more frequently associated with proximal esophageal reflux than typical symptoms. Methods A blinded assessment was rigorously applied. Themultichannel intraluminal impedance-pH (MII-pH) tracings analyzed for this study were edited by one of the investigators so that none of the symptom markers were visible and the reflux associated symptoms reviewed were simply marked as symptom 1-5 for each patient. 815 consecutive MII-pH reports were reviewed to identify 40 patients with at least 5 symptom events preceded by a reflux episode, thus a total of 50 reflux related events in each of 4 symptom groups: cough, throat clearing, heartburn, and regurgitation. A second investigator blindly analyzed all 200 episodes by reporting the extent of the refluxate at 7, 9, 15, and 17 cm above the LES. Results The percentage of symptom related reflux extending proximally to 17 cm above the LES is similar among all four symptom types (Figure 1). At least 50% of all symptoms were associated with proximal reflux to 17 cm above the LES, with the numerically highest being regurgitation (60%). There is no significant difference between any of the values. Conslusion This study confirms the frequent association of proximal reflux with GERDrelated symptoms previously identified. However, as opposed to common beliefs, our data indicate that EE GERD-related symptoms are not more frequently associated with proximal reflux than typical GERD symptoms. Both EE and esophageal symptoms are associated with reflux to 17cm at least 50% of the time.