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Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

Objective: Increased levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans., Subjects: A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included., Measurements: We examined IL-6 -174G-->C, -572C-->G, -597G-->A and -1363G-->T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP)., Results: Homozygosity for the rare G allele IL-6 -572C-->G was associated with a higher risk of T2DM [OR 1.69 (95%CI 1.11-2.58), P = 0.015]. Serum IL-6 concentrations were associated with the IL-6 -572C-->G genotype in control subjects (G/G: 2.33 +/- 0.41: C/G: 1.53 +/- 0.09: C/C: 1.72 +/- 0.08 ng/l, P = 0.023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13.6 +/- 2.9: C/G: 9.2 +/- 0.6: C/C: 7.8 +/- 0.4 mg/l, P = 0.003). The C-allele at the IL-6 -174 SNP was very rare (< 0.01) and -597G-->A and -1363G-->T were monomorphic in this population., Conclusions: Our data demonstrate that the IL-6 -572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM.

Background: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a lipoprotein-bound enzyme that can release atherogenic isoprostanes from esterified phospholipids and that may be involved in inflammation and atherosclerosis., Objective: This study investigates the association between Lp-PLA(2) activity and coronary artery disease (CAD) in relation to oxidative stress markers, in particular urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha))., Design: We conducted a case-control study in which the cross-sectional relation between Lp-PLA(2) activity, lipoproteins, and oxidative stress markers was determined in 799 patients with angiographically confirmed CAD and 925 healthy controls., Results: Lp-PLA(2) activity was significantly (P < 0.001) higher in CAD cases than in controls (32.9 +/- 0.46 and 29.7 +/- 0.42 nmol . mL(-1) . min(-1), respectively). Both elevated Lp-PLA(2) activity and urinary excretion concentrations of 8-epi-PGF(2alpha) were associated with greater CAD risk (P for trend < 0.001). Odds ratios for the upper quartiles of Lp-PLA(2) activity and 8-epi-PGF(2alpha).excretion were 2.47 (95% CI: 1.79, 3.40) and 2.19 (1.52, 3.15), respectively, after adjustment for sex, age, BMI, blood pressure, smoking and alcohol consumption status, and LDL and HDL cholesterol. When we examined the additive effect of both markers for CAD risk, the relation between 8-epi-PGF(2alpha) and CAD was weakened above the second quartile of Lp-PLA(2) activity. Moreover, Lp-PLA(2) activity was positively correlated with urinary excretion concentrations of 8-epi-PGF(2alpha) in controls (r = 0.277, P < 0.001) and cases (r = 0.202, P < 0.001) and with the tail moment of lymphocyte DNA (r = 0.213, P < 0.001) in controls., Conclusion: This study shows an association of elevated Lp-PLA(2) activity with CAD risk in relation to oxidant stress and thus supports a proatherogenic role of Lp-PLA(2).

Background: In clinical practice, using the patient's waist circumference (WC) to evaluate visceral obesity may underestimate disorders with a metabolic origin. This study examined whether or not the WC derived from the cut-off point of the visceral fat area (VFA) can reflect the features of metabolic syndrome (MetS) in premenopausal women., Methods and Results: Computed tomography-scanned VFA, MetS components and the concentrations of high-sensitivity C-reactive protein (CRP) and adiponectin were measured in a total of 349 premenopausal women. The VFA at the L1 and the L4 sites was a significant index (p<0.001) of incremental MetS risk. Receiver-operating characteristic curve analysis showed that 75 cm2 of VFA at L4 and 87.5 cm2 at L1 were the optimal thresholds for discrimination of MetS risk. Significant differences in all MetS components, as well as CRP (p<0.05) and adiponectin levels (p<0.005), were observed when subjects were subdivided by the L4 VFA cut-off point (<75/>or=75 cm2), whereas there was a significant difference only in the triglycerides level in the groups divided by WC (WC<88/>or=88 cm). Moreover, subjects with a lower WC-higher VFA showed a similar pattern in MetS components and lower adiponectin than those with a higher WC-higher VFA., Conclusions: This study clarified that VFA rather than WC is a major determinant of MetS risk in premenopausal women.

Growing evidence suggests that polymorphisms at position -174 and -572 in interleukin-6 (IL-6) gene are associated with various manifestations of atherosclerosis. We investigated the genotype effects of IL-6 -174 and -572 polymorphisms on circulating levels of inflammatory markers in Korean men with coronary artery disease (CAD). CAD patients were subdivided into 2 groups; those patients treated without lipid-lowering drug (LLD) (n = 173) and those treated with LLD (n = 353). No significant differences existed between the 2 groups in age, body mass index, blood pressure, serum glucose, alcohol consumption, cigarette smoking, and the proportions of antihypertensive and antiplatelet therapies. IL-6 - 572 C>G polymorphism was only observed in this population. In CAD patients not taking LLD, the G/G genotype of the -572C>G polymorphism was associated with greater concentrations of IL-6 (C/C: 4.1 +/- 0.8 pg/mL, C/G: 3.7 +/- 0.7, G/G: 12.4 +/- 6.6; P = 0.031), C-reactive protein (CRP) (C/C: 1.9 +/- 0.4 mg/dL, C/G: 2.7 +/- 0.8, G/G: 10.1 +/- 3.9; P = 0.002), fibrinogen (C/C: 334 +/- 6 mg/dL, C/G: 345 +/- 13, G/G: 429 +/- 38; P = 0.003), and oxidized low-density lipoprotein (ox-LDL) (C/C: 59 +/- 2 mg/dL, C/G: 55 +/- 3, G/G: 71 +/- 6; P = 0.041) than those with C/C or C/G. However, in the LLD group, no difference existed in circulating levels of IL-6, CRP, fibrinogen, and ox-LDL across the genotype after adjustment of age. This study suggests that circulating levels of IL-6 and its related proteins such as CRP and fibrinogen are associated with genotype at a promoter polymorphism (-572C>G) of the IL-6 gene in Korean men with CAD not taking LLD. LLD, mostly statin in this study, might reduce the exaggeration of G/G genotype-raising effect on inflammatory markers.

Background: Serum C-reactive protein (CRP) levels, closely associated with cardiovascular disease (CVD) risk are influenced by CRP or interleukin-6 (IL-6) single nucleotide polymorphism (SNPs). However, it is still controversial. Therefore, we investigated the association of IL-6/CRP SNPs and serum CRP levels or other CVD risk factors in healthy adult Korean men., Methods: In healthy adult men (age>or=20 years, n=677), we genotyped IL-6-572C>G and CRP SNPs (-717G>A, 1444C>T, 2147A>G) and measured anthropometric parameters, lipid profile, serum levels of CRP and IL-6 and insulin resistance., Results: At IL-6-572C>G (n=677), subjects with G/G genotype (n=42) showed higher concentrations of CRP (P=0.027) and IL-6 (P=0.028) as compared with C allele carriers after age-adjustment (C/C: n=371, C/G: n=264). Fasting insulin and homeostatis model assessment insulin resistance (HOMA-IR) were also higher in G/G genotype. However, there were no significant differences in other metabolic biomarkers. Among 677 study subjects, 676 were genotyped at CRP-717G>A (G/G: n=513, G/A: n=150, A/A: n=13), 672 at CRP+1444C>T (C/C: n=580, C/T: n=85, T/T: n=7), and 668 at CRP+2147A>G (A/A: n=273, A/G: n=296, G/G: n=99). There were no significant differences in CRP concentrations and other markers related to CVD risk according to each CRP SNP genotype. However, we could find the additive gene-gene interaction between IL-6-572C>G and CRP SNPs on CRP concentration; subjects with the 'G/G' at IL-6-572 showed the highest CRP levels when they have variant allele at CRP SNPs after adjusted for age, body mass index, cigarette smoking and alcohol drinking (-717G>A: F=7.806, P=0.005; CRP+1444C>T: F=8.398, P=0.004; and CRP+2147A>G: F=7.564, P=0.006, respectively) Particularly, G allele carriers at CRP+2147A>G in subjects with IL-6-572G/G showed highest HOMA-IR (F=9.092, P=0.003)., Conclusion: The present data showed that serum CRP levels and other CVD risk factors appeared more influenced by IL-6-572C>G rather than CRP SNPs (-717G>A, 1444C>T, and 2147A>G), however CRP levels and insulin resistance may be additively affected by IL-6-572 and CRP SNP, particularly when subjects with G/G genotype at IL-6-572 have allele variant at CRP SNPs.

Background: As information about the health risks associated with air pollution has become available, attention has focused increasingly on susceptible persons such as children and persons with preexisting respiratory diseases, such as asthma., Methods: We investigated the association between outdoor air pollution and asthma attacks among children under 15 years of age in Seoul, Korea. We estimated the relative risks of hospitalization associated with an interquartile range (IQR) increase in pollutant concentrations and used time series analysis of the counts by means of the generalized additive Poisson model., Results: The estimated relative risk of hospitalization for asthma was 1.07 (95% confidence interval [CI] = 1.04-1.11) for particulate matters less than or equal to 10 microm in aerodynamic diameter (IQR = 40.4 microg/m3); 1.11 (95% CI = 1.06-1.17) for sulfur dioxide (IQR = 4.4 ppb); 1.15 (95% CI = 1.10-1.20) for nitrogen dioxide (IQR = 14.6 ppb); 1.12 (95% CI = 1.07-1.16) for ozone (IQR = 21.7 ppb); and 1.16 (95% CI = 1.10-1.22) for carbon monoxide (IQR = 1.0 ppm)., Conclusions: These findings support the hypothesis that air pollution at levels below the current standards of Korea is harmful to sensitive subjects such as asthmatic children.