• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.303-311
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• 2002

This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.236-244
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• 2018

Taurine has been reported to prevent cardiovascular disease and improve liver function, diabetes, and platelet function. However, there are few studies on the effects of taurine in Koreans. The purpose of this study was to investigate the effect of basal doses of taurine on blood glucose, liver disease, and lipid diseases among Korean college students. The study included a taurine intake group and a control group; each group consisted of 15 students. Taurine was administered at a standard dose of 1,000 mg for 2 weeks postprandial. All subjects were excluded from medication or other food besides meals provided by the dormitory. The liver test gamma-glutamyl transferase (GGT) in the taurine group decreased to $23.53{\pm}25.73IU/L$ before intake and to $15.15{\pm}4.91IU/L$ after intake (P=0.186). Lipid metabolite triglyceride (TG) was $100.42{\pm}28.33mg/dL$ before intake and $80.22{\pm}17.08mg/dL$ after intake (P<0.05). Total cholesterol (T-Cho), low density cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). Consequently, taurine improved liver function and lipid metabolism. Hematologic tests showed a decrease in segmented neutrophil percentage and an increase in lymphocyte percentage. Thus, taurine also seems to be related to immunological function.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.3
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• pp.424-431
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• 2007

The aim of this study was to determine the effects of short road transportation in an open truck during hot season on live weight shrink, physiological responses, and carcass and meat quality of Omani sheep at 6 and 12 months of age. Thirty-six male sheep, 18 of each age group, were used. Age groups were assigned randomly to transported and not-transported groups. The transported group was transported to the slaughterhouse the day of slaughter in an open truck covering a distance of approximately 100 km. The average temperature during transportation was $37^{\circ}C$. The not-transported group was kept in a lairage of a commercial slaughterhouse with ad libitum feed and water for 48 h prior to slaughter. Blood samples were collected from sheep before loading and prior to slaughter via jugular venipuncture to assess their physiological response to transport in relation to hormonal levels. Animals were weighed just before loading onto a truck and after transport to assess shrinkage. Muscle ultimate pH, expressed juice, cooking loss percentage, WB-shear force value, sarcomere length and colour L*, a*, b* were measured on samples from longissimus dorsi, biceps femoris and semitendinosus muscles collected at 24 h postmortem at $1-3^{\circ}C$. Live weight shrinkage losses were 1.09 and 1.52 kg for 6 and 12 month transported sheep, respectively. The transported sheep had significantly (p<0.05) higher cortisol, adrenaline, noradrenaline, and dopamine concentration levels prior to slaughter at both ages than the not-transported sheep. Transportation significantly influenced meat quality characteristics of three muscles. Muscle ultimate pH and shear force values were significantly higher, while CIE L*, a*, b*, expressed juice and cooking loss were lower in transported than not-transported sheep. Age had a significant effect on meat quality characteristics of Omani sheep. These results indicated that short-term pre-slaughter transport at high ambient temperatures can cause noticeable changes in physiological and muscle metabolism responses in sheep.

• Journal of Preventive Medicine and Public Health
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• v.35 no.3
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• pp.229-235
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• 2002

Objectives : To evaluate the effects on the formation of benzidine-hemoglobin, and benzidine metabolite-hemoglobin adducts, caused by pretreatment with the known xenobiotic metabolism effectors, ethanol and phenobarbital, in rats administered Direct Black 38 dye. Methods : The experimental rats were divided into three groups: a control group, an ethanol group and a phenobarbital group. Rats were pretreated with ethanol (1g/kg) or phenobarbital (80mg/kg) 24 hours prior to the oral administration of Direct Black 38 (0.5mmol/kg), with the control group being administered the same amount of distilled water. Blood samples were obtained from the vena cava of 5 rats from each group prior to, and at 30 min, 3h, 5h, 9h, 12h, 24h, 48h, 72h, 96h, and 144h following the oral administration of Direct Black 38. Directly after sampling the blood was separated into hemoglobin and plasma, with the adducts being converted into aromatic amines by basic hydrolysis. Hydrolyzed benzidiene, monoacetylbenzidine and 4-aminobiphenyl were analyzed by reverse-phase liquid chromatography with an electrochemical detector, The quantitative amount of the metabolites was expressed by the hemoglobin binding index (HBI). Results : In the ethanol group, benzidine-, monoacetylbenzidine-, and 4-aminobiphenyl-HBI were increased to a greater extent than those in the control group. These results were attributed to the ethanol inducing N-hydrgxylation, which is related to the formation of the hemoglobin adduct, In the phenobarbital group, all the HBIs, with the exception of the benzidine-HBI, were increased to a greater extent than those of the control group. These results were attributed to the phenobarbital inducing N-hydroxylation related to the formation of the hemoglobin adduct. The N-acetylation ratio was only increased with the phenobarbital pretreatment due to the lower benzidine-HBI of the phenobarbital group compared to these of the control and ethanol groups. The N-acetylation ratios for all groups were higher than f for the duration of the experimental period. Although the azo reduction was unaffected by the ethanol, it was inhibited by the phenobarbital, The ratio of the benzidine-HBI in the phenobarbital group was lower than those of the ethanol the control groups for the entire experiment. Conclusion : Our results indicate that both ethanol and phenobarbital increase the formation of adducts by the induction of N-hydroxylation, but also induced N-acetylation. Phenobarbital decreased the formation of benzidine-HBI due to the decrease of the azo reduction. These results suggest that the effects or ethanol and phenobarbital need to be considered in the biochemical monitoring of Direct Black 38.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.311-319
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• 1996

DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins ($B_1\;and\;B_2$), is a drug currently being developed for hep atic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there's no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.3
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• pp.392-403
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• 2008

Four ruminally fistulated Hanwoo steers were used to determine the effects of level and degradability of dietary protein on ruminal fermentation, blood metabolites and concentration of soluble non-ammonia nitrogen (SNAN) in ruminal (RD) and omasal digesta (OD). Experiments were conducted in a $4{\times}4$ Latin square design with a $2{\times}2$ factorial arrangement of treatments. Factors were protein supplements with two ruminal crude protein (CP) degradabilities, corn gluten meal (CGM) that was low in degradability (rumen-degraded protein (RDP), 23.4% CP) or soybean meal (SBM) that was high in degradability (RDP, 62.1% CP), and two feeding levels of CP (12.2 or 15.9% dry matter). Ruminal fermentation rates and plasma metabolite concentrations were determined from the RD collected at 2-h intervals and from the blood taken by jugular puncture, respectively. The SNAN fractions (free amino acid, peptide and soluble protein) in RD and OD collected at 2-h intervals were assessed by ninhydrin assay. Mean ruminal ammonia concentrations were 40.5, 74.8, 103.4 and 127.0 mg/L for low CGM, high CGM, low SBM and high SBM, respectively, with statistically significant differences (p<0.01 for CP level and p<0.001 for CP degradability). Blood urea nitrogen concentrations were increased by high CP level (p<0.001) but unaffected by CP degradability. There was a significant (p<0.05) interaction between level and degradability of CP on blood albumin concentrations. Albumin was decreased to a greater extent by increasing degradability of low CP diets (0.26 g/dl) compared with high CP diets (0.02 g/dl). Concentrations of each SNAN fraction in RD (p<0.01) and OD (p<0.05) for high CP diets were higher than those for low CP diets, except for peptides but concentrations of the sum of peptide and free amino acid in RD and OD were significantly higher (p<0.05) for high CP diets than for low CP diets. Soybean meal diets increased free amino acid and peptide concentrations in both RD (p<0.01) and OD (p<0.05) compared to CGM diets. High level and greater degradability of CP increased (p<0.001) mean concentrations of total SNAN in RD and OD. These results suggest that RDP contents, increased by higher level and degradability of dietary protein, may increase release of free amino acids, peptides and soluble proteins in the rumen and omasum from ruminal degradation and solubilization of dietary proteins. Because SNAN in OD indicates the terminal product of ruminal metabolism, increasing CP level and degradability appears to increase the amount of intestine-available nitrogen in the liquid phase.

• Journal of Animal Science and Technology
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• v.52 no.4
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• pp.271-280
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• 2010

This study was conducted to investigate the effects of Aspergillus niger-derived multi-enzyme complex supplementation to feedrestricted lactating sows on performances, milk yield, blood profiles, and manure excretion as compared with ad libitum-fed sows without supplementation of enzyme. Fifty multiparous lactating Berkshire sows were allotted to 5 treatments of 10 sows per treatment during a 28-d lactation period and litter per sow was standardized to 9 suckling piglets. Treatments were ad libitum-fed sows without enzyme and feed-restricted sows supplemented with four increasing levels (0, 0.02, 0.04 and 0.08%) of multi-enzyme complex derived from Aspergillus niger. Blood samples from all sows were collected to determine serum metabolite concentrations before the morning feeding on d 27 of lactation. Litter body weight and a piglet weight at weaning, and litter weight gain significantly (P<0.05) increased with increasing levels of multi-enzyme complex, but there was no significant difference between ad libitum-fed sows without enzyme and feed-restricted sows supplemented with multi-enzyme complex. Body condition score and backfat depth at weaning significantly (P<0.05) increased as multi-enzyme complex level increased. Lactational backfat depth tended (P>0.05) to less decrease with increasing levels of enzyme complex. Serum inorganic phosphorus and non-esterified fatty acid concentrations significantly (P<0.05) increased with increasing levels of enzyme complex. Daily milk yield was not significantly different across treatments, but milk fat yield significantly (P<0.05) increased as multi-enzyme complex level increased. Manure output was significantly (P<0.01) higher for ad libitum-fed sows than for feed-restricted sows, but there was no significant difference among feed-restricted sows supplemented with increasing levels of multi-enzyme complex. Fecal phosphorus amount significantly (P<0.05) decreased with increasing levels of multi-enzyme complex. Feed costs of sows per litter weight gain were reduced by 1.25% to 9.67% with increasing levels of multi-enzyme complex as compared with ad libitum-fed sows without enzyme. The results indicated that multi-enzyme supplementation to feed-restricted lactating sows not only increased litter performances, but also was comparable to ad libitum-fed sows, resulting in reduced feed costs. Moreover, the reduction of fecal phosphorus amount with increasing levels of enzyme complex would contribute to the reduction of environmental pollution.

• Analytical Science and Technology
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• v.24 no.2
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• pp.69-77
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• 2011

Ethylene glycol (EG) is produced commercially in large amounts and is widely used as antifreeze or deicing solution for cars, boats, and aircraft. EG poisoning occurs in suicide attempts and infrequently, either intentionally through misuse or accidental as EG has a sweet taste. EG has in itself a low toxicity, but is in vivo broken down to higher toxic organic acids which are responsible for extensive cellular damage in various tissues caused principally by the metabolites glycolic acid and oxalic acid. The most conclusive analytical method of diagnosing EG poisoning is determination of EG concentration. However, victims are sometimes admitted at a late stage to hospitals or died during emergency treatment like a gastric lavage or found rotten dead, when blood EG concentrations are low or not detected. Therefore, in this study, the identification of EG was not only performed by gas chromatograpyc-mass spectrometry (GC-MS) following derivatization but also further toxicological analyses of metabolites, glycolic acid (GA) and oxalic acid (OA), were performed by ion chromatography in various biological specimens. A ranges of blood concentrations (3 cases) was $10\sim2,400\;{\mu}g/mL$ for EG, $224\sim1,164\;{\mu}g/mL$ for GA and ND $\sim40\;{\mu}g/mL$ for OA, respectively, In other biological specimens (liver, kidney, bile and pleural fluid), a range of concentrations (3 cases) was ND $\sim55,000\;{\mu}g/mL$ for EG, ND $\sim1,124\;{\mu}g/mL$ for GA and ND $\sim60\;{\mu}g/mL$ for OA, respectively. Liver and kidney tissues were recommended specimens including blood because OA, a final metabolite of EG, was identified large amounts in these despite no detectable EG caused by some therapy.

• Journal of Preventive Medicine and Public Health
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• v.36 no.2
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• pp.93-100
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• 2003

Objectives : Because shipyard workers are involved with various manufacturing process, they are exposed to many kinds of hazardous materials. Welders especially, are exposed to bisphenol-A (BPA) during the welding and flame cutting of coated steel, This study was conducted to assess the exposure status of the endocrine disrupter based on the job-exposure matrix. The effects of the genetic polymorphism of xenobiotic enzyme metabolisms involved in the metabolism of BPA on the levels of urinary metabolite were investigated. Methods : The study population was recruited from a shipyard company in the f province. A total of 84 shipbuilding workers 47 and 37 in the exposed and control groups, respectively, were recruited for this study. The questionnaire variables included, age, sex, use of personal protective equipment, smoking, drinking and work duration. The urinary metabolite was collected in the afternoon and correction made for the urinary creatinine concentration. The of the CYP1A1, CYP2E1 and UGT1A6 genotypes were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with the DNA extracted from venous blood. Results : The urinary BPA level in the welders group was significantly higher than in the control group (p<0.05). The urinary BPA concentration with the wild type UGT1A6 was higher than the other UGT1A6 genotypes, but with no statistical significant. From themultiple regression analysis of the urinary BPA, the regression coefficient for job grade was statistically significant (p<0.05). Conclusions : The grade of exposure to BPA affected the urinary BPA concentration was statistically significant. However, the genetic polymorphisms of xenobiotics enzyme metabolism were not statistically significant. Further investigation of the genetic polymorphisms with a larger sample size is needed.