• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.1-7
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• 1987

The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.27-37
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• 1990

The extrafetal transfer of $Li^{+}$ in amniotic fluid was studied in 45 pregnant rabbits. LiCl solution was administered either intravenously to mother or directly into the amniotic sac and monitored the appearance and disappearance of $Li^{+}$ in the amniotic fluid, then calculated the transfer rate of $Li^{+}$ of extrafetal origin. To study the transplacental $Li^{+}$ transfer, a solution of 150 mM LiCl was infused continuously via maternal vein (initial dose: 0.7 mmol/kg, maintaining dose: 0.03 mmol/kg/min) and the $Li^{+}$ concentration was measured in maternal blood and amniotic fluid after 60 and 120 minutes of infusion. Change in the volume of aminotic fluid was determined by Congo red dilution method at the same time. Effects of duration of gestation was not considered in this study. Extrafetal transport of $Li^{+}$ into the amniotic fluid was estimated by comparing the $Li^{+}$ concentration and volume of amniotic fluid determined before and after ligating the placental vessels. Extrafetal $Li^{+}$ transport from the amniotic fluid was determined by observing the time dependent disappearance of $Li^{+}$ and Congo red in amniotic fluid after injecting 0.5 ml solution of 15 mM or 90 mM LiCl and 50 mg/ml Congo red. Following are the results obtained: 1) During infusion of LiCl through maternal vein the ratio of the aminotic $Li^{+}$/maternal plasma $Li^{+}$ increased significantly along with the increment of fetal weight. 2) The volume of amniotic fluid of larger fetuses than 20.5 gm increased significantly during administration of LiCl while that of smaller fetuses did not change. 3) After umbilical cord ligation the $Li^{+}$ concentration of amniotic fluid of larger fetuses than 20.5 gm was decreased to $59.9{\pm}10.3%$ and $56.9{\pm}42.9%$ $(mean{\pm}S.D.)$ of those of control group after 60 and 120 minutes of LiCl infusion respectively. In amniotic fluid of smaller fetuses than 20.5 gm, there was no significant difference between control and ligation groups. 4) The disappearance rate of Congo red in the amniotic fluid was $45.2{\pm}8.2%/hr$. 5) The disappearance rate of $Li^{+}$ after intraamniotic injection of LiCl depended on the amount injected. On injecting $7.5\;{\mu}mol$ LiCl, $Li^{+}$ disappeared rapidly from the amniotic fluid and the rates after 60 min and 90 min were $97.0{\pm}2.8,\;98.5{\pm}2.0%$ respectively. On injecting $45\;{\mu}mol$ LiCl, the rates were $56.0{\pm}15.4,\;78.9{\pm}14.5%$ at 60 and 90 min. 6) From the above results it was concluded: a) $Li^{+}$ transfer into the amniotic fluid increased along with the fetal growth and one half of $Li^{+}$ influx is through the extrafetal route even after the maturation of fetal kidney. b) One half of the $Li^{+}$ transfer from the amniotic fluid was through swallowing of fetus, while the remaining half was transfered rapidly through amniotic membrane, which was concentration limited.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.815-822
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• 2020

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3⁺ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

• Korean Chemical Engineering Research
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• v.44 no.2
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• pp.200-206
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• 2006

In a biological aerated filter (BAF) packed with ceramic media (void fraction of BAF=0.32), nitrite accumulation was studied with the variation of hydraulic retention time (HRT) and superficial air velocity. Synthetic ammonium wastewater and petrochemical wastewater were fed at a constant load of $1.6kgNH_4^+-N/m^3{\cdot}d$. Ammonium removal rate was mainly affected by the superficial air velocity in BAF, but nitrite ratio($NO_2-N/NO_x-N$) in the effluent was dependent on both HRT and superficial air velocity. For a fixed HRT of 0.23 hr (corresponding to the empty bed contact time of 0.7 hr) ammonium removal rate was 73/90/92％ and nitrite ratio was 0.92/0.82/0.48 at the superficial air velocity of 0.23/0.45/0.56 cm/s, respectively. When HRT is increased to 0.9 hr with superficial air velocity ranging from 0.34 to 0.45 cm/s, the ammonium removal rate was 89％ on average. However nitrite ratio decreased significantly down to 0.13. When HRT was further increased to 1.4 hr, ammonium removal rate decreased, thereby resulting in the free ammonia ($NH_3-N$, FA) build-up and nitrite ratio gradually increased (>0.95). Although aeration rate and FA concentration at HRT of 0.23 hr were unfavorable for nitrite accumulation compared with those at HRT of 0.9 hr, nitrite ratio at HRT of 0.23 hr was higher. Taken together, HRT and nitrogen load were found to be critical, in addition to FA concentration and aeration condition, for nitrite accumulation in the BAF tested in the present study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.9
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• pp.1178-1184
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• 2006

This study was carried out to investigate the effect of ethanol extract of antler velvet (EAV) on common serum chemistry panels and histopathological change in rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Administration of TCDD ($50{\mu}g/kg$ body weight) induced significant decrease in platelet count (p<0.01), creatine phosphokinase (CPK, p<0.01), lactatate dehydrogenase (LDH, p<0.05) and glucose (p<0.05) levels and increase in hemoglobin (p<0.05), aspartate aminotransferase (AST, p<0.01), alanine amino transferase (ALT, p<0.05) and lipase activities (p<0.05), and blood urea nitrogen (BUN, p<0.05), triglyceride (p<0.01) and low density lipoptotein cholesterol (LDL-C, p<0.05) levels. However, pretreatment of EAV at daily dose of 20 mg/kg b.w. from 1 wk before TCDD exposure for 5 wks attenuated the abnormality of the overall serum chemistry panels but statistical difference between TE and TA groups was observed only in testicular weight (p<0.01), LDH activity (p<0.05), glucose (p<0.05) and lipase activity (p<0.01). In addition, TCDD induced significant histopathological changes including swelling, fatty metamorphosis, and vacuolar degeneration in liver; edema in proximal and distal convoluted tubules, and glomerulus in kidney; severe atrophy of red purple and appearance of significant number of macrophage in spleen; prominent atrophy and decrease in immune cells in thymus. On the other hand, administration of EAV attenuated histopathological damage induced by TCDD. These results further suggest that administration of EAV attenuates TCDD induced testicular, liver, pancreatic, hematopoietic and nephrotic toxicities in rats.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Food Hygiene and Safety
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• v.34 no.2
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• pp.124-134
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• 2019

An analytical method was developed for the determination of broflanilide and its metabolites in agricultural products. Sample preparation was conducted using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method and LC-MS/MS (liquid chromatograph-tandem mass spectrometer). The analytes were extracted with acetonitrile and cleaned up using d-SPE (dispersive solid phase extraction) sorbents such as anhydrous magnesium sulfate, primary secondary amine (PSA) and octadecyl ($C_{18}$). The limit of detection (LOD) and quantification (LOQ) were 0.004 and 0.01 mg/kg, respectively. The recovery results for broflanilide, DM-8007 and S(PFP-OH)-8007 ranged between 90.7 to 113.7%, 88.2 to 109.7% and 79.8 to 97.8% at different concentration levels (LOQ, 10LOQ, 50LOQ) with relative standard deviation (RSD) less than 8.8%. The inter-laboratory study recovery results for broflanilide and DM-8007 and S (PFP-OH)-8007 ranged between 86.3 to 109.1%, 87.8 to 109.7% and 78.8 to 102.1%, and RSD values were also below 21%. All values were consistent with the criteria ranges requested in the Codex guidelines (CAC/GL 40-1993, 2003) and the Food and Drug Safety Evaluation guidelines (2016). Therefore, the proposed analytical method was accurate, effective and sensitive for broflanilide determination in agricultural commodities.

• Journal of Aquaculture
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• v.18 no.4
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• pp.236-244
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• 2005

Experiments were performed to investigate the effects of the different anesthetic MS-222 and lidocaine-HCl doses on the blood physiological responses, on the time required for anesthesia and recovery, and on the survival rates of black rockfish (Sebastes schlegeli). Plasma cortisol was its highest levels (96.1$\pm$12.1 ng/ml) at 6 hours after the administration of 300 ppm of MS-222, and in all groups, plasma cortisol levels were higher than the initial levels during the anesthetic experiment. Fish receiving lidocaine-HCl also exhibited higher than initial plasma cortisol levels at almost experimental intervals. The middle size fish exhibited the highest glucose level (143.3$\pm$14.5 mg/dl) at 50 ppm of anesthesia after 1 hour, and every level was significantly higher than the initial level for at least 12 hours. Glucose levels in fish to which lidocaine-HCl was administered were comparable to the levels seen in conjunction with MS-222 treatment. In fish anesthetized with MS-222, K+ levels in the small size fish were significantly elevated after 1 hour, while Na+ levels did not change in any of the groups throughout the experiment. Anesthetic time was significantly attenuated with increases in the concentrations of MS-222 and lidocaine-HCl. We also noted a correlation between anesthetic time and fish size, in that larger fish took a longer time, followed by the middle size and then the small size fish. The all fish size groups showed above $95\%$ survival rates at every experimental concentration in MS-222 and 300-400 ppm in lidocaine-HCl. The results may indicate that 100-200 ppm MS-222 and 400 ppm lidocaine-HCl are the most effective doses as sedatives for the black rockfish and these doses could be used as the suitable anesthetics doses.

• Journal of Food Hygiene and Safety
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• v.31 no.3
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• pp.186-193
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• 2016

An analytical method was developed for the determination of oxathiapiprolin in agricultural commodities. Oxathiapiprolin is a new oomycide (fungicide of piperidinyl thiazole isoxazoline class) which controls downy mildew in cucurbits caused by Pseudoperonospora cubensis (oomycete plant pathogen). Agricultural commodities were extracted with acetonitrile and partitioned with dichloromethane to remove the interference, adjusting pH between 9 and 10 by 1 N sodium hydroxide. After purification by silica SPE cartridge to clean up the interference of organic compounds, they were finally quantified by HPLC-UVD (high performance liquid chromatograph ultraviolet detector) using a wavelength at 260 nm and confirmed by LC-MS (liquid chromatograph mass spectrometer) in electro-spray ionization positive ion mode. The standard calibration curve was linear with coefficients of determination ($r^2$) 1.00 over the calibration ranges (0.025-2.5 mg/L). Recoveries were ranged between 86.7 to 112.7%, with relative standard deviations less than 10% at three concentration levels (LOQ, 10LOQ, and 50LOQ) performing five replicates. The overall results were determined and estimated according to the CODEX guidelines (CAC/GL40). The proposed method for determination of oxathiapiprolin residues in agricultural commodities can be used as an official method.