• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.15-18
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• 2004

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.4
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• pp.603-607
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• 2003

To investigate the alcohol metabolizing system in liver of rats drunken 10% ethanol with Monascus pigment extract (MPE), Sprague-Dawley male rats weighing about 250 g have been drunken 10% ethanol containing 1, 2.5 and 5% Monascus pigment extract for a month. Three groups of rats drunken 10% ethanol with MPE gained somewhat less body weight than normal group, but the changes of body weight was not significantly different among the former groups. All groups drunken MPE supplemented alcohol had no remarkable changes in liver function on the basis of liver weight/body weight, the serum levels of alanine aminotransferase and xanthine oxidase activity. 10% alcohol drunken animals (control group) showed significantly increased activity of hepatic alcohol dehydrogenase (ADH) by 87% compared with normal group and the animals drunken 1%, 2.5% and 5% MPE showed respectively 34%, 29% and 21% increased activity of hepatic ADH, whileas Km value of ADH in 1, 2.5 and 5% MPE group decreased by 40%, 30% and 19% respectively compared with the control, but Vmax showed no significant changes among MPE groups. In case of aldehyde dehydrogenase (ALDH), 1% MPE group showed significantly increased activity by 32% and 2.5% or 5% MPE group showed increasing tendency compared with control, and Km value in three experimental groups declined by 27% and no particular changes were found among those. Furthermore, Vmax value in 1, 2.5 and 5% MEP group increased by 88,56 and 22% respectively with the control. In the aspect of the area under the curve of a ethanol concentration versus time (AUC) profile obtained after administration of 10% alcohol with 1 or 5% MPE, the decreasing rate of AUC to the control was 18% in 1% MPE treated rats whereas 10% in 5% MPE group.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.120-130
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• 1992

Background: Although there have been many studies on the pathogenetic mechanism of acute lung injury, it is still elusive. Recently interests have been focused on the role of oxygen free radicals. But the effect of hydroxyl radical on the neutrophil mobilization and the alveolar-capillary permeability is not clear especially in the endotoxin-induced acute lung injury model of rats. This investigation was performed to evaluate the pathogenetic role of hydroxyl radical on the neutrophil accumulation into the lung and the increased alveolar-capillary permeability in the endotoxin-induced acute lung injury in rats. Method: Fifty rats were divided into four groups: vehicle control group (n=5, 6hrs; n=5, 24hrs), endotoxin-treated group (n=10, 6hrs; n=10, 24hrs), Dimethylthiourea (DMTU)-pretreated group (n=10, 6hrs), and deferoxamine (DFX)-pretreated group (n=10, 6hrs). Thirty minutes before sacrifice, $^{125}I$-tagged bovine serum albumin was injected. Six and twenty four hours after endotoxin injection, the rats were sacrificed, and the radioactivity of lung tissue and peripheral blood was counted. Permeability index was defined as the ratio of radioactivity between lung tissue and peripheral blood. Another set of rats (n=52) were divided into the same four groups as before [vehicle control group (n=5, 6hrs; n=5, 24hrs), endotoxin·treated group (n=7, 6hrs; n=8, 24hrs), DMTU-pretreated group (n=6, 6hrs; n=9, 24hrs), and DFX-pretreated group (n=5, 6hrs; n=7, 24hrs)], and were sacrificed 6 and 24 hours after endotoxin injection. In these rats, cell profile of peripheral blood and bronchoalveolar lavage fluid was evaluated, and the pathologic examination of lung tissue was performed. Results: 1) Increased alveolar-capillary permeability was observed 6 hours after endotoxin injection, which was normalized after 24 hours, and this increase was attenuated by pretreatment with DMTU and DFX. 2) Neutrophil sequestration into the lung was observed 24 hours after endotoxin administration, but this was not influenced by DMTU and DFX pretreatment. Conclusion: These results suggest that hydroxyl radical would not be involved in the sequestration of neutrophils into the lung, but plays an important role in the increase of alveolar-capillary permeability in the endotoxin-induced acute lung injury in rats.

• KSBB Journal
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• v.11 no.3
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• pp.295-302
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• 1996

The measurements of rubisco parameters are important in photosynthetic studies. In this experiment, we used photometric assay method to detect these major parameters, such as activity, carbamylation and amount of rubisco. The main advantages of this method are very simple and as sensitive as conventional methods which usually produce radioactive waste. In this study, with kidney bean (Phaseolus vulgatis L.) leaves grown at normal $CO_2$ (350ppm) and high $CO_2$ (650 ppm), we investigated the effect of $CO_2$ concentration on activation and carbamylation of rubisco by measuring the rubisco activity, carbamylation rate and amount of rubisco using a dual beam (334nm and 405nm) spectrophotometer, and analyzed the polypeptide profiles of rubisco by SDS-PAGE. When $CO_2$ concentration was raised from 350ppm to 650ppm, all parameters of rubisco were decreased : $41.2{\mu}M/m^2/s and 52.2{\mu}M/m^2/s$ to $27.4{\mu}M/m^2/s and 46.1{\mu}M/m^2/s$ for initial and total rubisco activity, respectively ; from 79% to 58.9% for carbamylation rate ; from $1.94 {\mu}M/m^2$ to 1.58{\mu}M/m^2$ for amount of rubisco. These results suggests that the decrease in rubisco activity at high $CO_2$ was caused by carbamylation. The analysis of the preparation by SDS-PAGE showed two major polypeptides at 50 and 14.5 kD which were identified as the large and the small subunits of rubisco. There were no differences in the intensity compared high $CO_2$ to normal $CO_2$ in both 50 kD and 14.5 kD bands. We also found that these inhibitory effects of $CO_2$ were reversible. When high $CO_2$ was switched to normal $CO_2$, the parameters of rubisco changed were almost the same as normal rubisco parameters. These data provide an evidence that activity of rubisco was recovered by $CO_2$ concentration of 350 ppm.

• Journal of Life Science
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• v.27 no.8
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• pp.937-944
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• 2017

To investigate the beneficial effects of fiber derived from agar on the lipid and glucose metabolism of obese model mice, changes in the fat accumulation, lipid content, and insulin concentration were measured in C57BL/6N mice fed a high-fat diet (HFD) and treated with a beverage containing agar (BCA) for 9 weeks. The feed efficiency ratio was significantly decreased in the HFD+BCA treatment group, although the body weight and food intake were maintained a constant level. Also, the fat accumulation in the fatty tissue and liver were lower in the HFD+BCA treatment group than in the HFD+Vehicle treatment group. Furthermore, a significant decrease was detected in the levels of total cholesterol (TC) and LDL after the BCA treatment, while a constant HDL level was maintained in the same group. Moreover, the serum insulin concentration was significantly decreased in the HFD+BCALo (Low concentration) and HFD+BCAMi (Middle concentration) groups compared to the HFD+Vehicle group. Therefore, the results suggest that the long-term administration of dietary fiber from agar can improve fat accumulation in the fatty tissue and liver, the serum lipid profile, and the insulin concentration in the blood. Also, the results provide evidence that the inclusion of agar fiber in beverages results in significant hypolipidemic and hypoinsulinemic effects.

• Journal of fish pathology
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• v.24 no.1
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• pp.29-37
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• 2011

Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of nalidixic acid (NA) and piromidic acid (PA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of NA and PA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight. At $23{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 24 h post-dose, were 5.87 and $0.43\;{\mu}g/ml$, respectively. At $13{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 10 h post-dose, were 6.22 and $1.57\;{\mu}g/ml$, respectively. Better absorption of PA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. However, absorption of NA was not affected significantly by temperature. The elimination of NA and PA from serum of black rockfish was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. The kinetic profile of absorption, distribution and elimination of NA and PA in serum were analyzed by fitting to a one compartment model, with WinNonlin program. The AUC, $T_{1/2}$, $T_{max}$ and $C_{max}$, respectively, were: $161.25\;{\mu}g{\cdot}h/ml$, 0.15 h, 12.29 h and $8.91\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $134.12{\mu}g{\cdot}h/ml$, 0.18 h, 8.79 h and $5.00\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with NA; $41.57\;{\mu}g{\cdot}h/ml$, 0.58 h, 8.24 h and $0.21\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $40.36\;{\mu}g{\cdot}h/ml$, 0.59 h, 5.04 h and $1.20\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with PA.

• Korean journal of food and cookery science
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• v.29 no.4
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• pp.361-366
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• 2013

This research was performed to investigate the effect of Agarum cribrosum ethanol extracts on the levels of lipids in the serum of rats fed a high-fat diet for 10 weeks. Experimental groups were divided into basal diet only (BDG), high fat diet control (HFDCG), high-fat diet and 5% Agarum cribrosum ethanol extract powder (HF5S), and high-fat diet and 10% Agarum cribrosum ethanol extract powder(HF10S) groups. The levels of hematological variables were not significantly different among the four groups. Compared with the control group's serum total cholesterol level of 89.14 mg/dL, the levels of the HF5S and HF10S groups were significantly lowered to 77.26 and 75.47 mg/dL, respectively. Compared with the control group's LDL-cholesterol leve of 27.41 mg/dL, the LDL-cholesterol levels of the HF5S and HF10S groups were significantly lowered to 20.64 and 20.17 mg/dL, respectively. Also, compared to the control group's serum triglyceride level of 98.36 mg/dL, the triglyceride levels of the HF5S and HF10S groups were significantly lowered to 87.94 and 87.39 mg/dL, respectively. These results indicate that dietary intake of Agarum cribrosum ethanol extracts might have beneficial effects on obesity by reducing body weight and improving blood lipid profile.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.2
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• pp.68-73
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• 2015

Purpose The purpose of this study was to evaluate image quality change by truncated region in field of view (FOV) of attenuation correction computed tomography (AC-CT) in brain PET/CT. Materials and Methods Biograph Truepoint 40 with TrueV (Siemens) was used as a scanner. $^{68}Ge$ phantom scan was performed with and without applying brain holder using brain PET/CT protocol. PET attenuation correction factor (ACF) was evaluated according to existence of pallet in FOV of AC-CT. FBP, OSEM-3D and PSF methods were applied for PET reconstruction. Parameters of iteration 4, subsets 21 and gaussian 2 mm filter were applied for iterative reconstruction methods. Window level 2900, width 6000 and level 4, 200, width 1000 were set for visual evaluation of PET AC images. Vertical profiles of 5 slices and 20 slices summation images applied gaussian 5 mm filter were produced for evaluating integral uniformity. Results Patient pallet was not covered in FOV of AC-CT when without applying brain holder because of small size of FOV. It resulted in defect of ACF sinogram by truncated region in ACF evaluation. When without applying brain holder, defect was appeared in lower part of transverse image on condition of window level 4200, width 1000 in PET AC image evaluation. With and without applying brain holder, integral uniformities of 5 slices and 20 slices summation images were 7.2%, 6.7% and 11.7%, 6.7%. Conclusion Truncated region by small FOV results in count defect in occipital lobe of brain in clinical or research studies. It is necessary to understand effect of truncated region and apply appropriate accessory for brain PET/CT.

• Journal of Nutrition and Health
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• v.18 no.4
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• pp.301-311
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• 1985

Even though the anticarcinogenic effect of dietary factors especially beta - carotene has been reported by various investigators, the mechanism of the action of ${\beta}-carotene$ has not yet been identified. We carried out the present study to determine the possibilities of relative cancer risk related to dietary intake of vitamin A ( both ${\beta}-carotene$ and retinol ) and blood levels of vitamin A among Koreans. The subjects were divided into two groups; cancer patients and controls. Blood levels for ${\beta}-carotene$ and retinol were analyzed by alumina column chromatography and colorimetry. Dietary intake was examined by food profile and convenient method for evaluating nutritional status through recalling 10 years of food habits. The results obtained are as follows : 1 ) Calorie, protein, fat, and carbohydrate intakes of cancer patient were lower than those of control. Calorie and carbohydrate intakes showed no significant difference but protein and fat intakes were significantly lower in cancer patients. According to cancer sites, in stomach cancer only fat intake was significantly lower than that of control. In lung and larynx cancer calorie, protein, fat and carbohydrate intakes showed similar trend as in control. 2 ) Vitamin A intake of cancer patient was significantly lower than that of control. It was estimated that 83.6% of total Vitamin A intake were provided by ${\beta}-carotene$ for control and cancer patient respectively. 3 ) The mean intake of dietary ${\beta}-carotene$ in cancer patient was significantly lower than that in control ( $7002\;\mu}g/day$ versus $10326\;{\mu}g/day$ ) According to cancer sites in mean intake of dietary ${\beta}-carotene$ was significantly lower in all but stomach cancer compared with that of control. Lung and larynx cancer showed lowest ${\beta}-carotene$ intake with mean value of $5855{\mu}g/day$ and $5492{\mu}g/day$ respectively. 4 ) The mean intake of dietary retinol in cancer patient was significantly lower than that in control ( $245{\mu}g/day$ versus $338{\mu}g/day$ ), but the difference was not significant. 5 ) The relative risk of all cancers in the first (lowest) to the forth quartile level of ${\beta}-carotene$ consumption such as $0-5999{\mu}g/day$. $6000-8999{\mu}g/day$, $9000-11999{\mu}g/day$/ day and $12000-20000{\mu}g/day$ was 85 : 1.7 : 20 : 1.0. The relative risk of all cancers in the first (lowest) to the forth quartile level of retinol consumption, such as $0-299{\mu}g/day$, $300-599{\mu}g/day$, 600-899${\mu}g/day$, and $900-1200{\mu}g/day$, was 1.14 : 067 : 0.21 : 1.0. 6 ) The various food group consumption of cancer patient were significantly lower than those of control in green leafy vegetables, fruits, sea weeds, milk and cheese and eggs. But the Kimchie consumption in cancer patient was three fold higher than that of control ( $1840\;{\mu}g/day$ versus $562\;{\mu}g/day$ ) and in the stomach cancer, Kimchie consumption was the highest, ( $1890\;{\mu}g/day$) According to cancer sites, the consumption of green leafy vegetables was significantly lower in all but stomach cancer compared to control and other vegetables showed no difference between two. In lung and larynx cancer, green leafy vegetables consumption was lowest ( $6094{\mu}g/day$ $5921{\mu}g/day$) and milk and cheese consumption was also( $5\;{\mu}g/day$ and $11{\mu}g/day$) 7 ) The recovery of ${\beta}-carotene$ from human serum by alumina column chromatography was $94.4{\pm}2.3%$. 8 ) Cancer patients showed significantly lower serum retinol ($56.4{\pm}18.1\:{\mu}g/100ml$ versus $72.2{\pm}21.8\:{\mu}g/100ml$) and ${\beta}-carotene$ ($48.9{\pm}33.8\:{\mu}g/100ml$ versus $72.2{\pm}42.6\:{\mu}g/100ml$) concentrations than in controls. 9 ) But breast cancer patients were not significantly different from controls in their serum retinol and ${\beta}-carotene$ concentrations.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.54-63
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• 2010

Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.