• Toxicological Research
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• v.26 no.4
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• Toxicological Research
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• v.27 no.2
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• pp.61-70
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• 2011

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.

• Journal of the Korean Society for Nondestructive Testing
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• v.35 no.4
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• pp.239-244
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• 2015

Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection aganinst radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biblogical tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed. automatic control system.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.381-389
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• 2004

Objective : To compare the efficacy between SKI306X and Diclofenac by using generalized estimating equations (GEE) methodology in the analysis of correlated bivariate binary outcome data in Osteoarthritis (OA) diseases. Methods : A randomized, double-blind, active comparator-controlled, non-inferiority clinical trial was conducted at 5 institutions in Korea with the random assignment of 248 patients aged 35 to 75 years old with OA of the knee and clinical evidence of OA. Patients were enrolled in this study if they had at least moderate pain in the affected knee joint and a score larger than 35mm as assessed by VAS (Visual Analog Scale). The main exposure variable was treatment (SKI 306X vs. Diclofenac) and other covariates were age, sex, BMI, baseline VAS, center, operation history (Yes/No), NSAIDS (Y/N), acupuncture (Y/N), herbal medicine (Y/N), past history of musculoskeletal disease (Y/N), and previous therapy related with OA (Y/N). The main study outcome was the change of VAS pain scores from baseline to the 2nd and 4th weeks after treatment. Pain scores were obtained as baseline, 2nd and 4th weeks after treatment. We applied GEE approach with empirical covariance matrix and independent(or exchangeable) working correlation matrix to evaluate the relation of several risk factors to the change of VAS pain scores with correlated binary bivariate outcomes. Results : While baseline VAS, age, and acupuncture variables had protective effects for reducing the OA pain, its treatment (Joins/Diclofenac) was not statistically significant through GEE methodology (ITT:aOR=1.37, 95% CI=(0.8200, 2.26), PP:aOR=1.47, 95% CI=(0.73, 2.95)). The goodness-of-fit statistic for GEE (6.55, p=0.68) was computed to assess the adequacy of the fitted final model. Conclusions : Both ANCOVA and GEE methods yielded non statistical significance in the evaluation of non-inferiority of the efficacy between SKI306X and Diclofenac. While VAS outcome for each visit was applied in GEE, only VAS outcome for the fourth visit was applied in ANCOVA. So the GEE methodology is more accurate for the analysis of correlated outcomes.

• Journal of radiological science and technology
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• v.39 no.3
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• pp.329-336
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• 2016

The purpose of this study was to evaluate the usefulness of low-dose CT (LDCT) for emphysema compared with high-resolution CT (HRCT). Measurements of radiation dose and noise were repeated 3 times in same exposure condition which was similar with obtaining HRCT and LDCT images. We analysed reading results of 146 subjects. Six images per participants selected for emphysema grading. Emphysema was graded for all 6 zones on the left and right sides of the lungs by the consensus reading of two chest radiologists using a 4-point scale. Between the HRCT and LDCT images, diagnostic differences and agreements for emphysema were analyzed by McNemar's and unweighted kappa tests, and radiation doses and noise by a Mann-Whitney U-test, using the SPSS 19.0 program. Radiation dose from HRCT was significantly higher than that of LDCT, but the noise was significantly lower in HRCT than in LDCT. Diagnostic agreement for emphysema between HRCT and LDCT images was excellent (k-value=0.88). Emphysema grading scores were not significantly different between HRCT and LDCT images for all six lung zones. Emphysema grading scores from LDCT images were significantly correlated with increased scores on HRCT images (r=0.599, p < 0.001). Considering the tradeoff between radiation dose and image noise, LDCT could be used as the gold standard method instead of HRCT for emphysema detection and grading.

• Journal of Plant Biotechnology
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• v.31 no.2
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• pp.133-138
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• 2004

Growth of M.9 (Malus domestica Bark. cv) and M.26 (Malus domestica Bark. cv) of dwarf apple rootstock, cultured on MS agar medium in a vessel with ventilating stopper (VS) and then in vivo rooting and acclimatization under combined-treatment by some materials with IBA, were investigated. Concentration of $CO_2$ and ethylene in the vessel with VS was lower then in the vessel with non-VS. Change of temperature and humidity in the vessel with VS was repeated by light condition. Stomatal pares of tissue in the vessel with VS were immediately closed after plantlets were exposed to room humidity but those in the vessel with non-VS were opened after 20 minutes exposure to room humidity. Leaf area and chloroplast index of tissue in the vessel with VS was higher then in the vessel with non-VS. In vivo rooting ratio and acclimatization ratio of M.9 and M.26 was highest in 300mg/L IBA＋3％ sucrose dip-treatment among other combined- treatments.

• Imaging Science in Dentistry
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• v.34 no.3
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• pp.151-157
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• 2004

Purpose : To evaluate the quantitative accuracy of three-dimensional (3D) images by means of comparing distance measurements on the 3D images with direct measurements of dry human skull according to slice thickness and scanning modes. Materials and Mathods : An observer directly measured the distance of 21 line items between 12 orthodontic landmarks on the skull surface using a digital vernier caliper and each was repeated five times. The dry human skull was scanned with a Helical CT with various slice thickness (3, 5, 7 mm) and acquisition modes (Conventional and Helical). The same observer measured corresponding distance of the same items on reconstructed 3D images with the internal program of V-works 4.0/sup TM/(Cybermed Inc., Seoul, Korea). The quantitative accuracy of distance measurements were statistically evaluated with Wilcoxons' two-sample test. Results: 11 line items in Conventional 3 mm, 8 in Helical 3mm, 11 in Conventional 5mm, 10 in Helical 5mm, 5 in Conventional 7mm and 9 in Helical 7mm showed no statistically significant difference. Average difference between direct measurements and measurements on 3D CT images was within 2mm in 19 line items of Conventional 3mm, 20 of Helical 3mm, 15 of Conventional 5mm, 18 of Helical 5mm, II of Conventional 7mm and 16 of Helical 7mm. Conclusion: Considering image quality and patient's exposure time, scanning protocol of Helical 5mm is recommended for 3D image analysis of the skull in CT.

• Journal of Periodontal and Implant Science
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• v.27 no.1
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• pp.79-90
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• 1997

The purpose of this study was to evaluate the substantivity of experimentally developed gel type tetracycline HCl and a mixture of tetracycline-citric acid gel, and compare to those of solution type tetracycline HCl. 11 extracted anterior teeth were subjected to this study. After scaling and root planing teeth were randomly divided into 3 treatments groups : group 1; 3 teeth were irrigated with tetracycline HCl(50mg/ml) solution , group 2; tetracycline gel (5%) was inserted in the periodontal pockets of 3 teeth, group 3; a mixture of tetracycline and citric acid gel was inserted in the pockets of 3 teeth. And 2 teeth treated in 0.9 % sterile saline served as controls. After 5-minute exposure, each tooth immediately extracted and incubated at room temperature for 22 days in tris-buffered saline as a desorption media. The total volume of TBS was removed and replaced with fresh TBS, at 24-h intervals. Removed desorption media transferred to a sterile vial and stored at -70 oC. This procedure was repeated every 24 h throughout the 22-day desorption period. Using Porphyromonas gingivalis as an indicator organism, a microtiter assay was used to evaluate antimicrobial activity desorbed from the teeth. 1. 50mg/ml tetracycline HCl solution exhibited the longest antimicrobial activity. Compared to saline treated group, it showed significant difference on the day 1 and day 2 desorption period. 2. The ODs of 5% tetracycline gel and a mixture of tetracycline-citric acid gel were significantly different during the first 24 hour only. 3. There was no statistically significant difference after the day 3 between the groups.(p<0.05). Despite our expectation a mixture of tetracycline-citric acid gel did not show longer antimicrobial activities than those of tetracycline gel, and the solution type exhibited the longest activities. Because the gel type agents may stay in the subgingival environment longer than the solution, if the teeth were not extracted immediately after the delivery of the agent, the result could be different. hus this result suggests the possibilities of practical use of these kind of gel type agents.

• Korean Journal of Digital Imaging in Medicine
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• v.14 no.2
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• pp.1-8
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• 2012

Purpose : We aim at presenting the optimum radiologic factor through the evaluation of dose variation and of image quality through the use of a grid in Humerus examination and the change of dose because of the change of radiologic factor. Materials and Methods : We divided it in 3 cases: when using a grid or not and when using IP(Image Plate) in a digital system. Also, as fixing kVp to 70kVp it changed mAs, and fixing mAs to 10 it changed kVp, we put up resolution chart and Burger rose phantom on the acrylic phantom of 7cm (the same level of Humerus) to evaluate the dose and image. We used Image J program to evaluate the quantitative resolution of the obtained image, and made the qualitative evaluation and statistical analysis of the image saved in PACS for 20 radiologic technologist with more than 10 years of experience in order of evaluate its contrast. We used SPSS10(SPSS Inc. Chicago, Illinois) for statistical analysis. Results : We observed the analytic result of resolution by the change of kVp that it was $4.539dGycm^2$ in 60kVp and $757.472dGycm^2$ in 75kVp, which increased about 64.6% of dose, while for the resolution it had the pixel value 30.7% better with 851 in 60kVp than 651 in 75kVp. Also, we analyzed the result of resolution by the change of mAs that it was $3.106dGycm^2$ in 5mAs, and $12.470dGycm^2$ in 20mAs, which increased about 400% of dose, while for the resolution DR had 678 in 5mAs, and 724 in 20mAs that increased about 6.8% of resolution. We made the qualitative evaluation of contrast by the change of kVp that DR showed the higher quality than CR, but the contrast by the change of kVp had no special different at the moment of visual evaluation, nor statistically significant difference(P>0.05). We observed the qualitative evaluation of contraste by the change of mAs that the contrast increased as DR increased mAs, and had statistically significant difference(P<0.05). On the other hand, CR had no significant difference for more than 10mAs nor statistically significant difference(P>0.05). Conclusion : In case of some patients with radiographic exposure by the repeated examination such as emergent patient or Follow up patient, they are considered to try to limit the use of a grid, to set kVp under 65kVp in fixed mode, to select less than 10mAs and to reduce the possibility of patient being bombed.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.293-303
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• 1990

The contractile action of barium $(Ba^{2+})$ was investigated in the arterial strip of rabbit renal artery. The helical strip of isolated renal artery was immersed in the Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $37^{\circ}C$ and its isometric tension was measured. $Ba^{2+}-induced$ contraction of arterial strip was dose-dependent and its maximal tension corresponded to $92.1{\pm}4.5%$ of tension by $K^+(100\;mM)$. $Ba^{2+}-induced$ contraction did not show the tachyphylactic phenomenon in the normal Tyrode's solution. $Ba^{2+}$ induced the tonic contraction in the $Ca^{2+}-free$ tyrode's solution and that was increased by the extracellula addition of $Ca^{2+}$. During the repeated exposure of the same dose of $Ba^{2+}\;(10\;mM)$ in the $Ca^{2+}-free$ Tyrode's solution, $Ba^{2+}-induced$ contraction was progressively decreased. Even though the intracellular NE-and caffeine-sensitive $Ca^{2+}$ was depleted, $Ba^{2+}$ induced the tonic contraction. After the pretreatment of lanthnum or verapamil, $Ba^{2+}$ did not induce contraction. $Ba^{2+}-induced$contraction was suppressed by extracellular $K^+$ in the normal Tyrode's solution and that was dependent on $K^+$ concentration. Suppressive effect of $K^+\;(14\;mM)$ on the $Ba^{2+}-induced$ contraction was also dependent on the intracellular $Ca^{2+}$ concentration. From the above resuts, it is suggested that $Ba^{2+}$ activate indirectly the contractile process by promoting the mobilization of intracellular $Ca^{2+}$ and the influx of extracellular $Ca^{2+}$. It is also suggested that action of $Ba^{2+}$ on the $Ca^{2+}-activated$ $K^+$ channel can result in the depolarization of cell membrane in the rabbit renal artery.