• Title/Summary/Keyword: repeated exposure

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Effects of Hypobaric Conditions on Apoptosis Signalling Pathways in HeLa Cells

  • Arican, Gul Ozcan;Khalilia, Walid;Serbes, Ugur;Akman, Gizem;Cetin, Idil;Arican, Ercan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.5043-5047
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    • 2014
  • Nowadays increasing effectiveness in cancer therapy and investigation of formation of new strategies that enhance antiproliferative activity against target organs has become a subject of interest. Although the molecular mechanisms of apoptosis can not be fully explained, it is known that cell suicide program existing in their memory genetically is activated by pathophysiological conditions and events such as oxidative stress. Low pressure (hypobaric) conditions that create hypoxia promote apoptosis by inhibiting cell cycling. In this study, determination of the effects of fractional hypobaric applications at different times on HeLa cells at cellular and molecular levels were targeted. Experiments were carried out under hypobaric conditions (35.2 kPa) in a specially designed hypobaric cabin including 2% $O_2$ and 98% N. Application of fractional hypobaric conditions was repeated two times for 3 hours with an interval of 24 hours. At the end of the implementation period cells were allowed to incubate for 24 hours for activation of repair mechanisms. Cell kinetic parameters such as growth rate (MTT) and apoptotic index were used in determination of the effect of hypobaric conditions on HeLa cells. Also in our study expression levels of the Bcl-2 gene family that have regulatory roles in apoptosis were determined by the RT-PCR technique to evaluate molecular mechanisms. The results showed that antiproliferative effect of hypobaric conditions on HeLa cells started three hours from the time of application and increased depending on the period of exposure. While there was a significant decrease in growth rate values, there was a significant increase in apoptotic index values (p<0.01). Also molecular studies showed that hypobaric conditions caused a significant increase in expression level of proapoptotic gene Bax and significant decrease in antiapoptotic Bfl-1. Consequently fractional application of hypobaric conditions on HeLa cell cultures increased both antiproliferative and apoptotic effects and these effects were triggered by the Bax gene.

Altered Vascular Calcium Regulation in Hypertension

  • Kim, Won-Jae;Lee, Jong-Un;Park, Yong-Hyun;Nam, Sang-Chae
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.529-535
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    • 1997
  • The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine ($0.1{\sim}35\;mmol/L$) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular $^{45}Ca$ uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type $Ca^{2+}$ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular $^{45}Ca$ uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a $Na^+,\;K^+-ATPase$ inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular $^{45}Ca$ uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of $Ca^{2+}-ATPase$ of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired $Na^+-K^+$ pump activity of the cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

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Spontaneous bone regeneration after surgical extraction of a horizontally impacted mandibular third molar: a retrospective panoramic radiograph analysis

  • Kim, Eugene;Eo, Mi Young;Nguyen, Truc Thi Hoang;Yang, Hoon Joo;Myoung, Hoon;Kim, Soung Min
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.41
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    • pp.4.1-4.10
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    • 2019
  • Background: The mandibular third molar (M3) is typically the last permanent tooth to erupt because of insufficient space and thick soft tissues covering its surface. Problems such as alveolar bone loss, development of a periodontal pocket, exposure of cementum, gingival recession, and dental caries can be found in the adjacent second molars (M2) following M3 extraction. The specific aims of the study were to assess the amount and rate of bone regeneration on the distal surface of M2 and to evaluate the aspects of bone regeneration in terms of varying degree of impaction. Methods: Four series of panoramic radiographic images were obtained from the selected cases, including images from the first visit, immediately after extraction, 6 weeks, and 6 months after extraction. ImageJ software® (NIH, USA) was used to measure linear distance from the region of interest to the distal root of the adjacent M2. Radiographic infrabony defect (RID) values were calculated from the measured radiographic bone height and cementoenamel junction with distortion compensation. Repeated measures of analysis of variance and one-way analysis of variance were conducted to analyze the statistical significant difference between RID and time, and a Spearman correlation test was conducted to assess the relationship between Pederson's difficulty index (DI) and RID. Results: A large RID (> 6 mm) can be reduced gradually and consistently over time. More than half of the samples recovered nearly to their normal healthy condition (RID ≤ 3 mm) by the 6-month follow-up. DI affected the first 6 weeks of post-extraction period and only showed a significant positive correlation with respect to the difference between baseline and final RID. Conclusions: Additional treatments on M2 for a minimum of 6 months after an M3 extraction could be recommended. Although DI may affect bone regeneration during the early healing period, further study is required to elucidate any possible factors associated with the healing process. The DI does not cause any long-term adverse effects on bone regeneration after surgical extraction.

Placenta Transfer and Toxicokinetics of Valproic Acid in Pregnant Cynomolgus Monkeys

  • Jeong, Eun-Ju;Yu, Wook-Joon;Kim, Choong-Yong;Chung, Moon-Koo
    • 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.

Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats

  • Choi, Jae-Seok;Lee, Young-Jun;Kim, Tae-Hyung;Lim, Hyun-Jung;Ahn, Mee-Young;Kwack, Seung-Jun;Kang, Tae-Seok;Park, Kui-Lea;Lee, Jae-Won;Kim, Nam-Deuk;Jeong, Tae-Cheon;Kim, Sang-Geum;Jeong, Hye-Gwang;Lee, Byung-Mu;Kim, Hyung-Sik
    • 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.

Evaluation of Impedance on Biological Tissues Using Automatic Control Measurement System (자동제어 측정 시스템을 이용한 생체 조직의 임피던스 평가)

  • Kil, Sang-Hyeong;Lee, Moo-Seok;Kim, Sang-Sik;Shin, Dong-Hoon;Lee, Seong-Mo;Kim, Gun-do;Lee, Jong-Kyu
    • 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.

Analysis of Repeated Measured VAS in a Clinical Trial for Evaluating a New NSAID with GEE Method (퇴행성 관절염 환자를 대상으로 새로운 진통제 평가를 위한 임상시험자료의 GEE 분석)

  • Lim, Hoi-Jeong;Kim, Yoon-I;Jung, Young-Bok;Seong, Sang-Cheol;Ahn, Jin-Hwan;Roh, Kwon-Jae;Kim, Jung-Man;Park, Byung-Joo
    • 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.

Usefulness Evaluation of Low-dose CT for Emphysema : Compared with High-resolution CT (폐기종에 대한 저선량 CT의 유용성 평가: 고해상도 CT와 비교)

  • Lee, Won-Jeong
    • 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.

Effects of Growth Regulators and Culture Environment on ex vitro Rooting and Acclimatization of Apple Rootstock in vitro Propagated (기내배양 사과 대목의 기외 삽목 시 발근과 순화에 미치는 배양조건 및 생장조절물질의 효과)

  • Kwon, Soon-Il;Kim, Jeong-Hee;Kang, In-Kyu;Kim, Mok-Jong
    • 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.

Three-dimensional image analysis of the skull using variable CT scanning protocols-effect of slice thickness on measurement in the three-dimensional CT images (두개골의 3차원 영상 분석을 위한 전산화단층촬영 방법의 비교-상층 두께가 3차원 영상의 계측에 미치는 영향)

  • Jeong Ho-Gul;Kim Kee-Deog;Park Hyok;Kim Dong-Ook;Jeong Haijo;Kim Hee-Joung;Yoo Sun Koo;Kim Yong Oock;Park Chang-Seo
    • 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.

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