• Title/Summary/Keyword: drug exposure

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Monitoring and Risk Assessment of Heavy Metals in Perennial Root Vegetables (다년생 근채류 중 중금속 모니터링 및 위해성평가)

  • Cho, Min-Ja;Choi, Hoon;Kim, Hye-Jeong;Youn, Hye-Jung
    • Korean Journal of Environmental Agriculture
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    • v.35 no.1
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    • pp.55-61
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    • 2016
  • BACKGROUND: This study was carried out to survey the levels of heavy metals in perennial root vegetables and to assess dietary exposure and risk to the Korean population health.METHODS AND RESULTS: Perennial root vegetables (n=214) including Panax ginseng C.A mayer, Woodcultivated ginseng, Codonopsis lanceolata, and Platycodon granditloum were collected from markets or harvested from farmhouse in Korea. Lead(Pb), cadmium(Cd) and arsenic (As) analysis were performed with microwave device and inductively coupled plasma mass spectrometer. Limit of detection for heavy metals were 0.010~0.050 μg/kg, while limit of quantitation were 0.035~0.175 μg/kg. The recovery results were in the range of 76~102%. The average contents of heavy metals in perennial root vegetables were in the range of Pb 0.013(Panax ginseng C.A Mayer)~0.070 (Wood-cultivated ginseng) mg/kg, Cd 0.009(Panax ginseng C.A Mayer)~0.034(Codonopsis lanceolata) mg/kg, and As 0.002(Panax ginseng C.A Mayer)~0.004(Plafycodon grandiflorum) mg/kg, respectively. For risk assessment, daily intakes of heave metals were estimated and risk indices were calculated in comparison with reference dose. The dietary exposures of heavy metals through usual intake were Pb 0.070 μg/day, Cd 0.041 μg/day and As 0.008 μg/day, taking 0.03%, 0.08% and 0.0003% as risk indices, respectively.CONCLUSION: The risk level for Korean population exposed to heavy metals through intake of perennial root vegetables was far low, indicating of little possibility of concern.

Analysis of toluene diisocyanate of adhesives in food contact materials by GC/MS (GC/MS에 의한 식품 포장재에 사용되는 접착제의 Toluene diisocyanate 분석)

  • Oh, Chang-Hwan;Kim, Ji-Young;Jo, Cheon-Ho;Park, Heera;Kwun, Ki-Sung;Kim, Meehye;Myung, Seung-Woon
    • Analytical Science and Technology
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    • v.18 no.6
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    • pp.511-519
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    • 2005
  • A method for determination of toluene diisocyanates (TDI) in toluene diisocynate (TDI)-based polyurethane (PUR) packing material was investigated, and also the migration of TDI to food was studied. TDI was extracted using food simulants such as n-haptane and 4% aqueous acetic acid. The determinations were performed using gas chromatography/mass spectrometry (GC/MS). One of major components for polyurethane, toluene diisocyanates, were detected in ten samples among twenty six food contact materials with the concentration range of $0.51{\sim}60.88{\mu}g/ml$. However the highest extracted amount was just 0.7% of $60.88{\mu}g/ml$ if the contact surface of food packing for extracting liquid was limited to the outer layer without exposure of the cutting edge of food packing multi-layers. The result of this study and the analysis method for TDI diisocyanate will be very useful for further study about food contact material, and the monitoring result could be used for evaluating the safety of food contact material before it is to be used for food, preservation.

HSP90 inhibitor, AUY922, debilitates intrinsic and acquired lapatinib-resistant HER2-positive gastric cancer cells

  • Park, Kang-Seo;Hong, Yong Sang;Choi, Junyoung;Yoon, Shinkyo;Kang, Jihoon;Kim, Deokhoon;Lee, Kang-Pa;Im, Hyeon-Su;Lee, Chang Hoon;Seo, Seyoung;Kim, Sang-We;Lee, Dae Ho;Park, Sook Ryun
    • BMB Reports
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    • v.51 no.12
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    • pp.660-665
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    • 2018
  • Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib.

Environmentally friendly determination of urinary trans, trans-muconic acid for biological monitoring of benzene exposure by green high-performance liquid chromatography (소변 중 뮤콘산의 친환경 HPLC 분석방법을 이용한 벤젠 노출 생물학적 노출평가)

  • Yang, Dong-Hyug;Lee, Mi-Young;Won, Yong Lim
    • Analytical Science and Technology
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    • v.25 no.6
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    • pp.460-466
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    • 2012
  • An environmentally friendly, so-called green, high performance liquid chromatography method was developed and validated for the determination of trans, trans-muconic acid (t,t-MA) in human urine as a biomarker of benzene exposure. After urinary t,t-MA was extracted and enriched using solid-phase extraction, a MF-Ph1 SG80 ($150mm{\times}2.0mm$ I.D., 5 ${\mu}m$) column with a mobile phase of 10 mM $KH_2PO_4$ containing 0.1% $H_3PO_4$ was used for isocratic separation of t,t-MA with UV detection at 259 nm. The calibration curve was constructed in the range of 0.1-5.0 mg/L with good linearity ($r^2$=0.9992). The intra-day and inter-day precision (as RSD) were 0.9-8.5% and 3.1-4.5%, respectively. The average recovery ranged from 97.5% to 101.7%. The green sample preparation and separation with no organic solvents were successfully achieved. The validated method would be suitable for the routine biological monitoring of benzene exposure in the occupational settings.

ADOLESCENT VIOLENCE TOWARD PARENTS (청소년의 부모폭행에 대한 연구)

  • Chun, Ryo-Sook;Min, Sung-Kil;Oh, Kang-Sup;Lee, Si-Hyung;Lee, Ho-Bun
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.8 no.2
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    • pp.199-206
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    • 1997
  • Object:The purpose of this study was to investigate frequency and risk factor of violence toward parents seen in adolescents. We also want to apply this data toward developing a prevention program for adolescent violence. Method:A total of 1,345 students from 5 middle schools in Seoul, participated in this study:675 males, 670 females. We administered self-reporting questionnaire including violence toward parents, exposure to violence, family history of alcoholism, substance abuse of adolescetnt and dermographic data etc. Result:The frequency of boys’ violence toward parent was 2.8%, which was significantly higher than girls’(p<0.001). The frequency of violence toward the father was higher than the mother. The risk factors for violence toward parents were sex, parental alcohol problem, adolescent alcohol-smoking-drug problem, exposure to violence at home in the last year and exposure to violence in the life(p<0.0001). The grade, punishment, socioeconomic status, educational level of parent were not significantly related to violence toward parents. Conclusion:These suggest that adolescent violence toward parents is not rare problem any more and preventive intervention is needed for high-risk groups, that is related with experience domestic violence, substance abuse, alcoholic parent.

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Repeated Dose and Reproductive/Developmental Toxicities of Acetanilide in Rats (랫드를 이용한 Acetanilide의 반복투여 및 생식/발생독성 병행시험)

  • Chung, Moon-Koo;Baek, Sung-Soo;Lee, Sang-Hee;Kim, Hyun-Mi;Choi, Kyung-Hee;Han, Sang-Seop
    • Toxicological Research
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    • v.23 no.4
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    • pp.391-403
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    • 2007
  • The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

Cytokinesis-blocked micronuclei in the human peripheral lymphocytes following low dose γ-rays irradiation (저선량의 감마선 피폭된 사람 말초 임파구의 미소핵을 이용한 방사선 생물학적 피폭선량 측정법 연구)

  • Kim, Tae-hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.1
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    • pp.99-104
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    • 2001
  • To determine if micronucleus (MN) assay could be used to predict the absorbed dose of victims after accidental radiation exposure, we carried out to assess the absorbed dose depending on the numerical changes of MN in human peripheral blood lymphocytes after $^{60}Co\;{\gamma}-rays$ exposure in the range of 0.25 to 1 Gy, respectively. The MNs were observed at very low doses, and the numerical changes according to doses. Satisfactory dose-effect calibration curve is observed after low dose irradiation of human lymphocytes in vitro. When plotting on a linear scale against radiation dose, the line of best fit was $Y=(0.02{\pm}0.0009)+(0.033{\pm}0.010)D+(0.012{\pm}0.012)D^2$. The dose-response curve for MN induction immediately after irradiation was linear-quadratic and has a significant relationship between the frequencies of MN and dose. These data show a trend towards increase of the numbers of MN with increasing dose. The number of MN in lymphocytes that were observed in the control group is $0.1610{\pm}0.0093/cell$. Accordingly, MN assay in human peripheral lymphocytes could be a useful in viva model for studying radio-protective drug sensitivity or screening test, microdosimertic indicator and radiation-induced target organ injury. Since MN assay is simple, rapid and reproducible, it will also be a biodosimetric indicator for individual dose assessment after accidental exposure.

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Occupational Radiation Exposure in Korea: 2002 (2002년 국내 방사선 작업종사자의 직업군별 피폭선량)

  • Jeong, Je-Ho;Kwon, Jeong-Wan;Lee, Jai-Ki
    • Journal of Radiation Protection and Research
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    • v.30 no.4
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    • pp.175-183
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    • 2005
  • Dose distribution of Korean radiation workers classified by occupational categories was analyzed. Statistics of the occupational radiation exposure(ORE) in 2002 of the radiation workers in diagnostic and dental radiology were obtained from the Korea Food and Drug Agency(KFDA) who maintains the database for individual radiation dose records. Corresponding statistics for the rest of radiation workers were obtained by processing the individual annual doses provided by the Korea Radioisotope Association(KRIA) after deletion of individual information. The ORE distribution was classified in term of 28 occupational categories, annual individual dose levels, age groups and gender of 52733 radiation workers as of the year of 2002. The total collective dose was 66.4 man-Sv and resulting average individual ORE was 1.26 mSv. Around 80% of the workers were exposed to minimal doses less than 1.2 mSv. However, it appeared that the recorded doses exceeded 20 mSv for 43 workers in the industrial radiography and for 147 workers in the field of radiology. Particularly, recorded doses of 23 workers in radiology exceeded the annual dose limits of 50 mSv, which is extraordinary when the working environment is considered. It is uncertain whether those doses are real or caused by careless placing of dosimeters in the imaging rooms while the X-ray units are in operation. No one in the workforce of 16 operating nuclear power plant units was exposed over 20 mSv in 2002. Number of workers was the largest in their 30's of age and the mean individual dose was the highest in their 20's. Women were around 20% of the radiation workers and their average dose was around one half of that of man workers.

α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

  • Ittiudomrak, Teeranai;Puthong, Songchan;Roytrakul, Sittiruk;Chanchao, Chanpen
    • Toxicological Research
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    • v.35 no.2
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    • pp.167-179
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    • 2019
  • Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ${\alpha}$-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ${\alpha}$-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ${\alpha}$-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ${\alpha}$-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ${\alpha}$-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ${\alpha}$-mangostin and apigenin arrested the cell cycle at the $G_2/M$ phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ${\alpha}$-mangostin-treated SKOV-3 cells, respectively. ${\alpha}$-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ${\alpha}$-mangostin likely being involved with inflammation.

Effects of Olanzapine on the Schedule-Induced Polydipsic Rats (Olanzapine이 백서의 Schedule-Induced Polydipsia에 미치는 영향)

  • Lee, Gi-Chul;Lee, Kyung-Kyu;Chang, Hwan-Il;Lee, Jung-Ho;Kim, Hyun-Woo;Ha, Jun-Myung;Jeong, Jae-Hyun;Jeong, Hong-Kyung
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.240-245
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    • 1999
  • Object : This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. Methods : Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.p.), and vehicle(1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results and Conclusion : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

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