• Title/Summary/Keyword: 저독성

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새로운 nucleoside계 항암제, ara-CDP-DL-PCA.Na(BR-28702-2)의 약효연구 및 급성독성 시험.

  • 백우현;신원섭;채희상;노정구;강부연;차신우
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.169-169
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    • 1994
  • 항암 및 면역조절작용을 가지고 있으며 그 자체가 서방성 prodrug으로서 약효를 나타낼것으로 기대되는 ara-C와 etherphospholipid의 conjugate인 ara-CDP-DL-PCA.2Na, ara-CDP-DL-PBA.2Na, 및 ara-CDP-DL-PMA.2Na 3종의 BR-8702-2의 micellar soultion을 투여시료로 하여 제암력 평가를 실시하였다. DBA/2J 마우스(평균 체중 25g, 수컷)에 L$_{1210}$임파성 백혈병 세포를 이식한 후, 24시간 후 약물을 복강내에 투여하는 실험계 에서 400mg/kg/day, 단회투여 및 80 혹은 100mg/kg/day, 1~5일간 투여로 ILS%값이 229~543으로 우수한 제암력을 보였다. 또한 BDF$_1$ mice(15~20g)의 axillary region에 3㎣의 Lewis Lung Tumor를 피하로 이식한후 약물투여를 통한 제암효과를 관찰하였다. 100, 200, 300mg/kg/day의 단회 투여계 에서는 수명연장 효과가 없었다. 한편, 20, 40, 60mg/kg/day, 1~5일간의 투여계 에서는 ara-CDP-DL-PCA.2Na만이 효과가 있었는데 농도에 역순하여 저농도인 20mg/kg/day, 1~5일간의 투여계에서 가장 효과가 있었으며 그때의 ILS%는 32.3%였고 투여기간중의 체중변화는 거의 보이지 않았다. 한편 NICOM 370 Dynamic Light Scattering을 이용하여 투여시료로한 micellar solution의 입자도를 분석한 결과 ara-CDP-DL-PCA.2Na는 4.2nm size의 것이 99.48%를 차지하고 있었다. ara-CDP-DL-PCA.2Na의 ICR 마우스를 이용한 급성독성 시험에 있어서 경구투여에서의 LD$_{50}$값은 암,수컷 모두 5000mg/kg이상 이었고, 정맥내 투여 에서는 432mg/kg이었다. 실험과정중 생존동물의 일반적 이상소견등은 없었으나 정맥내 투여의 경우에서 체중증가 억제현상이 있었다.

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Analysis of Toxic-PCBs in Sediment by Isotope Dilution HRGC/HRMS (Isotope Dilution HRGC/HRMS 방법을 이용한 저니토중 Toxic-PCBs 분석)

  • Jang, Seong-Ki;Choi, Duk-Il;Park, Sun-Ku;Kim, Kyung-Sup
    • Analytical Science and Technology
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    • v.12 no.6
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    • pp.550-557
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    • 1999
  • This Analysis was conducted for 13 toxic-PCBs having TEF value among 209 PCBs isomers in sediment by isotope dilution HRGC/HRMS method. From the result, the recovery of surrogate standard was in the range of 71~99%. The concentration range for 13 toxic-PCBs in sediment was found to be 0.84~2.49 ng/g, among them the concentration levels of 2,2',3,3',4,4',5-HpCB(IUPAC No. 170) and 2,2',3,4,4',5,5'-HpCB(IUPAC No. 180) represented almost 50% of total concentrarion and that of 2,3,4,4,5-PeCB(IUPAC No. 114) showed over 10%. The TEQ concentration levelwas in the range of 0.38~2.63 pg-TEQ/g and 3,3',4,4',5-PeCB(IUPAC No. 126) concentration represented over 50% of total TEQ concentration.

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A Case of Severe Bleomycin-Induced Pneumonitis at Non-Hodgkin's Lymphoma (비호즈킨 림프종 환자에서 저용량의 Bleomycin에 의해 발생한 급성 중증 폐독성 1예)

  • Han, Dong-Ha;Min, Young-Joo;Yoon, Je-Hyun;Park, Jong-Ho;Ahn, Jong-Joon;Lee, Ki-Man;Park, Jae-Hoo
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.3
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    • pp.260-264
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    • 2002
  • Bleomycin-induced pulmonary toxicity usually occurs in the elderly patients (greater than 70 years old), patients with a cumulative dose above 400 units, previous chest radiotherapy, oxygen therapy, and renal failure. However, there are some reports of severe pneumonitis that developed after administering low bleomycin doses(less than 100 units). In severe bleomycin-induced pneumonitis in non-Hodgkin's lymphoma patients, the response to corticosteroid is poor and the mortality rate is very high, approximately 83%. Therefore, clinicians should have a low threshold for investigating and treating bleomycin-induced pneumonitis. Here, we report a case of severe bleomycin-induced pneumonitis as a complication of a non-Hodgkin's lymphoma treatment.

Toxicity of Bis(tri-n-butyltin)oxide (TBTO) on the Organ Structure of the Flounder, Paralichthys olivaceus (넙치(Paralichthys olivaceus)의 기관계 구조에 미치는 bis(tri-n-butyltin)oxide (TBTO) 독성)

  • 이정식;강주찬;신윤경;진영국;박정준
    • Korean Journal of Environmental Biology
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    • v.22 no.1
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    • pp.133-140
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    • 2004
  • The histopathologieal effects of his(tri-n-butyltin)oxide (TBTO) on the flounder, Paralichthys otivaceus were examined by means of histological methods. The experimental fishes were exposed to 0.17, 0.36, 0.60, 3.20, 6.30, 12.50 ${\mu}g \;L^{-1}$TBTO concentrations for 42 days. Histopathological change of the fish exposed to TBTO is dependent on the exposure duration and concentration. In the lower concentrations early histological changes included activated mucous cells and chloride cells, capillary hyperemia and epithelial hyperplasia in the gill; hepatocyte activation, degeneration of bile duct and pancyeatic zymogen reduction in the hepatopancreas; and capillary hyperemia, appearance of eosinophilic cell and melano-macrophagocytes in the kidney. At the higher concentrations histological changes of dysfunctionality included epithelial lifting and deformation of the lamellae in the gill; pycnosis and cytoplasmic degeneration of hepatocyte; pycnosis of haemopoietic cell and deformation of renal tubules and glomerulus in the kidney. It is indicated that TBTO induced histopathological changes in the fish as other aquatic pollutants.

A Case of Amiodarone-Induced Pulmonary Toxicity (Amiodarone에 의해 유발된 폐 독성 1예)

  • Shim, Jae-Jeong;Lee, Sang-Hwa;Yoo, Jae-Myung;Suh, Hong-Suk;Oh, Dong-Joo;Joh, Jae-Youn;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho;Kang, Eun-Young;Chae, Yang-Suk
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.1
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    • pp.51-57
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    • 1994
  • Amiodarone is a potent antiarrythmic agent used in the treatment of refractory tachyarrythmias and premature ventricular contractions. Amiodarone may be responsible for the frequent and various side effects including corneal deposits, abnormal liver function test, hyperthyriodism or hypothyroidism, bluish discoloration of the skin, neuropathies, and the others. However, pulmonary toxicity is most serious adverse reaction limiting the clinical efficacy. Rescently, we experienced a case of pulmonary toxicity induced by low dose 10-month amiodarone treatment for atrial fibrilation with rapid ventricular response. Lung biopsy reveals interstitial inflammation, fibrosis, hyperplasia of pneumocytes, and foamy macrophages. Respiratory symptoms and abnormal chest X-ray findings were nearly complete cleared after using steroid and withdrawal of amiodarone. We report a case of amiodarone-induced pulmonary toxicity with literature review.

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Establishment of Reporter Cell Lines that Monitor Activities of Hypoxia Inducible Factor-1, P53 and Nur77 for Assessment of Carcinogenicity (저산소유도인자 HIF-1, 암 억제인자 P53과 고아 핵수용체 Nur77의 발현을 지표로 하는 발암독성예측 세포주의 개발)

  • Hong, Il;Seo, Hee-Won;Lee, Min-Ho;Kim, Ji-Won;Chung, Jin-Ho;Lee, Byung-Hoon;Lee, Mi-Ock
    • Toxicological Research
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    • v.23 no.3
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    • pp.231-238
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    • 2007
  • Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.

Insidious Onset of Amiodarone Pulmonary Toxicity Presented with Hemoptysis (객혈 양상으로 발현된 Amiodarone 폐독성 1예)

  • Kim, Hearn Kook;Jung, Bock Hyun;Han, Kun Hee;Hwang, Jung Won;Cho, Young Ju;Park, Yong Jin;Jung, Hyoung Jung;Kim, Mi Hye;Ryu, Dae Sik;Kang, Gil Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.4
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    • pp.413-417
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    • 2005
  • Amiodarone is widely used to control fatal arrhythmia. However, amiodarone therapy is associated with a relatively high incidence of pulmonary toxicity, up to 5 to 10%. Typical symptoms are nonspecific and often manifest as nonproductive cough, dyspnea and interstitial infiltrates in patients with acute pneumonitis or chronic fibrosis. However, hemoptysis is a very rare symptom of amiodarone pulmonary toxicity. We report a case of amiodarone pulmonary toxicity, who presented with hemoptysis and was successfully treated with the cessation of amiodarone, with review of the relevant literature.

Changes of Toxicological Factors in Rats Short-Term Treated with Two Feeding Methods at Low Level of Microcystin-LR (저농도의 Microcystin-LR를 단기간 처리한 흰쥐에서 투여방법에 따른 독성 지표의 변화)

  • 함영국;김성완
    • Environmental Analysis Health and Toxicology
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    • v.18 no.3
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    • pp.209-217
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    • 2003
  • To investigate the effects of low dosed microcystin -LR (MCLR) on the initial stage of subacute hepatotoxicity in vivo, male Sprague-Dawley rats after weanling were divided in four groups. The orally treated group (OG) was administered orally by 1 $\mu\textrm{g}$/kg B.W. at an interval of three days. The free group (FG) has taken the drinking water including 1 $\mu\textrm{g}$/L freely and the control group (CC) was only treated with 0.9% saline solution All groups were treated for a period of 3 weeks. There was a significant correlation in body growth rate between OG and FC and especially, a deterioration of the growth of spleen was observed in the FG after 5 days. The protein levels were also decreased in OG and FG after 9 days. Level of total fat was increased to the 9th day but again decreased up to the initial level. High hemolysis of the isolated erythrocytes occurred only in OG. Activities of ${\gamma}$-G7 of 0G and FG were higher twice-fold than CG, but the values of OG were already higher at the first treatment day. No significant change in aspartate aminotransferase (AST) activity was shown in all groups, but the activity of alanine aminotransferase (ALT) was slightly increased at the beginning state. There were much similarities in the results of OG and FG. except the growth inhibition of spleen in FG. It may be concluded that long -term effects of the low doses of mycrocystins in animals including human being can lead to serious health problems, especially to liver and spleen.

Concentration Distribution of PBDEs in House Dust on Si-Hwa Industrial Complex (시화공단 인근 실내 더스트의 PBDEs 농도 분포)

  • Kim, Hyun-Seung;Kim, Il-Kyu
    • Journal of Korean Society of Environmental Engineers
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    • v.35 no.8
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    • pp.579-585
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    • 2013
  • Persistent Organic Pollutants (POPs) are chemical substances which persist in the environment, bioaccumulate through the food web, and pose a risk of causing adverse effects to human health and the environment. POPs are thermally stable, highly lipophilic and water-insoluble compounds which can induce various toxic influences including immunotoxicty, carcinogenicity adverse effects on reproduction, development and endocrine fuctions. Polybrominated diphenyl ethers or PBDEs, are organobromine compounds that are used as flame retardant. Because of their toxicity and persistence, the industrial production of some PBDEs is restricted under the Stockholm Convention, a treaty to control and phase out major POPs. In this study, PBDEs was measured in various site of Sihwa industrial complex to investigate concentration distribution of POPs. The levels of PBDEs in house dust samples were 0.722~44.024 ng/g-dry. In PBDEs congener, BDE-209 was relatively higher in the all sites. The concentration of BDE-209 measured over 80.0% of total PBDEs. In various site, high molecular PBDEs homologues are measured higher than low molecular.

A Case of Successful Resuscitation of 10,150 J Shocks and Therapeutic Hypothermia on Aconitine-induced Cardiovascular Collapse (10,150 J의 심장조율동과 치료적 저체온법으로 소생한 중증 초오 중독 환자 1례)

  • Moon, Hyung Jun;Lee, Jung Won;Kim, Ki Hwan;Jeong, Dong Kil;Kim, Jong Ho;Kim, Young Ki;Lee, Hyun Jung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.12 no.2
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    • pp.97-101
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    • 2014
  • Aconitine, found in the Aconitum species, is highly extremely toxic, and has been known to cause fatal cardiac arrhythmias and cardiovascular collapse. Although several reports have described treatment of aconitine intoxication, management strategy for the patient in a hemodynamically compromised state who experienced cardiopulmonary collapse is unknown. We report here on a case of a successful cardiopulmonary resuscitation and therapeutic hypothermia in an aconitine-induced cardiovascular collapsed patient. A 73-year-old male who presented with nausea, vomiting, chest discomfort, and drowsy mental state after eating an herbal decoction made from aconite roots was admitted to the emergency department. He showed hemodynamic compromise with monomorphic ventricular tachycardia resistant to amiodarone and lidocaine. After 3 minutes on admission, he collapsed, and cardiopulmonary resuscitation was initiated. We treated him with repeated cardioversion/defibrillation of 51 times, 10,150 joules and cardiopulmonary resuscitation of 12 times, 69 minutes for 14 hours and therapeutic hypothermia for 36 hours. He recovered fully in 7 days.

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