• Title/Summary/Keyword: 저독성

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Hypoxia and NF-${\kappa}B$; The Relation to Chemoresistance (저산소증과 NF-${\kappa}B$의 항암제내성과의 연관성 고찰)

  • Yoon, Seong-Woo
    • Journal of Korean Traditional Oncology
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    • v.15 no.1
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    • pp.119-128
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    • 2010
  • 항암치료는 현재 암환자의 주요한 치료임에도 불구하고 항암제내성과 같은 문제점을 가지고 있다. 약물내성은 다양한 기전에 의해 발생하는데 수송단백질의 과발현, 비독성화발현, 손상유전자의 복구, 세포사멸신호의 변화, STAT-3와 NF-${\kappa}B$의 발현 등이 포함된다. 암세포는 저산소환경에서 발생하며 일반세포에 비해 무산소해당에 상대적 의존도가 높고 이는 암세포의 성장과 전이를 촉진하는 인자가 된다. 항암제가 효과를 내기 위해서는 산소가 필요한데 저산소환경은 이를 방해하며 또한 유전자의 불안정화로 인해 약물내성이 유도된다. NF-${\kappa}B$는 주요 전사인자 중 하나로서 각종 염증과 암에서 지속적으로 활성화되며 암세포의 변화, 증식, 침윤, 전이에 관여한다. 환경적 스트레스 등과 대부분의 항암약제들이 NF-${\kappa}B$를 활성화시키며 임상적으로도 암환자의 생존과 연관된 중요한 예후인자이다. NF-${\kappa}B$의 발현은 항암제로 인한 암세포의 자멸을 회피하게 만들고 수송단백질을 활성화시켜 항암제내성을 유도한다. 강황, 적포도, 고추, 건칠 등 다양한 천연물에서 NF-${\kappa}B$를 억제시키는 효능이 발견되었으며 이는 항암제내성을 억제시키고 항암제의 효과를 증대시킨다. 저산소환경의 개선과 NF-${\kappa}B$의 억제는 상호연관성을 가지고 있으며 항암제내성의 개선뿐만 아니라 암치료제 개발의 새로운 연구목표가 될 수 있다.

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Effect of Xanthine Oxidase Inhibitor on Cerebral Hypoxia-Ischemia in Neonatal Rats (Xanthine Oxidase Inhibitor가 저산소성-허혈성 뇌손상이 유도된 신생쥐에 미치는 영향)

  • Choi, Dae-Ho;Oh, Yeon-Kyun;Park, Seung-Tak
    • Clinical and Experimental Pediatrics
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    • v.45 no.6
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    • pp.732-742
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    • 2002
  • Purpose : In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. Methods : Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons. Results : 72 hours from H-I, the cell numbers and viability were decreased significantly in time-dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment. Conclusion : From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

Responses and Toxicities of Risk-adapted Chemotherapy in Pediatric Intracranial Germ Cell Tumors (소아 두개 내 생식 세포종에서 위험군에 따른 화학요법의 치료 반응 및 독성)

  • You, Dong Kil;Lee, Soo Hyun;Yoo, Keon Hee;Sung, Ki Woong;Lim, Do Hoon;Shin, Hyung Jin;Koo, Hong Hoe
    • Clinical and Experimental Pediatrics
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    • v.48 no.2
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    • pp.186-190
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    • 2005
  • Purpose : The purpose of this study was to evaluate the responses and toxicities of risk-adapted chemotherapy in pediatric intracranial germ cell tumors(IC-GCT). Methods : Fourteen patients who were diagnosed as IC-GCT from October 2002 to December 2003 received chemotherapy as an initial treatment modality. The low risk(LR) group was defined as follows : Pure germinoma and normal AFP level. Beta-hCG level 50 mIU/mL or less. The others belonged to the high risk(HR) group. Chemotherapy was composed of cisplatin, cyclophosphamide, etoposide and vincristine. Double doses of cisplatin and cyclophosphamide was used in HR patients. Results : Pathologic confirmation was done in all but one. Median age at diagnosis was 11.6 yr (1.2-18.7 yr), and nine patients belonged to the HR group. Tumor markers were normalized after chemotherapy in all patients whose tumor markers had been elevated. Four LR patients(80 percent) and seven HR patients(77.8 percent) showed complete response(CR) at the end of chemotherapy. An additional two of the three patients with partial response(PR) achieved CR after radiation therapy (RT), and the remaining one relapsed before RT. Four LR and all HR patients experienced infectious episodes that required hospitalization. Four of the nine HR patients(44.4 percent) suffered from tinnitus, three of whom developed sensorineural hearing loss. All but one are surviving, event-free, with a median follow-up of 13.9 mo(8.1-22.3 mo). Conclusion : Risk-adapted cisplatin-based chemotherapy was effective even in HR patients, but regimen modification seems to be necessary to avoid an unacceptably high toxicity rate.

Historical Change of Population Abundances of Panonychus ulmi and Tetranychus urticae (Acari: Tetranychidae) in Selected Apple Orchards in Suwon and Its Hypothetical Explanation (수원 지역 사과원에서 사과응애와 점박이응애 개체군의 역사적 변천과정 및 해석)

  • Kim Dong Soon;Lee Joon Ho
    • Korean journal of applied entomology
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    • v.44 no.2
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    • pp.115-123
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    • 2005
  • Historical changes of population abundances of European red mite (ERM), Panonychus ulmi (Koch), and two-spotted spider mite (TSSM), Tetranychus urticae (Koch) (Acari: Tetranychidae), were described in selected apple orchards in the National Horticultural Research Institute (NHRI, Suwon, Korea), based on research reports of the NHRI from 1958 to 1998. ERM was an abundant species up to 1970, and TSSM became a dominant species after 1980. The change occurred around mid 1970. Three hypotheses were made to explain the change: TSSM competitively replaces ERM, ground cover weeds are a major influencing factor on movement of TSSM (TSSM movement into trees is accelerated by destroying weeds), and ERM and TSSM populations are regulated by natural enemy complexes when the orchard system is not disrupted. And long-term results of the interaction between two species were projected according to the combination of different orchard management strategies: pesticide sprays (non-selective toxic pesticide spray : heavy pesticide pressure (HPP), and selective soft pesticide spray = low pesticide pressure (LPP)) and weed control methods (grass planting, and clean culture system with herbicides). In the HPP and grass planting system, ERMs are abundant because ERM can avoid competition with TSSM as movement of TSSM to trees are restricted, and natural enemy complexes are destroyed by toxic pesticides. In the HPP and clean culture system, TSSMs are abundant because TSSM moves to trees from early season and competitively replaces ERM. In the LPP and grass planting system, ERMs are abundant because movement of TSSM to trees is reduced, but they do not build up a high population density since their densities are regulated by natural enemy complexes. In the LPP and clean culture system, TSSM moves to trees and competes with ERM, but the competition pressure is reduced because population densities of mites are regulated in a lower level by natural enemy complexes. So, ERM can occurs in late season. Thus, two species can coexist temporarily with more ERM in early season and more TSSM in late season. TSSM abundant phenomenon presented in this study can be partially explained as a result of long-term interaction between ERM and TSSM under the HPP and clean culture system.

Cytotoxicity of paraquat and compensatory effects of 3-methylcholanthrene in rat lung (Paraquat의 세포독성과 흰쥐의 폐에서 3-Methylcholanthrene의 독성경감효과)

  • Rim, Yo-Sup;Kim, Doc-Soo;Han, Du-Seok;Hwang, In-Taek
    • The Korean Journal of Pesticide Science
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    • v.6 no.2
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    • pp.96-104
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    • 2002
  • This study was carried out to investigate cytotoxicity of paraquat on NIH 3T3 fibroblasts, toxicity of paraquat and compensatory effects of 3-methylcholanthrene (3-MC) on the rat lung. In order to conduct MIT [3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyl -2H-tetrazolium-bromide] and NR (Neutral red) assay, the $5.0{\times}10^4cell/ml$ of NIH 3T3 fibroblast in each well of 24 multi-dish were cultured. After 24 hours, the cells were treated with solution of paraquat (1, 25, 50 and $100{\mu}M$ respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours. MIT and NR assay were performed to evaluate the cytotoxicity of cell organelles. $MTT_{50}\;and\;NR_{50}$ of paraquat were $1668.97{\mu}M\;and\;1030.85{\mu}M$, respectively. These $IC_{50}$ of Paraquat were decided as a low cytotoxicity by Borenfreund and Puemer (1984). In order to observe the toxicity and compensatory effects of paraquat on the rat lung, Spraque Dawley male rats were used as experimental animals and were divided into paraquat only treated group and simultaneous application group of paraquat and 3-MC, at 30 min and 1, 3, 6, 12, 24, 48 and 96 hrs interval after each treatment. The animals were sacrificed by decapitation and their or the lungs were immediately removed, immersed in fixatives, and were processed with routine method for light microscopic study. Paraffin sections were stained with H&E and iron hematoxylin of Verhoeff. Under the light microscopy, erythrocytes were full in alveolar capillaries at 3 hrs and congested at 24 hrs after paraquat administration. The great alveolar cells (Type II cell) were increased and mitosis of great alveolar were observed in interalveolar septa. Many lymphocytes, macrophages and polymorphonuclear (PMN) cells were observed in connective tissue surrounding lung tissue and germinal center in lymph follicles of terminal bronchiole. Alveolar macrophages were increased in interalveolar septa and alveoli at 48 hrs. And observed many alveolar macrophages at 96 hrs. In iron hematoxylin stain of Verhoeff, Collagen fiber were increased in respiratory bronchiole, interalveolar septa and alveoli and breath of alveoli, and alveolar pore were broaden. But, in paraquat plus 3-MC treated group, morphological changes were mild in lung tissue. These results indicate that 3-MC has a compensatory effects against toxicity of paraquat by conjugation with oxygen.

Decomposition of Low-toxic Propellant by Cu-La-Al/honeycomb Catalysts (Cu-La-Al/honeycomb 촉매를 이용한 저독성 추진제 분해)

  • Kim, Munjeong;Yoo, Dalsan;Lee, Jeongsub;Joen, Jong-Ki
    • Korean Chemical Engineering Research
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    • v.59 no.2
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    • pp.296-303
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    • 2021
  • The objective of this study is to investigate the applicability of a Cu-supported honeycomb catalyst as a catalyst for decomposition of a low toxic liquid propellant based on ammonium dinitramide (ADN). A mixture of copper, lanthanum, and alumina was supported on the honeycomb support by wash coating to prepare a Cu-La-Al/honeycomb catalyst. We elucidated that the effect of metal loading on the physicochemical properties of Cu-La-Al/honeycomb catalyst and catalytic performance in decomposition of the ADN-based liquid propellant. As the number of wash coatings increased, the amount of active metal Cu was increased to 4.1 wt%. The BET surface area of the Cu-La-Al/honeycomb catalyst was in the range of 3.1~4.1 ㎡/g. The micropores were hardly present in Cu-La-Al/honeycomb catalysts, however, the mesopores and macropores were well developed. The Cu (2.7 wt%)-La-Al/honeycomb catalyst exhibited the highest activity in the decomposition of the ADN-based liquid propellant, which is attributed to the largest surface area, the largest pore volume, and the well-developed mesopores and macropores.

Basic Properties and Solution Behavior of New Naturally Derived Cosmetic Preservative, and Stability of Cosmetic Formulation (신규 화장품용 천연유래 보존제의 물성 측정, 용액 거동 및 보존제 포함 화장품의 제형 안정성)

  • Subin Shin;Jeongeun Park;Nayeon Ko;Mijung Kim;Hyewon Shin;Dasom Lee;Narae Kim;Taeshik Earmme;Gugin Jeong;Joonwon Bae
    • Applied Chemistry for Engineering
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    • v.35 no.2
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    • pp.122-127
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    • 2024
  • Cosmetic preservatives are an important class of ingredients in terms of ensuring sustainable use and providing customer satisfaction. Recently, a great deal of interest has been drawn to the production and use of toxic-free, naturally derived preservatives. In this work, a new naturally derived preservative (laurimino bispropanediol, LB) was developed to replace the most widely used diol preservatives, such as 1,2-hexanediol or 1,2-octanediol. The basic properties of the obtained preservative were measured, and the solution behavior of the preservative in an aqueous medium was examined. The feasibility of micelle formation in the preservative solution was investigated using the fluorescence (FL) based pyrene method. Micelle formation was feasible owing to the relatively long hydrophobic chains and increased hydroxyl groups in the preservative molecules. The emulsification capability of the preservative was assessed using the Rosano and Kimura method, showing that the preservative possessed emulsifying capability in an organic solvent (benzene) and soy bean oil. In addition, the dispersion stability of cosmetic formulations, including the new LB preservatives such as essence and lotion, was demonstrated by comparing the light transmittance of the formulations. This article provides important information for future research regarding the synthesis and practical applications of new toxic-free naturally derived preservatives.

Toxicity and Endocrine Disrupting Effect of Parabens (파라벤류의 독성과 내분비계장애 효과)

  • Ahn, Hae-Sun;Nah, Won-Heum;Lee, Jae-Eun;Oh, Yeong-Seok;Gye, Myung-Chan
    • Korean Journal of Environmental Biology
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    • v.27 no.4
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    • pp.323-333
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    • 2009
  • Parabens are alkyl esters of p-hydroxybenzoic acid, which are widely used in foods, cosmetics, and pharmaceutic products as preservatives. Absorbed parabens are metabolized fastly and excreted. Actually human body is exposed to complex mixture of parabens. Safety assessment at various toxicological end points revealed parabens have a little acute, subacute and chronic toxicities. Some reports have argued that as parabens have estrogenic activity, they are associated with the incidence of breast cancer through dermal absorption by cosmetics. There is an inference that antiandrogenic activity of parabens may give rise to a lesion of male reproductive system, but also there is an contrary. At cellular level, parabens may inhibit mitochondrial function of sperms and androgen production in testis, but also there is an contrary. Parabens seem to have little or no toxicity in embryonic development. Parabens can cause hemolysis, membrane permeability change in mitochondria and apoptosis, suggesting cellular toxicity of parabens. Parabens evoked endocrine disruption in several fish species and have toxic effect on small invertebrates and microbes. Therefore, the toxicity of parabens should be considered as a potentially toxic chemical in the freshwater environment. In conclusion, though parabens may be considered as a low toxic chemical, more definite data are required concerning the endocrine disrupting effect of parabens on human body and aquatic animals according to route and term of exposure as well as the residual concentration of parabens.

Low Plasma Insulin Level Prolonged Hypoglycemia after High dose Insulin Lispro Injection (고용량 Insulin lispro 피하 주사 후 저 인슐린 혈증을 보인 지속적 저혈당성 혼수 환자 1례)

  • Kang, Jeong Ho;Park, Hyun Soo
    • Journal of The Korean Society of Clinical Toxicology
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    • v.14 no.2
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    • pp.151-154
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    • 2016
  • Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.

A Case of Pyrazinamide Induced Fulminant Hepatic Failure (Pyrazinamide에 의한 전격성 간부전 1예)

  • Moon, Dae Sung;Jang, Tae Won;Oak, Chul Ho;Jung, Maan Hong;Yoo, Chan Hui;Song, Jun Young;Kim, Sung Eun;Kim, Ja Kyung;Jang, Lee La;Lee, Eun Young;Jung, Gyu Sik
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.5
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    • pp.435-439
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    • 2007
  • Standard antituberculous therapy, including isoniazid (INH), rifampin, ethambutol, and pyrazinamide (PZA), is widely used to treat active tuberculosis. The most important side effect is hepatotoxicity. In a standard four-drug regimen, PZA was the most common cause of drug-induced hepatitis and was dose-related. The incidence of drug-induced hepatitis is high at doses of 40~70 mg/kg per day but has fallen significantly since the recommended dose was reduced. Liver toxicity induced by PZA is rare at doses of 25 mg/kg per day or less. PZA-induced fulminant hepatic failure is also rare but fatal. We report a case of fulminant hepatic failure caused by a re-challenge of PZA.