• Title/Summary/Keyword: 신경독성

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Protective Effect of the Ethyl Acetate-fraction of Methanol Extract of Ophiophogon japonicus on Amyloid beta Peptide-induced Cytotoxicity in PC12 Cells (소엽맥문동-에틸아세테이트 분획물의 아밀로이드 베타단백질-유발 세포독성에 대한 억제 효능)

  • Moon, Ja-Young;Kim, Eun-Sook;Choi, Soo-Jin;Kim, Jin-Ik;Choi, Nack-Shik;Lee, Kyoung;Park, Woo-Jin;Choi, Young-Whan
    • Journal of Life Science
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    • v.29 no.2
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    • pp.173-180
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    • 2019
  • Amyloid ${\beta}$-protein ($A{\beta}$) is the principal component of senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors, including antioxidants and proteoglycans, modify $A{\beta}$ toxicity. It is worthwhile to isolate novel natural compounds that could prove therapeutic for patients with AD without causing detrimental side effects. In this study, we investigated the in vitro neuroprotective effects of the ethyl acetate fraction of methanol extract of Ophiophogon japonicas (OJEA fraction). We used an MTT reduction assay to detect protective effects of the OJEA fraction on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used a cell-based ${\beta}$-secretase assay system to investigate the inhibitory effect of the OJEA fraction on ${\beta}$-secretase activity. In addition, we performed an in vitro lipid peroxidation assay to evaluate the protective effect of the OJEA fraction against oxidative stress induced by $A{\beta}_{25-35}$ in PC12 cells. The OJEA fraction had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and was strongly inhibitory to ${\beta}$-secretase activity, which resulted in the attenuation of $A{\beta}$ generation. In addition, the OJEA fraction significantly decreased malondialdehyde (MDA) content, which is induced by the exposure of PC12 cells to $A{\beta}_{25-35}$. Our results suggested that the OJEA fraction contained active compounds exhibiting a neuroprotective effect on $A{\beta}$ toxicity.

Cyclosporine-Assoc iated Central Neurotox ic its after Hearat Transplantat ion 1 Case Report (심장이식 환자에서 Cyclosporine에 의한 중추신경독성 -1례 보고-)

  • Kim, Young-Hee;Song, Hyun;Song, Meong-Gun
    • Journal of Chest Surgery
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    • v.30 no.11
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    • pp.1136-1138
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    • 1997
  • A 45-year-old man underwent heart transplantation due to dilated cardiomyopathy. Cyclosporine, 2 mg/kg per day, was intravenously givell postoperatively. As central neurotoxicity signs that were included pin-point pupil, no light reflex, coma, were presented at 8 postoperative hours, cyclosporine was decreased to 1 mg/kg er day. At that time the cyclosporine level was 345 $\mu\textrm{g}$/L, the serum creatinine level was 1.8mg/dl and the serum magnesium level was within normal limit. He awaked at 31 postoperative hours and all sign of cyclosporine-induced central neurotoxicity was resolved after postoperative days. He was discharged without sequale at postoperative day 28.

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Neurotoxicity Assessment of Methamphetamine and Cadmium Using Cultured Neuronal Cells of Long-Evans Rats (신경세포 배양법을 이용한 methamphetamine과 cadmium의 신경독성 평가)

  • Cho, Dae-Hyun;Kim, Jun-Gyon;Jeong, Yong;Lee, Bong-Hun;Kim, Eun-Youb;Kim, Jeong-Goo;Cho, Tai-Soon;Kim, Jin-Suk;Moon, Hwa-Hwey
    • Toxicological Research
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    • v.12 no.1
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    • pp.69-79
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    • 1996
  • Primary culture of cerebellar neuronal cells derived from 8-day old Long-Evans rats was used. Pure granule cells, astrocytes or mixed cells culture systems were prepared. These cells were differentiated and developed synaptic connections. And the astrocytes were identified by immunostaining with glial fibrillary acidic protein (GFAP). Methamphetamine (MAP), which acts on dopaminergic system and cadmium (Cd), a toxic heavy metal, were applied and biochemical assays and electrophysiological studies were performed. $LC_50$ values estimated by MTT assay of MAP and Cd were 3 mM and 2$\mu M$ respectively. Cells were treated with 1 mM or 2 mM MAP and 1$\mu M$ $CdCl_2$ for 48 hour, and the incubation media were analyzed for the content of released LDH. MAP (2 mM) and Cd significantly increased the LDH release. Cell viability was decreased in both groups and some cytopathological changes like cell swelling or vacuolization were seen. The cerebellar granule cells were used for measuring membrane currents using whole-cell clamp technique. Sodium and potassium currents were not affected by MAP neither Cd, but calcium current was significantly reduced by Cd but not affected by MAP. Therefore, in vitro neurotoxicity test system using neuronaI cells and astrocytes cultures were established and can be used in screening of potential neurotoxic chemicals.

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Performance Ranges of the Neurobehavioral Core Test Battery among Female Workers Occupationally Not Exposed to Neurotoxic Agents in Manufacturing Industries (신경독성 물질에 폭로되지 않은 제조업체 여성 근로자의 신경행동검사 수행능력범위)

  • Lee, Kyung-Jae;Lee, Se-Hoon;Kim, Hyoung-Ah;Lee, Won-Chul;Chang, Seong-Sil;Park, Chung-Yill;Chung, Chee-Kyung
    • Journal of Preventive Medicine and Public Health
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    • v.28 no.4 s.51
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    • pp.911-923
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    • 1995
  • With increased use of neurotoxic agents in manufacturing industries, hazardous effects of neurotoxic agents pose significant problems in protecting health of workers who work in these industries. A normal range of neurobehavioral performance is required to study hazardous effects of neurotoxic agents among workers. However, such reference for Korean population is not available yet. The objective of this study is to estimate a normal range of neurobehavioral test performance of female workers in Korea. Data for neurobehavioral test performance developed by the World Health Organization were obtained from 165 female workers. Study subjects, 140 production workers and 25 clerks, who voluntarily participated in this study were not occupationally exposed to neurotoxic agents. The mean age and the mean education years of them were 32 years and 10.9 years, respectively Santa Ana dexterity, pursuit aiming, digit symbol, simple reaction time, and Benton visual retention tests among the Neurobehavioral Core Test Battery(NCTB) were included in the evaluation. Subjects were interviewed by a trained interviewer for their detailed occupational history $Mean({\pm}SD)$ performance of the participants were: $45.7{\pm}7.1\;and\;41.9{\pm}6.4$ in the Santa Ana dexterity test of the preferred and non-preferred hands; $45.7{\pm}7.1\;and\;41.9{\pm}6.4$ in correct dot of the pursuit aiming test; $57.7{\pm}16.0$ in the digit symbol test; $274.8{\pm}44.6$ msec in the mean simple reaction time and $70.5{\pm}69.0$ msec in the mean standard deviation of it; and $7.8{\pm}1.7$ in the Benton visual retention test. Most neurobehavioral performance scores were correlated significantly with age and educational level. Educational level was found to be a significant independent variable which was associated with all test scores. Age was significantly associated with scores of pursuit aiming and digit symbol tests.

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Effects of Ulva lactuca Extracts on Cytotoxicity of Cancer Cell Lines and Immune Stimulation (갈파래(Ulva lactuca) 추출분획의 암 세포주에 대한 세포독성 및 면역활성 효과)

  • Jang, Min-Kyung;Kim, Nam-Young;Lee, Dong-Geun;Lee, Jae-Hwa;Ha, Jong-Myung;Ha, Bae-Jin;Kim, Mi-Hyang;Bae, Song-Ja;Jang, Jeong-Su;Lee, Sang-Hyeon
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1169-1173
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    • 2006
  • Extracted fractions of the green seaweed Ulva lactuca were studied to verify the cytotoxicity and immunostimulating activity. The fractions from the ethanol extract of U. lactuca were prepared by the systematic extraction procedure with solvents such as hexane, ethyl ether, methanol, butanol and $H_2O$. The cytotoxic effects of U. lactuca fractions against human leukemia cell line U937, mouse neuroblastoma cell line (NB41A3), human hepatoma cell line (HepG2) and rat glioma cell line (C6) were investigated. Ethyl ether fraction showed the highest cytotoxicity against all four cell lines tested. In addition, $H_2O$ fraction also showed relatively high cytotoxicity. Dose dependent patterns were observed on all four cell lines. The immune-stimulating effects of U. lactuca fractions on rat macrophage cell line (RAW 264.7) were also investigated. All five fractions of U. lactuca extract stimulated NO production with concentration dependant manner. These results suggest that U. lactuca may be a useful candidate for a natural cancer preventing and immune-stimulating agents.

A Neural Network-Based Tracking Method for the Estimation of Hazardous Gas Release Rate Using Sensor Network Data (센서네트워크 데이터를 이용하여 독성물질 누출속도를 예측하기 위한 신경망 기반의 역추적방법 연구)

  • So, Won;Shin, Dong-Il;Lee, Chang-Jun;Han, Chong-Hun;Yoon, En-Sup
    • Journal of the Korean Institute of Gas
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    • v.12 no.2
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    • pp.38-41
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    • 2008
  • In this research, we propose a new method for tracking the release rate using the concentration data obtained from the sensor. We used a sensor network that has already been set surrounding the area where hazardous gas releases can occur. From the real-time sensor data, we detected and analyzed releases of harmful materials and their concentrations. Based on the results, the release rate is estimated using the neural network. This model consists of 14 input variables (sensor data, material properties, process information, meteorological conditions) and one output (release rate). The dispersion model then performs the simulation of the expected dispersion consequence by combining the sensor data, GIS data and the diagnostic result of the source term. The result of this study will improve the safety-concerns of residents living next to storage facilities containing hazardous materials by providing the enhanced emergency response plan and monitoring system for toxic gas releases.

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The study on cytotoxicity of cytokines produced by the activated human NKT cells on neuroblastoma (활성화된 자연살상 T 세포(NKT)에서 생성된 사이토카인에 의한 신경모세포종의 세포독성에 관한 연구)

  • Cho, Jin Young;Yoon, Young Wook;Yoon, Hyang Suk;Kim, Jong Duk;Choi, Du Young
    • Clinical and Experimental Pediatrics
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    • v.49 no.4
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    • pp.439-445
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    • 2006
  • Purpose : ${\alpha}$-Galactosylceramide (${\alpha}$-GalCer)-stimulated human $V{\alpha}24$ natural killer T (NKT) cells exert antitumor activity against some leukemia in a CD1d dependent and TCR-mediated manner, but could not kill CD1d - negative neuroblastoma (NB) cells. There are few reports about the direct antitumor effect of highly secreted cytokines by these cells on activation. In this study, using a cell-free supernatant (SPN) collected from plate bound hCD1d/${\alpha}$ GalCer tetramers-stimulated NKT cells, we examined whether they could be helpful in the immunotherapeutic treatment of NB. Methods : Cells were cultured in IMDM. The cytokines produced by NKT cells were measured with Cytometric Bead Array (CBA) analysis. Cell viability was evaluated by calcein-AM fluorescence with digital image microscopy scanning (DIMSCAN). The percentage of specific apoptosis was calculated by flow cytometric detection of apoptosis using annexin V and 7-AAD. Results : The activated NKT cells secreted high levels of IL-2, INF-${\gamma}$, TNF-${\alpha}$. The SPN was significantly cytotoxic against four out of eight tested NB cell lines, through mainly apoptosis as evidenced by annexin-V staining and inhibition with the pretreatment of pancaspase blocker. This apoptosis was significantly inhibited when anti-TNF-${\alpha}$ and anti-IFN-${\gamma}$ neutralizing mAbs were used separately and it was completely abolished when the two mAbs were combined. Conclusion : IFN-${\gamma}$ and TNF-${\alpha}$ produced by NKT cells could exert synergistically direct antitumor activity through apoptosis on some NB cell lines.

Regulation of Acetylcholine Esterase and Monoamine Oxidase in Oryzias Latipes by Carbofuran (카보푸란에 의한 송사리 acetylcholine esterase 및 monoamine oxidase의 활성조절)

  • Kim, Sung-Hee;Kim, Woo-Keun;Lee, Jeong-Soon;Koh, Sung-Cheol;Lee, Sung-Kyu;Chon, Tae-Soo;Kim, Jong-Sang
    • Environmental Analysis Health and Toxicology
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    • v.18 no.1
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    • pp.21-25
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    • 2003
  • 카바메이트계 농약인 카보푸란은 어류에 대한 독성이 매우 높으며, 낮은 농도에서 어류의 척추기형이나 행동이상을 유발한다. 이러한 카보푸란의 독성기전을 밝히기 위한 일환으로 신경물질대사와 관련이 깊은 acetylcholine esterase(AChE)와 monoamine oxidase(MAO)에 미치는 농약의 효과를 송사리(Oryzias latipes; Medaka fish)를 이용하여 평가하였다. Medaka fish에 대한 카보푸란의 반수치사농도(LC$_{50}$)는 2.5 ppm이었으며, 1 ppb 카보푸란에 24시간 노출된 경우, AChE 효소활성이 머리와 몸통부위에서 각각 30, 20%씩 감소되었다. 한편, MAO 효소활성은 카보푸란의 농도가 증가함에 따라 머리부위에서는 감소한 반면, 몸통부위에서는 증가하는 경향을 보였다. 특히 카보푸란의 농도가 1 ppb에서도 송사리의 MAO 효소활성이 영향을 받는 것으로 나타나, 카보푸란에 의한 송사리의 행동이상은 AChE 활성 뿐 아니라 MAO활성의 변화에 의한 복합적인 효과일 가능성이 높다.

A Case of Central Nervous System (CNS) Toxicity in Acute Organophosphate Intoxication (유기인계 농약 중독 환자에서 중추신경 독성으로 지속적인 의식장애를 보인 1례)

  • Lee, Jae Sung;Paik, Jin Hui;Yun, Sung Hyun;Kim, Ji Hye;Han, Seung Baik;Kim, Jun Sig;Jung, Hyun Min
    • Journal of The Korean Society of Clinical Toxicology
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    • v.11 no.1
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    • pp.31-35
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    • 2013
  • Acute organophosphate intoxication is important because of its high morbidity and mortality. The mortality is still high despite the use of atropine as specific antidotal therapy and oximes for reactivation of acetylcholinesterase. Inhibition of acetylcholinesterase by organophosphate can cause acute parasympathetic system dysfunction, muscle weakness, seizure, coma, and respiratory failure. Acute alteration in conscious state or a coma, which may occur following organophosphate intoxication, is an indication of severe intoxication and poorer prognosis. This acute decline in conscious state often reverses when the cholinergic crisis settles; however, it may be prolonged in some patients. We report on a case of a 60-year-old male who showed prolonged decline in conscious state due to of Central Nervous System (CNS) toxicity after a suicide attempt with organophosphate.

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A Sensorimotor Polyneuropathy Caused by Chronic Phenytoin Therapy (페니토인의 장기 복용으로 발생한 감각운동성 다발성 신경병증)

  • Han, Dong-Chul;Park, Hyeon-Mi;Shin, Dong-Jin;Lee, Yeong-Bae
    • Journal of The Korean Society of Clinical Toxicology
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    • v.4 no.2
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    • pp.128-130
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    • 2006
  • Phenytoin has been used globally as an effective anticonvulsant. Among its adverse effects, peripheral neuropathy including polyneuropathy has sometimes been reported. We report a case of sensorimotor polyneuropathy associated with high serum level and long-term phenytoin therapy. A 29-year-old male presented with motor weakness in all extremities. He was treated with phenytoin (400 mg/day) for about eight years because of generalized tonic clonic seizure. During none conduction assessment, sensorimotor polyneuropathy was discovered.

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