• Journal of Applied Biological Chemistry
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• 제63권4호
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• pp.357-363
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• 2020

Oxidative stress caused by the overproduction of reactive oxygen species (ROS) is known as an etiology of neurodegenerative diseases. Populus tomentiglandulosa (PT), a member of the Salicaceae family, is widely grown in Korea and has been reported to exert protective effects on cerebral ischemia by attenuating of oxidative stress and neuronal damage. In the present study, we investigated the antioxidant activity and neuroprotective effects of an ethanol extract and four fractions [n-butanol, ethyl acetate (EtOAc), chloroform, and n-hexane] of PT under in vitro and cellular systems. The extract and four fractions of PT showed 1,1-diphenyl-2-picrylhydrazyl (DPPH), •OH, and O2- radical scavenging activities in a dose-dependent manner. In particular, the EtOAc fraction of PT had the strongest DPPH, •OH, and O2- radical scavenging activities among the extract and other fractions. Therefore, we further investigated the neuroprotective effect of the EtOAc fraction of PT against oxidative stress in H2O2-induced SH-SY5Y cells. Treatment with H2O2 significantly decreased cell viability and lactate dehydrogenase (LDH) release, and it also increased the ROS levels compared to the normal group. However, treatment with the EtOAc fraction of PT significantly increased cell viability. Moreover, the EtOAc fraction of PT-treated group significantly suppressed ROS production and LDH release compared to the H2O2-induced control group. In conclusion, our findings indicated that PT had in vitro antioxidant activity and neuroprotective effects against oxidative stress. Therefore, PT could be used as a natural agent for protection against oxidative stress.

• 화훼연구
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• 제17권4호
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• pp.242-245
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• 2009

중금속의 하나인 $Cr0_3$의 세포독성과 이에 대한 연꽃(Nelumbo nucifera GAERTN(NNG))의 수술에서 채취한 연꽃추출물의 방어효과를 배양 대뇌신경교세포(C6 glioma cell)를 대상으로 항산화 측면에서 조사하였다. $Cr0_3$의 세포독성을 조사하기 위하여 배양된 C6 glioma 세포를 $4{\sim}55{\mu}M$ 농도의 $Cr0_3$로 48시간동안 처리하였다. XTT 분석법에 의하여 세포생존율을 조사하였다. 그 결과 $Cr0_3$는 처리 농도에 비례하여 C6 glioma세포의 생존율을 유의하게 감소시켰으며 $Cr0_3$의 $55{\mu}M$ 농도 처리에서는 $XTT_{50}$ 값이, $10{\mu}M$에서는$XTT_{90}$ 값이 나타났다. 따라서 세포독성판정기준에 의하여 $Cr0_3$는 C6 glioma세포에 고독성인 것으로 나타났다. 한편, $Cr0_3$의 세포독성에 대한 연꽃추출물의 방어효과를 항산화 측면에서 조사하기 위하여 먼저 연꽃추출물의 항산화활성을 SOD-유사활성에 의하여 조사하였다. 그 결과 $130{\sim}150{\mu}g{\cdot}mL^{-1}$의 연꽃추출물 농도에서 SOD-유사활성이 대조군에 비하여 모두 증가하였으며 특히 $150{\mu}g{\cdot}mL^{-1}$의 NNG추출물의 처리에서는 대조군에 비하여 유의하게 증가한 것으로 나타났다(p<0.05). 이는 또한 비교군으로 사용한 $15{\mu}M$, vitamin E의 SOD유사활성과 매우 유사한 활성을 나타냈다. 따라서 연꽃추출물은 SOD 유사활성을 보임으로서 항산화활성을 나타냈다. 한편, $Cr0_3$의 세포독성에 대한 연꽃추출물의 방어효과를 조사하기 위하여 $Cr0_3$의 $XTT_{50}$ 농도인 $55{\mu}M$에서 배양 C6 glioma 세포를 처리하기 전에 연꽃추출물이 $90-120{\mu}g{\cdot}mL^{-1}$ 농도로 각각 포함된 배양액에서 2시간 동안 배양한 후 이에 대한 세포생존율을 조사하였다. 그 결과 연꽃추출물을 처리한 실험군에서는 $Cr0_3$을 처리한 실험군에 비하여 유의한 세포생존율의 증가를 보였다. 본 실험 결과는 연꽃추출물이 $Cr0_3$의 세포독성을 효과적으로 방어하였음을 알 수 있었다. 이상의 실험 결과로부터 $Cr0_3$는 배양 C6 glioma세포에 고독성을 나타냈으며 항산화활성을 가지고 있는 연꽃추출물은 $Cr0_3$에 의한 세포독성을 효과적으로 방어함으로서 $Cr0_3$의 독성이 산화적 손상과 관련이 있음을 알 수 있었다.

• 대한의생명과학회지
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• 제12권2호
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• pp.81-89
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• 2006

The ischemia-responsive 94 gene (irp94) encoding a 94 kDa endoplasmic reticulum resident protein was investigated its molecular properties associated with unfoled protein responses. First, the expression of irp94 mRNA was tested after the reperfusion of the transient forebrain ischemia induction at the central nervous system in three Mongolian gerbils. Second, irp94 expression in PC12 cells, which are derived from transplantable rat pheochromocytoma cultured in the DMEM media, was tested at transcriptional and translational levels. The half life of irp94 mRNA was also determined In PC12 cells. Last, the changes of irp94 mRNA expression were investigated by the addition of various ER stress inducible chemicals (A23187, BFA, tunicamycin, DTT and $H_2O_2$) and proteasome inhibitors, and heat shock. High level expression of irp94 mRNA was detected after 3 hours reperfusion in the both sites of the cerebral cortex and hippocampus of the gerbil brain. The main regulation of irp94 mRNA expression in PC 12 cells was determined at the transcriptional level. The half life of irp94 mRNA in PC12 cells was approximately 5 hours after the initial translation. The remarkable expression of irp94 mRNA was detected by the treatment of tunicamycin, which blocks glycosylation of newly synthesized polypeptides, and $H_2O_2$, which induces apoptosis. When PC12 cells were treated with the cytosol proteasome inhibitors such as ALLN (N-acetyl-leucyl-norleucinal) and MG 132 (methylguanidine), irp94 mRNA expression was increased. These results indicate that expression of irp94 was induced by ER stress including oxidation condition and glycosylation blocking in proteins. Expression of irp94 was increased when the cells were chased after heat shock, suggesting that irp94 may be involved in recovery rather than protection against ER stresses. In addition, irp94 expression was remarkably increased when cytosol proteasomes were inhibited by ALLN and MG 132, suggesting that irp94 plays an important role for maintaining the ERAD (endoplasmic reticulum associated degradation) function.

• 한국한의학연구원논문집
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• 제5권1호
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• pp.111-117
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• 1999

세포열을 이용한 허혈/재관류 환경에서 청폐사간탕의 세포보호능을 측정하였다. 청폐사간탕 추출물은 허혈/재관류 환경하에서 발생하는 세포 독성으로부터 대표적 수용성 항산화제인 ascorbic acid보다 높은 세포 보호 활성을 나타내었으며, 산화적 손상의 지표로서 사용되는 지질과산화물(TBARS)를 측정한 결과에서도 ASA와 유사한 활성을 나타내었다. 또한, 허혈/재관류 환경하에서 활성이 증가하여 세포에 산화적 손상을 일으키는 활성 산소종을 유발하는 것으로 알려진 xanthine oxidase 활성 측정에서는 청폐사간탕이 ASA보도 높은 xanthine oxidase 활성 억제능을 보였으며, xanthine oxidase 효소 표품을 이용한 활성 억제능 측정에서도 ASA보다 뛰어난 결과를 보였다. 따라서, 청폐사간탕은 허혈/재관류 환경하에서 세포 보호능이 있는 것으로 추측이되며, 이러한 보호능은 항산화 활성과 더불어서 xanthine oxidase 활성 억제능이 공동 작용의 결과로 사료된다.

• 대한한방내과학회지
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• 제22권4호
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• pp.503-512
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• 2001

Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

• Journal of Chest Surgery
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• 제31권12호
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• pp.1159-1164
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• 1998

배경: 수술수기와 심근보호법의 발달로 인하여 최근 관상동맥우회로 이식술의 수술성적이 향상되고 있지만 술후 사망과 이환에 직면하고 있는 일부 환자들은 점점 증가하고 있어 수술후 이환과 사망에 대한 관심이 높아지고 있다. 대상 및 방법: 저자들은 관상동맥우회로 이식술을 받은 총 137명을 대상으로 술전 위험요인과 술후 이환 및 사망(이하 이환)과의 관계를 후향적으로 조사하였다. 수술전 위험요인으로는 나이, 성별, 술전심근경색, 응급수술, 좌심실박출계수, 비만 그리고 3혈관 질환 등 7개의 변수를 선택하였으며 수술후 이환은 부정맥, 상처감염, 뇌손상, 술후입원기간의 장기화, 폐렴, 급성신부전증, 인공호흡기의 장기간 사용 그리고 수술사망 등으로 하고 이중 하나만 발생하여도 이환이 있다고 간주하였다. 결과: 전체 환자의 평균 나이는 56.7세였고, 27세부터 74세까지의 분포를 보였다. 전체 환자의 수술사망률은 6.6%였고 이중 계획수술은 3.9%(5/128), 응급 또는 긴급수술은 44.4%(4/9)의 사망률을 보였다. 65세 이상의 환자에서 이환율은 65세 미만의 환자보다 통계적으로 유의하게 높았다. 성별에 의한 이환율의 차이는 없었으나 수술 사망률은 여자(5/41, 12.19%)에게서 남자(4/96, 4.17%)보다 더 높게 나타났다. 응급수술의 이환율은 100%로 계획수술의 환자에서보다 유의하게 높게 나타났다. 술전 좌심실 박출계수가 50% 미만인 환자에서 50% 이상인 환자보다 사망률이 유의하게 높게 나타났다. 결론: 결론적으로 관상동맥우회로 이식술 후 이환의 위험요인은 65세 이상의 고령과 응급 또는 긴급수술이었고 수술사망의 위험요인은 50% 미만의 술전 좌심실 박출계수와 응급 또는 긴급수술이었다.

• Journal of Trauma and Injury
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• 제19권1호
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• pp.47-53
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• 2006

Purpose: Recently, the American Heart Association recommended that routine cervical spine protection in submerged patients was not necessary, except in high-energy injury situations. However, until now, this recommendation has few supportive studies and literatures. This retrospective study was performed to demonstrate the risk of cervical spine injury in patients who had been submerged in a river. Methods: Seventy-nine submerged patients who visited St. Mary's Hospital between January 2000 and December 2005 were included in this retrospective study. We investigated and analyzed the victim's age, sex, activity on submersion, mental status and level of severity at admission, prognosis at discharge, associated injuries, and risk group by using the medical records and cervical spine lateral images. According to the activity on submersion, victims were classified into three groups: high risk, low risk, and unknown risk. The reports of radiologic studies were classified into unstable fracture, stable fracture, sprain, degenerative change, and normal. Results: The patients' mean age was 36.8 yrs, and 54% were males. Of the 79 patients, adult and adolescent populations (80%) were dominant. Jumping from a high bridge (48%) was the most common activity on submersion and accounted for 52% of the high-risk group. The Glasgow coma scale at admission and the cerebral performance scale at discharge showed bimodal patterns. The results of the radiologic studies showed one stable fracture, one suspicious stable fracture, and 18 sprains. The incidence of cervical spine fracture in submerged patients was 2.5% in our study. The incidence of cervical spine injury was higher in the high-risk group than it was in the low-risk group, especially in the jumping-from-high-bridge subgroup; however this observation was not statistically significant. No other factors had any significant effect on the incidence of cervical spine injury. Conclusion: Our study showed that even submerged patients in the high risk group had a low incidence of cervical spine fracture and that the prognosis of a patient did not seem to be influenced by the cervical spine fracture itself.

• 대한환경공학회지
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• 제28권7호
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• pp.776-781
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• 2006

제초제, 로켓 추진제 등에 주로 사용되는 과염소산(perchlorate, $ClO_4^-$)은 갑상선의 요오드 섭취를 방해하여 갑상선 암을 유발할 수 있으며 임산부가 섭취 시 태아의 뇌 발달을 저해하는 등 인체 독성을 나타내는 것으로 알려져 있다. 최근 미국을 중심으로 perchlorate 관련 연구가 활발하게 진행되고 있으며 2006년 US. EPA에서 먹는물에서의 perchlorate 가이드라인을 설정하였다. 그러나 아직 국내에서는 perchlorate에 관한 독성 및 환경 내 오염 정도 등에 관해 구체적으로 조사된 바가 없다. 따라서 본 연구에서 국내 수 환경에서의 Perchlorate 오염 정도 파악을 위해 영남권 지역 주민들의 주 상수원수로 사용되고 있는 낙동강 수계와 낙동강 권역에 위치한 도시들의 수돗물을 대상으로 perchlorate를 분석하였다. 분석 결과 낙동강 수계 중에서는 $ND{\sim}278.4$ ${\mu}g/L$의 범위로 perchlorate가 검출되었으며 구미공단천(2차)에서 가장 높게 나타났으며 하류로 내려올수록 perchlorate 농도가 감소하였다. 수돗물의 경우 대상 도시에 따라 다소 편차를 나타냈으며 농도 범위는 $ND{\sim}34.1$ ${\mu}g/L$이었다. 조사 대상 지역 중 대구 달서 감삼동에서 가장 높게 검출되었고 부산에서는 비슷한 농도($9{\sim}11$ ${\mu}g/L$)로 대부분의 구에서 검출되었다. 본 조사결과는 낙동강 수계에 perchlorate 오염원이 있으며 낙동강을 상수원수로 사용하는 지역은 수돗물에서 perchlorate 관리대책이 필요함을 의미한다.

• 대한한방내과학회지
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• 제22권2호
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• pp.161-174
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• 2001

Objectives : The purpose of this investigation is to evaluate the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats. Methods : the volume of cerebral infarction and edema, the pathohistological change of neurons, the number of survived neurons, neurotransmitters through immunohistochemical methods, proteins connected with neurotransmitters through immunohistochemical methods and the pathohistological change of neurons through electro-microscopy were investigated. From these reseach data, the protection of neurons and the activity of brain cells were examined. Results : 1. The infaction volume of the control group was 23.9%, and that of the sample group was 16%. 2. The brain edema volume of the control group increased by 17% compared to the normal group and that of the sample group increased by 10%. 3. The light microscopy revealed that the neurons in the ischemia-induced area and CA1 area of hippocampus were most heavily damaged and that the sample group was less damaged compared with the control group. Most pyramidal neurons died in 7 days when brain ischemia was induced. 4. The number of survived pyramidal neurons in the CA1 area of the hippocampus were studied. The normal group had 93 neurons/mm, survived the control group(after 3 days) had 21/mm, the control group(after 7 days) had 3/mm and the sample group 33/mm. 5. The immunohistochemical methods revealed that: (1) In the control group, the sensitivity of GABA, NOS, DBH were increased, and those of Synapsin, eEF-$1{\alpha}$ decreased. NOS and DBH had positive reactions in the control group, but negative in the normal group. (2) In thd sample group, the sensitivity of GABA, NOS, DBH were attenuated, and those of NPY, Synapsin, CaMKII, eEF-$1{\alpha}$ increased when compared to the control group. 6. The electro-microscopy revealed that most neurons died by necrosis and some neurons died by apoptosis. Several imflammation cells appeared in the injured area of neurons. The number of neurons in the sample group that died by ischemia decreased. But, the number that died by apoptosis did not significantly change. Conclusions : The data shows that the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats is significant.

• Journal of Korean Neurosurgical Society
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• 제29권4호
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• pp.461-470
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• 2000

Objective : Many investigators have demonstrated the protective effects of hypothermia following traumatic brain injury(TBI) in both animals and humans. It has long been recognized that mild to moderate hypothermia improves neurologic outcomes as well as reduces histologic and biochemical sequelae after TBI. In this study, two immunohistochemical staining using terminal deoxynucleotidyl-transferase-mediated biotin dUTP nick end labeling(TUNEL), staining of apoptosis, and ${\beta}$-amyloid precursor protein(${\beta}$-APP), a marker of axonal injury, were done and the authors evaluated the protective effects of hypothermia on axonal and neuronal injury after TBI in rats. Material and Method : The animals were prepared for the delivery of impact-acceleration brain injury as described by Marmarou and colleagues. TBI is achieved by allowing of a weight drop of 450gm, 1 m height to fall onto a metallic disc fixed on the intact skull of the rats. Fourty Sprague-Dawley rats weighing 400 to 450g were subjected to experimental TBI induced by an impact-acceleration device. Twenty rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After this 1-hour period of hypothermia, rewarming to normothermic levels was accomplished over 30-minute period. Following 12 hours, 24 hours, 1 week and 2 weeks later the animals were killed and semiserial sagittal sections of the brain were reacted for visualization of the apoptosis and ${\beta}$-APP. Results : The density of ${\beta}$-APP marked damaged axons within the corticospinal tract at the pontomedullary junction and apoptotic cells at the contused cerebral cortex were calculated for each animal. In comparison with the untreated controls, a significant reduction in ${\beta}$-APP marked damaged axonal density and apoptotic cells were found in all hypothermic animals(p<0.05). Conclusion : This study shows that the posttraumatic hypothermia result in substantial protection in TBI, at least in terms of the injured axons and neurons.