• Toxicological Research
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• 제4권1호
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• pp.23-35
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• 1988

The role of calcium in the production of oxygen radical which causes reperfusion damage of ischemic heart has been examined. The reperfusion damage was indrced in isolated Langendorff perfused rat hearts by aortic clamping for 60 min followed by reperfusion with oxygenated Krebs-Henseleit solution with or without 1.25 mM $CaCl_2.$ On reperfusion of the ischemic hearts with the calcium containing solution, the release of cytosolic enzymes (LDH and CPK) increased abruptly. These increased release of enzymes were significantly inhibited by additions of oxygen radical scavengers (SOD, 5,000 U; catalase, 12,500 U) into the reperfusion solution. In the hearts isolated from rats pretreated with allopurinol(20 mg/kg orally, 24 hr and 2 hr prior to the experiments), the levels of enzymes being released during reperfusion were significantly lower than that of the control. However, in the hearts perfused with the calcium-free but oxygenated solution, the increase in the release of cytosolic enzymes during reperfusion was neither inhibited by oxygen radical scavengers nor by allopurinol pretreatment. For providing the evidence of oxygen radical generation during the reperfusion of ischemic hearts in situ, the SOD-inhibitable reduction of exogenously administered ferricytochrome C was measured. In the hearts perfused with the calcium containing solution, the SOD-inhibitable ferricytochrome C reduction increased within the first minute of reperfusion, and was almost completely inhibited by allopurinol pretreatment. When the heart was perfused with the calcium free solution, however, the reduction of ferricytochrome C was not only less than that in the calcium containing condition, but also was not so completely inhibited by allopurinol pretreatment. By ischemia, xanthine oxidase (XOD) in the ventricular tissue was changed qualitatively, but not quantitatively. In the heart made ischemic with the calcium containing condition, the oxygen radical producing O-form of XOD increased, while the D- and D/O-form decreased. However, in the ischemic heart reperfused with the calcium free condition, the D/O-form of XOD was elevated without significant increase in O-form of the enzyme. It is suggested from these results that the calclum may play a contributing role in the genesis of reperfusion damage by promoting the conversion of xanthine oxidase from the D/O-form to the oxygen radical producing O-form in the ischemic myocardium.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.239-246
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• 2005

In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC)1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.

• 대한약리학회지
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• 제26권2호
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• pp.145-152
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• 1990

최근 본 교실에서는 two-bath system을 이용하여 혈관 내피세포에서 superoxide에 의존한 혈관 이완성 물질을 동정하여 발표하였다. 본 실험에서는 상기 system을 이용하여 돼지의 관상동맥 내피세포에서 유리되는 superoxide에 의존한 이완성 물질이 고양이의 흥부 대동맥 내피 및 소의 대동맥 배양내피세포에서 얻어진 이완성 물질에 의한 이완과 매우 유사함을 관찰하여 다음과 같은 결과를 얻었다. 1. 고양이 흥부 대동맥, 돼지 관상동맥의 내피세포 및 소 대동맥 배양 내피세포 등에서 유리되는 superoxide에 의존한 이완 물질은 모두 유사한 이완 작용을 나타내었다. 2. 돼지 관상 동맥 내피세포에서 유리되는 superoxide 의존성 이완 물질이 고양이의 흥부 대동맥 내피세포나 소의 대동맥 배양 내피세포에서 유리되는 이완 물질과는 다소 다른 점도 있었다. 즉, 돼지 관상동맥 내피세포에서 유리되는 이완 물질의 작용은 catalase나 superoxide dismutase(SOD)에 의하여 억제되었으나, 후자의 두 동맥 내피세포에서 유리되는 이완 물질은 SOD에 의해서만 억제되었다. 3. 이러한 이완성 물질들의 생성은 여러 lipoxygenase억제제인 gossypol, nordihydroguaiaretic acid, AA 861 및 eicosatetraynoic acid 등의 전처치에 의하여 봉쇄되었다. 4. Cyclooxygenase 억제제인 indomethacin이 나 cytochrome P-450 monooxygenase 억제제인 proadifen과 cimetidine에 의하여는 봉쇄되지 아니하였다. 이상의 결과로부터 이러한 이완성 물질들은 비록 각기 다른 종의 동물 모델에서 얻었다고 하더라도 장기에 따라 다소 반응의 차이는 있으나 동질성 이완 물질이며, 나아가 이러한 이완성 물질은 여러 조직의 허혈-재관류 손상에 있어서 병리생리학적으로 관련될 것으로 사료된다.

• Journal of Korean Biological Nursing Science
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• 제4권1호
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• pp.51-69
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• 2002

The purpose of this study was to identify the effect of cerebral ischemia on affected(Lt) and unaffected(Rt) side of soleus, plantaris and gastrocnemius muscle mass and determine the effect of exercise on affected and unaffected side on soleus, plantaris and gastrocnemius muscle mass during acute stage of stroke. Sixteen male Sprague-Dawley rate with 200-270g body weight were randomly divided into three groups: control, stroke, and exercise after stroke(St+Ex) group. The control group received sham operation and the stroke group and St+Ex group received transient right MCA(middle cerebral artery) occlusion operation. The St+Ex groups ran on a treadmill for 20min/day at 10m/min and $10^{\circ}$ grade for 6days. During the experimental period body weight and diet intake was measured every morning. On the 7th day after operation, muscles were dissected from both affected and unaffected side of hindlimb. Cerebral infarction of stroke and St+Ex groups were identified by staining with TCC for 30 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. Significance was accepted at the level of p<0.05. The results were summarized follows : 1) There were no significant difference of the body weight on the first day of experiment among 3 groups. Whereas on the 7th day, the body weight of both stroke group and St+Ex group were significantly smaller than that of control group. Body weight of St+Ex group on the 7th day tended to be larger than that of stroke group. 2) Total diet intake of both stroke group and St+Ex group were also significantly smaller than that of control group. While total amount of diet intake in St+Ex group tended to be larger than that of stroke group. 3) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of control group and the weight of soleus and plantaris muscle of affected side in stroke group tended to decrease compared to that of control group. 4) The weight of plantaris muscle of unaffected side in stroke group significantly decreased compared to that of control group and the weight of soleus and gastrocnemius muscle of unaffected side in stroke group tended to decrease compared to those of control group. 5) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of unaffected side and there was no significant difference of the weight of soleus and plantaris muscle in stroke group between affected side and unaffected side. 6) The weight of soleus, plantaris and gastrocnemius muscle of both affected side and unaffected side in St+Ex group had a tendency of increase compared to those of stroke group. The relative weight of soleus and gastrocnemius muscle of affected side and soleus muscle of unaffected side in St+Ex group had a tendency to increase compared to those of stroke group. Based on these results, exercise during acute stage of stroke might attenuate muscle atrophy of both affected and unaffected side of hindlimb muscles.

• 전자공학회논문지SC
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• 제43권5호
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• pp.89-100
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• 2006

두꺼워진 경동맥 내중막 두께는 일과성 뇌 허혈, 뇌졸중, 그리고 심근경색과 같은 관상동맥질환을 예고하는 독립적 인자로서 매우 중요하다. 경동맥 내중막 두께를 측정하기 위한 기존의 영상처리 방법은 전체 초음파 영상 가운데 수작업에 의해 구획을 임의로 설정한 다음, 그 부분만의 색도분포 미분치 산출에 의한 구간 분할로 두께를 추정하는 것이었기 때문에 임의성에 의한 한계는 물론이고 구간별 색도분포가 혼재하는 경우 정확한 두께 측정에는 역부족이었다. 우리는 본 논문을 통하여 경동맥과 같이 영상입력 대상물이 일관된 벡터 형성 특성을 갖고 관측영상의 화소 색도 집합의 원소들 또한 그 고유한 방향성을 내재하고 있는 경우, 이를 층위별로 군집 처리하여 원하는 특징을 효과적으로 추출하는 새로운 영상처리기술을 소개한다 우리는 보다 정확한 측정을 위해, 인체를 구성하고 있는 장기나 혈관과 같은 여러 조직이 동일조직 내에서 타조직과 다른 층위적 특성이 있음에 착안하여, 이의 초음파영상을 수직 및 수평축으로 성분 분석하여 차별된 군집들로 분류해 내고 군집들 사이의 색도 특성과 상호 연관을 수학적으로 규명한 다음, 특징별로 축진행에 따른 순차적인 영역처리를 시행함으로서 혈관 조직에 대한 층위적 형성 판별과 혈관 막(膜)들의 정확한 두께측정이 가능함을 보이고 영상 분석과 실험을 통해 입증하였다. 이러한 접근 방법은 경동맥영상과 같이, 영역간 색도분포의 혼재와 문턱치 산출의 어려움에도 불구하고 일관된 벡터 흐름과 방향성을 형성하고 있는 영상인 경우, 그 영역처리와 특징추출에 효과가 높으므로 응용이 가능하다.

• Journal of Acupuncture Research
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• 제21권2호
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• pp.1-20
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• 2004

Objective : The aim of this study was to investigate effects of Angelica gigas Nakai(AGN) on the ischemic injury by intraluminal filament insertion in the rats. Methods : The ischemia was induced by intraluminal filament insertion into middle cerebral artery. AGN herbal acupuncture into SP10 was carried out during 3 weeks after ischemic injury. Eight-arm radial maze was designed for the behavioral task. AGN herbal acupuncture showed neuroprotective agents in cresyl violet, acetylcholinesterase(AchE), choline acetyltransferase(ChAT) and nerve growth factor(NGF)-stain. Then check the effect of regional cerebral blood flow(rCBF) according to AGN herbal acupuncture in rats. Results : The errors in the eight-arm radial maze task were significantly decreased in normal group compared with control group on 1~6days, AGN2(0.02g/kg) herbal acupuncture group on 1~5days, AGN3(0.1g/kg) on 1~3days, AGN4(0.5g/kg) on 1, 3~6days. The rate of correct choice was significantly increased in AGN1(0.01g/kg) and AGN4 herbal acupuncture groups. The density of neurons in the hippocampal CA1 was the most increased in normal group and AGN1, AGN3, AGN4 herbal acupuncture groups compared with control group. The density of AchE in the hippocampal CA1 had a tendency to increase in all the groups when they were compared with control group, but not significant. The density of ChAT in the hippocampal CA1 was significantly increased in normal group and AGN1, AGN4 herbal acupuncture groups compared with control group. The density of NGF in the hippocampal CA1 was significantly increased AGN4 herbal acupuncture group compared with control group. The rCBF was significantly increased in AGN1, AGN3 and AGN4 herbal acupuncture groups without the change of blood pressure. Conclusions : These results suggest that AGN herbal acupuncture can be used for controlling stroke in early stage as herbal medication.

• 한국전문물리치료학회지
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• 제12권2호
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• pp.1-10
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• 2005

Pressure ulcers are serious complications of tissue damage that can develop in patients with diminished pain sensation and diminished mobility. Pressure ulcers can result in irreversible tissue damage caused by ischemia resulting from external loading. There are many intrinsic and extrinsic contributors to the problem, including interface tissue pressure, shear, temperature, moisture, hygiene, nutrition, tissue tolerance, sensory and motor dysfunction, disease and infection, posture, and body support systems. The purposes of this study were to investigate the relationship between buttock interface pressure and seating position, wheelchair propulsion speed. Seated-interface pressure was measured using the Force Sensing Array pressure mapping system. Twenty subjects propelled wheelchair handrim on a motor-driven treadmill at different velocities (40, 60, 80 m/min) and seating position used recline ($100^{\circ}$, $110^{\circ}$, $120^{\circ}$) with a wheelchair simulator. Interface pressure consists of average (mean of the pressure sensor values) and maximum pressure (highest individual sensor value). The results of this study were as follows; No significant correlation in maximum/average pressure was found between a static position and a 40 m/min wheelchair propulsion (p>.05). However, a significant increase in maximum/average pressure were identified between conditions of a static position and 60 m/min, and 80 m/min wheelchair propulsion (p<.05). No significant correlation in maximum pressure were found between a $90^{\circ}$ recline (neutral position) and a $100^{\circ}$, $110^{\circ}$, or $120^{\circ}$ recline of the wheelchair back (p>.05). No significant difference in average pressure was found between conditions of a $90^{\circ}$ recline and both a $100^{\circ}$ and $110^{\circ}$ recline of wheelchair back. However, a significant reduction in average pressure was identified between conditions of a $90^{\circ}$ and $120^{\circ}$ recline of wheelchair back (p<.05). This study has shown some interesting results that reclining the seat by $120^{\circ}$ reduced average interface pressure, including the reduction or prevention in edema. And interface pressure was greater during dynamic wheelchair propulsion compared with static seating. Therefore, the optimal seating position and seating system ought to provide postural control and pressure relief. We need an education on optimal seating position and a suitable propulsion speeds for wheelchair users.

• BMB Reports
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• 제44권10호
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• pp.647-652
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• 2011

The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1-CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by $H_2O_2$. Additionally, the group of PEP-1-CAT + imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT + imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders.

• Investigative Magnetic Resonance Imaging
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• 제6권1호
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• pp.55-63
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• 2002

목적 급성 허혈성 뇌졸중에서 관류 MR영상으로 측정한 상대적 뇌혈용적과 단광자방출전산화단층촬영으로 측정한 상대적 뇌혈류량이 나중에 발생할 뇌경색을 예측할 수 있는지 알아보고자 하였다. 대상 및 방법 급성 일측성 중대뇌동맥 폐색 환자에서 증상 발생 6시간 이내에 관류 MR영상과 99mTc-HMPAO 단광자방출전산화단층촬영을 모두 시행한 13명을 대상으로 하였다. 동맥 폐색에 의한 허혈 부위와 반대측 정상 부위에서 각 관류 변수를 측정하여 그 비(허혈 부위 관류변수 값 / 정상 부위 관류 변수 값)를 구한 후, 나중에 경색으로 이행할 부위와 그렇지 않을 부위를 판별할 수 있는 관류변수 비의 절단값을 계산하였다. 결과 : 경색으로 이행한 부위와 그렇지 않은 부위에서 상대적 뇌혈용적 비의 평균값은 각각 $0.58{\pm}0.27{\;}and{\;}0.99{\pm}0.17$ (p<0.001)이었고, 상대적 뇌혈류량 비의 평균 값은 $0.41{\pm}0.22{\;}and{\;}0.71{\pm}0.14$ (p<0.001)이었다. 경색으로 이행할 부위와 그렇지 않을 부위를 판별하는 절단값은 상대적 뇌혈용적 비가 0.80, 상대적 뇌혈류량 비가 0.56이었다. 각 절단값의 민감도, 특이도, 능률은 뇌혈용적 비가 80.6, 87.5, 82.7%이었고 상대적 뇌혈류량 비가 72.2, 75.0, 73.0%이었다. (두 관류변수 사이에서 p>0.05). 결론 : 급성 허혈성 뇌졸중에서 상대적 뇌혈용적과 상대적 뇌혈류량의 측정은 뇌경색의 발생을 예측하는 데에 유용한 것으로 사료된다.

• 동의생리병리학회지
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• 제18권6호
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• pp.1643-1651
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• 2004

This experimental study was designed to investigate the effects of SIEGESBECKIAE HERBA extract (SHE) on the change of cerebral hemodynamics 〔regional cerebral blood flow (rCBF) and mean arterial blood pressure(MABP)〕 in normal condition and cerebral ischemic rats, and to determine the mechanism of action of SHE. This study was designed to investigate whether or not SHE inhibit lactate dehydrogenase (LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows SHE increased rCBF significantly in a dose-dependent manner, but MABP was not changed by SHE in normal rats. The SHE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (IDN), an inhibitor of cyclooxygenase but was increased by methylene blue (MTB), an inhibitor of guanylate cyclase. SHE inhibited lactate dehydrogenase (LDH) activity significantly in neuronal cells. rCBF was increased significantly and stably by SHE(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group in ischemic rats. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) for 1hr and reperfusion for 1hr, the sample group was decreased IL-1β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO 1hr and reperfusion 1hr, sample group decreased TNF-α production significantly compared to that of the control grolilp. In serum by drawing from femoral arterial blood after reperfusion 1hr, sample group increased TGF-β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO for 1hr and reperfusion for 1hr, IL-10 production of the sample group was similar to that of control group. These results suggested that SHE had inhibitive effect on the brain damage by inhibited LDH activity, IL-1β and TNF-α production, but accelerated TGF-β production.