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      • Study of the Antinociception Induced by Opioids and the Proenkephalin Gene Expression in Spontaneously Hypertensive Rats

        서홍원,이태희,송동근,최성란,정전섭,김영희,Suh Hong-Won,Lee Tae-Hee,Song Dong-Keun,Choi Seong-Ran,Jung Jun-Sub,Kim Yung-Hi The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.1

        8주, 18주, 그리고 32주된 Spontaneously Hypertensive Rats (SHR)과 Wistar-Kyoto Rats(WKY)과의 blood pressure(혈압)를 측정하여본 결과 SHR 그룹이 WKY에 비해 19에서 70 mmHg 차이로 SHR 그룹이 WKY group에 비하여 혈압이 높았다. 18주된 SHR과 WKY에서 제 3 뇌실내 (intraventricular)로 투여된 morphine과 ${\beta}-endorphin$의 진통작용을 검색하여 보았다. WKY group에 비하여 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 진통작용에 있어서 상승작용 (potentiation)을 보임을 발견하였고 뇌실내로 투여된 morphine은 SHR group에서 약간만 상승작용을 보였다. SHR과 WKY group간에 opioid의 진통작용에 있어서 중요한 역할을 하는 Midbrain과 Medulla (pons), 그리고 spinal cord (척수)의 lumbar부위의 $[Met^5]-enkephalin$과 proenkep-halin A mRNA level을 측정하여 보았다. SHR과 WKY group간의 $[Met^5]-enkephalin$과 proenkephalin mRNA의 양은 별로 차이를 보이지 않았다. 이러한 결과로 미루어 볼때 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 그의 진통효과에 있어서 보인 상승작용은 척수상부에 위치하고 있는 opioid deptide의 양이 변해서가 아니라 다른 기전에 의하여 조절되어지고 있음을 시사한다. The present studies were carried out to determine if antinociceptive action of morphine and ${\beta}-endorphin$ administered intraventricularly was changed in. pentobarbital anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Antinociception was assessed by the tail-flick test. The $ED_{50}$ values of antinociception for morphine administered intraventricularly were 1.9 and 1.2 nmol for WKY and SHR rats, respectively. The $ED_{50}$ values of antinociception for ${\beta}-endorphin$ administered intraventricularly were 0.40 and 0.12 nmol for WKY and SHR rats, respectively. The $[Met^5]-enkephalin$ (ME) and proenkephalin mRNA levels in midbrain, pons and medulla, or lumbar section of the spinal cord in WKY and SHR rats were measured by the radioimmunoassay and Northern blot assay, respectively. There were no differences of ME and proenkephalin mRNA levels in these tissues between WKY and SHR rats. The results suggest that ${\beta}-endorphin$ but not morphine administered intraventricularly produces a greater antinociception in SHR rats. This increased antinociceptive effect of ${\beta}-endorphin$ in SHR rats may be not, at least, due to the alterations of ME And proenkephalin mRNA levels in the midbrain, pons and medulla, or spinal cord.

      • SCOPUSKCI등재

        생쥐에서 5-Hydroxytryptophan에 의한 설사에 대한 각종 전통 생약 추출물의 억제 효과

        유재선,정전섭,이태희,손건호,서홍원,송동근,김영희,Yoo, Jae-Sun,Jung, Jun-Sub,Lee, Tae-Hee,Son, Kun-Ho,Suh, Hong-Won,Song, Dong-Keun,Kim, Yung-Hi 한국생약학회 1995 생약학회지 Vol.26 No.4

        To find serotonin(5-hydroxytryptamine, 5-HT)-antagonizing activities in traditional herbal drugs, crude extracts from 66 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptophan(HTP)-induced diarrhea in mice. Intraperitoneal injection of 5-HTP(2.5 mg/kg) induced diarrhea in 92% of mice, when observed from 10 to 15 min after injection. Crude extracts(2 g/kg) from 66 kinds of traditional herbal drugs were orally pretreated for 1 h before 5-HTP injection. Of the 66 herbal drugs screened, Ephedrae Herba(麻黃), Cimicifugae Rhizoma(升麻), Anisi stellati Fructus(八角茴香), Aurantii Fructus(枳實), Polygalae Radix(遠志) showed the most potent inhibiting activities against 5-HTP(2.5 mg/kg)-induced diarrhea in mice. There are at least 3 possible mechanisms that would be responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea; 1) crude extract-induced inhibition of the activity of aromatic aminoacid decarboxylase catalyzing the conversion of 5-HTP to 5-HT, 2) crude extract-induced blockade of 5-HT receptor(s) in the gastrointestinal tract responsible for 5-HTP-induced diarrhea, 3) crude extract-induced inhibition of gastrointestinal activity, irrespective of 5-HT system. The exact mechanisms and molecules, responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea remain to be clarified.

      • SCOPUSKCI등재

        배양된 흰쥐 뇌간 신경세포에서 5-Hydroxytryptamine 흡수에 대한 각종 전통 생약 추출물의 억제 효과

        조현미,정전섭,이태희,손건호,서홍원,송동근,김영희,Cho, Hyun-Mi,Jung, Jun-Sup,Lee, Tae-Hee,Son, Kun-Ho,Suh, Hong-Won,Song, Dong-Keun,Kim, Yung-Hi 한국생약학회 1995 생약학회지 Vol.26 No.4

        Crude methanolic(80%) extracts from 109 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptamine(5-HT) uptake in primary cultured rat brainstem neurons. Rat brainstem neurons were cultured from embryonic day 14, and maintained for 7-9 days in vitro. Clomipramine (500 nM), a reference drug, decreased 5-HT uptake to 16% of control values. Of the 109 herbal drugs screened, Citri immaturi Pericarpium(靑皮), Coptidis Rhizoma(黃蓮), Cnidii Rhizoma(土川芎) showed the most potent 5-HT uptake inhibiting activities. These herbal drugs, at the concentration of $10{\;}{\mu}g/ml$, inhibited 5-HT uptake 69, 69, and 57% respectively, when inhibition(%) was expressed as a relative value compared to the 500 nM clomipramine-induced inhibition.

      • Effect of Cholecystokinin on Serotonin Release from Cultured Neurons of Fetal Rat Medulla Oblongata

        송동근,조현미,이태희,서홍원,김영희,Song Dong-Keun,Cho Hyun-Mi,Lee Tae-Hee,Suh Hong-Won,Kim Yung-Hi The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.1

        연수의 세로토닌 신경계는 내재성 하행성 동통 억제계 (endogenous descending pain inhibitory system) 에 있어서 중추적인 역할을 하고 있다. 연수의 세로토닌 신경세포에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물들의 작용을 알아보기 위하여, 쥐의 태자 (태생 14일) 로부터 연수를 분리하여 10동안 배양한 후 5-hydroxytryptamine (5-HT)의 분비에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물의 영향을 연구하였다. 배양 10일된 세포에 여러 neuropeptide들을 $10{\mu}M$ 농도로 48 시간동안 자극한 결과, CCK 와 substance P에 의하여 5-HT의 분비가 증가됨을 관찰하였다. Somatostatin, proctolin, thyrotropin releasing hormone, 및 interleukin-6 은 5-HT의 분비에 있어서 아무런 영향이 없었다. 어떠한 second messenger가 CCK에 의한 5-HT 분비에 연관되어 있나를 알아보기 위하여 calcium channel 봉쇄제인 nimodipine, 그리고 calmodulin 길항제인 calmidazolium의 영향을 살펴본 결과 nimodipine ($1{\mu}M$)은 거의 완전하게, 그리고 calmidazolium ($1{\mu}M$)은 부분적으로 유의하게 CCK에 의한 5-HT의 분비를 억제하였다. 또한 adenyl cyclase의 활성도를 높이는 forskolin ($5{\mu}M$)은 5-HT의 분비를 증가시켰지만 protein kinase C(PKC)를 활성화시키는 phorbol myristate acetate (PMA)는 $2{\mu}M$ 농도에서 5-HT의 분비에 아무런 영향을 미치지 아니하였다. 이상의 연구결과, calcium channel을 통한 calcium influx와 세포내 calmodulin이 CCK에 의한 5-HT분비 증가에 있어서 중요한 역할을 함을 제시한다. 또한, 5-HT의 분비에 있어서 cyclic AMP system이 중요한 역할을 하나, PKC system은 5-HT의 분비에 연관이 없음을 제시하고 있다. Serotonergic neurons in medulla oblongata play an important role in the endogenous descending pain inhibitory system. To illucidate the factors involved in the regulation of medullary serotonergic neurons, we studied the effects of cholecystokinin (CCK) and agents acting on various second messenger systems on 5-hydroxytryptamine (5-HT) release from cultured neurons of rat fetal (gestational age 14th day) medulla oblongata. Cultured cells maintained for 10 days in vitro were stimulated for 48 hours with CCK or other neuropeptides at 10 micromolar concentration. CCK ($10{\mu}M$) and substance P ($10{\mu}M$) significantly increased. 5-HT release. However, somatostatin, proctolin, thyrotropin releasing hormone, and interleukin-6 did not have any effects on 5-HT release. Nimodipine ($1{\mu}M$), a calcium channel blocker, almost completely, and calmidazolium ($1{\mu}M$), a calmodulin antagonist, significantly inhibited the CCK-induced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by CCK. However, the intracellular 5-HT content was not significantly changed by CCK. Forskolin ($5{\mu}M$), an adenylate cyclase activiator, but not $2{\mu}M$ phorbol myristate acetate (PMA), a protein kinase C activator, significantly enhanced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by forskolin. However, the intracellular 5-HT content was not significantly changed by forskolin. PMA had no effect on intracellular 5-HT levels. These results suggest that CCK regulates serotonergic neurons in the medulla oblongata by enhancing 5-HT secretion through calcium influx and caimodulin, and that cyclic AMP system but not protein kinase C system is involved in 5-HT release.

      • 선천성 고혈압쥐에서의 Opioid에 의한 진통작용과 Proenkephalin유전자 발현에 대한 연구

        서홍원(Hong-Won Suh),이태희(Tae-Hee Lee),송동근(Dong-Keun Song),최성란(Seong-Ran Choi),정전섭(Jun-Sub Jung),김영희(Yung-Hi Kim) 대한약리학회 1995 대한약리학잡지 Vol.31 No.1

        8주, 18주, 그리고 32주된 Spontaneously Hypertensive Rats (SHR)과 Wistar-Kyoto Rats(WKY)과의 blood pressure(혈압)를 측정하여본 결과 SHR 그룹이 WKY에 비해 19에서 70 mmHg 차이로 SHR 그룹이 WKY group에 비하여 혈압이 높았다. 18주된 SHR과 WKY에서 제 3 뇌실내 (intraventricular)로 투여된 morphine과 β-endorphin의 진통작용을 검색하여 보았다. WKY group에 비하여 SHR group에서 뇌실내로 투여된 β-endorphin은 진통작용에 있어서 상승작용 (potentiation)을 보임을 발견하였고 뇌실내로 투여된 morphine은 SHR group에서 약간만 상승작용을 보였다. SHR과 WKY group간에 opioid의 진통작용에 있어서 중요한 역할을 하는 Midbrain과 Medulla (pons), 그리고 spinal cord (척수)의 lumbar부위의 [Met<sup>5</sup>]-enkephalin과 proenkep-halin A mRNA level을 측정하여 보았다. SHR과 WKY group간의 [Met<sup>5</sup>]-enkephalin과 proenkephalin mRNA의 양은 별로 차이를 보이지 않았다. 이러한 결과로 미루어 볼때 SHR group에서 뇌실내로 투여된 β-endorphin은 그의 진통효과에 있어서 보인 상승작용은 척수상부에 위치하고 있는 opioid deptide의 양이 변해서가 아니라 다른 기전에 의하여 조절되어지고 있음을 시사한다. The present studies were carried out to determine if antinociceptive action of morphine and β-endorphin administered intraventricularly was changed in. pentobarbital anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Antinociception was assessed by the tail-flick test. The ED<sub>50</sub> values of antinociception for morphine administered intraventricularly were 1.9 and 1.2 nmol for WKY and SHR rats, respectively. The ED<sub>50</sub> values of antinociception for β-endorphin administered intraventricularly were 0.40 and 0.12 nmol for WKY and SHR rats, respectively. The [Met<sup>5</sup>]-enkephalin (ME) and proenkephalin mRNA levels in midbrain, pons and medulla, or lumbar section of the spinal cord in WKY and SHR rats were measured by the radioimmunoassay and Northern blot assay, respectively. There were no differences of ME and proenkephalin mRNA levels in these tissues between WKY and SHR rats. The results suggest that β-endorphin but not morphine administered intraventricularly produces a greater antinociception in SHR rats. This increased antinociceptive effect of β-endorphin in SHR rats may be not, at least, due to the alterations of ME And proenkephalin mRNA levels in the midbrain, pons and medulla, or spinal cord.

      • SCOPUSKCI등재

        각종 간질환에 (肝疾患) 있어서 r - GTP 와 SGOT , SGPT 의 활성에 관한 연구

        김세종(Sei Jong Kim),유종선(Jong Sun Rew),양동희(Dong Hi Yang),장건성(Kun Sung Jang),박종춘(Jong Chun Park),이태희(Tae Hi Lee) 대한소화기학회 1982 대한소화기학회지 Vol.14 No.1

        N/A Of the many hepatic enzymes, only a few are generally used for diagnosis of liver disease. Alkaline phosphatase and aminotransferases are example of two differnet groups of enzymes providing information about pathologic conditions. Aminotransferase reflects hepatic cellular injury with sorbital dehydrogenase and 5-lactic dehydrogenase. Alkaline phosphatase refrects cholestasis and its activity can easily be corrected with that of other enzymes like leucine- aminopepeptidase and 5-nucleotidase. Enzymes indicating alterations of the liver, but not belonging to one of those groups mentioned, include gamma-glutamyl transpeptidase(r-GTP), which was introduced as a test of liver function by Polish authors to indicate chronic hepatitis. A special feature of this enzyme is its increasement with prolonged intake of some drugs or alcohol. This enzyme has been used for differentiating viral hepatitis from obstructive jaundice mainly correlating SGOT or SGPT with r-GTP. Later, r-GTP was not only recommended as an indicator of minor alterations of the liver but also it was introduced as a most sensitive test for alcoholic hepatic cellular injury. The SGOT/SGPT ratio is used as an indicator of minor viral hepatitis and alcoholic induced liver injury. It should be due to the different location in the hepatocyte of the enzyme, as SGPT is present free at cytosol, whereas SGOT is demonstrable at mitochondria and cytosol in hepatocyte. r-GTP in the liver is found in hepatocyte and small bile ductules. The enzyme can be detect by enzyme histochemical methods in hepatocyte and by cytochemical techniques bound to membranes and microsomes. So the observations of SGOT/SGPT, SGOT/r-GTP and r-GTP/SGPT in various hepatic diseases concurrently might be helpful for making the differential diagnosis of the hepatic diseases. So we have observed the ratios of the enzyme activities, SGOT/SGPT, SGOT/r-GTP and r-GTP/SGPT in 20 cases of control group and 130 cases of various hepatic diseases group (Male 107, Female 42), which is including 25 cases of acute viral hepatitis(A.V.H.: Male )9, Female 8 ), 17 cases of chronic active hepatitis(C.A.H.: Male 9, Female 8.), )14cases of chronic persistent hepatitis(C.P.H.: Male 10, Female 4), 14 cases of liver cirrhosis(Male 34, Female 6), 20 cases of primary hepatocellular carcinoma(Male 16, Female 4. ), 8 cases of liver abscess(Male 4, Female 4,) and 12 cases of gall stone(Male 5, Female,7) The results were as follows: 1) In normal control group, the SGOT/SGPT is l.76+- 0.44, SGOT/r-GTP 1.20+-0.67 and r-GTP/SGPT 1, 931+-l. 14 The activity of alkaline phosphatase is 2.6+-0.6 Bessey-Lowry unit 2) In A.V.H. group, the SGOT/SGPT is 0. 78+-0.46, SGOT/r-GTP 3. 46+-2.36 and r-GTP/ SGPT 0.47+-0.91. The ratio af the SGOT/SGPT and r-GPT/SGPT are decreased significantly than the nor mal(p(0.005, p(0.005), but the SGOT/r-GTP is increased significantly, 2.5 times than the normal(p(0.005) It were helpful for differentiating A.V.H. for the other hepatic diseases 3) In C.A.H. group, the SGOT/SGPT is 0. 7+-0.35, SGOT/r-GPT is 1. 63+-1.23 and r-GTP/ SGPT is l.76+-1.38. The each ratio of SGOT/r-GTP and SGPT/SGPT is slightly increased and decreased than the normal(p=0.10, p<0.05) The SGOT/SGPT ratio was markedly decreased. It was helpful for the differentiation of the C.A.H. from the other hepatic diseases. In cirrhosis of liver group, the SGOT/SGPT is 2.05+0.88, SGOT/r-GTP is 1.27+-1.59 and r-GTP/SGPT is 2.97+-2.48. All of the ratios were increased slightly with mild elevation of the alkaline phosphatase activity. It svas also helpful for differential diagnosis of the liver diseases. 5) In primary hepatocellular carcinoma, The SGOT/SGPT is 1.82+-0.97, SGOT/r-GTP is 0.49+-0.29 and r-GTP/SGPT is 5.02+-3.80,The alkaline phosphatase activity was elevated over 2.5 times than the normal as 7.2+-5.2 Bessey-Lowry unit. With the marked elevation of r-GTP/SGPT ratio and alkaline phosphatase activity, the markedly decreased ratio of SGOT/r-GTP were

      • 연수 신경세포 배양에서 세로토닌 분비에 대한 Cholecystokinin의 작용

        송동근(Dong-Keun Song),조현미(Hyun-Mi Cho),이태희(Tae-Hee Lee),서홍원(Hong-Won Suh),김영희(Yung-Hi Kim) 대한약리학회 1995 대한약리학잡지 Vol.31 No.1

        연수의 세로토닌 신경계는 내재성 하행성 동통 억제계 (endogenous descending pain inhibitory system) 에 있어서 중추적인 역할을 하고 있다. 연수의 세로토닌 신경세포에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물들의 작용을 알아보기 위하여, 쥐의 태자 (태생 14일) 로부터 연수를 분리하여 10동안 배양한 후 5-hydroxytryptamine (5-HT)의 분비에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물의 영향을 연구하였다. 배양 10일된 세포에 여러 neuropeptide들을 10μM 농도로 48 시간동안 자극한 결과, CCK 와 substance P에 의하여 5-HT의 분비가 증가됨을 관찰하였다. Somatostatin, proctolin, thyrotropin releasing hormone, 및 interleukin-6 은 5-HT의 분비에 있어서 아무런 영향이 없었다. 어떠한 second messenger가 CCK에 의한 5-HT 분비에 연관되어 있나를 알아보기 위하여 calcium channel 봉쇄제인 nimodipine, 그리고 calmodulin 길항제인 calmidazolium의 영향을 살펴본 결과 nimodipine (1μM)은 거의 완전하게, 그리고 calmidazolium (1μM)은 부분적으로 유의하게 CCK에 의한 5-HT의 분비를 억제하였다. 또한 adenyl cyclase의 활성도를 높이는 forskolin (5μM)은 5-HT의 분비를 증가시켰지만 protein kinase C(PKC)를 활성화시키는 phorbol myristate acetate (PMA)는 2μM 농도에서 5-HT의 분비에 아무런 영향을 미치지 아니하였다. 이상의 연구결과, calcium channel을 통한 calcium influx와 세포내 calmodulin이 CCK에 의한 5-HT분비 증가에 있어서 중요한 역할을 함을 제시한다. 또한, 5-HT의 분비에 있어서 cyclic AMP system이 중요한 역할을 하나, PKC system은 5-HT의 분비에 연관이 없음을 제시하고 있다. Serotonergic neurons in medulla oblongata play an important role in the endogenous descending pain inhibitory system. To illucidate the factors involved in the regulation of medullary serotonergic neurons, we studied the effects of cholecystokinin (CCK) and agents acting on various second messenger systems on 5-hydroxytryptamine (5-HT) release from cultured neurons of rat fetal (gestational age 14th day) medulla oblongata. Cultured cells maintained for 10 days in vitro were stimulated for 48 hours with CCK or other neuropeptides at 10 micromolar concentration. CCK (10μM) and substance P (10μM) significantly increased. 5-HT release. However, somatostatin, proctolin, thyrotropin releasing hormone, and interleukin-6 did not have any effects on 5-HT release. Nimodipine (1μM), a calcium channel blocker, almost completely, and calmidazolium (1μM), a calmodulin antagonist, significantly inhibited the CCK-induced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by CCK. However, the intracellular 5-HT content was not significantly changed by CCK. Forskolin (5μM), an adenylate cyclase activiator, but not 2μM phorbol myristate acetate (PMA), a protein kinase C activator, significantly enhanced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by forskolin. However, the intracellular 5-HT content was not significantly changed by forskolin. PMA had no effect on intracellular 5-HT levels. These results suggest that CCK regulates serotonergic neurons in the medulla oblongata by enhancing 5-HT secretion through calcium influx and caimodulin, and that cyclic AMP system but not protein kinase C system is involved in 5-HT release.

      • 저에너지 He-Ne 레이저 정맥내 照射( ILIB)가 뇌졸중 후유증에 미치는 영향

        李泰熙,權貞南,朴東一 대한한방성인병학회 1997 韓方成人病學會誌 Vol.3 No.1

        We made this study with 35 CVA patients after acute state who visited the 5th department of Med. of Dongeui Univ. Oriental Hospital from 18th, June, 1997 to 30th, September, 1997 and took the He-Ne laser treatment more than five times. The results were as follows 1. See the each rate of sex and age, among the 35 cases of CVA treated with He-Ne laser, in all patients, the rate of men was 60.0%(21 cases), women 40.0%(14 cases), therefore they came out the ratio of one and a half to one(1.5:1). In age, the ratio of patients between 51 and 60 years old occupied 42.9%(15 cases), 61∼70 was 28.6%(10 cases), 41∼50 was 20.0%(7cases), 71∼80 was 5.7%(2 cases), and 31∼40 was 2.9%(1 case) orderly. 2. In the distribution of chief clinical symptoms, motor hemiparesis occupied 97.1% of all appealed symptoms, dysarthria 71.4%, fatigue 34.3%, facial palsy 31.4%, numbness of one side 25.7%, headache 22.9%, chest discomfort 11.4%, each of dizziness and shoulder pain were 8.6%, unpleasantness, diplopia and urinary disorder were 5.7% each, insomnia, deviation of eyeball, dysphagia were 2.9% each, olderly. 3. On the effect of laser treatment, in all cases with the symptoms of fatigue, unpleasantness and insomnia, they were all improved but it had little voluntariness with unpleasantness and insomnia on the other hand the rate of improvement in all cases with fatigue was 100.0%, each of headache, chest discomfort and urinary disorder were 50.0%, numbness of one side and shoulder pain were 33.3% each, motor hemiparesis 8.8%, dysarthria 8.0% and the mean number of all rates of improvement was 35.6%. 4. In a few cases, laser treatment had much influence on the patients with the symptom of spasm of muscles. As mentioned above, it is considered that He-Ne laser treatment, ILIB, has an effect on the development in treatment of CVA patients after acute state.

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