• 대한본초학회지
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• 제29권6호
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• Journal of Korean Neurosurgical Society
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• 제63권1호
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• pp.69-79
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• 2020

Objective : To analyze trends in the incidence and treatment of diseases associated with ischemic stroke, namely, cerebral infarction (CI), cerebral arterial stenosis (CASTN), and moyamoya disease (MMD), based on Korean National Health Insurance Service (NHIS) data from 2008 to 2016. Methods : Data was extracted from the national health-claim database provided by the NHIS for 2008-2016 using International Classification of Diseases codes. The crude and age-standardized incidences of each disease (CI, CASTN without a history of CI, and MMD) were calculated; additional analyses were conducted according to age and sex. Trends in the number of patients undergoing treatment according to treatment method were analyzed for each disease using the Korean Classification of Diseases procedure codes. Results : In 2016, the total number of adults with newly diagnosed CI was 83939, reflecting a 9.4% decrease from that in 2008. The age-standardized incidence of CI in adults was 153.2 per 100000 person-years in 2016, reflecting a 37.2% decrease from that in 2008, while that of CASTN was 167.3 per 100000 person-years in 2016, reflecting a 73.3% increase from that in 2008. Among treated cases, the number of patients who underwent intra-arterial (IA) treatment, including IA fibrinolysis and mechanical thrombectomy, showed the most prominent increase, increasing at an annual rate of 25.8%. For CASTN, the number of cases treated with carotid artery stenting or balloon angioplasty (CAS) showed the most prominent increase, increasing at a rate of 69.8% over the 9-year period. For MMD, the total number of patients with newly diagnosed MMD and that with adult MMD demonstrated significantly increasing trends, while the number of pediatric patients with newly diagnosed MMD declined by 18.0% over the 9-year period. The age-standardized incidences of pediatric and adult MMD in 2016 were 2.4 and 3.4 per 100000 person-years, respectively. Conclusion : Although the incidence of CI showed a declining trend over a 9-year period, the number and proportion of patients treated for CI increased. Meanwhile, the incidence of CASTN and the number of patients treated for CASTN have demonstrated increasing trends since 2008. On the other hand, the number of patients diagnosed with pediatric MMD decreased, despite no significant change in the incidence. In contrast, the number of patients and the incidence of adult MMD increased. These trends reflect changes in the population structure, gains in the accessibility of imaging examinations, and the development of endovascular techniques.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.11-18
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• 2020

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

• 한국전문물리치료학회지
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• 제12권2호
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• pp.90-97
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• 2005

By measuring changes in blood lactate and plasma enzyme (CPK, GOT, GPT) with electrical stimulation applied at two duty cycles, this study is intended to look into which type of duty cycle may have more effects on blood lactate and plasma enzyme constituents through animal experiment so as to determine any duty cycle appropriate for electrical treatment. In this study, electrical stimulation was applied to total 20 Korean house rabbits (weight: 3~3.5 kg) by means of an electrical therapeutic apparatus called TS6000 (made in Netherlands) at duty cycle of 50% and 20% respectively for 30 minutes. Here, 5 cc of blood was collected from their carotid artery before stimulation and in 30 minutes after stimulation respectively to carry out biochemical experiment and analysis. As determined through the above experiment, blood lactate rate was increased to 333.07% at 50% duty cycle after experiment and 185.71% at 20% duty cycle after experiment respectively. In both cases, blood lactate rate was significantly increased to higher level after electrical stimulation than before. Moreover, the rate of change in the average of blood lactate rate at both duty cycles also showed significant differences. CPK rate was boosted to 301.82% at 50% duty cycle after experiment and 321.35% at 20% duty cycle after experiment respectively. In both cases, CPK rate was remarkably boosted to higher level after stimulation than before (p<.05). However, there was not any significant difference in the rate of change in average CPK at both duty cycles (p<.05). GOT rate was significantly boosted up to 38.97% at 50% duty cycle after experiment (p<.05), while it was slightly increased to 1.68% at 20% duty cycle after experiment without any significant difference. Rather, GPT rate dropped slightly at both duty cycles after experiment, but there was not any significant difference. Although blood lactate and GOT were relatively less generated at 20% duty cycle after electrical stimulation than at 50% duty cycle, the change of duty cycle didn't have any significant influence on CPK rate. In this regard, this study failed to come any consistent conclusion about the association between change of duty cycle and muscle fatigue. Therefore, it is advisable that follow-up studies seek various ways to a little more effectively apply electrical stimulation to laboratory animals by avoiding their muscle fatigue. GOT rate was significantly boosted up to 38.97% at 50% duty cycle after experiment (p<.05), while it was slightly increased to 1.68% at 20% duty cycle after experiment without any significant difference. Rather, GPT rate dropped slightly at both duty cycles after experiment, but there was not any significant difference. Although blood lactate and GOT were relatively less generated at 20% duty cycle after electrical stimulation than at 50% duty cycle, the change of duty cycle didn't have any significant influence on CPK rate. In this regard, this study failed to come any consistent conclusion about the association between change of duty cycle and muscle fatigue. Therefore, it is advisable that follow-up studies seek various ways to a little more effectively apply electrical stimulation to laboratory animals by avoiding their muscle fatigue.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.246-246
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• 1996

The glucuronide conjugates of morphine have been claimed to exert significant neuropharmacological effects. Morphine-6-glucuronide (M6G) may be a potent opioid agonist in vivo, and morphine-3-glucuronide (M3G) may act as a weak opioid antagonist. The present study addressed the permeability of the blood-brain barrier (BBB) for these metabolites compared to morphine. Tracers were prepared by enzymatic glucuronidation of U-methyl-$^3$H]-morphine. Brain uptake in rats was measured by the internal carotid artery perfusion technique and after i.v. bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52${\pm}$0.61 ${\mu}$L min$\^$-1/ g$\^$-1/ Uptake seems to be mediated by passive diffusion and was not saturable by 100 ${\mu}$M morphine in the perfusate. The BBB permeability of [$^3$H]-M3G and [$^3$H]-M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [$^3$H]-M3G and [$^3$H]-M6G 60 min after i.v. bolus injection reached 0.0060${\pm}$0.0003 and 0.0030${\pm}$0.0005% injected dose per g, respectively. From these brain concentrations and from the corresponding plasma concentration - time curves, BBB PS values of 0.14${\pm}$ 0.02 ${\mu}$L min$\^$-1/g$\^$-1/ and 0.11 ${\pm}$ 0.01 ${\mu}$L min$\^$-1/g$\^$-1/, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of MSG explains, why it is approximate]y equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.

• Journal of Nutrition and Health
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• 제32권6호
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• pp.644-653
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• 1999

Background : Excessive intakes of $\omega$6 polyunsaturated fatty acid (PUFA) can increase oxidative stress, which may increase insulin resistance and could be the cause of metabolic syndrome X such as diabetes mellitus. One of the ways to reduce oxidative stress is the consumption of antioxidants such as vitamin E. It is controversial that vitamin E intakes may alleviate insulin resistance. The purpose of the study was whether high vitamin E intake may influence whole body glucose disposal rate(GDR), glycogen deposites, triglyceride content, lipid peroxide levels and antioxidant enzyme activities in Sprague Dawley rats fed high $\omega$6 PUFA diest. Methods : Sprague Dawley rats were divided into three groups. The control group consumed chow diet. High and low vitamin E groups consumed 40% PUFA of total energy intakes. One kilogram of diet mixture contained 300IU of $\alpha$-tocopherol in high vitamin E group, while it had 30 IU in low vitamin E group. Diets were given for 8 weeks. After 7 were of diet consumption, indwelling catheters were inserted in carotid artery and jugular vein of all rats so that GDR could be measured in awake and unstressed state. Results : Daily PUFA intakes were lower in the control group than others. Daily vitamin E intake of high vitamin E group was about ten times higher than those of low vitamin E group and the control group(p<0.0001). $\alpha$-tocopherol content in lier was highest in the high vitamin E group. GDR of the control group was 24% higher than others, and vitamin E intakes did not affect GDR. Glycogen deposit of liver in the control group was significantly higher than others, and it was not altered by vitamin E supplementation. Muscle glycogne content showed a similar tendency as liver glycogen in different diet groups. Triglyceride deposit in muscle was not different among groups. Lipid peroxide content of liver in the high vitamin E group was lower than the low of glutathione peroxidase were lowered in low vitamin E group than others, however, those of superoxide dismutase and catalase were not different. Conclusions : High vitamin E intakes can decrease oxidative stress in rats fed high (())-6 PUFA diet, but they cannot alleviate insulin resistance. Thus, increased oxidative stress through high (())-6 PUFA diet may be minimal for influencing insulin resistance.

• 대한핵의학회지
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• 제27권2호
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• pp.175-182
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• 1993

지주막하출혈은 혈관경련, 재출혈, 수두증의 합병증이 빈번히 동반되며, 이 합병증 유무에 따라 예후에 큰 영향을 받는다. 뇌동맥파열에 의한 지주막하출혈 환자 21명과 지주막하출혈 환자 중 10명(48%)의 환자에서 SPECT 검사상 양측성 관류저하가 관찰되었으며, 일측성 관류저하가 7명(33%), 관류저하가 없는 예가 4명 (19%)이었다. 반면에 CT/MRI에서 양측성 병소가 관찰된 예는 3예(14%)이었다. 발견된 병소의 수도 SPECT의 경우는 56개었으나 CT/MRI에서는 25개만이 관찰되었다. 언어장애 또는 편측 운동장애가 발생한 환자에서 SPECT로 관련영역의 관류전하를 확인할 수 있었으며 Matastest를 시행하여 뇌동맥폐쇄시술 시 위험유무를 판정할 수 있었다. 이상의 결과로 $^{99m}Tc$-HMPAO SPECT 검사는 지주 막하출혈 환자에서 CT/MRI에 비하여 기능변화를 정확히 반영하여, 환자의 정확한 임상상을 비관혈적으로 객관적으로 평가할 수 있는 유용한 검사법으로 생각되었다.

• 대한한방내과학회지
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• 제31권3호
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• pp.578-585
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• 2010

Objectives : Coldness of hands and feet has been regarded to be associated with blood circulation. This study was performed to assess the correlation between erythrocyte deformability and coldness of hands and feet. Methods : 145 patients who had taken an erythrocyte deformability test were selected for this study among hospitalized patients within 4 weeks after their cerebral infarction at the Internal Medical Department at Kyunghee Oriental Medical Center from August 2008 to August 2009. We divided the selected patients into two groups, with and without of coldness of hands and feet groups. The two groups were compared on risk factors for atherosclerosis and examined for variables including erythrocyte deformability. Results : 1. On demographic variables of the patients, only body mass index was significantly lower in the coldness of hands and feet group than the control group. There was no significant difference of the rate of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, smoking, drinking and carotid artery stenosis between the two groups. 2. According to blood test, the coldness of hands and feet group showed significantly lower erythrocyte deformability index than the control group. 3. Body mass index and erythrocyte deformability index showed a close relationship with coldness of hands and feet in multivariate analysis. Conclusions : The correlation between the erythrocyte deformability and coldness of hands and feet in cerebral infarction patients were decreased erythrocyte deformability participated in the mechanism of coldness of hands and feet.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.393-404
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• 1999

We have reported that hypoxia stimulates EDRF(s) release from endothelial cells and the release may be augmented by previous hypoxia. As a mechanism, it was hypothesized that reoxygenation can stimulate EDRF(s) release from endothelial cells and we tested the hypothesis via bioassay experiment. In the bioassay experiment, rabbit aorta with endothelium was used as EDRF donor vessel and rabbit carotid artery without endothelium as a bioassay test ring. The test ring was contracted by prostaglandin $F_{2a}\;(3{\times}10^{-6}\;M)$ which was added to the solution perfusing through the aorta. Hypoxia was evoked by switching the solution aerated with 95% $O_2/5%\;CO_2$ mixed gas to one aerated with 95% $O_2/5%\;CO_2$ mixed gas. Hypoxia/reoxygenation were interexchanged at intervals of 2 minutes (intermittent hypoxia). In some experiments, endothelial cells were exposed to 10-minute hypoxia (continuous hypoxia) and then exposed to reoxygenation and intermittent hypoxia. In other experiments, the duration of reoxygenation was extended from 2 minutes to 5 minutes. When the donor aorta was exposed to intermittent hypoxia, hypoxia stimulated EDRF(s) release from endothelial cells and the hypoxia-induced EDRF(s) release was augmented by previous hypoxia/reoxygenation. When the donor aorta was exposed to continuous hypoxia, there was no increase of hypoxia-induced EDRF(s) release during hypoxia. But, after the donor aorta was exposed to reoxygenation, hypoxia-induced EDRF(s) release was markedly increased. When the donor aorta was pretreated with nitro-L-arginine $(10^{-5}$ M for 30 minutes), the initial hypoxia-induced EDRF(s) release was almost completely abolished, but the mechanism for EDRF(s) release by the reoxygenation and subsequent hypoxia still remained to be clarified. TEA also blocked incompletely hypoxia-induced and hypoxia/reoxygenation-induced EDRF(s) release. EDRF(s) release by repetitive hypoxia and reoxygenation was completely blocked by the combined treatment with nitro-L-arginine and TEA. Cytochrome P450 blocker, SKF-525A, inhibited the EDRF(s) release reversibly and endothelin antgonists, BQ 123 and BQ 788, had no effect on the release of endothelium-derived vasoactive factors. Superoxide dismutase (SOD) and catalase inhibited the EDRF(s) release from endothelial cells. From these data, it could be concluded that reoxygenation stimulates EDRF(s) release and hypoxia/reoxygenation can release not only NO but also another EDRF from endothelial cells by the production of oxygen free radicals.

• Clinical and Experimental Pediatrics
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• 제52권2호
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• pp.187-193
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• 2009

목 적 : Adiponectin은 대사 증후군에서 중요한 역할을 하는 물질이며, 비만, 2형 당뇨, 관동맥 질환 등에서 그 수치가 감소하는 것으로 알려져 있다. 고혈압과 혈청 adiponectin치의 관계는 여러 저자에 의하여 발표되었으나 아직 논란의 여지가 남아있는 상태이다. 우리는 낮은 adiponectin치가 청소년 고혈압과 어떤 관계가 있는지, 또 영향을 끼치는 기전이 유전적인지 혹은 생물학적인 것인지 알고자 유전자 다형성 분석을 하였다. 방 법 : 16에서 17세 사이의 40명의 고혈압 청소년과 20명의 대조군 청소년을 대상으로 각 군의 혈청 adiponectin, insulin, renin, aldosterone, ACE를 측정하여 비교하였다. cIMT와 PWV도 측정하였다. PCR법으로 adiponectin I164T 유전자 다형성을 조사하였다. 결 과 : 고혈압 청소년군에서 cIMT와 PWV가 의미있게 높았다. 혈청 insulin, renin, aldosterone치도 고혈압군에서 의미있게 높았다. 두 군간에 adiponectin치는 의미있는 차이를 보이지 않았다. 본 연구에 참여한 청소년에서는 TC genotype은 발견되지 않았고 모두 TT genotype을 보였다. 결 론 : 결론적으로 adiponectin치는 고혈압 청소년 군에서나 정상군에서나 차이가 없었다. 두 군에서 유전적인 다형성도 보이지 않았다. 더 큰 규모의 연구가 필요할 것으로 생각된다.