• 대한핵의학회지
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• 제37권6호
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• pp.374-381
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• 2003

목적: 오류발견율 조절법을 PET 영상분석에 이용하면 다중비교에 따르는 위양성율을 줄이면서 동시에 검정력을 높일 수 있다. 조기 알츠하이머 치매 환자에서 오류발견율 조절법을 적용하였을 때와 비보정역치, 무작위 가우스장 보정역치를 적용하였울 때 FDG PET에 나타난 포도당 대사 감소영역이 어떻게 달라지는지 조사하였다. 방법: 28명의 평균 66세 (${\pm}7$)인 조기 알츠하이머성 치매 환자와 연령을 맞춘 18명의 정상인($68{\pm}6$세)의 FDG PET 영상을 SPM99 소프트웨어로 분석하였다. 환자군과 정상군의 차이와 각 환자와 정상군의 차이를 각각 비보정 역치 p값 0.001, 무작위장 보정 역치 p값 0.001, 오류발견율 조절법에 의한 오류발견율 0.001일 때을 정하여 이 세 통계적 역치에서 각각 뇌 포도당 대사감소 영역을 결정하였다. 결과: 집단 분석결과 비보정 역치를 사용하였을 때 가장 넓은 영역에서, 보정역치를 사용하였을 때 가장 좁은 영역에서, 오류발견율 조절법을 적용하였을 때 중간크기의 영역에 대사가 감소하였다. 개인분석결과 비보정 역치 경우 발견된 대사감소 화소보다 오류발견율 조절시 많은 화소가 나타난 경우(8/28, 29%)와 보정 역치 경우와 오류발견율 조절시에는 대사감소 부위가 나타나지 않고 비보정 역치 경우에만 넓은 부위에 대사감소부위가 나타난 경우(6/28, 21%), 그리고 보정역치보다 오류 발견율 조절시에 훨씬 많은 화소가 이상부위로 나타나서 비보정역치 경우에 근접하는 넓이를 찾을 수 있는 경우(14/28 50%)이었다. 결론: 조기 알츠하이머 치매 환자의 FDG PET을 오류발견율 조절법으로 분석한 결과 집단분석이나 개인분석 모두 대사감소부위를 잘 찾을 수 있었다. 집단의 크기가 작은 환자의 집단분석이나 특히 개인분석의 경우 오류발견율 조절법을 이용하여 FDG PET을 분석하는 것이 좋을 것이라 제안한다.

• 동의신경정신과학회지
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• 제9궈1호
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• pp.1-24
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• 1998

The effects of Hyungbangjiwhangrang on the enhancement of learning and memory of AD model rats were studied with Morris water maze and radial arm maze. Sample group was electrolytically lesioned on nbM, and then daily treated with the medicine for two months. Control group with nbM lesion, and sham group with the sham operation were treated the vehicle for same duration. The following results were observed.1. As the learning trials of Morris water maze processed repeatedly, sham group achiened 201.64${\pm}$33.13 seconds in 1st trial, 153.14${\pm}$61.80 seconds in 2nd, 106.21${\pm}$46.81 seconds in 3rd, 76.64${\pm}$48.40 seconds in 4th, and 52.29${\pm}$38.25 seconds in 5th. The control group achieved 224.08${\pm}$29.16 in 1st trial, 191.77${\pm}$67.97 seconds in 2nd, 177.77${\pm}$65.44 seconds in 3rd, 140.92${\pm}$68.27 seconds in 4th, and 126.46${\pm}$79.15 seconds in 5th. The sample group achieved 223.36${\pm}$23.33 seconds in 1st trial, 215.86${\pm}$38.93 seconds in 2nd, 190.79${\pm}$51.57 seconds in 3rd, 155.79${\pm}$62.67 seconds in 4th, and 127.93${\pm}$62.11 seconds in 5th. Therefore, these data shows that all three groups were improved in learning capacity as trials were repeated, but the shame group showed prominent improvement in learning compared with the control group(p<0.05).2. In memory retention test of Morris water maze that counts the staying time in the target area, sham group stayed for 15.36${\pm}$5.39 seconds, the control group stayed for 5.54${\pm}$5.64 seconds, and the sample group stayed for 7.43${\pm}$6.09 seconds. The analysis of the memory retention data shows that the sham group marked more significant improvement stati- stically in memory retention compared with the control group(p<0.05).3. In the learning of radial arm maze, the number and rate of animals that arrive the learning criteria amounted 12 out of 14, 85.7% in sham group, 4 out of 13, 30.8% in the control group, and 10 out of 14, 71.4% in the sample group So, the sample group shows better learning capacity significantly compared with the control group(p<0.05). With the experimental results above, Hyungbangjiwhangtang can be supposed to have the improving effects on the learning and memory of AD rats induced by eletronical injury of nbM.

• 전자공학회논문지CI
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• 제49권1호
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• pp.16-22
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• 2012

본 논문에서는 알츠하이머병이 유도된 형질전환 마우스로부터 획득한 혈소판 라만 스펙트럼의 분석을 위해 가우시안 모델을 이용한 커브 피팅으로 기준선을 추정하고 보정하는 방법을 제안하였다. 측정된 라만 스펙트럼은 의미 있는 정보와 불필요한 노이즈 성분인 기준선과 가산 노이즈를 포함하고 있다. 스펙트럼의 효율적인 분석을 위해 노이즈를 포함하고 있는 스펙트럼을 몇 개의 피크를 포함하는 영역으로 분할하고 각 로컬 영역의 스펙트럼을 가우시안 모델을 이용한 커브 피팅으로 모델링한다. 가산 노이즈는 원 스펙트럼을 이 델로 대체하는 과정에서 명백하게 제거된다. 피팅된 모델의 로컬 최저점을 linear, piecewise cubic Hermite, cubic spline 알고리즘으로 보간하고 기준선을 보정한다. 기준선을 보정한 피팅 모델은 PCA(principal component analysis) 방법을 이용하여 특징을 추출하고 SVM(support vector machine)과 MAP(maximum $a$ posteriori probability) 분류 방법으로 성능 비교 실험을 하였다. 실험 결과에 따르면 linear 보간법이 모든 주성분 수에 대한 분류율의 평균에서 우세하였고 특히 piecewise cubic Hermite 보간법은 주성분의 수가 5개인 경우에서 SVM 분류율이 약 97.3%로 가장 좋은 성능을 보였다. 또한 이전의 연구 결과와 비교를 통해 제안한 기준선 보정 방법이 혈소판 라만 스펙트럼의 분석에 효과적으로 적용될 수 있음을 확인하였다.

• 동의신경정신과학회지
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• 제21권2호
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• 사상체질의학회지
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• 제21권3호
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• pp.138-153
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• 2009

1. Objectives: Yeolda-Hanso tang (YH) has long been used as traditional herbal formula in Korea as various diseases. Now we modified Yeolda-Hanso tang (YH) for neurodegenerative diseases treatment and named New-Yeolda-Hanso tang (NYH). We investigated neuroprotective effects of NYH on NGF-differentiated PC12 cells cytotoxicity induced by $\beta$-Amyloid peptide (A$\beta$25-35) and evaluated the ability of NYH to prevent and treat for neurodegenerative diseases via autophagy enhancement. 2. Methods and Results: 1) Protective effect of NYH on PC12 cells cytotoxity induced by A$\beta$25-35. PC12 cells survival was measured by MTT and lactate dehydrogenase (LDH) assay. $20{\mu}M$ $\beta$-Amyloid peptide (A$\beta$25-35) induced cytotoxicity on NGF-differentiated PC12 cells. NYH attenuated the cytotoxic effects of A$\beta$25-35 in a dose-dependent manner. 2) Pharmacological induction of Autophagy by NYH in PC12 cells Autophagy induction and activation was measured by immunoblot assay. Marker of autophagy, LC3 II expression and the ratio of LC3-II/I was slightly increased in the protein treated with YH, and significantly augmented in the protein treated with NYH. NYH-induced increase of LC3-II protein level was inhibited by 3MA. 3) Induction of Autophagy by NYH on A$\beta$25-35-induced injury in PC12 cells In MTT assay, $100{\mu}g/ml$ re-treated NYH attenuated $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. Protection effect of NYH was blocked by autophagy inhibitor 3MA. In immunoblot assay, $1200{\mu}g/ml$ pre-treated NYH activated autophagy in $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. The observed effect was partially blocked by 3MA. 3. Conclusions: All the results indicated that NYH possesses neuroprotective potential partially mediated by autophagy enhancement and NYH may be considered to be a promising new herbal formula to prevent and treat for neurodegenerative diseases including Alzheimer's disease (AD).

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• 생명과학회지
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• 제30권4호
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• pp.331-342
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• 2020

미세교세포(Microglial cells)에서 신경염증반응(neuroinflammatory responses)의 억제는 알츠하이머질환, 파킨슨질환, 헌팅턴질환과 같은 신경퇴행성질환(neurodegenerative diseases)을 치료하기 위한 주요 표적으로 고려되고 있다. 천문동(Asparagus cochinchinesis)은 열, 기침, 신장 질환, 유방암, 염증성질환 및 뇌질환을 치료하는 데 오랫동안 사용 되어온 전통 치료제(Traditional medicine)이다. 본 연구에서는 lipopolysaccharide (LPS)로 활성화된 BV-2 미세교세포에서 항염증효과가 있는 천문동 뿌리 열수추출물(Aqueous extract from A. cochinchinesis root, AEAC)의 신경보호 메커니즘을 연구하였다. 먼저, 어떤 유의적인 세포독성은 플라보노이드(flavonoid), 페놀(phenol), 사포닌(saponin)을 함유하는 AEAC를 4가지 농도로 처리된 BV-2세포에서 검출되지 않았다. 또한, nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA 및 inducible nitric oxide synthase (iNOS) mRNA 수준은 AEAC+LPS 처리군에서 비하여 21%정도 감소하였다. 전염증성 사이토카인(TNF-α과 IL-1β) 및 항염증성 사이토카인(IL-6와 IL-10)농도에 대한 유사한 감소는 비록 감소비율은 다르지만, Vehicle+LPS 처리군에 비해 AEAC+LPS 처리군에서 검출되었다. 더불어, LPS 처리 후 mitogen-activated protein (MAP) kinase의 인산화수준의 증가는 AEAC 전처리군에서 유의하게 회복되었고, 세포주기에서 G2/M의 억제(arrest)는 AEAC+LPS 처리군에서 개선되었다. 또한, LPS 처리로 유도된 ROS의 증가도 AEAC 전처리군에서 감소되었다. 따라서, 이러한 결과는 AEAC가 MAPK 신호전달 경로, 세포주기 및 ROS (reactive oxygen species) 생성의 조절을 통해 LPS 자극에 대한 항신경염증 활성을 유도함을 제시하고 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제24권5호
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• pp.662-669
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• 2011

An experiment was conducted with broiler (Cobb 400) male chicks (n = 480) to determine the effect of betaine (Bet) supplementation (0 and 800 mg/kg) to diets containing five concentrations (15, 18, 20, 22 and 24 g/kg crude protein, CP) of methionine (Met) in a $2{\times}5$ factorial study for performance, carcass traits, immune responses, and serum parameters. Each diet was fed ad libitum from 1 to 42 d of age to 8 replicates of 6 chicks. Birds were housed in battery brooders placed in an open-sided poultry shed. Body weight gain, feed intake, feed conversion efficiency and slaughter variables were recorded at 21 and 42 d of age. Serum biochemical profile, antibody production against Newcastle disease (ND) and lymphocyte proliferation ratio (LPR) were analysed at 42 d of age. Supplementing Bet to diets containing sub-optimal concentrations of Met (15 g/kg) improved weight gain and breast yield at 21 d of age (p<0.01), and feed conversion efficiency at 42 d of age (p<0.05). Feed efficiency at 21 d of age, body weight gain at 42 d of age, slaughter variables except breast yield at 21 d of age and ND antibody titres were not affected (p>0.05) by the interaction. LPR increased (p<0.05) with Bet supplementation at 20 g Met/kg CP equal to those broilers fed 24 g Met without Bet. Bet supplementation enhanced the concentrations of protein, globulin and cholesterol in serum of broilers fed sub-optimal concentrations of Met. Results suggested that Bet supplementation (800 mg/kg diet) enhanced growth (21 d), feed conversion efficiency (42 d), breast yield and lymphocyte proliferation in broilers fed a diet containing 15 g Met/kg CP.

• Food Quality and Culture
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• 제1권1호
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• pp.46-57
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• 2007

The purpose of the present study was to examine the nutrient intake status of elderly dementia patients. We surveyed the dietary intake of 50 demented elderly patients receiving a regular diet, who were hospitalized in a geriatric hospital in Yongin, Gyeonggi-do. The average age of the subjects was $79.6{\pm}6.5$ for the males and $80.5{\pm}6.3$ for the females. The average heights were $169.5{\pm}6.0\;cm$ (males) and $154.6{\pm}5.2\;cm$ (females), and the average weights were $58.5{\pm}7.4$ (males) and $51.7{\pm}8.9\;kg$ (females). Depending on the type of dementia, the male patients showed significant differences in their intakes of vegetable protein, fiber, total iron, and non-heme iron between the Alzheimer's disease (AD) and the vascular dementia (VD) groups, and the female patients showed significant differences in their intakes of total protein, phosphorus, zinc, and vitamin $B_6$ between the two groups. The male patients showed significant differences in their intakes of animal-source calcium and carotene according to ability to self-feed. According to physical activity, the male patients showed significant differences in vegetable fat and vitamin A intake, and the females showed significant differences in their intakes of total protein, animal protein, fiber, ash, total calcium, vegetable-source calcium, animal-source calcium, phosphorous, total iron, non-heme iron, heme iron, sodium, vitamins $B_1$, $B_2$, $B_6$, niacin, vitamin C, folate, and potassium. We found that the patients consumed excessive protein, but low amounts of calcium, vitamin $B_2$, and folate. Also, the patients' physical activity abilities appeared to affect their nutrient intakes.

• The Korean Journal of Physiology and Pharmacology
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• 제8권4호
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• pp.173-179
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• 2004

Amyloid ${\beta}-peptide\;(A{\beta})$ contributes to the pathogenesis of Alzheimer's disease (AD), causing neuronal death through apoptosis. In this study, the neuroprotective role of BF-7, extracted form sericultural product, was examined against $A{\beta}-induced$ toxicity in cultured human neuronal cell SKN-SH. In order to know if the BF-7 has positive role on the cognition and memory in human, the mixture of BF-7, DHA and EPA (BDE) was examined using Rey Kim and K-WAIS test with 50 healthy high school student. We report here that BDE significantly attenuated $A{\beta}-induced$ apoptosis through the reduction of ROS accumulation, and diminished caspase-like protease activity. Moreover, the memory index and memory preservation, and attentative concentration of BDE treated group for 1 month were significantly improved, in contrast to the case of placebo control treated with DHA and EPA. This result represent that the BF-7 play significant positive role on learning memory. Taken together, our result suggested the natural product BF-7 is a good substance for the brain functionally and physiologically.