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Electronic Pen-based Cognitive Dysfunction Assessment System (전자펜을 활용한 인지기능장애 환자 검사 시스템)

  • Shin, Sangho;Jee, Haemi;Park, Jaehyun
    • KIISE Transactions on Computing Practices
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    • v.24 no.1
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    • pp.17-23
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    • 2018
  • The assessment and rehabilitation of patients with cognitive dysfunction is a field that currently requires assistive technology. While the paper-and-pencil test, such as the line tracing test (LTT), is one of the most commonly used assessment methods for cognitive dysfunction, it has become time-consuming due to its manual characteristic. The aim of this study was therefore to establish a computer-based real-time assessment system for patients without compromising the usefulness of the conventional paper-and-pencil based user tools. A digital pen-based assessment and rehabilitation system, the ePen System, could eliminate the time required for manual assessment while maintaining the measurement accuracy. The proposed system may assist rehabilitation specialists to assess and diagnose patients with unilateral visual neglect. This system can be applied to a range of assessment and rehabilitation modalities based on pen and paper. It can also be used for various patients such as those with Parkinson's disease, stroke, or different forms of brain lesions.

Effects of Fetal Mesencephalic Cell Grafts on the Intrastriatal 6-hydroxydoapmine Lesioned Rats

  • Joo, Wan Seok;Nam, Eun-Joo;Im, Heh-ln;Jung, Jin-Ah;Lee, Eun-Sun;Hwang, Yu-Jin;Kim, Yong-Sik
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.5
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    • pp.245-251
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    • 2004
  • The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH + cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc $(91.9{\pm}9.8%)$ in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.

Transforming Growth Factor-$\alpha$ Increases the Yield of Functional Dopaminergic Neurons from in vitro Differentiated Human Embryonic Stem Cells Induced by Basic Fibroblast Growth Factor

  • Lee, Keum-Sil;Shin, Hyun-Ah;Cho, Hwang-Yoon;Kim, Eun-Young;Lee, Young-Jae;Wang, Kyu-Chang;Kim, Yong-Sik;Lee, Hoon-Taek;Chung, Kil-Saeng
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.102-102
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    • 2003
  • Embryonic stem (ES) cells proliferate extensively in the undifferentiated state and have the potential to differentiate into a variety of cell types in response to various environmental cues. The generation of functional dopaminergic neurons from ES cells is promising for cell replacement therapy to treat Parkinson's disease. We compared the in vitro differentiation potential of pluripotent human embryonic stem (hES, MB03) cells induced with basic fibroblast growth factor (bFGF) or retinoic acid (RA). Both types of treatment resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with brain derived neurotrophic factor (BDNF) or transforming growth factor (TGF)- $\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression, compared to control (P<0.05). In contrast, no effect was observed on the rate of mature or glutamic acid decarboxylase-positive neurons. Immunostaining and HPLC analyses revealed the higher levels of TH (20.3%) and dopamine in bFGF and TGF-$\alpha$ treated hES cells than in RA or BDNF treated hES cells. The results indicate that TGF-$\alpha$ may be successfully used in the bFGF induction protocol to yield higher numbers of functional dopaminergic neurons from hES cells.

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Neuroprotective Effects of Carpinus tschonoskii MAX on 6-Hydroxydopamine-Induced Death of PC12 Cells

  • Kim, Min-Kyoung;Kim, Sang-Cheol;Kang, Jung-Il;Boo, Hye-Jin;Hyun, Jin-Won;Koh, Young-Sang;Park, Deok-Bae;Yoo, Eun-Sook;Kang, Ji-Hoon;Kang, Hee-Kyoung
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.454-462
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    • 2010
  • The present study investigated the neuroprotective effect of Carpinus tschonoskii MAX and its intracellular protective mechanism on 6-hydroxydopamine (6-OHDA)-induced oxidative damage in PC12 cells. We found that pretreatment of PC12 cells with C. tschonoskii extract significantly inhibited the cell death induced by 6-OHDA in a dose dependent manner. C. tschonoskii extract decreased 6-OHDA-induced apoptotic events such as chromatin condensation, DNA fragmentation, the decrease of Bcl-2/Bax ratio, caspase-3 activation and PARP cleavage. C. tschonoskii extract also reduced generation of 6-OHDA-induced reactive oxygen species and nitric oxide. Furthermore, C. tschonoskii extract up-regulated the myocyte enhancer factor 2 D (MEF2D), a critical transcription factor for neuronal survival, and Akt activity, whereas it inhibited the activity of ERK1/2 and JNK. The results suggest that C. tschonoskii extract decreases 6-OHDA-induced oxidative stress and could prevent PC12 cell apoptosis induced by 6-OHDA via the up-regulation of MEF2D and Akt activity, and thus may have application in developing therapeutic agents for Parkinson's disease.

The Literary Trends of Herbal Prescription Ukgan-san and its Application in Modern Traditional Korean Medicine (동의보감에 수록되지 않았던 억간산의 문헌상 흐름과 현대 한의학에서의 응용 현황)

  • Cho, Ki-Ho;Kim, Tae-Hun;Jin, Chul;Lee, Ji-Eun;Kwon, Seungwon
    • The Journal of Korean Medicine
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    • v.39 no.3
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    • pp.17-27
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    • 2018
  • Objectives: Ukgan-san does not appear in Traditional Korean Medicine classics. However, it has been used in research and clinical applications in Korea. In this paper, we are aiming to examine the records concerned with Ukgan-san to the present, and announce the present usage state in Korea. Methods: We searched and summarized the contents of previous medical books about Ukgan-san. In order to investigate the current status of utilization of Ukgan-san in Korea, a bibliographic database of Korea, a database of clinical researches, and a database of pharmaceuticals of the Korea Food and Drug Administration were searched. Results: As a result of searching Ukgan-san related documents, Ukgan-san has been developed in China (Ming dynasty). However, its clinical application has been expanded by modern Japanese kampo medicine doctors. In Korea, cases of Parkinson's disease, other movement disorders, and psychiatric disorders have been reported, and randomized controlled trials had been done and planned. In addition, some extracts which are consisted of Ukgan-san are also available. Conclusions: In Korea, Ukgan-san has been influenced by Japan and has been used for clinical and research purposes. The utilization rate in Korea is still small, but the utilization rate will increase according to the results of clinical studies.

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

  • Hahm, Eu-Teum;Seo, Jung-Woo;Hur, Jin-Young;Cho, Young-Wuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.127-132
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    • 2010
  • Reactive oxygen species (ROS), which include hydrogen peroxide ($H_2O_2$), the superoxide anion (${O_2}^-{\cdot}$), and the hydroxyl radical ($OH{\cdot}$), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of $H_2O_2$ on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM $H_2O_2$ gradually potentiated mIPSCs. This potentiating effect of $H_2O_2$ was blocked by the pretreatment with either 10,000-unit/mL catalase or $300-{\mu}M$ N-acetyl-cysteine. The potentiating effect of $H_2O_2$ was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N -(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.

Effects of Glycerol and Shikimic Acid on Rapamycin Production in Streptomyces rapamycinicus

  • La, Huyen Thi Huong;Nguyen, Thao Kim Nu;Dinh, Hang Thuy;Nguyen, Quyen Minh Huynh;Nguyen, Minh Hong
    • Microbiology and Biotechnology Letters
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    • v.48 no.3
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    • pp.296-302
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    • 2020
  • Rapamycin, derived from Streptomyces rapamycinicus, is an important bioactive compound having a therapeutic value in managing Parkinson's disease, rheumatoid arthritis, cancer, and AIDS. Because of its pharmaceutical activity, studies over the past decade have focused on the biosynthesis of rapamycin to enhance its yield. In this study, the effect of rapG on rapamycin production was investigated. The rapG expression vector was constructed by utilizing the integration vector pSET152 under the control of the erythromycin resistance gene (ermE), a strong constitutive promoter. The rapamycin yield of wild type (WT) and WT/rapG overexpression mutant strains, under fermentation conditions, was analyzed by high-performance liquid chromatography (HPLC). Our results revealed that overexpression of rapG increased rapamycin production by approximately 4.9-fold (211.4 mg/l) in MD1 containing 15 g/l of glycerol, compared to that of the WT strain. It was also found that Illicium verum powder (10 g/l), containing shikimic acid, enhanced rapamycin production in both WT and WT/rapG strains. Moreover, the amount of rapamycin produced by the WT/rapG strain was statistically higher than that produced by the WT strain. In conclusion, the addition 15 g/l glycerol and 15 g/l I. verum powder produced the optimal conditions for rapamycin production by WT and WT/rapG strains.

Neuroprotective Effect of l-Deprenyl Against 6-OHDA-Induced Dopamine Depletion in Rat Striatum and 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells (흰쥐 선조체에서 6-OHDA-유도 도파민 고갈 및 SH-SY5Y 세포주에서 6-OHDA-유도 산화적 스트레스에 대한 l-Deprenyl의 신경 보호효과)

  • Kim Eun-Mi;Choi Sinkyu;Lee Kyunglim;Kim Hwa-Jung
    • YAKHAK HOEJI
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    • v.49 no.4
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    • pp.355-364
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    • 2005
  • A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway. Whereas l-deprenyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity. Pretreatment of l-deprenyl significantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl $(0.1\~100{\mu}M)$ did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

Synthesis of 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (6-Amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan의 합성)

  • Kim, Min-Kyeom;Ma, Eun-Sook
    • YAKHAK HOEJI
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    • v.52 no.1
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    • pp.20-26
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    • 2008
  • 2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. Selenium was reported to have an improved antioxidant ability and to reduce the loss of dopamine. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine agonist with low neurotoxocity. In order to develop a novel dopamine agonist, we tried to synthesize the selenazoloaminoindan derivative that is a hybrid structure of aminoindan and aminoselenazole instead of aminothiazole. 2-Indanone-2-oxime was reduced with $TiCl_4$ and $NaBH_4$ to form 2-aminoindan, which was reacted with propionyl chloride to give 2-N-n-propionylaminoindan (2). Compound 2 was reduced with $TiCl_4$ and $NaBH_4$ to afford 2-N-n-propylaminoindan (3) and it was nitrated and reduced to form 5-amino-2-N-n-propylaminoindan (5), which was reacted with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5- amino-2-N-n-propylaminoindan (7) instead of selenazole ring formation. Otherwise, compound 2 was nitrated and hydrogenated to form 5-amino-2-N-n-propionylaminoindan (9), which was treated with KSeCN, $Br_2$, and glacial acetic acid to give 4,6-dibromo-5-amino-2-N-n-propionylaminoindan (10). Compound 9 was cyc1ized with KSeCN and glacial acetic acid in the absence of $Br_2$ to give 6-amino-2-N-(n-propionylamino)selenazolo[4,5-f]indan (11).

Nutrition composition differences among steamed and freeze-dried mature silkworm larval powders made from 3 Bombyx mori varieties weaving different colored cocoons

  • Ji, Sang-Deok;Kim, Nam-Suk;Kweon, HaeYong;Choi, Bo Hye;Kim, Kee-Young;Koh, Young Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • v.33 no.1
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    • pp.6-14
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    • 2016
  • The mulberry silkworm, Bombyx mori has been one of the most important domestic animals which have provided with silk fibers for weaving fabrics and a food for a protein and lipid source. In addition, various health improvement effects of diverse silkworm larval powders were reported. Recently we found that steamed and freeze-dried mature silkworm larval powder (SMSP) generated using white-jade (also known as Backokjam) silkworm variety extended healthspan and increased resistance to Parkinson's disease in animal models. Because the colors of cocoons in silkworm varieties were caused by altered signal transduction pathways transporting phytochemicals from intestinal lumens to silk glands, we performed the proximate, amino acid, mineral, carbohydrates, fatty acid, and cholesterol composition analyses of SMSPs of 3 silkworm varieties which were weaving light yellow, golden, and red cocoons. Although most of nutrient compositions among 3 SMSPs were similar, there were significant differences in certain amino acids, minerals, and fatty acid compositions. Red silk silkworm (RS)-SMSP had higher contents of crude proteins and total amino acids than other SMSPs. In addition, the ratio of n-3/n-6 unsaturated fatty acids were higher than the other SMSPs. In contrast Golden silk silkworm (GS)-SMSP had higher ratio of potassium/sodium than the other SMSPs. These nutrient analysis results suggested that 3 SMSPs might have common and unique health improvement effects. Thus, further studies in the functionalities of the 3 SMSPs will reveal unknown their health improvements effects.