Dong Hyun Park

Kyung Hee University, Sŏul, Seoul, South Korea

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Publications (17)39.54 Total impact

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    ABSTRACT: Alzheimer's disease, one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by declines in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is maintaining levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, coumarin derivatives were designed and synthesized as AChE inhibitors based on the lead structure of scopoletin. Of those synthesized, pyrrolidine-substituted coumarins 3b and 3f showed ca. 160-fold higher AChE inhibitory activities than scopoletin. These compounds also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2mg/kg.
    Bioorganic & medicinal chemistry 01/2014; DOI:10.1016/j.bmc.2014.01.010 · 2.95 Impact Factor
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    ABSTRACT: Opuntia ficus-indica var. saboten Makino (Cactaceae) is used to treat burns, edema, dyspepsia, and asthma in traditional medicine. The present study investigated the beneficial effects of the n-butanolic extract of O. ficus-indica var. saboten (BOF) on memory performance in mice and attempts to uncover the mechanisms underlying its action. Memory performance was assessed with the passive avoidance task, and western blotting and immunohistochemistry were used to measure changes in protein expression and cell survival. After the oral administration of BOF for 7 days, the latency time in the passive avoidance task was significantly increased relative to vehicle-treated controls (P<0.05). Western blotting revealed that the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding-protein (pCREB), and phosphorylated extracellular signal-regulated kinase (pERK) 1/2 were significantly increased in hippocampal tissue after 7 days of BOF administration (P<0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining also revealed that BOF significantly enhanced the survival of immature neurons, but did not affect neuronal cell proliferation in the subgranular zone of the hippocampal dentate gyrus. These results suggest that the subchronic administration of BOF enhances long-term memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 08/2010; 34(6):1011-7. DOI:10.1016/j.pnpbp.2010.05.015 · 4.03 Impact Factor
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    ABSTRACT: Quercetin is a naturally occurring dietary flavonol and several reports have shown that quercetin substantially affects cognitive function in disease models, which suggests that quercetin might be a useful agent for treatment of memory dysfunction. However, only one report has examined the effects of quercetin on normal cognitive function. In the present study, we investigated the potential deleterious effects of quercetin on normal cognitive function using Western blot assays and the following behavioral tasks: passive avoidance, Y-maze, and Morris water maze. In the passive avoidance task, pre-acquisition administration of quercetin (10, 20, or 40 mg/kg, p.o.) caused significant cognitive impairments in mice (P < 0.05 or P < 0.01). Quercetin-treated groups (10, 20, or 40 mg/kg, p.o.) also showed significant memory impairments compared with the control group in the Y-maze task (P < 0.05). In the Morris water maze task, there were no significant differences among the groups during training trial sessions, but at the probe trial session, the quercetin-treated group (40 mg/kg, p.o.) spent significantly less time in the target quadrant than did the control group (P < 0.05). In Western blot assays of hippocampal tissue, we found that quercetin-treated groups showed decreased expression of phosphorylated Akt (pAkt), phosphorylated calcium-calmodulin kinase II (pCaMKII), and phosphorylated cyclic AMP response element-binding protein (pCREB). These results suggest that acute administration of quercetin impairs cognitive function by suppression of pAkt and pCaMKII, which, in turn, decreases pCREB expression in the hippocampus.
    Toxicology Letters 05/2010; 197(2):97-105. DOI:10.1016/j.toxlet.2010.05.001 · 3.36 Impact Factor
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    ABSTRACT: Excitotoxin induces neurodegeneration via glutamatergic activation or oxidative stress, which means that the blockade of glutamate receptors and the scavenging of free radicals are potential therapeutic targets in neurodegenerative diseases. Sinapic acid (SA) has a GABA(A) receptor agonistic property and free radical scavenging activity. We investigated the neuroprotective effects of SA on kainic acid (KA)-induced hippocampal brain damage in mice. SA (10 mg/kg) by oral administration has an anticonvulsant effect on KA-induced seizure-like behavior. Moreover, SA (10 mg/kg) significantly attenuated KA-induced neuronal cell death in the CA1 and CA3 hippocampal regions when administered as late as 6 h after KA. In addition, flumazenil, a GABA(A) antagonist, blocked the effect of SA administered immediately after KA but not the effect of SA administered 6 h after KA. This late protective effect of SA was accompanied by reduced levels of reactive gliosis, inducible nitric oxide synthase expression, and nitrotyrosine formation in the hippocampus. In the passive avoidance task, KA-induced memory impairments were ameliorated by SA. These results suggest that the potential therapeutic effect of SA is due to its attenuation of KA-induced neuronal damage in the brain via its anti-convulsive activity through GABA(A) receptor activation and radical scavenging activity.
    Neuropharmacology 04/2010; 59(1-2):20-30. DOI:10.1016/j.neuropharm.2010.03.012 · 4.82 Impact Factor
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    ABSTRACT: The fruit of Euphoria longan (Lour.) Steud. (Sapindaceae) is sweet and edible. Dried Euphoria longan fruit is prescribed as a tonic and for the treatment of forgetfulness, insomnia, or palpitations caused by fright in traditional Chinese medicine. The effects of aqueous extract of Euphoria longan fruit (ELE) on learning and memory and their underlying mechanisms were investigated. Aqueous extract of Euphoria longan fruit (ELE) was administered to ICR mice for 14 days. Piracetam was used as a positive control for its known memory-enhancing effects. Memory performances were assessed using the passive avoidance task. The expressions of phosphorylated extracellular signal-regulated kinase (pERK) 1/2, phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF), doublecortin (DCX) and the incorporation of 5-bromo-2-deoxyuridine (BrdU) in hippocampal dentate gyrus and CA1 regions were investigated using immunohistochemical methods. The step-through latency in the ELE-treated group was significantly increased compared with that in the vehicle-treated controls (P<0.05) in the passive avoidance task. Piracetam-treated group also showed enhanced cognitive performaces in the passive avoidance task. Immunohistochemical studies revealed that the number of cells immunopositive for BDNF, pCREB, or pERK 1/2 was significantly increased in the hippocampal dentate gyrus and CA1 regions after ELE treatment for 14 days (P<0.05). DCX and BrdU immunostaining also revealed that ELE significantly enhanced immature neuronal survival, but not neuronal cell proliferation in the subgranular zone of the dentate gyrus. The present results suggest that subchronic administration of aqueous extract of Euphoria longan fruit enhances learning and memory, and that its beneficial effects are mediated, in part, by BDNF expression and immature neuronal survival.
    Journal of ethnopharmacology 03/2010; 128(1):160-5. DOI:10.1016/j.jep.2010.01.001 · 2.94 Impact Factor
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    ABSTRACT: Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and its flowers are used to treat inflammation in traditional Chinese medicine. In the present study, we studied the effects of the ethanolic extract of the flower of P. vulgaris var. lilacina (EEPV) on drug-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. EEPV (25 or 50 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (P<0.05). In the Morris water maze task, EEPV (25 mg/kg, p.o.) significantly shortened escape latencies in training-trials. Furthermore, swimming times within the target zone during the probe-trial were significantly increased as compared with scopolamine-treated mice (P<0.05). In addition, the reduced latency induced by MK-801 treatment in the passive avoidance task was ameliorated by EEPV (25 mg/kg, p.o.) (P<0.05). Additionally, the ameliorating effect of EEPV on scopolamine-induced memory dysfunction was antagonized by a sub-effective dose of MK-801. These results suggest that EEPV would be useful for treating cognitive impairments induced by cholinergic dysfunction, and that it exerts its effects via NMDA receptor signaling.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2010; 48(6):1671-6. DOI:10.1016/j.fct.2010.03.042 · 2.61 Impact Factor
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    ABSTRACT: It is well known that inhibition of prolyl oligopeptidase (POP) is involved in memory-related function. In this study, we observed that rosmarinic acid (RA) inhibits POP activity with an IC(50) of 63.7 microM. Subsequently, we investigated the cognitive-enhancing effects of RA employing the Morris water maze paradigm. The results demonstrated that RA is non-competitive POP inhibitor and that acute and subchronic RA treatments showed an inverted U-shaped dose-response curve in the platform crossings. Furthermore, chronic RA treatment significantly increased the platform crossings. These results suggest that RA has a cognitive-enhancing effect which may be mediated by inhibition of POP.
    Fitoterapia 03/2010; 81(6):644-8. DOI:10.1016/j.fitote.2010.03.010 · 2.22 Impact Factor
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    ABSTRACT: Multiwalled carbon nanotube (MWCNT)-filled polycarbonate composites were prepared by a corotating intermeshing twin-screw extruder. The surface resistivities of compression- and injection-molded specimens were quite different, the difference ranging from 103 to 107 Ω/sq at varying MWCNT concentrations. The surface resistivity of the injection-molded specimen at 2 wt % loading varied up to 105 Ω/sq in the specimen thickness direction and up 104 Ω/sq in the polymer flow direction with respect to the gate. The difference in surface resistivity with the positions of injection-molded specimen was confirmed with the morphology, which showed the difference in MWCNT number density (numbers/surface area). There was no significant effect on surface resistivity with injection pressure, holding pressure, and molding temperature. The specimens prepared at the injection speed of 13 mm/s showed surface resistivities 103–104 Ω/sq depending on the positions, which was comparable with the compression-molded specimens, which had a surface resistivity of 103 Ω/sq. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
    Journal of Applied Polymer Science 07/2009; 113(1):450-455. DOI:10.1002/app.29989 · 1.64 Impact Factor
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    ABSTRACT: During the operation, surgeons in neurosurgical area usually performed the multiple temporary occlusions of parental artery which may induce the neuronal damage. It is generally thought that neuronal damage by cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. In this experiment, we measured the dynamics of extracellular glutamate release in 11 vessel occlusion (VO) model during repeated within short interval. Changes in cerebral blood flow were monitored by laser-Doppler flowmetry simultaneously with cortical glutamate level measured by amperometric biosensor. During ischemia, the peak level of glutamate release was gradually decreased as 112.38±26.21 μM in first period, 82.63±18.50 μM in second period, and 48.58±11.89 μM in third period. The time interval between the ischemia induction and the beginning of glutamate release was increased as 106.7 ± 10.89 (sec) at first attack, 139.11 ± 3.87 (sec) in second attack, 169.00 ± 14.56 (sec) in third ischemic period. From the results of real-time monitoring about glutamate release in 11-VO model during repetitive ischemic episode, it was demonstrated that repetitive ischemia induced less glutamate release from neuronal cell than single ischemia due to endogeneous protective mechanism which delayed glutamate release time in later ischemic injury.
    ASME 2009 Summer Bioengineering Conference; 06/2009
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    ABSTRACT: The aim of this study was to determine the mechanism underlying the neuroprotective effects of the ethanolic extract of the seeds of Cassia obtusifolia (COE) (10 or 50mg/kg/day, p.o) on transient cerebral global ischemia induced by bilateral common carotid artery occlusion (2VO) in mice. Immunohistochemical and western blot studies showed that levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hippocampal CA1 region at 1day post-2VO were attenuated by COE (50mg/kg/day, p.o), which was administered immediately after 2VO. Furthermore, OX-42 - and glial fibrillary acidic protein (GFAP)-positive cell numbers at 4 days post-2VO were markedly attenuated by COE (50mg/kg/day, p.o) treatment for 4 days in CA1. Viable neurons detected by Nissl at 7 days post-2VO were increased by administering COE (50mg/kg/day, p.o) for 7 days. In addition, COE increased the expressions of phosphorylated cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in CA1 in naïve-control within 1 and 6h, respectively, and these expressions were also profoundly increased in 2VO-treated mice by COE at immediately post-2VO. These results suggest that the neuroprotective effects of COE are due to its anti-inflammatory effects and to its upregulation of BDNF expression and CREB phosphorylation.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2009; 47(7):1473-9. DOI:10.1016/j.fct.2009.03.028 · 2.61 Impact Factor
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    ABSTRACT: A novel SLM (spatial light modulator), named SOM (spatial optical modulator) has been developed. SOM is one dimensional mirror array device, so the pixel number and the dimension of the mirror array could be easily designed for application specific. Full-HD rear projection displays with 1080-pixel SOM devices and VGA resolution embedded mobile projection displays with 480-pixel SOM devices have been developed. SOM device packaging was designed, characterized and fabricated for high resolution and high quality displays. Fine-pitch interconnections as well as submount fabrication, hermetic sealing, PCB bonding, wire bonding and bond wire passivation processes were designed and accomplished. The dimension of the packaged SOM chip modules were 27.4times68.3times4.6 mm<sup>3</sup> and 13.4times12.0times3.1 mm<sup>3</sup> for RPTV(rear projection tele-vision) and pico-projection modules, respectively. The mechanical, electrical, thermal and optical characteristics like as bending, thermal distribution and its uniformity, electrical noise characteristics were controlled.
    Electronic Components and Technology Conference, 2008. ECTC 2008. 58th; 06/2008
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    ABSTRACT: We develop a new method with a global optimization for registering films to calculate doses for intensity-modulated radiation therapy (IMRT) and intensity-modulated radiosurgery (IMRS) quality assurance (QA). Both absolute point dosimetry and two-dimensional (2D) film dosimetry are performed through the IMRT and IMRS using Clinac 21EX's 120 millenium MLC and BrainLab's micro-MLC, respectively. The measured and calculated dose distributions are superimposed by coincidence of their origins, followed by comparison of the point doses at all matched positions. Then, with the optimization algorithm the setup error of the dosimeter is corrected. An example of IMRT cases shows that the average percentage showing 3% of dose difference for 10 patients has been reduced from 19% to 9%, before and after optimization and weight, respectively. Similar results are obtained for IMRS. This method dramatically reduces the difference between measured and calculated dose distributions in all cases investigated.
    Physica Medica 07/2007; 23(2):49-57. DOI:10.1016/j.ejmp.2007.03.001 · 1.85 Impact Factor
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    ABSTRACT: Intensity-modulated radiation therapy (IMRT) is one of the most complex applications of radiotherapy that requires patient-specific quality assurance (QA). Here, we describe a novel method of 3-dimensional (3D) dose-verification using 12 acrylic slabs in a 3D phantom (30 x 30 x 12 cm(3)) with extended dose rate (EDR2) films, which is both faster than conventionally used methods, and clinically useful. With custom-written software modules written in Microsoft Excel Visual Basic Application, the measured and planned dose distributions for the axial, coronal, and sagittal planes were superimposed by matching their origins, and the point doses were compared at all matched positions. Then, an optimization algorithm was used to correct the detected setup errors. The results show that this optimization method significantly reduces the average maximum dose difference by 7.73% and the number of points showing dose differences of more than 5% by 8.82% relative to the dose differences without an optimization. Our results indicate that the dose difference was significantly decreased with optimization and this optimization method is statistically reliable and effective. The results of 3D optimization are discussed in terms of various patient-specific QA data obtained from statistical analyses.
    Medical Dosimetry 02/2007; 32(4):316-24. DOI:10.1016/j.meddos.2007.08.001 · 0.95 Impact Factor
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    ABSTRACT: In order to get insight into the mechanism of cadmium (Cd)-induced brain injury, we investigated the effects of Cd on the induction of COX-2 and ICAM-1 in bEnd.3 mouse brain endothelial cells (EC). Cd stimulated PGE(2) release in a time and dose dependent manner, which was accompanied by increase of COX-2 expression. The thiol-reducing antioxidant N-acetylcyteine attenuated Cd-induced PGE(2) production and COX-2 expression. Cd increased phosphorylation of p38 MAPK, but not of JNK and ERK1/2. A blockade of p38 MAPK pathway abrogated Cd-induced COX-2 expression and PGE(2) production. Cd-induced ICAM-1 expression and leukocyte-EC adhesion were diminished by non-steroidal anti-inflammatory drugs such as indomethacin and NS-398, which was reversed by addition of PGE(2). Together, these data suggest that Cd induces COX-2 expression through the activation of p38 MAPK, an oxidative stress-sensitive cellular signaling molecule, and induction of COX-2 is associated with ICAM-1 expression in brain endothelial cells following Cd exposure.
    Toxicology Letters 10/2006; 165(3):212-20. DOI:10.1016/j.toxlet.2006.04.007 · 3.36 Impact Factor
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    ABSTRACT: To accurately verify the dose of intensity-modulated radiation therapy (IMRT), we have used a global optimization method to investigate a new dose-verification algorithm. In practical application of this quality assurance (QA) procedure, verification of the dose using calculated and measured dose distributions involves a subtle problem in the region of high dose gradient. Consideration of systematic errors shows that the large dose differences in high-dose-gradient regions are due to the unexpected shift of measuring devices. We have proposed an optimization algorithm to correct this error, and an optimization method to minimize the average dose difference has been used in this study. The relationship between the dose-verification procedure and the applied optimization algorithm is explained precisely. Optimization dramatically reduced the difference between measured and calculated dose distributions in all cases investigated. The obtained results support the relevance of our explanations for the problem in the high-dose-gradient region. We have described this dose-verification procedure for IMRT and intensity-modulated radiosurgery. Through this study we have also developed an intuitive reporting method that is statistically reasonable.
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    Yoonbai Kim, Dong Hyun Park
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    ABSTRACT: We consider a complex scalar field in (p+3)-dimensional bulk with a negative cosmological constant and study global vortices in two extra-dimensions. We reexamine carefully the coupled scalar and Einstein equations, and show that the boundary value of scalar amplitude at infinity of the extra-dimensions should be smaller than vacuum expectation value. The brane world has a cigar-like geometry with an exponentially decaying warp factor and a flat thick p-brane is embedded. Since a coordinate transformation identifies the obtained brane world as a black p-brane world bounded by a horizon, this strange boundary condition of the scalar amplitude is understood as existence of a short scalar hair. Comment: 26 pages, 2 figures
    Journal of High Energy Physics 01/2004; 2004(06). DOI:10.1088/1126-6708/2004/06/052 · 6.22 Impact Factor
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    ABSTRACT: We construct dynamically a black p-brane world of an exponentially decaying warped factor in arbitrary but larger than one extra-dimensions. Our fine tuned brane world is identified by the interior of an extremal charged black hole.

Publication Stats

122 Citations
39.54 Total Impact Points

Institutions

  • 2009–2014
    • Kyung Hee University
      • Department of Life and Nanopharmaceutical Science
      Sŏul, Seoul, South Korea
    • Kumoh National Institute of Technology
      Sŏul, Seoul, South Korea
  • 2007
    • National Cancer Center Korea
      • Specific Organs Cancer Branch
      Kōyō, Gyeonggi-do, South Korea
  • 2006
    • Ajou University
      • Department of Medicine
      Seoul, Seoul, South Korea