• Title/Summary/Keyword: CNS effects

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NSA9, a human prothrombin kringle-2-derived peptide, acts as an inhibitor of kringle-2-induced activation in EOC2 microglia

  • Kim, Ji-Yeon;Kim, Tae-Hyong;Kim, Soung-Soo
    • BMB Reports
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    • v.42 no.6
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    • pp.380-386
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    • 2009
  • In neurodegenerative diseases, such as Alzheimer' and Parkinson', microglial cell activation is thought to contribute to CNS injury by producing neurotoxic compounds. Prothrombin and kringle-2 increase levels of NO and the mRNA expression of iNOS, IL-1$\beta$, and TNF-$\alpha$ in microglial cells. In contrast, the human prothrombin kringle-2 derived peptide NSA9 inhibits NO release and the production of pro-inflammatory cytokines such as IL-1$\beta$, TNF-$\alpha$, and IL-6 in LPS-activated EOC2 microglia. In this study, we investigated the anti-inflammatory effects of NSA9 in human prothrombin- and kringle-2-stimulated EOC2 microglia. Treatment with 20-100 ${\mu}M$ of NSA9 attenuated both prothrombin- and kringle-2-induced microglial activation. NO production induced by MAPKs and NF-$\kappa$B was similarly reduced by inhibitors of ERK (PD98059), p38 (SB203580), NF-$\kappa$B (N-acetylcysteine), and NSA9. These results suggest that NSA9 acts independently as an inhibitor of microglial activation and that its effects in EOC2 microglia are not influenced by the presence of kringle-2.

Neuroprotective Effects of the Extract of Zingiberis Rhizoma (건강 추출물의 뇌세포 보호 작용)

  • Jeong, Gil-Saeng;Li, Bin;Lee, Dong-Sung;Choi, Hyun-Gyu;Kim, Youn-Chul
    • Korean Journal of Pharmacognosy
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    • v.41 no.3
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    • pp.190-195
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    • 2010
  • Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS098, a composition comprising the water insoluble of the 70% EtOH extract of Zingiberis Rhizoma, showed the potent neuroprotective effects on glutamateinduced neurotoxicity by induced the expression of heme oxygenase (HO)-1 and increased HO activity in the mouse hippocampal HT22 cells. Furthermore, NNMBS098 caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in mouse hippocampal HT22 cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced NNMBS098-induced HO-1 expression and NNMBS098 also increased JNK phosphorylation. Therefore, these results suggest that NNMBS098 increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.

Inhibitory Effect of Ginsenosides on NMDA Receptor-mediated Signals in Rat Hippocampal Neurons

  • Kim Sunoh;Choo Min-Kyung;Nah Seung-Yeol;Kim Dong-Hyun;Rhim Hyewhon
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.531-544
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    • 2002
  • Ginseng is the best known and most popular herbal medicine used worldwide. Ameliorating effects of ginseng were observed on the models of scopolamine-induced, aged or hippocampal lesioned learning and memory deficits. Further beneficial effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. In spite of these beneficial effects of ginseng on the CNS, little scientific evidence shows at the cellular level. In the present study, we have employed cultures of rat hippocampal neurons and examined the direct modulation of ginseng on NMDA receptor-induced changes in $[Ca^{2+}]_i$ and -gated currents using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques, respectively. We found that ginseng total saponins inhibited NMDA-induced but less effectively glutamate-induced increase in $[Ca^{2+}]_i$ Ginseng total saponins also modulated $Ca^{2+}$ transients evoked by depolarization with 50 mM KCI along with its own effects on $[Ca^{2+}]_i$. Among ginsenosides tested, ginsenoside $Rg_3$ was found to be the most potent component for ginseng actions on NMDA receptors. Furthermore, we examined the inhibitory effects ofbiotransformants of ginsenosides on NMDA receptor using purified stereoisomers of ginsenosides. 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_3$, produced the strongest inhibition while 20(S)-ginsenoside $Rh_1$ and Compound K produced the moderate inhibition on NMDA-induced increase in $[Ca^{2+}]_i$. The data obtained suggest that the inhibition of NMDA receptors by ginseng, in particular by 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_2$, could be one of mechanisms for ginsengmediated neuroprotective actions.

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Asymmetric GARCH model via Yeo-Johnson transformation (Yeo-Johnson 변환을 통한 비대칭 GARCH 모형)

  • Hwan Sik Jung;Sinsup Cho;In-Kwon Yeo
    • The Korean Journal of Applied Statistics
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    • v.37 no.1
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    • pp.39-48
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    • 2024
  • In this paper, we introduce an extended GARCH model designed to address asymmetric leverage effects. The variance in the standard GARCH model is composed of past conditional variances and past squared residuals. However, it is not possible to model asymmetric leverage effects with squared residuals alone, so in this paper, we propose a new extended GARCH model to explain the leverage effects using the Yeo-Johnson transformation which adjusts transformation parameter to make asymmetric data more normal or symmetric. We utilize the reverse properties of Yeo-Johnson transformation to model asymmetric volatility. We investigate the characteristics of the proposed model and parameter estimation. We also explore how to derive forecasts and forecast intervals in the proposed model. We compare it with standard GARCH and other extended GARCH models that model asymmetric leverage effects through empirical data analysis.

Neural Substrates and Functional Hypothesis of Acupuncture Mechanisms - Neural substrates and humoral-, neural-, and immune-responses related to acupuncture stimulation- (침의 치료기전에 대한 신경기반 및 신경기능 가설 -침자극과 관계된 신경기반 및 체액성 반응, 신경적 반응, 면역반응-)

  • Cho, Z.H;Hwang, S.C;Wong, E.K.;Son, Y.D;Kang, C.K;Park, T.S;Bai, S.J;Sung, K.K
    • Journal of Acupuncture Research
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    • v.20 no.5
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    • pp.172-186
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    • 2003
  • Acupuncture therapy has demonstrated efficacy in several clinical areas, and of these areas the understanding of pain has progressed immensely in the last two decades. The underlying mechanisms of acupuncture in general and the analgesic effect in particular are still not clearly delineated. The leading hypothesis include the effects of local stimulation, neuronal gating, release of endogenous opiates, and the placebo effect. Accumulating evidence suggests that the central nervous system(CNS) is essential for the processing of these effects, via its modulation of the autonomic nervous system, neuro-immune system, and hormonal regulation. These processes tap into basic survival mechanisms. As such, understanding the effects of acupuncture within a neuroscience-based framework becomes vital. We propose a model which incorporates the stress-induced hypothalamus-pituitary-adrenal axis(HPA-axis) model of Akil et al., the cholinergic anti-inflamatory observations of Tracey et al., and Petrovic et al.

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Natriuresis Induced by Intracerebroventricular Diazepam in Rabbits

  • Koh, Jeong-Tae;Kook, Young-Johng
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.5
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    • pp.555-563
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    • 1998
  • The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 ${\mu}g/kg,$ elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 ${\mu}g/kg$ diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 ${\mu}g/kg$ icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 ${\mu}g/kg$ given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 ${\mu}g/kg$ muscimol was given 3 min prior to 30 ${\mu}g/kg$ of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.

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Antioxidant and Hepatoprotective Effects of Hydroponic-cultured Ginseng Folium by fermentation (발효에 의한 수경재배 인삼 잎의 항산화 및 간 보호 효과)

  • Lee, Ah Reum;Park, Jae Ho
    • The Korea Journal of Herbology
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    • v.30 no.4
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    • pp.101-108
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    • 2015
  • Objectives : Positive effects of Ginseng has great research attentions such as anticancer, anti-diabetic, antiaging, liver, immune function, CNS, etc. In this study, we investigated Hydroponic-cultured Ginseng Folium fermented byBacillus subtilisto establish fermentation conditions for enhancing functionality.Methods : Ginseng Folium were cultivated hydroponic-cultured and were extracted with methanol. We inoculateBacillus subtilisfor fermentation by adding to 0%, 3% and 5% sugar respectively and checked antioxidant activities, total phenolic content and total saponin content in 2 days intervals during 11 days. The antioxidant activities were studied by the 1,1-diphenyl-2-picryl hydrazyl(DPPH) radical, 2, 2'-Azino-bis(3-ethylbenzothiazoline-6 sulfonic acid) diammonium salt(ABTS) radical scavenging assay and Reducing power assay. We analyzed the Total phenol content, crude saponin content and ginsenoside content. Moreever, Hepatoprotective effects by Glutamic oxaloacetic transaminase(GOT) and Glutamic pyruvic transaminase(GPT) in Sprague-Dawley rat.Results : The results of DPPH and ABTS were 66.89% and 96.72%, respectively. The reducing power was resulted in optical density of 0.7312 with 3% sugar after 9 days of fermentation. and the concentration at 200 ㎍/㎖. Total phenol content was 36.92㎎/g with 3% sugar after 9 days of fermentation, in which crude saponin content wasn't changed, and ginsenoside content such as Rg3, Re and Rb was increased. Activities of GOT and GPT concentration were decreased in rat.Conclusions : This study suggests that hydroponic-cultured Ginseng Folium fermented byBacillus subtilisin 9 days showed significant efficacy of hepato-protection as well as antioxidant compared to the others. In addition, it shows not only improved value but also utilized hydroponic-cultured Ginseng Folium by fermentation.

Estimation of Pull-out force by using modified Direct Shear Apparatus (개설된 직접전단시험기(CNS)를 이용한 보강재의 인발력 추정)

  • 유병선;이학무;장기태;한희수
    • Proceedings of the Korean Geotechical Society Conference
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    • 2003.06a
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    • pp.145-154
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    • 2003
  • When a nail pulled out in dense, granular soil, the soil in the vicinity of the nail tends to dilate, but its dilatancy results in a normal stress concentration at the soil/nail interface, thereby increasing the pull-out resistance of the inclusion. It is thought to be occurring within the resistance zone where the soil mass is at stationary state and the reinforcement are held in position by the soil, due to the friction or bond. In this paper, A series of direct shear and interface tests were conducted by using so called‘Constant Normal Stiffness Test Apparatus’which was modified and improved from the conventional direct shear box test rig. Unlikely the normal shear box test, this enables to simulate the different constraint effects of surrounding soil during shear under the conditions of constant stress and volume, constant normal stiffness. The aim of the research programme is to get better understanding of pull-out bond mechanism, thus to explore the possibility of evaluating the pull-out bond capacity of soil/reinforcement at the preliminary design stage from the laboratory test.

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Clinical Features of the TMD Patients with Degenerative Joint Disease (퇴행성 악관절장애환자의 임상양태에 관한 연구)

  • Myung-Yun Ko
    • Journal of Oral Medicine and Pain
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    • v.20 no.2
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    • pp.257-267
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    • 1995
  • An Epidemiologic study was carried out on 77 TMD patients with degenerative joint disease who had visited the Orofacial Pain Clinic in Pusan National University Hospital. Al subjects were interviewed and examined clinically and radiologically using a standardized examination form. As related to gender and duration, subjective and objective sysmptoms in DJD patients were studied. The obtained results were as follows : 1. There were much more patients in the twenties or thirties, women and histories such as chronic duration and microtrauma. 2. Most patients responded positively more often to the questions of jaw function, unilateral chewing in habits, poot appetite and depression in behavioral response and shoulder pain in worsening prognosis 3. While the most common reasons for treatment were pain, noise, and limitation of opening, the associated symptoms such as headache, neckache, earache, jaw dysfunction, neck dysfunction, acute bite change and dizziness, ringing or fullness in the ears as secondary CNS excitatory effects were complained. 4. Opening the mouth in 25 to 40mm, soft end feel and deflective incisal pathway were seen and more tenderness to lateral or dorsal capsule of joint than intra or extra oral muscles were complained. 5. While there appeared no click, crepitus and single click in acute group, in chronic group, crepitus, single click and no click appeared in order of sequence. 6. Tomogram or bone scan revealed more bony changes than panorama and transcranial view.

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Memory-improving Effects of Fermented Sea Tangle Saccharina japonica in Normal Mice (정상 동물모델에서 다시마(Saccharina japonica) 발효물의 기억력 개선 효과)

  • Ryu, Jehkwang;Jo, Young-Hong;Chang, Seong-Jun;Lee, Bae-Jin
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.49 no.2
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    • pp.131-136
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    • 2016
  • Marine organisms are sources of many bioactive compounds, such as essential fatty acids, essential amino acids, vitamins, and minerals, making them useful candidates for the production of safe bioactive substances. They also synthesize glutamic acid, which can be used to produce γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system (CNS), via fermentation with Lactobacillus brevis BJ-20. This study investigated the degree to which fermented sea tangle (FST) inhibits enzymes such as acetylcholine esterase (AChE) and prolyl endopeptidase (PEP) and affects memory of normal mice using the T-maze test. FST inhibited more than 90% of AChE at 1 mg/mL and 50% of PEP at 8 mg/mL. Oral FST (100 mg/kg) significantly improved performance of normal mice on the T-maze. Therefore, sea tangle fermented with L. brevis BJ20 effectively contributes to memory improvement and might be a useful functional food ingredient.