• Clinical and Experimental Pediatrics
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• v.54 no.1
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• pp.11-16
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• 2011

Purpose: Enterovirus 71, one of the enteroviruses that are responsible for both hand-foot-and-mouth disease and herpangina, can cause neural injury. During periods of endemic spread of hand-foot-andmouth disease caused by enterovirus 71, CNS infections are also frequently diagnosed and may lead to increased complications from neural injury, as well as death. We present the results of our epidemiologic research on the clinical manifestations of children with CNS infections caused by enterovirus 71. Methods: The study group consisted of 42 patients admitted for CNS infection by enterovirus 71 between April 2009 and October 2009 at the Department of Pediatrics of 5 major hospitals affiliated with the Catholic University of Korea. We retrospectively reviewed initial symptoms and laboratory findings on admission, the specimen from which enterovirus 71 was isolated, fever duration, admission period, treatment and progress, and complications. We compared aseptic meningitis patients with encephalitis patients. Results: Of the 42 patients (23 men, 19 women), hand-foot-and-mouth disease was most prevalent (n=39), followed by herpangina (n=3), upon initial clinical diagnosis. Among the 42 patients, 15 (35.7%) were classified as severe, while 27 (64.3%) were classified as mild. Factors such as age, fever duration, presence of seizure, and use of intravenous immunoglobulin (IVIG) were statistically different between the 2 groups. Conclusion: Our results indicate that patients with severe infection caused by enterovirus 71 tended to be less than 3 years old, presented with at least 3 days of fever as well as seizure activity, and received IVIG treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.135-141
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• 2014

The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

• Journal of Oriental Neuropsychiatry
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• v.12 no.1
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• pp.137-149
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• 2001

Cytokines are polypeptides which possess various biological properties affecting. host defense function and response to disease. Inflammatory cytokines, tumor necrosis $factor-{\alpha}$(TNF-${\alpha}$), interleukin(IL)-1 and IL-6 induce inflammation, fever, hypotension and pain when injected into animals or human subject. When glial cell cultures were prepared from neonatal mice or rats, astrocytes were reported to produce these inflammatory cytokines to viral infection, lipopolysaccharide(LPS), or cytokines. The purpose of this study was to investigate the regulatory effect of these cytokines secretion from primary cultures of rat astrocytes. Substance P(SP) can stimulate secretion of TNF-${\alpha}$ from astrocytes stimulated with LPS. Sesim-Tang significantly inhibited the TNF-${\alpha}$ secretion by astrocytes stimulated with SP and LPS. IL-1 has been shown to elevate TNF-${\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-${\alpha}$ secretion from primary astrocytes by Sesim-Tang. Treatment of Sesim-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of TNF-${\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Furthermore Sesim-Tang inhibited the IL-6 secretion by astrocytes stimulated with SP and LPS. The inhibitory effect of inflammatory cytokines by Sesim-Tang, observed in this study, might reflect an antiinflammatory activity and a reduction of various-type pains, fever etc. in the central nervous system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.628-634
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• 2011

The roots of Polygala tenuifolia Willd. is a well-known traditional medicine used as expectorant, tonic, tranquilizer in Asia including China and Korea. And also have been used to treat amnesia, neurasthenia, palpitation, insomnia, and disorientation. 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. NNMBS269, acid hydrolysis EtOAc fraction of the P. tenuifolia showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells while general EtOAc fraction of the P. tenuifolia (NNMBS268) not shown. NNMBS269 induced the expression of HO-1 protein that has been proposed to play an important cellular defense role against oxidant injury. In addition increased HO activity. In mouse hippocampal HT22 cells, NNMBS269 makes the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2). In conclusion, acid hydrolysis EtOAc fraction the P. enuifolia. (NNMBS269) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 translocation in mouse hippocampal HT22 cells.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• The Journal of Korean Physical Therapy
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• v.16 no.4
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• pp.23-37
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• 2004

Fibromyalgia syndrome(FMS) is a chronic pain disorder of unknown etiology characterized by widespread musculoskeletal aches and pains, stiffness, and general fatigue, disturbed sleep and sleepiness. Frequently misdiagnosed, FMS is often confused with myofascial pain syndrome, polymyalgia rheumatica, polymyositis, hypothyroidism, metastatic carcinoma, rheumatoid arthritis (RA), juvenile rheumatoid arthritis, chronic fatigue syndrome, or systemic lupus erythematosus, any of which may occur concomitantly with FMS. The management of FMS often begins with a thorough examination and a diagnosis from a physician who is formally trained in tender-point/trigger-point recognition. An initial diagnosis provides reassurance to the patient and often reduces the anxiety and depression patterns associated with FMS. The most common goals in the management of FMS are (1) to break the pain cycle, (2) to restore sleep patterns, and (3) to increase functional activity levels. Because FMS is a multifactorial syndrome, it is likely that the best treatment will encompass multiple strategies. Medication with analgesics and antidepressants and also physiotherapy, are often prescribed and give some relief. The other most effective intervention for long-term management of FS to date is physical exercise. Physical therapists can instruct patients in the use of heat at home (moist hot packs, heating pads, whirlpools, warm showers or baths, and hot pads) to increase local blood flow and to decrease muscle spasm and tension. Also instruct patients in the proper use of cold modalities (ice packs, ice massage, and cool baths) to anesthetize localized areas of pain (tender points) and break the pain cycle. Massage and tender-point massage also may promote muscle relaxation. To date, the two most important interventions for the long-term management of FS are patient education and physical exercise. Lately, is handling FMS and Chronic Fatigue syndrome(CFS) together, becuase FMS and CFS are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction.

• Journal of Oral Medicine and Pain
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• v.32 no.2
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• pp.201-210
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• 2007

Many diseases occur by stress or effect of stress. The basis for using hormones in research of stress is the observation that most systems in the body show changes during stress and that hormonal markers in these changes are related with stress. Conceptually, the central role of sympathetic nervous system(SNS) and hypothalamus-pituitary-adrenal(HPA) axis activity in stress provides copious justification for measuring hormonal changes. Catecholamines like epinephrine and norepinephrine, cortisol, testosterone and growth hormone and so on show sensitive reaction to stress. The major advantage of salivary sample to stress research is that its sampling technique can be performed in non-stressful conditions and without physical restraint and ethical problems. Because hormone levels in saliva is a good reflection of hormone levels in plasma, application of stress hormones in saliva is very useful for research of orofacial pain related with stress.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.440-448
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• 1996

Bronchial carcinoid tumors are uncommon, constituting approximately 3-5% of all primary lung cancers. Classification of these tumors has evolved substantially as our understanding of the cellular, biologic, and clinical aspects of these neoplasms has improved. Initially, bronchial carcinoids were thought to be benign and therefore were classified as bronchial adenomas. Currently, however, they are well recognized as having the potential for both local invasion and distant metastatic involvement. Consequently, carcinoid tumors are frankly malignant. Thus bronchial adenoma is a misnomer that should no longer be used for bronchial carcinoids. Most investigators currently favor classifying carcinoid tumors as a type of neuroendocrine neoplasm because of their potential to secrete a variety of chemical substances found in both the central nervous system and the epithelial cells of numerous organs. Bronchial carcinoids are usually characterized by a slow growth pattern and a low incidence of metastasis, and histologically conformed by the azurophil staining and the presence of the characteristic neurosecretary granule on electron microscopy. Atypical carcinoid tumor was first defined by Arrigoni et al, who proposed the following criteria for separation of atypical carcinoid from typical carcinoid tumor : 1) increased mitotic activity with 1 mitotic figure per 1-2 high power fields(or 5-10 mitoses /10 HPF), 2) nuclear pleomorphism, hyperchromatism, and an abnormal nuclear-cytoplasmic ratio, 3) areas of increased cellularity with disorganization of the architecture, and 4) tumor necrosis. In contrast, typical carcinoid tumor may have focal cytologic pleomorphism, but necrosis is absent and mitotic figures are rare. Recently we experienced a case of atypical bronchial carcinoid with multiple distant metastasis, so we report this case with a review of the literature.

• BMB Reports
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• v.37 no.4
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• pp.480-486
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• 2004

Brain ischemia brings about hypoxic insults. Hypoxia is one of the major pathological factors inducing neuronal injury and central nervous system infection. We studied the involvement of mitogen-activated protein (MAP) kinase in hypoxia-induced apoptosis using cobalt chloride in C6 glioma cells. In vitro cytotoxicity of cobalt chloride was tested by MTT assay. Its $IC_{50}$ value was $400\;{\mu}M$. The DNA fragment became evident after incubation of the cells with $300\;{\mu}M$ cobalt chloride for 24 h. We also evidenced nuclear cleavage with morphological changes of the cells undergoing apoptosis with electron microscopy. Next, we examined the signal pathway of cobalt chloride-induced apoptosis in C6 cells. The activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) started to increase at 1 h and was activated further at 6 h after treatment of 400 M cobalt chloride. In addition, pretreatment of PD98059 inhibited cobalt chloride-induced apoptotic cell morphology in Electron Microscopy. These results suggest that cobalt chloride is able to induce the apoptotic activity in C6 glioma cells, and its apoptotic mechanism may be associated with signal transduction via MAP kinase (ERK 1/2).

• International Journal of Oral Biology
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• v.30 no.3
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• pp.91-98
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• 2005

Gamma-aminobutyric acid (GABA) is known as an inhibitory neurotransmitter in the neurons of the central nervous system. However, its detailed action mechanisms in the rostral gustatory zone of the nucleus tractus solitarius (rNTS) have not been established. The present study was aimed to investigate the distribution, role and action mechanisms of GABA in rNTS. Membrane potentials were recorded by whole cell recordings in isolated brain slices of the rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in the neurons in rNTS. The change in input resistance ws accompanied by response to a depolarizing pulse were diminished by GABA. Superfusion of the slices with either $GABA_A$ agonist, muscimol, $GABA_B$ agonist, baclofen or $GABA_C$ agonist, TACA, decreased input resistance and reduced the nerve activity in association with membrane hyperpolarization. It is suggested that inhibitory signals playa role in sensory processing by the rNTS, in that GABA actions occur through activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptor. These results suggest that GABA has an inhibitory effect on the rNTS through an activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptors and that the GABAergic inhibition probably plays an important role in sensory processing by the rNTS.