The Effect of Topiramate on Hippocampal Neuronal Death and Expression of Glutamate Receptor in Kainate-induced Status Epilepticus Model

박민정,하세운,배혜란,김상호,Park Min-Jeong,Ha Se-Un,Bae Hae-Rahn,Kim Sang-Ho Korean Society of Life Science 2005 생명과학회지 Vol.15 No.3

신경흥분독성과 간질발작발현은 glutamate 수용체활성과 연관이 있다고 알려져 있다. a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), kainate 수용체에 대한 glutamate 활성을 포함하는 다양한 기전을 가진 항전간제인 Topiramate는 신경보호작용을 가진다는 증거가 제시되어 Topiramate가 간질발작 후 해마의 glutamate 수용체 발현에 미치는 효과를 관찰하였다. 흰쥐에 kainate를 복강 내 주사하여 간질중첩증을 유발시킨 후 Topiramate를 1주일 주사하였다 Apop tag in situ detection kit를 이용하여 세포손상을 관찰한 결과 kainate 유발 간질중첩증 1주일 후 해마의 CA1, CA3에서 심각한 세포사를 보였으나, Topiramte 처리 군에서는 세포사가 현저히 감소하였다. 간질중첩증 이후 NMDA 수용체 아형 1,2a, 2b 발현이 현저히 증가했으나 Topiramate 처치에 의해 NMDA수용체의 발현에는 뚜렷한 변화가 없었다. AMPA수용체에서는 GluR1이 간질중첩증 이후 현저히 상향 조정되었고 GluR2는 현저히 하향조정 되었다 Topiramate 1주일 처리 시 간질중첩증으로 인해 변화된 CluR1과 GluR2의 발현이 역전되었다. 결론적으로 Topiramate는 간질중침증에 의한 CluR1/CluR2 발현비의 증가로 유발되는 흥분성 신경세포사를 억제시킴으로써 신경보호작용이 있는 것으로 보인다. Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

S-477 : Solitary Abdominal Tuberculous Lymphadenopathy Misdiagnosed as the Recurrence of Ovarian Cancer

( Un Seok Lee ),( Won Sup Lee ),( Gyeong Won Lee ),( Jung Hun Kang ),( Myung Hee Kang ),( Se Il Go ),( Anna Lee ),( Hoon-gu Kim ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Monitoring cancer antigen 125 (CA-125) serum levels is very useful for determining how epithelial ovarian cancer is responding to treatment and for predicting a patient`s prognosis after treatment. An increase in CA-125 levels within patients in a remission is a strong predictor of the recurrence of ovarian cancer. However, while CA-125 is best known as a tumor marker for ovarian cancer, it may also be elevated in other various malignancies and in some benign conditions such as peritonitis, pancreatitis, chronic liver diseases, pelvic inflammatory diseases, or endometriosis. We describe herein a case of solitary intra-abdominal tuberculous lymphadenopathy mimicking a local relapse of epithelial ovarian cancer. A 51-year-old woman presented with progressive rise in serum CA-125. She had been diagnosed with advanced epithelial ovarian malignancy and undergone debulking surgery about 4 years ago. She had been given platinum-based adjuvant chemotherapy and achieved complete remission (CR). During regular follow-up in CR, a progressive rise in serum CA-125 was detected. The abdominal computed tomography (CT) showed a cystic mass, 3.6 cm in diameter, located adjacent to the right common iliac artery, suggesting a metastatic lymph node. We had planned second-look operation in settings of suspected focal recurrence of ovarian cancer, supported by evidence of rising CA-125 levels. However, the suspected tuberculous lesion was detected incidentally on preoperative chest CT. The patient had no symptoms and signs associated with tuberculosis (TB) and chest X-ray was also normal. We postponed the planned second-look operation and anti-TB medication was started. Mycobacterium TB was identified on culture of sputum specimens later. During anti-TB medication, the suspected metastatic isolated intra-abdominal lymphadenopathy improved and serum CA-125 level was also normalized. We emphasize here to consider not only the recurrence or progression of ovarian cancer itself but also benign conditions including TB in their differential diagnoses, when serum CA-125 level increases during the follow-up of epithelial ovarian cancer patients.

Effects of Fermented Cottonseed and Soybean Meal with Phytase Supplementation on Gossypol Degradation, Phosphorus Availability, and Growth Performance of Olive Flounder : Paralichthys olivaceus

Se Jin Lim,Sung Sam Kim,Minh Anh Pham,Jin Woo Song,Ji Hoon Cha,Jin Dong Kim,Jung Un Kim,Kyeong Jun Lee 한국수산과학회 2010 Fisheries and Aquatic Sciences Vol.13 No.4

To reduce anti-nutritional factors in plant protein sources for fish meal replacement in fish feeds, cottonseed and soybean meal (CS) were fermented with Aspergillus oryzae. A feeding trial was conducted to verify the effects of fermented CS (FCS) with phytase supplementation on gossypol detoxification, phosphorus digestibility, antioxidant activity, and growth performance of juvenile olive flounder over 10 weeks. Four diets were formulated to replace 0, 30, or 40% fish meal protein with CS or FCS (designated as CS0, CS30, FCS30P, and FCS40P). Phytase (1,000 FTU/kg) was added to FCS30P and FCS40P. The microbial fermentation significantly increased dietary total polyphenols and consequently led to higher DPPH radical-scavenging activities in fish feed and fish tissue. Dietary and liver gossypol concentrations were dramatically decreased by the fermentation process. Phosphorus digestibility was significantly increased in fish fed the FCS40P diet. However, growth performance decreased in fish fed FCS diets. This study demonstrates that the fermentation process and phytase supplementation can improve the phosphorus availability of plant protein sources in fish. The fermentation of CS by A. oryzae could increase antioxidant activities in feed and fish and effectively degrade toxic gossypol in cottonseed meal.

Anti-Neurodegenerative Biflavonoid Glycosides from <i>Impatiens balsamina</i>

Kim, Chung Sub,Bae, Munhyung,Oh, Joonseok,Subedi, Lalita,Suh, Won Se,Choi, Sang Zin,Son, Mi Won,Kim, Sun Yeou,Choi, Sang Un,Oh, Dong-Chan,Lee, Kang Ro American Society of Pharmacognosy 2017 Journal of natural products Vol.80 No.2

<P>Four biflavonoid glycosides, balsamisides A-D (1-4), and nine known compounds (5-13) were obtained from the white petals of Impatiens balsamina. The 2D structures of the purified phytochemicals were established using conventional NMR techniques in addition to the new long-range HSQMBC NMR experiment. Acid hydrolysis followed by experimental and quantum-mechanics-based ECD data analysis permitted full configurational assignment of the purified metabolites. Compounds 1-13 were assessed for their potential to impede the generation of nitric oxide in lipopolysaccharide-stimulated BV2 cells. They were also investigated for potential neuroprotective activity using C6 cells and cytotoxicity against some human tumor cell lines, but were inactive (IC50 > 10 mu M) against all the cell lines.</P>

Genetic association of MYH genes with hereditary hearing loss in Korea

Kim, Sang-Joo,Lee, Seokwon,Park, Hong-Joon,Kang, Tae-Hun,Sagong, Borum,Baek, Jeong-In,Oh, Se-Kyung,Choi, Jae Young,Lee, Kyu-Yup,Kim, Un-Kyung Elsevier 2016 Gene Vol.591 No.1

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Myosin is a key protein involved in regulating the shape and motility of cells. The <I>MYH9</I> and <I>MYH14</I> genes, which encode non-muscle myosin heavy chain IIA (NMMHC II-A) and IIC (NMMHC II-C), respectively, are expressed in the inner ear. These myosin genes are known to be associated with autosomal dominant non-syndromic hearing loss (ADNSHL); however, genetic studies in patients with ADNSHL in Korea have rarely been reported.</P> <P><B>Methods</B></P> <P>We analyzed the <I>MYH9</I> and <I>MYH14</I> genes in 75 Korean patients with ADNSHL.</P> <P><B>Results</B></P> <P>We identified 4 possible pathogenic variants: a novel variant p.F1303L and 2 previously reported variants (p.R1730C and p.R1785C) in the <I>MYH9</I> gene, and a novel variant p.A1868T in the <I>MYH14</I> gene. All the variants were located in the myosin tail domain, which is essential for the interaction of myosin with actin. These variants were predicted to be possibly pathogenic by functional prediction tools and were absent in 100 unrelated normal controls.</P> <P><B>Conclusion</B></P> <P>These results suggest that all the variants identified in this study have a strong potential to affect the structural stability and/or function of non-muscle myosin in the inner ear, which might lead to ADNSHL. This study establishes the link between the genotype and development of ADNSHL and contributes to the establishment of Korean database for hereditary hearing loss.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We performed genetic analysis of <I>MYH</I> genes in Korean patients with ADNSHL. </LI> <LI> We found three and one possibly pathogenic variants in <I>MYH9</I> and <I>MYH14</I>, respectively. </LI> <LI> Our research will improve understanding of relations between MYH genes and ADNSHL. </LI> </UL> </P>

Methionine Sulfoxide Reductase B3-Targeted <i>In Utero</i> Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss

Kim, Min-A,Cho, Hyun-Ju,Bae, Seung-Hyun,Lee, Byeonghyeon,Oh, Se-Kyung,Kwon, Tae-Jun,Ryoo, Zae-Young,Kim, Hwa-Young,Cho, Jin-Ho,Kim, Un-Kyung,Lee, Kyu-Yup Mary Ann Liebert 2016 ANTIOXIDANTS AND REDOX SIGNALING Vol.24 No.11

Disseminated Mycobacterium intracellulare Infection in an Immunocompetent Host

Kim, Won-Young,Jang, Sun-Joo,Ok, Tae-Jin,Kim, Gwang-Un,Park, Han-Seung,Leem, Jae-Chan,Kang, Bo-Hyoung,Park, Se-Jeong,Oh, Dong-Kyu,Kang, Byung-Ju,Lee, Bo-Young,Ji, Won-Jun,Shim, Tae-Sun The Korean Academy of Tuberculosis and Respiratory 2012 Tuberculosis and Respiratory Diseases Vol.72 No.5

Disseminated Mycobacterium avium complex (MAC) infection can occur in immunocompromised patients, and rarely in immunocompetent subjects. Due to the extensive distribution of the disease, clinical presentation of disseminated MAC may mimic malignancies, and thorough examinations are required in order to make accurate diagnosis. We report a case of disseminated Mycobacterium intracellulare disease in an immunocompetent patient, which involved the lung, lymph nodes, spleen, and multiple bones. F-18 fluorodeoxyglucose positron-emission tomography imaging showed multiple hypermetabolic lesions, which are suggestive of typical hematogenous metastasis. However, there was no evidence of malignancy in serial biopsies, and M. intracellulare was repeatedly cultured from respiratory specimens and bones. Herein, we should know that disseminated infection can occur in the immunocompetent subjects, and it can mimic malignancies.

Effects of Intravenous Magnesium Sulfate on the Prevention of Pain Following Injection of Microemulsion Propofol

Se Jin Lee,Soon Im Kim,Sun Young Park,un-Gyu Kim,Ho Bum Cho,Yoo Mi Han 순천향대학교 순천향의학연구소 2015 Journal of Soonchunhyang Medical Science Vol.21 No.2

Objective: The aim of this study was to investigate the effects of intravenous magnesium sulfate on the prevention of pain during the injection of microemulsion propofol. Magnesium is a known calcium channel blocker and a physiological N-methyl-D-aspartate receptor antagonist. Methods: American Society of Anesthesiologists I and II adults (n=114) undergoing general anesthesia for surgery were randomly assigned into two groups (n=57 per group). This study was designed in prospective and double-blind manner. Patients in the LM group (n=57) received pretreatment with 2% lidocaine (40 mg) and magnesium sulfate 10 mg/kg, while patients in group L (n=57) received pretreatment with 2% lidocaine (40 mg) and normal saline (2 mL) accompanied by venous occlusion. Induction with microemulsion propofol (Aquafol) 2 mg/kg was accomplished following the release of venous occlusion. Pain intensity was assessed on a four-point scale according to patient movement (grade 0, no movement; grade 1, movement in wrist only; grade 2, movement in the upper arm & shoulder of injected arm; grade 3, generalized movement). Systolic blood pressure, diastolic blood pressure, and heart rate were evaluated. Results: A significant difference in pain intensity following injection of microemulsion propofol between the groups was found (P<0.05). In addition, the incidence of hypertension after injection was lower in the LM group than in the L group (P<0.05). Conclusion: The combination of magnesium and lidocaine are effective in attenuating the pain induced by microemulsion propofol injection when compared with lidocaine alone.

Nucleoside Diphosphate Kinase and Flagellin from <i>Pseudomonas aeruginosa</i> Induce Interleukin 1 Expression via the Akt/NF-κB Signaling Pathways

Kim, Yong-Jae,Lee, Jung-Hoon,Lee, Yeji,Jia, Jingyue,Paek, Se-Hwan,Kim, Hyong-Bai,Jin, Shouguang,Ha, Un-Hwan American Society for Microbiology 2014 Infection and immunity Vol.82 No.8

<P>Inflammatory responses are a first line of host defense against a range of invading pathogens, consisting of the release of proinflammatory cytokines followed by attraction of polymorphonuclear neutrophils (PMNs) to the site of inflammation. Among the many virulence factors that contribute to the pathogenesis of infections, nucleoside diphosphate kinase (Ndk) mediates bacterially induced toxicity against eukaryotic cells. However, no study has examined how Ndk affects inflammatory responses. The present study examined the mechanisms by which <I>Pseudomonas aeruginosa</I> activates inflammatory responses upon infection of cells. The results showed that bacterial Ndk, with the aid of an additional bacterial factor, flagellin, induced expression of the proinflammatory cytokines interleukin-1α (IL-1α) and IL-1β. Cytokine induction appeared to be dependent on the kinase activity of Ndk and was mediated via the NF-κB signaling pathway. Notably, Ndk activated the Akt signaling pathway, which acts upstream of NF-κB, as well as caspase-1, which is a key component of inflammasome. Thus, this study demonstrated that <I>P. aeruginosa</I>, through the combined effects of Ndk and flagellin, upregulates the expression of proinflammatory cytokines via the Akt/NF-κB signaling pathways.</P>

Test and Simulation of an Active Vibration Control System for Helicopter Applications

Kim, Do-Hyung,Kim, Tae-Joo,Jung, Se-Un,Kwak, Dong-Il The Korean Society for Aeronautical and Space Scie 2016 International Journal of Aeronautical and Space Sc Vol.17 No.3

A significant source of vibration in helicopters is the main rotor system, and it is a technical challenge to reduce the vibration in order to ensure the comfort of crew and passengers. Several types of passive devices have been applied to conventional helicopters in order to reduce the vibration. In recent years, helicopter manufacturers have increasingly adopted active vibration control systems (AVCSs) due to their superior performance with lower weight compared with passive devices. AVCSs can also maintain their performance over aircraft configuration and flight condition changes. As part of the development of AVCS software for light civil helicopter (LCH) applications, a test bench is constructed and vibration control tests and simulations are performed in this study. The test bench, which represents the airframe, is excited using a pair of counter rotating force generators (CRFGs) and a multiple input single output (MISO) AVCS that consists of three accelerometer sensors and a pair of CRFGs; a filtered-x least mean square (LMS) algorithm is applied for the vibration reduction. First, the vibration control tests are performed with uniform sensor weights; then, the change in the control performance according to changes in the sensor weight is investigated and compared with the simulation results. It is found that the vibration control performance can be tuned through adjusting the weights of the three sensors, even if only one actuator is used.