Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

Cha Kyung Youn,Seon Joo Park,Mei Hong Li,Min Young Lee,Kun Yeong Lee,Man Jin Cha,Ok Hyeun Kim,Ho Jin You,In Youp Chang,Sang Pil Yoon,Young Jin Jeon 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-Ձ, IFN-Ճ, and IL-1Ղ). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-ՊB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

Youn, Cha Kyung,Park, Seon Joo,Li, Mei Hong,Lee, Min Young,Lee, Kun Yeong,Cha, Man Jin,Kim, Ok Hyeun,You, Ho Jin,Chang, In Youp,Yoon, Sang Pil,Jeon, Young Jin The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

인체혈장 중 에탐부톨의 HPLC 분석법의 검증 및 단일용량 투여에 의한 약물동태 연구

곽혜선,박경호,최준식,송진아,성민경,장정옥,이화정 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

An HPLC method was employed for the determination of ethambutol in human plasma. After addition of internal standard (IS, octylamine, 2 μg/mL) and alkalinization of the plasma with 5 M sodium hydroxide, the drug and IS were extracted into the mixture of chloroform and diethyl ether (40:60, v/v). Following a 15-min vortex-mixing and a 10-min centrifugation, the organic phase was spiked with 100 pL of phenylethylisocyanate (2000 μg/mL) for chemical derivatization, mixed for 5 min and evaporated to dryness under a stream of nitrogen. The residue was reconstituted with 100 μL of mobile phase and 20 pL was injected into Cl8 column with a mobile phase consisting of methanol:water (70:30, v/v). The samples were detected utilizing an ultraviolet detector at 200 nm. The method was specific and validated with a limit of 0.15 μg/mL. Infra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of this method was demonstrated by analysis of human plasma after oral administration of a single 1200-mg dose to 20 healthy subjects. From the plasma ethambutol concentration vs. time curves, the mean AUC was 9.61 ± 1.64 μg hr/mL. and Cmax of 2.68 μg/mL reached 2.73 hr after administration. The mean biological half-life of ethambutol was 3.46 ± 1.21 hr. Based on the results, this simple and validated assay could readily be used in any pharmacokinetic studies using humans.

수두백신의 역가시험법 표준화를 위한 연구

민경일,백선영,신진호,김재옥,류승렬,민복순,김병국,김도근,김훈,이석호,박순희 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

수두(chicltenpo즈) 및 대상포진(shingles)의 예방을 위해 사용되는 수두 생 바이러스 백근은 현재 국내 -외 제조사들이 정상사람 2배체 폐 태아 세포 주들을 이용하여 바이러스를 배양 · 증식시켜 생산하고 있으나, 품질관리를 쒸한 역가 시험에는 t·fRC튼 띤 LB딘EL 세포 주외에 제조사가 설정한 세포 주를 이용하고 있으며, 역파신험 방법인 fH Ui'rFO Plaque 3SSaIT에도 조사별로 다소 차이가 있는 시헌법을 사용하고 있다. 그러므로 일반적으로 세포 주간우 감수성 차이, 계대력(passa딩e level)간의 차이,varicelta-zoster virus(4'2V) diluent medium 등에 의한 차이에 의해 역가시힘 결과에 많은 차이를 나타낼 수 있다. 이에 본 연구에서는 역가 시험 결과꼭 편차를 촉소화 할 수 있는 시헌방법을 극힙하고자 Ok퍼 백신 주와 세로 주간 및 기타 요인에 따른 차이를 비교 분석하고 이를 표준확하여 일관겅있는 국가 및 제조사의 품질관리예 활용하고 나아가 수두 생 바이러스 백신 역가시헌 국가 표준품 거달에 활용하고자 하는데 목적이 운.다. 수두 생 바이러스 빅신의 역가 시험에 영향을 띠칠 수 꿀.는 모민으로 우선 바이러스 흡착에 사용되는 1#Z)·'diluent medium이 가장 큰 오인으로 확인되.고. 현개까기 최종적으로 if4 sucrose, 10% FBS, 0.1% sodiun) rrlonog)utamate in PBS(-), fIH 7.2가 가당 두수글 L'z).「 린luent medium 조성으로 확인되었단. 또한 '·:~l포 주별로 다소의 차이는 잇.으나 최대 바이러스 흡착시간은 90분으론:÷잰착인 되었다. 다른 negati)Fe effect를 보일 수 있는 요인으로 항생물질 및 항츤 제인 fuugiBone이 곡이러스의 역가에 영향을 미치는 것으로 확인되었다 따라서 이러한 항생물 띤 항균제를 standard solid agarose overla?·(5.tO) 시헌방법에는 사용하지 않는 것이 역가 시험의 편차를 줄일 수 있는 요인이라 판단된다. 최적의 조건하데서 Oka 수두 백신 주의 j 종의 세포 쭈에 대한 역가시험 수행 결과 각 세포 주의 감수성의 차이는 크지 않았으나, 반복시헌에 대한 표준편차는 다소 차이를 나타났다. Until now in Korea, the international and domestic vaccine maufacturers produce and sale live attenuated daricella vaccines, used to prevent chickenpox and shinglees, which are propagated in and done the potency test with various originated human diploid embryonic lung cells. Also manufacturers perform in vitro plaque assay with a little different methods to their quality control tests. Therefore, in general, there is slight or big difference among in vitro plaque assay results because of the difference in susceptibility of various originated human diploid embryonic lung cells and in assay methods. The purpose of this study is to confirm what factors occurring deviation to establish the standardized method which minimize deviation intracellularly and intercellularly. Eventually the standadized method will be used in consistent national and manufacturer's quality control and moreover intra and inter laboratory's validation assay of national standard for live varicella vaccine candidate. We confirmed VZV diluent medium was the biggest factor influencing in vitor plaque assay and the excellent composition of VZV diluent medium was final 5% sucrose, 10% FBS, 0.1% sodium monoglutamate in PBS(-), pH 7.2. We confirmed 90 minutes was maximum and optimum VZV adsorption time, but a little different among cells Also we recommended not use antibiotics and antimycotic, fungizone in standard solid agarose overlay assay in varicella potency test. Eventually 5 different originated human diploid embryonic lung cells showed little difference in susceptibility to Oka vaccine strain, but showed a lot of difference in reproducibility.

한국어 말실행증 발화의 음향음성적 연구

민경옥,김순희,김수정 용인대학교 자연과학연구소 2007 自然科學硏究所論文誌 Vol.12 No.1

One of the noticeable linguistic characteristics that the patients with apraxia had was that they segmentalized syllables and pronounced articulation longer than others. For this reason, their speech was slower than others on the whole. The subject of this study included 5 patients with apraxia as well as aphasia and 5 patients with aphasia and no apraxia, and the purpose of this study was to analyze the characteristics of segmental sound and rhythm of the patients with apraxia by means of suggesting a stop sound in a form of description and interrogation. Experiment data of this study were limited to one-syllable words and two-syllable words and this study attempted to examine an ability of realizing the rhythm of apraxia by providing them with a stop sound in a form of description and interrogation as well as in a form of ‘CV’ formula and ‘VCV’ formula so as to find out the characteristics of the stop sound according to the phonetic environments. As a result, it has been demonstrated on the whole that the length of acoustic variable in apraxia was significantly longer than aphasia and normal group. Keywords : apraxia of speech (AOS), Aphasia, Stop sound, VOT(Voice Onset Time)

급성 충수염으로 진단된 예측 불가 염증성 맹장 종물에 대한 외과적 고찰

민경진,백무준,채만규,김성용,이문수,김창호,김재준,송옥평 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: An unexpected inflammatory cecal mass of uncertain etiology was encountered during surgery for presumed appendicitis. In this case, the surgeon couldn't exclude differential diagnosis which were severe appendicitis involving the cecal region, diverticular disease, other inflammatory bowel diseases, and neoplasm. Therefore, this finding leads to a therapeutic dilemma for the surgeon, when making surgical decisions during the operation. The aim of this study was to resolve this dilemma, a retrospective review was undertaken in this study. Methods: A retrospective study was performed to review the management of this problem at Soonchunhyang University Chunan Hospital for eight and half years from July 1991 to December 1999. A review of the emergency operation records identified 50 patients who had undergone ileocecal resection or right hemicolectomy for an inflammatory ileocecal mass of uncertain etiology when operated on for probable appendicitis. Results: Altogether, 39 patients underwent ileocecal resection, and 11 patients underwent right hemicolectomy. The final pathologic diagnosis was appendiceal abscess in 32 patients (63%), cecal diverticulitis in 7 patients (14%), neoplasm in 6 patients (12%), appendiceal phlegmon in 3 patients (6%), ileal tuberculosis in 1 patient (2%) and Anisakiasis in another patient (2%). The neoplasm of the 6 neoplasm patients was ascending colon cancer for 4 patients and cecal cancer for 2 patients. There was no mortality in this group. Conclusion: Although most inflammatory cecal masses are caused by benign disease, all cases in which the intraoperative diagnosis is unclear, any pathologic diagnosis including neoplasm cannot be ruled out. So this suggest ileocecal resection or right hemicolectomy to remove a possible underlying malignancy, and to decrease morbidity and mortality.

자동차 배기계의 비선형 모델링에 관한 연구

이민호,이준서,차경옥 明知大學校 産業技術硏究所 2002 産業技術硏究所論文集 Vol.21 No.-

This thesis is concerned with the development of useful engineering techniques to detect and analyze nonlinearities in mechanical systems. The methods developed are based on the concepts of higher order spectra, in particular the bispectrum and the Volterra series. The Volterra series is presented and discussed in some detail. Techniques for calculating a system's Volterra kernels from cross higher order spectra are derived. The application of these techniques to dada from actual automotive exhaust systems is performed. The pulsating pressure waves in internal combustion engine exhaust systems is applicable with above techniques.

Memory 소자 응용을 위한 BST(Ba_xSr_1-_xTiO_3) 강유전체 박막과 전극과의 계면특성

정민재,조정희,홍석민,김호건,김옥경 漢陽大學校 工學技術硏究所 1997 工學技術論文集 Vol.6 No.1

BaxSr1-xTiO3 powders were prepared by changing stoichiometry of Ba and Sr. After they were calcined and sintered at 1,200℃ and 1,300℃ respectively, BST sputtering targets were made in 3inch mould. For MIM structure capacitors. Pt-based structures such as Pt/TiN/SiO2/Si, Pt/Ti/Si3N4/Si, Pt/SiO2/Si, Ru/SiO2/Si and Ru/Si3N4/Si were used for bottom electrodes, and subsequently, the BaxSrl-xTiO3 thin films were sputtered on them. After the analysis of their structures by XRD, Al was evaporated on the BST films for MIM capacitor. We found that the structures of the films showed good crystallinity above 550℃ from the results of XRD measurements. The largest dielectric constant of films was obtained with 0.7mol% of Ba. The electric properties of the capacitors were very good with Pt/TiN/SiO2/Si electrodes.

Flavobacterium odoratum의 TOL 플라스미드를 전달받은 광합성세균으로부터의 수소 생성

오순옥,조인선,이희경,민경희 숙명여자대학교 자연과학연구소 1991 자연과학논문집 Vol.- No.3

Flavobacterium odoratum SUB53의 TOL 플라스미드의 크기는 83 Md 이었으며 TOL 플라스미드에 의한 m-toluate의 최고분해농도는 5 mM이었다. Rhodopseudomonas sphaeroides KCTC1425의 수소생성은 nitrogenase의 활성과 비례하였으며 30 mM malate acid와 질소원으로서 7mM glutamate의 최적농도에서 최고의 수소생성을 보여 주었다. 한편, 0.3mM NH ion에 의해 nitrogenase의 활성이 저해되어 수소 생성이 현저히 감소하였다. F. odoratum SUB53과 Pseudomonas putida mt-2의 TOL 플라스미드는 R. sphaeroides에로의 접합시 수용세포의 대수증식기에서 10시간-15시간 동안에 최적이었으며 helper plasmid pRK2013에 의해 접합능이 증가하였다. Transconjugants인 R. sphaeroides C1(TOL SUB53)과 C2 (TOL mt-2)의 catechol-1,2-oxygenase(C-1,2-O)와 catechol-2,3-oxygenase(C-2,3-O)의 활성을 비교 검토한 결과 C-2,3-O 유전자를 code하는 유전인자는 TOL 플라스미드 위에 있으며, C-1,2-O 유전자의 위치는 chromosome 위에 있는 것으로 사료된다. 전자 공여체로서, m-Toluate는 R. sphaeroides C1과 C2의 TOL 플라스미드에 의하여 분해되어 수소를 생성함을 알 수 있었다. 이 결과는 TOL플라스미드에 의하여 m-toluate가 일차적으로 분해되고 생성된 이차산물로 부터 광선하에서 수소를 생성하는 것으로 추정된다. TOL plsmid size of Flavobacterium odoratum SUB53 was estimated as 83 Md and the optimum concentration of m-toluate degradation by TOL plasmid was 5 mM. H₂ production by Rhodopseudomonas sphaeroides KCTC1425 was largely dependent on nitrogenase activity and showed the highest at 30 mM malate with 7mM glutamate as nitrogen source. Nitrogenase activities were inhibited by 0.3mM NH ions, to be appeared the decrease of H₂ production. Conjugation of TOL plasmids from F. odoratum SUB53 and Pseudomonas putida mt-2 to R. sphaeroides showed the optimum at the exponential stage of recipient cells in presence of helper plasmid pRK2013. According to the investigation of catechol-1,2-oxygenase(C-1,2-O) and catechol-2,3-oxygenase (C-2,3-O) activities of R. sphaeroides C1 (TOL SUB53) and C2 (TOL mt-2), the gene for C-2,3-O is located on TOL plasmid and gene for C-1,2-O on the chromosome of R. sphaeroides. m-Toluate was biodegraded by TOL plasmid in R. sphaeroides C1 and C2, presumably to be produced H₂ gas from the secondary metabolites of m-toluate.

Sol-Gel 법으로 제작한 (Pb_xBa_₁-_x)TiO₃박막의 특성에 관한 연구

홍석민,이정아,조정희,김옥경 漢陽大學校 工學技術硏究所 1996 工學技術論文集 Vol.5 No.1

We tried to find optimal condition of (PbxBa1-x)TiO3(x=0.0, 0.2, 0.5, 0.8, 1.0) thin films produced by sol-gel spin coating. Barium acetate, Lead acetate trihydrate and Ti-isopropoxide are used as the coating sol for producing the thin film, and acetic acid, methanol, and distilled water are used as the solvent. It is found that the manufactured sol was at the most stable condition when the component content satisfied H2O/Ba=65, after observing the state transition for a specified period. We coated sol for coating on the various kinds of substrate and pre-annealed on 68℃ and 460℃. Then we annealed them on 700℃ for 30 minutes and found that they showed a good growth of crystal by the XRD measurement. We selected Pt as the bottom electrode, using the substrate Pt/SiO2/Si in order, we raised the different conditional thin films and obtained the capacitor by evaporating Al as the top electrode. We measured the electric capacitance and dielectric loss by changing the frequency for three step as 1, 10, 100kHz for each and calculated the dielectric constant. The dielectric constant of the thin film (PbxBa1-x)TiO3 was decreased below x=0.8 and increased upto x=1.0 as x increases.