Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

Kim, Si-Hyung,Choi, In-Sun,Cho, Jin-Hwa,Park, Eun-Ju,Jang, Il-Sung,Choi, Byung-Ju,Kim, Hyun-Jung,Kim, Young-Jin,Nam, Soon-Hyeun The Korean Academy of Oral Biology 2006 International Journal of Oral Biology Vol.31 No.2

Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injucted control animals. Field potential recordings were used to monitor amplitude and numbers population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5mg/kg;phenytoin 40, 60mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

응급실을 내원한 65세 이상 노인 환자의 분석

김진년,김태훈,강양욱,오명,김상철,김성훈,권계형,남홍우,이홍순,유형준 대한노인병학회 2001 대한노인병학회지 Vol.5 No.3

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

Kim, Kyeong Seok,Yang, Hun Yong,Song, Hosup,Kang, Ye Rim,Kwon, JiHoon,An, JiHye,Son, Ji Yeon,Kwack, Seung Jun,Kim, Young-Mi,Bae, Ok-Nam,Ahn, Mee-Young,Lee, Jaewon,Yoon, Sungpil,Lee, Byung μ,Kim, Hyung TAYLOR & FRANCIS 2017 Journal of Toxicology and Environmental Health Vol.80 No.9

<P>Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.</P>

Benzoate, m-Toluate, Phenol의 Pseudomonas putida에 의한 생분해

김장규,김석형,김태환,이대광,김남기 成均館大學校 科學技術硏究所 1993 論文集 Vol.44 No.1

It this study, basic data were obtained for the treatment of industrial waste water which includes aromatic compounds. Substrate concentrations used were 100ppm, 500ppm, and 1,000pprn and initial pH's were pH6, pH7, and pH8 in order to obtain the optimum conditions for treating benzoate, m-toluate, and phenol by Pseudomonas putida(KCTC 1644). Durations were 20hrs for 100ppm, 40hrs for 500ppm, and 60hrs for 1,000ppm before the static growth of Pseudomonas putida. 100% of 100ppm benzoate(0.31g cell/1) was biodegraded at pH6, pH7, and pH8 before 20hrs, 52.8% of 500ppm at pH8 in 40hrs, and 27.9% of 1,000ppm at pH8 in 60hrs. The best initial pH was pH8 for the biodegradation and the growth of Pseudomonas putida in benzoate medium. For m-toluate, the best initial pH was also pH8. At this pH, 40.6% of 10Dppm(0.31 cell/1), 21.9% of 500ppm, and 14.1% of 1,000ppm m-toluate were biodegraded respectively in limited time. But for phenol, the best initial pH was pH7. At this point, 9.8% of 100ppm(0.218 cell/1), 7.1% of 500ppm, and 4.7% of 1,000ppm phenol were biodegraded respectively. Therefore, the best carbon source in this experiment was benzoate. Pseudomonas putida was also able to biodegrade m-cresol, p-hydroxybenzoic acid, and benzaldehyde.

HID 램프용 디지털제어 전자식 안정기에 관한 연구

김영동,강원찬,김남오,김형곤,김병철 조선대학교 에너지.자원신기술연구소 2004 에너지·자원신기술연구소 논문지 Vol.26 No.1

In this paper, digitally controlled electronic ballast for the HID lamps driven by proposed frequency conversion method is described. This electronic ballast consists of a buck converter, a low frequency square wave full bridge inverter, a high voltage pulse generator for the lamp ignition, an over current protection circuit and an 8-bit microcontroller. The fuzzy logic digital control operation is carried out by the 8-bit microcontroller. In spite of the limited control bandwidth caused by low operation speed of the 8-bit microcontroller, the good control performance for the constant lamp current in the warm-up period is obtained using the proposed frequency conversion driving method. The HID lamp is controlled in a constant current mode during the lighting warm up process and is controlled in a constant power mode during lighting steady state. A controlled variable power mode is used to extend the lamp lifetime.

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

대황황련해독탕의 항고지혈증 작용

김영석,정은아,장종철,양형길,김남재,조기호,배형섭,이경섭,김동현 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2001 No.-

Whangryunhaedok-Tang (WT) is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus, and Daewhang-whangryunhaedok-Tang (DWT) is made by the combination of Rhei Rhizoma, a wellknown anticostipation drug in WT. Therefore, DWT has been evaluated for antihyperlipidemic effects on experimental hyperlipidemic rats and mice induced by corn oil and high cholesterol-diet. Oral administration of DWT significantly inhibited the increase of serum triglyceride and LDL-cholesterol levels, and the decrease of serum HDL-cholesterol levels in hyperlipidemic rats induced by corn oil. Also, oral administration of DWT significantly prevented the increase of serum total cholesterol, triglyceride and LDL-cholesterol, and liver total cholesterol and triglyceride in 1% cholesterol-diet fed mice. These results suggest that DWT is effective for the treatment of hyperlipidemia.

대황황련해독탕의 사염화탄소 유발 간장해 보호효과 미치 급성독성

김영석,정은아,장종철,양형길,김남재,조기호,배형섭,이경섭,김동현 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2002 東西醫學硏究所 論文集 Vol.2002 No.-

ABSTRACT - This study was performed to evaluate hepatoprotective effect of daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by CCI_4 and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase(LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid perotidation, catalase and glutathione-S-transfrease(GST) in liver microsome were determined in hepatotoxic rats induced by CCI_4. DWT was significantly reduced the serum ALT, AST, ALP, LDH. TC and TG lecels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of CCI_4-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5.000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks.DWT did not induce any toxic signs in the mortalitie, clinical signs, body weight changes, and gross necropsy finfings of mice. Based in these results. It is concluded that DWT may have the hepatoprotective effect on CCI_4 induced hepatotoxicity in rats. Also. DWT may have no side effect and its LD_50 value may be over 5.000mg/kg b.w. in mice.

녹동균 세포외막 단백질 백신 CFC-1-101의 안정성 및 면역원성 검토 : 임상 제 Ⅰ/Ⅱa상 시험

장인진,김익상,유경상,임동석,김형기,신상구,장우현,박완제,이나경,정상보,안동호,조양제,안보영,이윤하,김영지,남성우,김현수 대한감염학회 1998 감염 Vol.30 No.3

목적 : 제일제당에서는 녹농균의 세포외막 단밸질을 유효성분으로 하는 백신인 CFC-101을 개발하였으며, 동물시험에서 이 백신의 안전성과 유효성을 입증하였다. 본 연구에서는 이 녹농균 백신의 인체에 대한 안전성과 면역원성을 평가하는 동시에 인체 접종시의 최적 투여 용량을 결정하기 위하여 제 I/Ⅱa상 임상시험을 수행하였다. 방법 : 건강한 성인 남자를 피험자로 선별하여 각 용량군에 백신투여자 6명, 위약투여자 2명을 배정하였다. 백신 투여군은 0.25mg, 0.5mg 또는 1.0mg 용량의 녹농균 백신을 7일 간격으로 3회에 걸쳐 근육주사 하였으며, 위약 투여군에게는 세포외막 단백질을 제외한 동일한 성분을 투여하였다. 백신접종 후 국소적 또는 전신적인 반응의 발생여부를 관찰하고, 혈액시료를 체취하여 백신의 역가와 유효성을 검정하였다. 결과 : 녹농균 백신 CFC-101은 모든 접종자에서 양호한 내약성을 보였다. 또한 0.5mg 과 1.0mg 백신 투여군에서는 100%의 항체양전율을 나타내었다. 생성된 항체는 녹농균 세포외막단백질에 특이성을 보였고, 녹농균 감염에 대해 방어효능이 있었다. 결론 : 이와같은 결과로부터 이 녹농균 백신은 인체에 안전하게 투여할 수 있으며, 높은 항체 생성능으로 감염방어 효능을 보이고 0.5mg과 1.0mg이 최적용량인 것으로 판단되었다. Background : We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/Ⅱa clinical trial in healthy male volunteers. Methods : Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Sings of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. Results : The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. Conclusion : We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.

혈우병 환자의 임상 양상에 관한 단일기관 연구

허지혜,김형욱,김영대,이영호,김남수,설인준,김상우 인제대학교 2006 仁濟醫學 Vol.27 No.-

Objective : We analyzed and investigated clinical manifestations, laboratory tests, and inhibitor development of hemophilia that had not been thoroughly studied. Methods : We retrospectively reviewed 96 patients with hemophilia who were registered in the Hanyang University hospital from Jan, 1984 to Dec, 2003, Results : The total patients, whose median age at onset was 46.0 months, in clude 84 cases of type A (87.5%) and 12 cases of type B (12.5%). The most common chief complaint was a traumatic hemorrhage. The family histories of hemophilia were revealed in 41 cases (42.7%). The median activated partial thromboplastin time (aPTT) was 66.7 seconds. The number of severe cases was 39 (40.6%). Inhibitors were present in 13 cases (13.5%) and seven cases (53.8%) were high responders. aPTT and factor levels showed reverse correlation (r=-0.467). aPTT is more prolonged in group without family history than the group with family history (P=0.037). Conclusion : In this study, the diagnosis of hemophilia are made at the lower age and the serological positivity of the HCV is decreased. Activated partial thromboplastin time and factor levels shows reverse correlation. Activated partial thromboplastin time is more prolonged in group without family history compared with group with family history. The frequencies of family history are lower than those of other developed countries, because of concealing the family history of hemophilia. The prevalence of the development of inhibitors increased compared with those of previous studies in Korea, but was lower than those of other countries. Further studies would be necessary to decrease the inhibitor development.