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      • 펜틸렌테트라졸 투여 흰쥐에서의 천마의 항경련 작용기전

        허근,김진숙,권태협,김정애,용철순,하정희,이동웅 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-

        Gastrodia elata (GE) is a oriental medicinal herb which has been used traditionally for the treatment of various brain diseases including convulsion and epilepsy. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of GE (500 mg/kg, P.O) to the pentylenetetrazole (PTZ)-induced convulsive rats. Methanol extracts of GE siginificantly inhibited (35%) the convulsion state as well as the level of lipid peroxidation (25%) in the brain. The ether fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently (5.0×10^(-6)~2.0×10^(-5) g/ml). The scavenging effect on hydroxy radicals was found in all the fractions of ether, butanol, and dichloromethane. These results suggest that the anticonvulsive effect of GE is possibly due to the antioxidative effects of the active components in GE.

      • KCI등재
      • KCI등재
      • 급성 췌장염의 합병이 추정되는 한국형 출혈열 1예

        박영수,김창오,김영근,홍성관,장경희,허애정,염준섭,송영구,김준명 대한감염학회 2001 감염 Vol.33 No.5

        The Korean hemorrhagic fever (KHF) is an acute febrile disease with characteristic of fever, bleeding tendency, and renal failure. There are many complications of Korean hemorrhagic fever such as infection, anemia, internal bleeding, hypopituitarism, respiratory, and neurologic complication. A few cases were reported on acute pancreatitis with hemorrhagic fever abroad, but there was no case about Korean hemorrhagic fever with acute pancreatitis in this country. We experienced a case of Korean hemorrhagic fever associated with suspected acute pancreatits. With review of articles, we report a case of 51 year-old woman with KHF, where acute pancreatitis developed during management, (Korean J Infect Dis 33:376∼379, 2001)

      • Allopurinol에 의한 박탈성 피부염 환자에서의 탈감작 요법

        홍천수,조영준,박중원,김철우,김중선,윤영연,정혜원,박정엽,허애정 대한알레르기학회 1999 천식 및 알레르기 Vol.19 No.6

        Allopurinol is widely used for chronic tophaceous gout as a uric acid lowering agent. Hyperse- nsitivity to allopurinol occurrs in about 10% of patients, which limits the usage of allopurinol. The successful oral and intravenous desensitization of allopurinol has been reported worldwide since 1976. We recently experienced a 51-year-old male patient with gouty arthritis and hyperuricemia, who had previously experienced skin rash after allopurinol treatment. When allopurinol was retried, erythematous and foliative skin rash developed on entire body. Because allopurinol was essential in controlling hyperuricemia, the oral desensitization of allopurinol was tried. We report successful rapid oral allopurinol desensitization in the patient with chronic tophaceous gout, who exhibited exfoliative dermatitis as allopurinol hypersensitivity.

      • SCOPUSKCI등재

        체지방분포도가 당대사, 지질대사 및 성장호르몬 분비에 미치는 영향

        허갑범,이현철,임승길,김경래,송영득,남수연,김경욱,정대호,최병기,허애정 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.3

        Background: Body fat distribution, rather than the level of obesity per se, appears to be a strong predictor of abnormalities in metabolic complication. Visceral fat accumulation is significantly correlated with glucose intolerance and constitutes as an independent risk factor for the diabetes mellitus. Methods: We investigated the impact of body fat distribution on the glucose, lipid metabolism and growth hormone secretion in obese subjects with varying glucose tolerance and lean controls matched with sex and age. 69 obese Koreans (34 men, 35 women; 43.8 yrs) and 21 lean Koreans (10 men, 11 women; 40.8 yrs) were recruited. Anthropometric measurement and impedence for measurement of total body fat, and computed tomography for visceral and subcutaneous fat area at umbilicus level were performed. All subjects underwent a standard oral glucose tolerance test and GH stimulation test by L-dopa. Results: The results are summarized as follows. 1. Obese patients had greater ideal body weight (%, IBW) and lean body mass (LBM) than lean controls. But no significant differences were found in IBW and LBM between 3 obese groups. 2. The 25 obese NIDDM had the highest FFA-AUC during OGTI and the lowest GH-AUC to L-Dopa stimulation test. The insulin-AUC during OGTT was the highest in 24 obese subjects with normal glucose tolerance. 3. All male groups have VSR of more than 0.4, which has been designated visceral fat obesity. In contrast all female groups have VSR of lesser than 0.4 but obese DM subjects have the highest VSR. Visceral fat area per body weight ratio(VWR) showed increasing tendency in obese, IGT, and DM group. 4. Waist circumference and VWR showed strong correlation with metabolic parameters among anthropometric parameters. They were positively correlated with FFA-AUC during OGTT and negatively correlated with GH-AUC to L-dopa stimulation. Conclusion: Visceral fat accumulation are associated with insulin resistance, dyslipidemia and impairment of growth hormone secretion via increase of free fatty acid. The simple waist circumference may provide a more practical indicator that correlated with aMominal fat distribution and metabolic complications associated with obesity (J Kor Soc Endocrinol 14:541-552, 1999).

      • SCIESCOPUSKCI등재

        The Mechanism of t-Butylhydroperoxide-Induced Apoptosis in IMR- 32 Human Neuroblastoma Cells

        Jung-Ae Kim,Yong Soo Lee,Keun Huh 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.1

        <P> Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with <I>tert</I>- butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular Ca<SUP>2⁢</SUP> concentration, which was completely prevented either by EGTA, an extracellular Ca<SUP>2⁢</SUP> chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular Ca<SUP>2⁢</SUP> increase may be due to Ca<SUP>2⁢</SUP> influx through the activation of NSCCs. In addition, treatment with either an intracellular Ca<SUP>2⁢</SUP> chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular Ca<SUP>2⁢</SUP> signals and altered expression of <I>p53</I> and <I>c-myc</I>.

      • KCI등재

        Is Radiotherapy Necessary for Stage 1 Testicular Seminoma?

        Jung Ae Lee(이정애),Won Park(박원),Do Hoon Lim(임도훈),Yong Chan Ahn(안용찬),Seung Jae Huh(허승재),Jeong Il Yu(유정일),Han Yong Choi(최한용),Hyun Moo Lee(이현무),Eun Yoon Cho(조은윤) 대한방사선종양학회 2009 Radiation Oncology Journal Vol.27 No.2

        목 적: 제 1 병기 성인 고환 정상피종 환자에 대한 임상적 고찰과 함께 근치적 고환절제술 후 보조적 방사선 치료와 고환절제술 단독치료의 결과를 후향적으로 분석 비교하고자 하였다. 대상 및 방법: 1996년 1월부터 2005년 9월까지 삼성서울병원에서 제 1 병기 정상피종으로 진단을 받은 환자 32명의 순수 정상피종(pure seminoma) 환자를 대상으로 하였다. 근치적 고환절제술 후 22명은 보조적 방사선 치료를 시행하였고, 10명은 추가치료 없이 종양표지자와 복부골반 전산화단층촬영을 이용한 정기적 추적관찰을 행하였다. 방사선 치료는 10∼15 MV 광자선을 사용하였으며 일일치료선량 1.8∼2 Gy로 총 24∼30.6 Gy (중앙값, 25.2Gy)를 대동맥주위림프절(L1∼L5)에 이문조사하였다. 전체 추적관찰기간은 근치적 고환절제술 시행일을 기준으로 24∼155개월(중앙값, 96개월)이었다. 결 과: 환자의 연령은 22∼58세(중앙값 34세)였고, 임상적으로 진단 전 주증상은 음낭 종괴 및 불편감이 대부분이었다. 이중 2명에서 잠복고환의 병력이 있었으며, 병리적으로 32명 중 23명에서 정상피종에 관내배아세포종(intratubular germ cell neoplasia)이 동반되어 있었다. 술후 보조적 방사선 치료를 시행한 군은 분석시점에 모든 환자가 무병상태로 100%의 국소제어율 및 생존율을 보였다. 술후 추적관찰만을 시행한 군은 10명 중 1명에서 좌측대동맥주위 림프절에 재발하여 구제 항암화학요법 후 완전관해되었으며 국소제어율 88.9%, 생존율 100%를 보였다. 결 론: 제 1 병기 정상피종에서 근치적 고환절제술 후 보조적 방사선 치료를 시행한 군과 추적관찰만을 시행한 군간에 생존율의 차이는 없었다. 환자수가 적고 추적관찰기간이 짧기는 하지만 재발 후 항암화학요법으로 구제가 잘되고, 방사선 치료시 이차암의 가능성이 있음을 고려한다면 정기적인 추적관찰이 가능한 환자에서 수술 후 방사선치료를 생략할 수도 있겠다. Purpose: To report on the clinical outcome of patients with stage I testicular seminoma by postoperative radiotherapy (PORT) or surveillance after radical inguinal orchiectomy. Materials and Methods: This study is a retrospective review of 32 stage I pure seminoma patients treated between 1996 and 2005 at the Samsung Medical Center. Twenty two of the patients were treated by PORT, which was directed at the paraaortic lymphatics with a median dose of 25.2 Gy in 14 fractions for 3 weeks. The 10 remaining patients were managed by surveillance. The median follow-up period was 96 months with a range of 24 to 155 months. Results: Clinically, most patients presented with a testicular mass or discomfort. Two of the patients had a history of undescended testes. Pathologically, 23 of the patients had intratubular germ cell neoplasia with seminoma. Both recurrence-free survival (RFS) and overall survival (OS) rates of patients treated by PORT were 100%. In the control group, 1 of the 10 patients suffered a para-aortic lymph node relapse. The RFS and OS rates of the surveillance group were 88.9% and 100%, respectively. Conclusion: No difference in survival was observed between the two groups. Moreover, symptom recurrence was only observed in 1 patient in the control group. The use of PORT may reduce the risk of relapse. With the availability of effective diagnostic and salvage modalities, surveillance monitoring may be considered for patients in good compliance.

      • SCIESCOPUSKCI등재
      • 인면역결핍바이러스감염에서 Ribavirin의 Lamivudine에 대한 길항효과

        허애정,남정구,장경희,염준섭,최준용,송영구,김성순,이주실,이꽃실,김영근,김명수,박우일,김준명 대한화학요법학회 2002 대한화학요법학회지 Vol.20 No.1

        배경 : HIV 감염자 수의 증가와 다양한 치료제 개발로 인해 HIV 감염자의 수명이 연장되면서 HCV 감염이 HIV 감염의 자연경과 및 사망률에 악영향을 미치는 중요한 병원균으로 대두되고 있다. 또한 HIV가 HCV의 질병경화를 악화시킬 수 있음이 밝혀지면서 동시감염의 치료에 대한 관심이 높아지고 있으며, 약물 상호작용도 그 주요 관심사 중 하나이다 RBV과 다양한 항레트로바이러스제제들간의 약물 상호작용에 대한 연구가 진행된 결과 ZDV과 d4T에 대하서 길항작용을, ddI에 대해서는 상승작용을 보임이 밝혀져 있다. 본 연구에서는 이러한 뉴클레오시드 유사체들과 세포내 대사과정을 달리하는 3TC에 대한 영향을 알아보고자 하였다. 방법 : 분주하여 부관되어 있던 세포주 MT-4를 48-72시간마다 계대배양하여 1.96×10^(6)cell/㎖의 수준으로 유지하였고, 96 well plate에 각 well 당 1.0×10⁴cells/㎖씩 분주하였다. ZDV(0.0001-1000μM/L)과 3TC(0.00001-100mM/L)의 농도를 각각 10배씩 희석하여 투여한 후 세포를 5일간 배양하여 각농도에서의 세포독성을 MTT assay로 평가하였으며, RBV(2μM/L) 투여전후의 변화를 비교하였다. 항바이러스 효과를 평가하기 위하여 MT-4세포에 각 well 당 100 TCID_(50)의 HIV-1 strain HTLV-Ⅲ을 첨가하여 감염시킨 상태에서 유사한 방법으로 ZDV과 3TC의 농도를 10배씩 희석하여 투여한 후 37℃, 5% CO₂ incubator에서 배양하였다. 배양 1주일후 상층액을 얻어 HIV-1 p24 core profile ELISA를 사용하여 p24 Ag을 정량적으로 측정하였고, IC_(50)를 평가하였다. 약물들과 함께 RBV을 투여한 후 같은 방법으로 세포독성 및 항바이러스 효과를 평가하였다. ZDV, 3TC를 단독투여한 결과와 RBV을 함께 투여한 결과를 비교분석 하기 위하여 Wilcoxon rank sum test로 분석하였다. 결과 : ZDV 단독투여시 CD_(50)는 36.8μM이었고 RBV을 함께 투여시 CD_(50)가 39.9μM로 증가하였으며, 3TC의 경우 RBV 투여전후의 CD_(50)는 각각 2357.2μM, 2248.8μM이었다. MTT assay상 ZDV 0.01 및 0.1μM/L 농도에서 (p=0.003, 0.039), 3TC 100μM/L 농도에서(p=0.027) RBV 투여 전후 세포생존율의 차이를 보였다. 3TC 단독 투여시에 비해 RBV과 병용투여한 경우 통계적으로 유의하게 p24 Ag 생성이 증가하였고 (p=0.007) 이러한 결과는 ZDV에서와 유사하였다(p=0.026). ZDV 단독투여시 IC_(50)는 0.03μM였고, ribavirin을 함께 투여후 0.067μM에서 0.152μM로 2.3배 증가된 소견을 보였다. 결론 : 이상의 실험결과로부터 RBV 투여가 3TC의 세포독성 및 항바이러스효과를 감소시키며 이러한 길항작용은 농도의존적임을 알 수 있었다. 본연구는 이전에 제시된 연구들과 함께 RBV이 항레트로바이러스제제와 병합투여 되었을 때 약물대사에 미치는 영향을 보여준 중요한 자료중 하나가 될 것이다. HIV/HCV 동시감염자에서 상용량의 RBV을 병용투여할 경우 3TC의 농도가 낮게 유지되어 HIV의 내성을 유도할 가능성을 내포한다고 볼 수 있겠으나, 실제로 직접 임상에 적용하기는 어려우며 생체내에서의 이들 약물의 상호작용 및 대사변화를 평가하기 위해서는 생체내에서의 약동학 및 약력학적 평가를 포함한 광범위한 임상연구가 필요할 것으로 생각된다. Background : One of the main concerns of interferon/ribavirin(RBV) treatment in Human immunodeficiency virus(HIV)/Hepatitis C virus(HCV) coinfected patients is that of drug-drug interactions. Recent studies reveal that RBV is antagonistic with zidovudine(ZDV), stavudine(d4T) and synergistic with didanosine(ddl). The phosphorylation of lamivudine(3TC) utilizes the enzyme deoxycytidine kinase. Manipulation of 3TC phosphorylation is a possible therapeutic strategy for modulating antiretroviral efficacy and cytotoxicity of 3TC. Methods : MT-4 cell lines were maintained in RPMI 1640 growth medium as a cell suspension 1.96 × 106cells/㎖), doubling approximately every 48-72 hr. Cells were incubated with ZDV(0.0001-1000mM) and 3TC(0.00001-100mM) in the presence and absence of RBV(2uM) in 96-well microtiter plates and cytotoxicity was determined using modified MTT assay. At the end of the 7 days, the cell-free supernatant was serially diluted and samples(100uL) were then assayed for p24 antigen with ELISA to evaluate the inhibitory effect on HIV-1 replication. The results were expressed in terms of the 50% inhibitory concentration(IC50). Analysis was done by Wilcoxon rank sum test. Results : 3TC alone significantly reduced p24 antigen production, with an IC50 0.067mM and addition of RBV increased the IC50 approximately 8.4 fold (0.563mM). However, at higher concentration of 3TC, the antagonistc effect of RBV was lost The decrease in the cytotoxic and antiviral efficacy of ZDV in the presence of RBV is consistent with previous studies that have demonstrated reduced ZDV activation. Conclusion : The addition of RBV siginificantly reduced cytotoxicity and antiretroviral efficacy of 3TC in MT-4 cell lines and the antagonistic effect of RBV is concentration dependent. This study provides further insight into the complex interaction between RBV and 3TC in vitro.

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