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      • 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.

      • KCI등재

        Parasitemia Characteristics of Plasmodium vivax Malaria Patients in the Republic of Korea

        허애정,곽이경,김의석,이꽃실,염준섭,조용균,김창석,박재원 대한의학회 2011 Journal of Korean medical science Vol.26 No.1

        Parasitemia characteristics of Plasmodium vivax malaria in temperate regions may differ from those in tropical zones. However, most parasitological and clinical features of P. vivax malaria have been investigated in the latter. In this study, we investigated 383 malaria patients to clarify the parasitemia characteristics of a P. vivax strain in the Republic of Korea (ROK). The mean parasitemia (8,396/μL) was less than half of tropical P. vivax malaria, and multiple invasions of erythrocytes were not rare (53.5% of the patients, 2.4%of the total investigated RBCs), but less than the observations in tropical zones. The intervals between the first symptom onset and diagnosis were significantly longer in gametocyte (+) patients than in gametocyte (-) patients. Only half of the total patients had both genders of gametocytes (191 of 353), and the male gametocyte density (169/μL) was lower than that of P. vivax strains of a previous study. Multiple invasions of erythrocytes and gametocytemia were coincident factors of the degree of anemia in P. vivax malaria. The present findings demonstrate the P. vivax strain in ROK reveals relatively low parasitemia and low male to female gametocyte ratio. The low ratio may be related with low transmission efficacy.

      • 에이즈환자에게 구강질환은 흔해

        허애정 대한에이즈예방협회 2003 레드리본 Vol.53 No.-

        모든 HIV 감염자는 구강질환을 적어도 한가지 이상 가지고 있는데, 그 범위는 양성질환에서 중증질환 및 사망에 이르는 치명적인 상태에 이르기까지 다양하다.

      • 논문 : 오디추출액 급여가 일부 류머티즘 환자의 혈액성상 및 심혈관계 지표에 미친 영향

        애정 ( Ae Jung Kim ),종일 ( Jong Il Hur ),이종국 ( Jong Kug Lee ),이유시 ( You Si Lee ),배윤정 ( Yun Jung Bae ),성미경 ( Mi Kyung Sung ),승정자 ( Chung Ja Chung ) 국제통합대체의학협회 2005 국제통합대체의학회지 Vol.1 No.1

        Rheumatoid arthritis(RA) is a chronic syndrome of unknown etiology and characterizod by non-specific inflammation of the peripheral joints. Recent studies have indicated that pathogenesis of RA related tissues damages and inflammation are induced by excess production of reactive oxygen species and/or reduced ability to decrease oxidative stresses. The antocyanin pigments composed of red colored fruits such as mulberry fruits have the anti-inflammatory and anti-oxidantive effects. So this study was done to investigate the anti-inflammatory and anti-oxidantive effects of mulberry fruit extract(MFE) on the serum biochemical indices especially inflammatory indices in seven rheumatoid patients visited Health Center in Taeangun area Anthropometry measurement, serum biochemical parameters including lipid profiles, cardiovascular disease indices, inflammatory factors and serum oxidative stress makers were compared before and after administration of MFE for 2 weeks. After administration of MFE, there were no significant differences, but appeared a tendency to decrease in anthropometry measurements(BMI: body mass index, % of body fat and body fat), serum biochemical indices(serum total cholesterol, triglyceride, LDL-cholesterol, uric acid, carbon-reactive protein, rheumatoid factor, ASP: aspartate transaminase and ALT alanine transaminase) and cardiovascular disease indices(CRF: cardiac risk factor, LHR: low density lipoprotein cholesterol and Al: atherogenic index). On the other hand, there was tendency to increase in lean body mass, serum HDL-cholesterol and HTR(high density lipoprotein cholesterol and total cholesterol ratio). These results suggested careful monitoring of MFE intakes is required for these patients.

      • SCOPUSKCI등재

        진균성 부비동염의 병리학적 유형에 따른 치료 효과 및 임상 양상

        김유미,허애정,임홍석,규연,장경희,홍성관,김창오,염준섭,최영화,송영구,김준명 대한의진균학회 2001 대한의진균학회지 Vol.6 No.3

        Background: There are three basic types of fungal sinusitis: noninvasive, invasive, and allergic. Both noninvasive and invasive fungal sinusitis necessarily require surgery with or without antifungal treatment. This study was performed to evaluate the efficacy of treatment modalities and clinical characteristics between pathologically proven noninvasive and invasive fungal sinusitis. Methods: 40 patients pathologically proven to have fungal sinusitis from July, 1990 to January, 2000 were enrolled in this study. This retrospective study was performed in Severance Hospital, Yong-Dong Severance Hostpital and Ah-Joo University Hospital. The efficacy of treatment modalities and prognosis between pathologically proven noninvasive group (group A) and invasive group (group B) were evaluated. Results: Of the to total 140 patients, 13 were male and 27 were female, and the mean age was 51.6± 14.2 years, 32 patients belonged to noninvasive group and 8 Patients belonged to invasive group. Of the total 40 patients, 20 (50%) patients had underlying diseases, such as 8 cases of Diabetes Mellitus, 3 cases of hematologic malignancy, 2 cases of solid cancer, 1 case of steroid overuse, and the others 6 cases. In group A, only 12 patients (37.5%) had underlying diseases, however, all 8 patients (100%) in groups B had underlying diseases. All 32 patients of groups A went chronic course but in group B, all 8 patients appeard to be acute in course. The pathogens were classified to 36 cases of Aspergillus spp. (69.2%),3 cases of Rhizopus spp. (5.8%), and 1 case of Candida spp. (1.9%). As for the treatment modalities, in group A, 30 cases had surgery only and 2 cases performed surgery and antifungal treatment. Both showed 100% of treatment efficacy. In group B, 5 cases were treated with antifungal therapy only and 2 cases performed surgery and antifungal treatment. The former showed 20% and the latter, 33% of treatment efficacy. Noninvasive fungal sinusitis revealed good results even in surgery only therapy, but invasive fungal sinusitis tended to reveal better results in both surgery and antifungal treatment. Conclusion: The pathologic type of fungal sinusitis is now thought to be very important for the choice of treatment modalities and efficacy of treatment. Also the type of pathogens, immunologic state of patients, and early diagnosis of fungal sinusitis attribute to the treatment efficacy of fungal sinusitis. [Kor J Mee Mycol 6(3): 167-173]

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