Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

췌십이지장절제술 후 발생한 지속적인 구토증과 Wernicke 뇌병증

박우영,김성완,이삼연,신일선,김재민,박기형,양수진,윤진상 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.3

Wernicke encephalopathy is an acute neurologic disorder attributable to thiamine (vitamin B1) deficiency. We report the case of a 61-year-old female patient who presented Wernicke encephalopathy after surgery for pancreatic head cancer. From the ninth postoperative day, she had suffered from nausea and vomiting and had difficulties ingesting food, she was given total parenteral nutrition (TPN), but lacked adequate vitamin (thiamine) supplementation. After 28 days, she developed ataxia, ophthalmoplegia, and mental confusion. The magnetic resonance image showed pathologic changes in the medial thalamus,periaqueductal gray matter, medulla and mamillary bodies. The blood level of thiamine was very low. After intravenous and oral supplementation of thiamine (200 mg/day), consciousness was soon normalized and neurologic symptoms have gradually been improving. Nausea and vomiting disappeared after administration of a low dose of mirtazapine (7.5 mg/day). We emphasize the importance of thiamine supplementation to the patients who suffer from vomiting which hinders them from taking food and who require prolonged TPN.

저독성 난연제를 첨가한 에폭시 수지의 경화 동력학 및 유변학적 특성

박수진,송수완,이재락,민병각,신재섭 한국공업화학회 2004 공업화학 Vol.15 No.1

본 실험에서는 2관능성 에폭시 수지(EP)에 저독성 난연제인 tris (chloroisopropyl) phosphate (TCPP) 를 100:0~100:40 phr의 비율로 첨가한 후 이에 따른 경화 동력학과 유변학적 특성을 고찰하였다. 2EP/TCPP 시스템의 경화 활성화 에너지(E_(a))와 진화량(α)은 동적 DSC를 통하여 알아 보았으며, 유변학적 특성은 레오미터를 이용하여 등온 조건하에서 고찰하였다. 또한, 난연성 test인 UL94를 통하여 TCPP 함량에 따른 난연성의 변화를 살펴보았다. 실험 결과, E_(a)는 에폭시 수지 내에 TCPP의 함량이 증가할수록 증가하는 반면, 전화량(α)과 전환속도(d/dt)는 감소하는 경향을 나타내었다. 가교 활성화 에너지(E_(c)) 값은 구한 E_(a) 값과 유사한 경향을 나타내었으며, 이러한 결과는 TCPP의 증가로 인해 2EP 고유의 interpenetrating polymer network (IPN) 구조형성이 방해받기 때문이라 판단된다. 또한, TCPP의 함량이 30 phr 이상인 경우 난연성이 향상되었는데, 이는 TCPP 내의 난연성을 갖는 인과 염소의 영향으로 판단된다. In this work. the cure kinetics and rheological properties of difunctional epoxy (2EP) resins containing a low toxicity flame-retardant based on tris(chloroisopropyl) phosphate (TCPP) are investigated. The 2EP/TCPP content was varied within 100 : 0 ∼100 : 40 phr. The cure system are studied under the isothermal condition using a rheometer, Also, the flame resistance is determined by UL94 vertical test. From experimental results, the Ea of 2EP/TCPP system is higher than that of pure 2EP. While, the conversion (α1 and conversion rate (d/dt) are decreased with increasing of the TCPP content. The cross-linking activation energy (E_(e)) of the system is similar to (E_(a)). This is probably due to the increase of TCPP content. which obstructs the formation of interpenetrating polymer network (IPN) structure of the 2EP. Also, the improvement of flame resistance is achieved by addition of 30 phr TCPP in the 2EP/TCPP system. which can be attributed to the existence of incombustible phosphorous and chlorines in the TCPP.

급성 파라쿼트 중독에서 혈중 파라쿼트 농도

박승민,김세현,최수진,김현,이완구,김영남,이광영,이영희,신성혜 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

Background: Paraquat is a bipyridyl compound, and when ingested, concentrated paraquat can cause either rapid death from multisystem failure and cardiovascular shock or delayed death from progressive pulmonary fibrosis. Paraquat is poorly absorbed by inhalation, but when ingested orally, severe illness can occur. Death usually occurs within 2 days if more than 50 ㎎/㎏ of paraquat is ingested . The most important prognostic indicator is the quantity of paraquat absorbed, as shown by the plasma paraquat concentration, and the prognostic indication depends mostly on the description given by the patients and their families about the amount of paraquat ingested, which is often underestimated or overestimagted. For these reasons, we tried to compare the plasma paraquat concentrations with amount of paraquat described by patients or their families. Methods: We reviewed the medical records of 59 patients with acute paraquat poisoning from February 1998 through February 1999, the paraquat concentrations in plasma were measured at Presbyterian Medical Center by using high performance liquid chromatography. Results: There was a striking discrepancy between the plasma paraquat concentration and the ingested amount described by the patients or their families. Conclusion: We recommend that the plasma paraquat concentration be measured in patients being treated for acute paraquat poisoning.

타리비드 정(오플록사신 100㎎)에 대한 파비드 정의 생물학적동등성

박완수,조성희,이헌우,임호택,홍성제,서성훈,류재환,이경태 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

The purpose of the present study was designed to evaluate the bioequivalence of two ofloxacin tablets, Tarivid (Jell Pharm. Co., Ltd.) and Favid (ILHWA Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, 23.67±3.12 year in age and 68.50±7.23 kg in body weight, were divided into two groups and a randomized 2x2 cross-over study was employed. After four tablets containing 100 mg of ofloxacin were orally administered, blood was taken at predetermined time intervals and concentrations of ofloxacin in plasma were deter mined using HPLC. Pharmacokinetic parameters such as AUC_(t) and T_(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC_(t), and C_(max) and untransformed T_(max). There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log 0.8 to log 1.25 (e.g., log 0.94-log 1.04 and log 0.90-log 1.07 for AUC_(t) and C_(max) respectively). The major parameters. AUC_(t) and C_(max) met the criteria of KDFA for bioequivalence indicating that Favid tablet is bioequivalent to Tarivid tablet.

국제물류 환경변화에 따른 경제자유구역 물류거점기능 강화방안

서수완,박영태 한국물류학회 2005 물류학회지 Vol.15 No.1

본 연구는 중국 물류시장의 급속한 성장에 대응하고 한국내 글로벌 물류기업 유치 및 물류산업 육성을 위한 대안의 일환으로 경제자유구역의 물류거점기능 강화방안을 분석하였다. 본 연구에서 검토한 바에 따르면 경제자유구역의 성공가능성은 투자대상국의 발전가능성과 시장규모, 배후연계수송능력, 물류비수준과 물류기반시설 및 화물처리시설 확보수준 및 국가지원 등의 변수에 의해 결정될 수 있으며, 아울러 한국 물류기업의 경쟁성 향상 또한 매우 중요한 변수로 간주되고 있다. 이러한 사실로부터 경제자유구역에 대한 외국기업을 비롯한 관련 물류기업의 투자를 이끌어내기 위해서는 비용요인 보다는 시장요인 개선전략을 통해 경제자유구역의 물류거점기능 강화전략이 추진되어야 한다는 결론을 도출할 수 있었다. 이는 한국 자체시장 규모를 확대시킬 수 있는 전략의 추진이 선행되어야 함을 의미하는 것이며, 이를 위해서는 국내 물류기업의 경제자유구역 참여를 확보할 수 있는 정책적 보완이 요구된다. 아울러 한국의 주요 거점지역과 외국 주요 거점간에 보다 많은 물류네트워크 관계를 형성할 수 있는 방안을 모색하는 것이 순차적인 전략이라고 판단할 수 있다. This paper investigated strengthening the function of logistics hub in free economic zone(FTZ) in order to attract investments from global logistics companies and to raise logistics industry. The successfully probability of FTZ will be decide by potential growth of host country and market size, transportability connected with hinterland, logistics cost level, logistics infrastructure, level of cargo handling facility, government support, competitiveness of Korean logistics companies, etc. Therefore, to attract investment from the foreign companies and related logistics companies, the strategy to strengthen the function of logistics hub in FTZ have to performed through improvement of market factors rather than cost factors was deduced. It is mean that the procurement strategy to expand market size in Korea is pre-performed, and political supplementation, the investment on FTZ is guaranteed by domestic logistics companies, should be needed. Also, it is that the more and more logistics network inter major logistics hub in domestic and foreign is build will be successively strategy.

Carbonyl 화합물에 대한 Trimethyl-Silylcyanide의 첨가 반응

한완수,박철영,이일규 中央大學校 自然科學硏究所 1988 自然科學硏究所 論文集 Vol.2 No.-

Trimethylsilylcyanide is found to be a good reagent for the formation fo trimethylsilylcyanohydrin ethers from the direct reaction with carbonyl compounds. To obtain organic cyanoderivatives, trimethylsilylcyanide was addes to vbarious carbonyl compounds (acetaldehyde, acetone, cyclohexanone, propiophenone, benzophenone) in the presence of Lewis acid catalysts at room temperature. Addition of small amounts of Lewis acid catalysts to the reactions increased the yields of trimethylsilylcyanide carbonyl addition products. The results of these reactions indicated that the yields in trimethylsilycyanide addition reaction to the highly hindered carbonyl compounds were affected by the nature of catalysts employed, and increased as below. AlCl₃>SnCl₄≫ZnCl₂

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

국내 조혈모세포이식 환자에서 Human Cytomegalovirus gB 유전형의 분포와 질환과의 연관성 : 예비 보고

최수미,김진희,이동건,박선희,최정현,유진홍,박철민,이종욱,민우성,황응수,신완식,김춘추 대한감염학회 2007 감염과 화학요법 Vol.39 No.2

목적 : 사람 거대세포바이러스(Human cytomegalovirus, 이하 HCMV) glycoprotein B (gB)는 UL55 유전자에 의해 부호화되는 당단백으로, UL55 유전자의 염기서열변화에 따라 4가지 유전형으로 나뉜다. 본 연구에서는 국내 조혈모세포이식 환자들에서 HCMV gB 유전형의 분포와 그 특성을 알아보고, gB 유전형에 따라 특정 HCMV 질환 발생과 연관이 있는지 그 임상적 의미를 분석해 보고자 하였다. 재료 및 방법 : 동종 조혈모세포이식 환자 52명의 혈액검체 94개에 대해, Chou 등이 제시한 방법에 따라, 먼저 UL55 유전자 부위를 nested PCR로 증폭한 후, RsaI과HinfI으로 Restriction fragment length polymorphism(RFLP) 분석을 시행하였다. 결과 : gB type 1은 73.1% (38/52), gB type 2는 13.5%(7/52), gB type 3는 1.9% (1/52), gB type 1과 type 2에 의한 혼합감염은 9.6% (5/52)로 나타났다. gB type 4는 관찰되지 않았다. 1명(1.9%)에서 gB 유전형을 결정할 수 없었는데, RFLP 패턴으로 보아 Trincado 등이 제시한 gB type 7에 해당하는 것으로 생각되었고, 이 새로운 아형에 대해서는 현재 염기서열 분석 중이다. 52명 중 5명(9.6%)에서 HCMV 질환이 발생하였고, 3명에서 HCMV 폐렴, 1명에서 망막염과 위장관염, 나머지 1명에서 망막염이 발생하였다. 5명 중 HCMV 질환과 관련하여 사망한 예는 없었고, 감염된 HCMV는 모두 gB type 1이었다. HCMV gB유전형과 HCMV 질환 발생 사이에 유의한 연관성은 없었고, 단일 주에 의한 감염과 혼합감염에 따른 HCMV 질환발생 사이에도 유의한 연관성은 관찰되지 않았다. 자료 분석 중 gB type 2에 감염되어 있던 환자에서 gB type 1에 재감염 되면서 발열, 간효소 수치 상승 및 pp65 HCMV 항원혈증이 나타난 예가 있었다. 결론 : 연구결과 gB type 1이 아주 우세하고, gB type 4는 검출되지 않았으며, 혼합감염의 빈도가 비교적 낮은 분포를 보였다. 이는 외국의 보고와는 다른 국내 조혈모세포이식 환자에서의 독톡한 감염 양상으로 추정된다. 본 연구에서 HCMV gB 유전형과 질환 발생과의 연관성을 밝힐 수는 없었으나, HCMV 유전형에 대한 연구는 바이러스 감염의 발병기전이나 전파 경로 및 양식과 같은 역학적 연구에 중요한 자료가 될 것이다. 현재 더 많은 수의 조혈모세포이식 환자를 대상으로 연구가 진행 중에 있으며, 앞으로 다른 질환군의 환자나 건강한 잠복 감염자에서의 추가 연구가 필요할 것으로 생각된다. Background : Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. Materials and Methods : DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. Results : The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days’ follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. Conclusion : HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.