• 제목/요약/키워드: First-in-human dose

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BIDAS프로그램 : 방사성 핵종의 섭취량과 선량 평가용 생물학적분석 자료 해석 소프트웨어 프로그램 (The BIDAS Program : Bioassay Data Analysis Software for Evaluating Radionuclide Intake and Dose)

  • Tae-Yong Lee;Jong-Kyung Kim;Jong-Il Lee;Si-Young Chang
    • 방사성폐기물학회지
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    • 제2권2호
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    • pp.113-124
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    • 2004
  • 본 연구에서는 인체 내에서 방사성핵종의 거동에 관하여 국제방사선방호위원회에서 권고한 최근 호흡기 모델, 소화기 모델 및 생체동역학 모델을 사용하여 생물학적분석 자료로부터 섭취량과 예탁유효선량을 평가하기 위한 BIDAS 프로그램을 개발하였다. 프로그램은 생물학적분석 자료를 관리하는 데이터베이스 모듈, 각 방사성 핵종에 대한 예측 생물학적분석 양을 내장하고 있는 모듈, 측정된 생물학적분석 양에 근거하여 급성 및 만성 피폭으로부터 섭취량과 선량을 평가하는 계산모듈 등으로 구성되어 있다. 본 논문은 프로그램의 특성과 검증결과에 대해 기술한다.

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지하수로부터 방출된 라돈에 의한 현실적인 체내축적량 평가 (A Realistic Human Exposure Assessment of Indoor Radon released from Groundwater)

  • 유동한;한문희
    • Journal of Radiation Protection and Research
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    • 제27권2호
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    • pp.121-126
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    • 2002
  • 본 연구는 지하수로부터 방출되어 가옥의 실내에 존재하는 라돈에 의한 체내축적량을 현실적으로 평가하는 방법을 보여준다. 먼저 지하수로부터 실내공기로 전달되는 과정을 모의하기 위해 2_구역모델을 개발하였다. 이 모델은 실내에서 발생하는 생활활동, 즉, 목욕, 세수, 세탁, 변기에서의 물사용에 의해 실내로 휘발, 이동하는 시간에 따를 라돈농도분포를 계산한다. 다음, 이 모델의 불확실성이 존재하는 입력인자들에 대해 불확실성분석을 수행하여 최종 실내라돈 농도분포를 결정하였다. 그리고 이러한 실내 라돈을 호흡하여 체내에 축적되는 양을 보다 정량적으로 모의하기 위해 PBPK 모델을 개발하였다. 불확실성이 포함된 라돈농도분포와 정량적인 체내축적모의를 위한 PBPK 모델의 결합으로 보다 현실적인 라돈의 체내축적량을 분석할 수 있다. 이러한 연구의 결과는 지하수로부터 발생하는 라돈에 의한 인체위해평가시 도움을 주리라고 판단된다.

Role of Calmodulin in the Generation of Reactive Oxygen Species and Apoptosis Induced by Tamoxifen in HepG2 Human Hepatoma Cells

  • Lee, Yong-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • 제6권4호
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    • pp.187-191
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    • 2002
  • Tamoxifen, an antiestrogen, has previously been shown to induce apoptosis in HepG2 human hepatoblastoma cells through activation of the pathways independent of estrogen receptors, i.e., intracellular $Ca^{2+}$ increase and generation of reactive oxygen species (ROS). However, the mechanism of tamoxifen to link increased intracellular $Ca^{2+}$ to ROS generation is currently unknown. Thus, in this study we investigated the possible involvement of calmodulin, a $Ca^{2+}$ activated protein, and $Ca^{2+}$/calmodulin-dependent protein kinase II in the above tamoxifen-induced events. Treatment with calmodulin antagonists (calmidazolium and trifluoroperazine) or specific inhibitors of $Ca^{2+}$/calmodulin-dependent protein kinase II (KN-93 and KN-62) inhibited the tamoxifen-induced apoptosis in a dose-dependent manner. In addition, these agents blocked the tamoxifen-induced ROS generation in a concentration-dependent fashion, which was completely suppressed by intracellular $Ca^{2+}$ chelation. These results demonstrate for the first time that, despite of its well-known direct calmodulin-inhibitory activity, tamoxifen may generate ROS and induce apoptosis through indirect activation of calmodulin and $Ca^{2+}$/calmodulin-dependent protein kinase II in HepG2 cells.

The Significance of the Analytical Sciences In Environmental Assessment

  • Chung, Yong;Ahn, Hye-Won
    • 분석과학
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    • 제8권4호
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    • pp.1079-1087
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    • 1995
  • The quality of human life is directly related to the quality of the environment. To assess environmental quality we must first determine the MCLG(Maximum Contaminant Level Goal), MCL(Maximum Contaminant Level), environmental impact and so on. The MCLG is the concentration at which no known adverse health effects occur. The MCLG is determined by risk assessment identifying which process is hazardous assessing, dose-response, human exposure, and characteristics of risk. With consideration of analytical methods, treatment technology, cost and regulatory impact, the MCL is set as close to the MCLG as possible. In this way, determination of the concentration and national distribution of contaminants is important for assessment of environmental quality The analytical sciences pose potential problems in assessing environmental quality. Continuing improvement in the performance of analytical instruments and operating technique has been lowering the limits of detectability. Contaminant concentration below the detection limit has usually been reported as ND(Not-Detected) and this has often been misunderstood as equivalent to zero. Because of this, more the contaminant concentration in the past was below the detection limit, whereas contaminants can be quantified now even though the contaminant concentration might remain the same or may even have decreased. In addition, environmental sampling has various components due to heterogeneous matrices. These samples are used to overestimate the concentration of the contaminant due to large variability, resulting in excess readings for MCL. In this paper, the significance of the analytical sciences is emphasized in both a conceptual and a technical approach to environmental assessment.

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Lithocholic Acid Activates Mas-Related G Protein-Coupled Receptors, Contributing to Itch in Mice

  • Song, Myung-Hyun;Shim, Won-Sik
    • Biomolecules & Therapeutics
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    • 제30권1호
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    • pp.38-47
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    • 2022
  • The present study focused on lithocholic acid (LCA), a secondary bile acid that contributes to cholestatic pruritus. Although recent studies have found that LCA acts on MAS-related G protein-coupled receptor family member X4 (MRGPRX4) in humans, it is unclear which subtypes of MRGPRs are activated by LCA in mice since there is no precise ortholog of human MRGPRX4 in the mouse genome. Using calcium imaging, we found that LCA could activate mouse Mrgpra1 when transiently expressed in HEK293T cells. Moreover, LCA similarly activates mouse Mrgprb2. Importantly, LCA-induced responses showed dose-dependent effects through Mrgpra1 and Mrgprb2. Moreover, treatment with QWF (an antagonist of Mrgpra1 and Mrgprb2), YM254890 (Gαq inhibitor), and U73122 (an inhibitor of phospholipase C) significantly suppressed the LCA-induced responses, implying that the LCA-induced responses are indeed mediated by Mrgpra1 and Mrgprb2. Furthermore, LCA activated primary cultures of mouse sensory neurons and peritoneal mast cells, suggesting that Mrgpra1 and Mrgprb2 contribute to LCA-induced pruritus. However, acute injection of LCA did not induce noticeable differences in scratching behavior, implying that the pruritogenic role of LCA may be marginal in non-cholestatic conditions. In summary, the present study identified for the first time that LCA can activate Mrgpra1 and Mrgprb2. The current findings provide further insight into the similarities and differences between human and mouse MRGPR families, paving a way to understand the complex roles of these pruriceptors.

Generation of a Human Monoclonal Antibody to Cross-Reactive Material 197 (CRM197) and Development of a Sandwich ELISA for CRM197 Conjugate Vaccines

  • Kim, Dain;Yoon, Hyeseon;Kim, Sangkyu;Wi, Jimin;Chae, Heesu;Jo, Gyunghee;Yoon, Jun-Yeol;Kim, Heeyoun;Lee, Chankyu;Kim, Se-Ho;Hong, Hyo Jeong
    • Journal of Microbiology and Biotechnology
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    • 제28권12호
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    • pp.2113-2120
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    • 2018
  • Cross-reactive material 197 ($CRM_{197}$) is a non-toxic mutant of diphtheria toxin containing a single amino acid substitution of glycine 52 with glutamic acid. $CRM_{197}$ has been used as a carrier protein for poorly immunogenic polysaccharide antigens to improve immune responses. In this study, to develop a sandwich ELISA that can detect $CRM_{197}$ and $CRM_{197}$ conjugate vaccines, we generated a human anti-$CRM_{197}$ monoclonal antibody (mAb) 3F9 using a phage-displayed human synthetic Fab library and produced mouse anti-$CRM_{197}$ polyclonal antibody. The affinity ($K_D$) of 3F9 for $CRM_{197}$ was 3.55 nM, based on Bio-Layer interferometry, and it bound specifically to the B fragment of $CRM_{197}$. The sandwich ELISA was carried out using 3F9 as a capture antibody and the mouse polyclonal antibody as a detection antibody. The detection limit of the sandwich ELISA was <1 ng/ml $CRM_{197}$. In addition, the 3F9 antibody bound to the $CRM_{197}$-polysaccharide conjugates tested in a dose-dependent manner. This ELISA system will be useful for the quantification and characterization of $CRM_{197}$ and $CRM_{197}$ conjugate vaccines. To our knowledge, this study is the first to generate a human monoclonal antibody against $CRM_{197}$ and to develop a sandwich ELISA for $CRM_{197}$ conjugate vaccines.

한국의 장흡충에 관한 연구 Vlll. 호르텐스 극구흡충(Echinostomu hoytense)의 인체감염 1예 (Studies on Intestinal Trematodes in Korea VIII. A Human Case of Echinostoma hortense Infection)

  • 서병고;홍성태채종일이순형
    • Parasites, Hosts and Diseases
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    • 제21권2호
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    • pp.219-223
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    • 1983
  • 경상북도 문경군에 주소를 둔 21세 한국인 남자에서, 1983년 10월에 실시한 집단 검변 도중 크기가 0.127∼0.139min인 흡충란을 발견하였다. 이를 극구흡충류 충란으로 생각하고, 국산 프라지관텔(디스토시드) 20mg/kg을 1회 투여하고 염류하제를 1시간 후에 복용시켜 설사변을 4회 수집 조사한 결과, 극구흡충의 성충 1 마리와 간흡충 4마리가 수집되었다. 이 홉충은 성충과 충란의 계측치, 난소와 고환의 위치 등을 근거로 하여 호르텐스극단흡충(Echinostoma hortense)으로 동정되었고 국내 최초의 인체감염임이 확인되었다. 이 환자는 고향에서 많은 종류의 민물고기를 날로 먹은 경험이 있다고 하나 미꾸리 등 알려진 중간숙주는 생식한 기억이 없다 하므로 정확한 감염원을 파악할 수는 없었다. 초상적 문제나 증후는 전혀 관찰되지 않았으며 말초혈액중의 호산량는 6%이었다.

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에토석시미드의 HPLC 분석법 및 한국인에서의 약동학적 특징 (HPLC Determination and Pharmacokinetic Profile of Ethosuximide in Korean Subjects)

  • 배정우;김지홍;양상인;김현경;장춘곤;한혜원;박영서;손의동;이석용
    • 약학회지
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    • 제47권6호
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    • pp.444-459
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    • 2003
  • Ethosuximide is an oral anticonvulsantic agent used in the first choice anti-absence seizure drug. The purpose of this study was to assess the pharmacokinetic profile of the ethosuximide in healthy Korean volunteers and to develop the efficient assay method of ethosuximide in human plasma. The pharmacokinetics of ethosuximide administered orally was evaluated after a dose of 500 mg. Ethosuximide was assayed from plasma by a specific HPLC method reading absorbance at 195 nm. AUC was 1222$\pm$160 $\mu\textrm{g}$/$m\ell$$.$hr, $C_{max}$ 14.2l$\pm$1.74 $\mu\textrm{g}$/$m\ell$, $T_{max}$ 1.06$\pm$0.62 hr and half-life 77.83$\pm$12.46 hr. The half-life in Korean was longer than, in Caucasian (53∼56 hr).).).

태반성 성선 자극 호르몬 (Human Chorionic Gonadotropin) 처리에 의한 미꾸라지의 산란 유도 및 연중 다산란 유도를 위한 연구 (Induced and Multiple Spawnings by Human Chorionic Gonadotropin Injection of the Loach, Misgurnus mizolepis (Teleostomi : Cobitidae))

  • 김동수;김종현;박인석
    • 한국양식학회지
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    • 제5권2호
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    • pp.109-115
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    • 1992
  • 미꾸라지 양식시 기본 요건인 종묘의 안정적 공급을 위하여 호르몬 처리에 의한 산란 유도와 연중 다산란 유도 가능성을 조사하였다. 미꾸라지는 어체중 g당 $2\~10$ IU 농도의 태반성 성선자극 호르몬(HCG) 1회 주사로 $23.1\~100{\%}$ 산란이 유발되었으며, 특히 6 IU/g의 농도 이상에서는 모든 실험어가 산란하였다. 호르몬 주사 후 산란까지 대개 $13\~25$시간이 소요되었고 HCG농도 증가에 따른 수정율, 부화율 및 위생식소 숙도지수의 변화는 관찰되지 않았다. 어체중 증가에 따라 포란수도 증가하여 어체중 g당 평균 약 $500\~600$의 난을 산란하는 것으로 나타났다. 다산란 유도를 위해 $25^{\circ}C$ 조건하에서 사육하면서 첫 산란 후 사육 일수에 따른 비만도, 간 숙도지수 및 생식소 숙도지수를 조사하고 이를 토대로 재산란을 유도한 결과 미꾸라지 암컷은 최초 산란 후 40 일이 경과하면 양질의 난을 재산란하는 것으로 나타났다.

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일부 공단지역 PM2.5에 부착된 중금속 노출에 의한 건강위해성평가 (Health Risk Assessment of Heavy Metals in PM2.5 in Industrial Areas)

  • 전준민;강병욱;이학성;이철민
    • 한국환경보건학회지
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    • 제36권4호
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    • pp.294-305
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    • 2010
  • This study estimated the health risk of heavy metals in particulate matter $(PM)_{2.5}$ in a Gwangyang industrial complex. The $PM_{2.5}$ containing heavy metal was collected from January to November, 2008 using a denuder air sampler and by IC (Ion Chromatograph). The risk assessment was performed in a four-step process; hazard identification, exposure assessment, dose-response assessment and risk characterization. In the hazard identification process, $Cr^{6+}$, Ni, As, and Pb were categorized as human carcinogens and probable human carcinogens, while Ti, Mn, Se, P, $Cr^{3+}$, Cu, and Zn were not classified as human carcinogens. It was found that the excess cancer risk by Central Tendency Exposure (CTE) of $Cr^{6+}$ and As in $PM_{2.5}$ was > $10^{-6}$, and the total excess cancer risk posed by carcinogen heavy metals in $PM_{2.5}$ was > $10^{-6}$. It was also determined that the total hazard index by CTE of non-carcinogen heavy metals in $PM_{2.5}$ was <1. Taken together, these results indicate a high cancer risk associated whit inhalation of heavy metal-containing$PM_{2.5}$ in industrial areas.