A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom

Kiwon Han,Kikyung Jung,Hokyung Oh,Hojin Song,Sangmi Park,Ji-Hye Kim,Garam Min,Byung-Hwa Lee,Hyun-sik Nam,Yang Jin Kim,Manabu Ato,Jayoung Jeong,Chiyoung Ahn 한국독성학회 2018 Toxicological Research Vol.34 No.3

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of 90.13 ㎍/TD (95% confidence interval = 87.39~92.86 ㎍) and a hemorrhagic titer of 10.80 ㎍/TD (95% confidence interval = 10.46~11.14 ㎍). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom

Han, Kiwon,Jung, Kikyung,Oh, Hokyung,Song, Hojin,Park, Sangmi,Kim, Ji-Hye,Min, Garam,Lee, Byung-Hwa,Nam, Hyun-sik,Kim, Yang Jin,Ato, Manabu,Jeong, Jayoung,Ahn, Chiyoung Korean Society of ToxicologyKorea Environmental Mu 2018 Toxicological Research Vol.34 No.3

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of $90.13{\mu}g/TD$ (95% confidence interval = $87.39{\sim}92.86{\mu}g$) and a hemorrhagic titer of $10.80{\mu}g/TD$ (95% confidence interval = $10.46{\sim}11.14{\mu}g$). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

VO, Thuy T. B.,JUNG, Eui-Man,DANG, Vu Hoang,JUNG, Kikyung,BAEK, Jounghee,CHOI, Kyung-Chul,JEUNG, Eui-Bae Society for Reproduction and Development 2009 Journal of Reproduction and Development Vol.55 No.4

<P>Endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function by binding to androgenic receptors (AR) and inducing or modulating AR-dependent responses in the male reproductive system. However, the molecular mechanism(s) underlying these events remains unclear. In the present study, pregnant Sprague Dawley (SD) rats were treated with testosterone propionate (TP), flutamide (Flu) and di-(2-ethylhexyl) phthalate (DEHP) from gestation days (GD) 11 to 21. Interestingly, maternal exposure to Flu or DEHP caused fluctuations in the neonatal levels of serum testosterone (T) and luteinizing hormone (LH). Serum testosterone and LH were upregulated by Flu, but these hormones were down-regulated by DEHP. The anogenital distances (AGD) of male newborns were determined at post-neonatal days (PND) 1, 21 and 63. Male rats treated prenatally with DEHP (100 mg/kg mother's body weight) or Flu showed an AGD shorter than that of control rats. At PND 63, sperm concentration, viability and motility were reduced in the maternal DEHP and Flu-treated groups. The numbers of seminiferous tubules were reduced in the Flu and DEHP-treated offspring when compared with the vehicle- and TP-treated groups, and the tubules of the testes at PND 63 were disrupted by a high dose of Flu. In addition, we found differential gene expression patterns by microarray analysis following ED exposure, particularly in sex determination-related genes. Although Flu and DEHP are considered to be identical with regard to their anti-androgenic effects, their effects on developing male reproductive organs were distinct, suggesting that Flu competes with endogenous T, while DEHP influences a different step in androgenesis.</P>

사회적 배제자들에게 쾌락재는 기부를 자극시키는가?

오민정(Oh, Min Jung),박기경(Park , Kikyung),박종철(Park, Jong Chul) 한국문화산업학회 2017 문화산업연구 Vol.17 No.3

본 연구는 사회적 배제(배제 vs. 통제)조건에서 제품유형이 준거기준으로 제시되었을 때 기부의도에 미치는 영향을 살펴봄과 동시에 수혜자의 표정(슬픔 vs. 기쁨)에 따라 기부자의 기부설득에 미치는 태도가 어떻게 달라지는지를 파악하였다. 즉 기존 선행연구에 따르면, 쾌락적 제품을 구매한 기부자들의 부의도가 높았으며, 수혜자의 슬픈 표정이 기부자들의 동정심을 자극하여 기부행동을 높여주었다. 하지만 아직까지 사회적 배제상황에서의 제품유형과 수혜자의 표정에 따른 조절효과를 살펴본 연구가 없으며 특히 본 연구에서는 제품유형을 준거기준으로 제시하여 선택맥락효과를 확인하고자 하였다. 하지만 연구결과 사회적 배제 조건에서 제품유형은 기부의도에 영향을 미치지 않았고, 수혜자의 표정 역시 조절변수로서 영향을 미치지 않았다. 이러한 조절상황을 보다 심도 있게 분석하기 위해 제품이 실용적인지 쾌락적인지, 또한 수혜자의 표정이 슬픈 표정인지 기쁜 표정인지에 따라 기부의도가 어떻게 달라지는지를 검증하기 위해 삼원상호작용 효과를 살펴보았다. 그 결과, 흥미롭게도 제품유형과 수혜자의 표정이 동시에 기부의도에 영향을 미치고 있었는데 특히 사회적 배제 집단에게서 그 차이가 뚜렷이 나타났다. 구체적으로, 사회적배제집단의 기부자들이 실용적 제품을 준거기준으로 제시받았을 때는 수혜자가 웃는 표정을 보일 때 기부의도가 높아진 반면, 쾌락적 제품을 먼저 접한 기부자들의 경우는 슬픈 표정의 수혜자에게 높은 기부의도 성향을 보이는 것으로 나타났다. The purpose of this study is to investigate the effect of product type on the donation intention when the product type is presented on the basis of social exclusion(exclusion vs control) and to examine the attitude toward donor`s donation persuasion according to the recipient`s facial expression(sadness vs happy). According to the previous study, donors who purchased hedonic products had a high degree of donation intention, and the sad facial expression of the recipient stimulated the sympathy of the donors and increased donation. However, there is no study on the effect of product type and recipient"s facial expression on social exclusion. Especially in this study we tried to confirm the effect of selective context by presenting product type as reference. But, in the social exclusion condition, the product type did not affect the donation intention and the recipient"s expression did not affect as a moderating variable either. However, in order to analyze the moderating situation more deeply, we examined the effect of 3-way interaction to test whether the product is utilitarian or hedonic and whether the recipient`s facial expression is sad or happy. As a result, interestingly, the product type and the recipient`s expression influenced donation intention at the same time, especially in the social exclusion group. In particular, donors of the social exclusion group are more likely to donate when the recipient shows a smiling face when the utilitarian product, but in the case of donors who have first experienced hedonic products are more likely to donate when the recipient shows a sad expression. 본 연구는 사회적 배제(배제 vs. 통제)조건에서 제품유형이 준거기준으로 제시되었을 때 기부의도에 미치는 영향을 살펴봄과 동시에 수혜자의 표정(슬픔 vs. 기쁨)에 따라 기부자의 기부설득에 미치는 태도가 어떻게 달라지는지를 파악하였다. 즉 기존 선행연구에 따르면, 쾌락적 제품을 구매한 기부자들의 부의도가 높았으며, 수혜자의 슬픈 표정이 기부자들의 동정심을 자극하여 기부행동을 높여주었다. 하지만 아직까지 사회적 배제상황에서의 제품유형과 수혜자의 표정에 따른 조절효과를 살펴본 연구가 없으며 특히 본 연구에서는 제품유형을 준거기준으로 제시하여 선택맥락효과를 확인하고자 하였다. 하지만 연구결과 사회적 배제 조건에서 제품유형은 기부의도에 영향을 미치지 않았고, 수혜자의 표정 역시 조절변수로서 영향을 미치지 않았다. 이러한 조절상황을 보다 심도 있게 분석하기 위해 제품이 실용적인지 쾌락적인지, 또한 수혜자의 표정이 슬픈 표정인지 기쁜 표정인지에 따라 기부의도가 어떻게 달라지는지를 검증하기 위해 삼원상호작용 효과를 살펴보았다. 그 결과, 흥미롭게도 제품유형과 수혜자의 표정이 동시에 기부의도에 영향을 미치고 있었는데 특히 사회적 배제 집단에게서 그 차이가 뚜렷이 나타났다. 구체적으로, 사회적배제집단의 기부자들이 실용적 제품을 준거기준으로 제시받았을 때는 수혜자가 웃는 표정을 보일 때 기부의도가 높아진 반면, 쾌락적 제품을 먼저 접한 기부자들의 경우는 슬픈 표정의 수혜자에게 높은 기부의도 성향을 보이는 것으로 나타났다. The purpose of this study is to investigate the effect of product type on the donation intention when the product type is presented on the basis of social exclusion(exclusion vs control) and to examine the attitude toward donor`s donation persuasion according to the recipient`s facial expression(sadness vs happy). According to the previous study, donors who purchased hedonic products had a high degree of donation intention, and the sad facial expression of the recipient stimulated the sympathy of the donors and increased donation. However, there is no study on the effect of product type and recipient"s facial expression on social exclusion. Especially in this study we tried to confirm the effect of selective context by presenting product type as reference. But, in the social exclusion condition, the product type did not affect the donation intention and the recipient"s expression did not affect as a moderating variable either. However, in order to analyze the moderating situation more deeply, we examined the effect of 3-way interaction to test whether the product is utilitarian or hedonic and whether the recipient`s facial expression is sad or happy. As a result, interestingly, the product type and the recipient`s expression influenced donation intention at the same time, especially in the social exclusion group. In particular, donors of the social exclusion group are more likely to donate when the recipient shows a smiling face when the utilitarian product, but in the case of donors who have first experienced hedonic products are more likely to donate when the recipient shows a sad expression.

Posters ( 1998 . 11 . 12 - 17 ) : Characterization of Protein L - isoaspartyl Methyltransferase Purified from Porcine Testis

(young Keun Lee),(Kikyung Jung),(Mi Hee Shin),(Hyung Mee Han),(Seogyeon Kang),(Taegyun Kim),(Sungryoul Hong),(Seung Hee Kim) 한국응용약물학회 1998 학술대회 Vol.1998 No.1

The roles of neurons on the nitric oxide production of microglia stimulated by LPS and IFN-γ

Kim, Minsun,Lee, Sangjin,Jung, Kikyung,Hong, Sungyoul 성균관대학교 생명공학연구소 2001 生命工學硏究 Vol.7 No.1

Activation of glial cells often occurs at neuronal injury or death. But interaction between neuronal cells and microglia on the production of nitric oxide (NO) are not fully understood. This study aimed to elucidate whether neurons is important in modulating the production of NO in microglia stimulated by the lipopolysaccharide (LPS) and interferon-γ (IFN-γ). When PC12 cells were cocultured with microglia through direct or indirect contact, PC12 cells enhanced nitrite production in particularly LPS and IFN-γ-stimulated microglia. The NO production was decreased by a neutralizing anti-neural cell adhesion molecule (NCAM) and anti-tumor necrosis factor alpha (TNF-α) antibodies in LPS and IFN-γ-treated coculture, while neuraminidase, MMP-1 inhibitor had no effects on the cells. When TNF-α was added to PC12 cells or microglia in absence or presence of LPS and IFN-γ, results of immunoblotting and RT-PCR showed that levels of iNOS mRNA and iNOS expression were upregulated. But, level of TNF-α mRNA made no difference in untreated or treated cells. The PC12-conditioned medium (PC12CM) enhanced the nitrite production in microglia treated with LPS and IFN-γ. Blockade of the MAP kinase signal transduction pathway with either PD98059 (an inhibitor of ERK kinase) or SP203580 (an inhibitor of p38 kinase) did not inhibit the action of PC12CM. However, TPCK (an inhibitor of NF_-k B) decreased the effect of PC12CM in dose-dependent manner. These results suggest that PC12 cells induce nitrite production in microglia treated with LPS and IFN_-γ through release of soluble factors. And the soluble factors are postulated to be TNF_-α or NCAM.

Single- and repeated-dose 28-day oral toxicity study of MDM hydantoin in Sprague–Dawley rats

Won Hansol,Lee Jin Hee,Seok Ji-Hyun,Jung Kikyung,Yang Jun-Young,Jeong Jayoung,Lee Jong Kwon 한국독성학회 2021 Toxicological Research Vol.37 No.1

1-(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (MDM hydantoin) is a commonly used antiseptic preservative in cosmetics. However, limited toxicity information data are available for this chemical. The aim of this study was to obtain toxicity data for MDM hydantoin through single- and repeated-dose toxicity studies in Sprague–Dawley (SD) rats. In the single-dose toxicity study, MDM hydantoin was administered once orally to SD rats at four doses (5, 50, 300, and 2000 mg/ kg/day). There was no significant difference in mortality, clinical signs, and body weight change for 14 days among the animals treated with the different doses in this study. Hence, the approximate lethal dose of MDM hydantoin was considered higher than 2000 mg/kg/day. Based on the results of the dose-range finding study, a 28-day repeated-dose oral toxicity study was conducted. MDM hydantoin was administered orally to SD rats at doses of 125, 250, 500, and 1000 mg/kg/day throughout an experimental period of 28 days. In the repeated-dose oral toxicity study, the adverse effects caused by MDM hydantoin were not detected in terms of body weight, clinical signs, food and water intake, hematology, organ weights, gross pathology, and histopathology. Therefore, the no-observed-adverse-effect level of MDM hydantoin was considered to be greater than 1000 mg/kg/day.

Evaluation of the skin sensitization potential of metal oxide nanoparticles using the ARE-Nrf2 Luciferase KeratinoSensTM assay

Kim Sung-Hyun,Lee DongHan,Lee JinHee,Yang Jun-Young,Seok JiHyun,Jung Kikyung,Lee JongKwon 한국독성학회 2021 Toxicological Research Vol.37 No.2

Numerous studies have reported the potential of chemicals for inducing skin sensitization; however, few studies have examined skin sensitization induced by nanomaterials. This study aimed to evaluate skin sensitization induced by metal oxide nanoparticles (NPs) using the ARE-Nrf2 Luciferase KeratinoSens™ assay. Seven different metal oxide NPs, including copper oxide, cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide, were assessed on KeratinoSens™ cells. We selected an appropriate vehicle among three vehicles (DMSO, DW, and culture medium) by assessing the hydrodynamic size at vehicle selection process. Seven metal oxide NPs were analyzed, and their physicochemical properties, including hydrodynamic size, polydispersity, and zeta potential, were determined in the selected vehicle. Thereafter, we assessed the sensitization potential of the NPs using the ARE-Nrf2 Luciferase KeratinoSens™ assay. Copper oxide NPs induced a positive response, whereas cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide NPs induced no response. These results suggest that the ARE-Nrf2 Luciferase KeratinoSens™ assay may be useful for evaluating the potential for skin sensitization induced by metal oxide NPs.

Standardization of the first Korean national reference standard for snake (Gloydius brevicaudus) antivenom

Han Kiwon,Song Hojin,Choi Chan Woong,Park Sangmi,Kang Yong Seok,Jung Kikyung,Lee Byung-Hwa,Takahashi Yoshimasa,Matsumura Takayuki,Yamamoto Akihiko,Kim Yang Jin,Jee Seung-wan,Kim Jaeok 한국독성학회 2020 Toxicological Research Vol.36 No.4

In 2017, the second national reference standard (NRS) for Gloydius snake venom was established to replace the first NRS for Gloydius snake venom. In connection with the second venom NRS, a candidate for the first NRS for Gloydius snake antivenom was produced in 2017. In this study, the qualification of the candidate was estimated and the potency was determined by a collaborative study. The potency (anti-lethal titer and anti-hemorrhagic titer) of the candidate was determined by measuring the capability of the antivenom to neutralize the lethal and hemorrhagic effects of the second NRS for Gloydius snake venom, which was calibrated against the regional reference standard for Gloydius snake antivenom established in 2006. Two Korean facilities contributed data from 20 independent assays. Subsequently, one foreign national control research laboratories participated in this collaborative study. The general common potency of the anti-lethal and anti-hemorrhagic titers was obtained from the results of a total of 25 tests performed at three facilities. According to the results of the present study, the candidate preparation showed good quality and is judged to be suitable to serve as the first NRS for Gloydius snake antivenom with the following potency: an anti-lethal titer of 3100 unit (U) (95% confidence interval 2991–3276 U) and anti-hemorrhagic titer of 3000 U (95% confidence interval 2849–3159 U). In conclusion, the first NRS for Gloydius snake antivenom was established in this study. This reference standard will be used routinely for quality control of a snake antivenom product by manufacturer in Korea, which also can be used for national quality control, including a national lotrelease test of the snake antivenom product.

Evaluation of the skin sensitization potential of carbon nanotubes using alternative test methods

Sung-Hyun Kim,Dong Han Lee,Jin Hee Lee,Jun-Young Yang,Hyo-Sook Shin,Jeong Pyo Lee,Kikyung Jung,Jayoung Jeong,Jae-Ho Oh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.1