Inhibitory Effects of Panaxatriol from Panax ginseng C. A. Meyer on Phosphoinositide Breakdown Induced by Thrombin in Platelets

Kyeong-Mee Park,Man-Hee Rhee,Han-Jae Shin,Yong-Bum Song,Hak-Chul Hyun,Ki-Hyun Park,Hyun-Jeong Cho,Sun-A Choi,Hyo-Chan Kang,Kyoung Jin Kim,Hyeong-Soo Kim,Hee-Jin Kang,Woo-Jeong Ok,Dong-Ha Lee,Hwa-Jin P 고려인삼학회 2008 Journal of Ginseng Research Vol.32 No.2

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and Ca<SUP>2+</SUP>-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase Cβ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate (PIP₂) was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of PIP₂, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, PT inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free Ca<SUP>2+</SUP>[Ca<SUP>2+</SUP>]i) up to 72% as compared with control (30.8±0.9 nM) in intact platelet. However, PT (100 ㎍/ml) inhibited the thrombin-elevated [Ca<SUP>2+</SUP>]i to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the [Ca<SUP>2+</SUP>]i level and PIS breakdown.

Inhibitory Effects of Panaxatriol from Panax ginseng C. A. Meyer on Phosphoinositide Breakdown Induced by Thrombin in Platelets

Park, Kyeong-Mee,Rhee, Man-Hee,Shin, Han-Jae,Song, Yong-Bum,Hyun, Hak-Chul,Park, Ki-Hyun,Cho, Hyun-Jeong,Choi, Sun-A,Kang, Hyo-Chan,Kim, Kyoung-Jin,Kim, Hyeong-Soo,Kang, Hee-Jin,Ok, Woo-Jeong,Lee, Don The Korean Society of Ginseng 2008 Journal of Ginseng Research Vol.32 No.2

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and $Ca^{2+}$-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase $C_{\beta}$ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate $(PIP_2)$ was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of $PIP_2$, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free $Ca^{2+}([Ca^{2+}])_i$) up to 72% as compared with control $(30.8{\pm}0.9 nM)$ in intact platelet. However, PT (100 ${\mu}g/ml$) inhibited the thrombin-elevated $[Ca^{2+}]_i$ to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the $[Ca^{2+}]_i$ level and PIS breakdown.

The association between prion proteins and Aβ1-42 oligomers in cytotoxicity and apoptosis

Hyeon, Jae Wook,Kim, Su Yeon,Park, Jun Sun,Choi, Bo Yeong,Lee, Sol Moe,Ju, Young Ran,An, Seong Soo A.,Kim, Chi-Kyeong Elsevier 2012 Biochemical and biophysical research communication Vol.424 No.2

<P>Misfolding of prion protein (PrP to PrPSc) can cause neurodegenerative prion diseases. As a glycosylphosphatidylinositol (GPI)-anchored membrane protein, the normal form of PrP (PrPC) can function as a receptor for ligands in the extracellular space. PrPC was suggested to be involved in memory, synaptic neuronal communication, and anti-oxidation as a neuroprotective agent. The recently identified interaction between PrPC and Aβ(1-42) oligomers suggested another role for PrP as a receptor for Aβ(1-42) oligomers, thereby influencing cytotoxicity and apoptosis. Here, the association between PrPC and Aβ(1-42) oligomers was investigated by visualizing protein localization in neuronal cells by immunocytochemistry. Aβ(1-42) oligomer-induced cytotoxicity was tested in respective expressions of PrPC by using mouse neuroblastoma-2a (N2a) cells, the prion protein overexpressed cells (L2-2B1), and a Prnp-null mouse hippocampal cell line (HpL 3-4). Moreover, apoptotic proteins such as caspase-8 were used to assess the effect of PrPC on Aβ(1-42) oligomer-mediated apoptosis. In L2-2B1 and HpL 3-4 cells, the difference in the cytotoxicity of Aβ(1-42) oligomers could be clearly distinguished. In addition, Aβ(1-42) oligomers induced mitochondria dysfunction, reactive oxygen species (ROS) generation, and calcium influx PrPC-dependently. Apoptosis, related to mitochondria dysfunction, was further investigated to determine the cytotoxic pathway; the results suggest that PrPC could be involved in both the intrinsic and extrinsic apoptotic pathways. Finally, cells with abundant PrPC expression seemed to be more susceptible to Aβ(1-42) oligomer toxicity, suggesting the importance of the level of PrPC expression in the induction of apoptosis.</P>

일차의료에 내원한 성인에서 대사증후군의 유병률 및 관련 요인에 대한 연구

박혜순,신호철,김병성,이가영,최환석,신정아,남윤덕,배상필,천경수 대한비만학회 2003 The Korean journal of obesity Vol.12 No.2

연구배경: 심혈관 질환은 치근 국내에서 그 발생률과 유병률이 급증하여 점점 중요한 국민 건강 문제로 대두되고 있다. 2001년 NCEP ATP Ⅲ에서는 대사증후군에 대해 임상적으로 손쉽게 적용할 수 있는 기준을 제시하면서 심혈관 질환의 주 관리 차상으로 취급하였다. 본 연구에서는 일차의료에서 대사증후군의 유병률을 파악하고, 대사증후군과 관련된 요인을 규명하여 한국인에게 적절한 대사증후군 관리전략을 개발하고자 하였다. 방법: 전국 9개 병·의원 가정의학과에 내원한 20세 이상 80세 미만 성인에서 건강 문제와 무관하게 연속적 조사를 시행하여 총2,134명이 연구에 참여하였다. 대사증후군에 대해서 복부비만은 남자 ≥ 90cm, 여자 ≥ 80 cm으로 하였고 다른 위험인자들은 NCEP ATP Ⅲ의 기준에 따라 정의하였다. 신체 계측, 심혈관 위험인자를 측정하고 생활 습관을 조사하여 대사증후군의 유병률과 관련 요인을 파악하였다. 결과: 일차의료에 내원한 성인에서 대사증루군의 유병률은 남자에서 31.3%, 여자에서 29.5%로 나타났으며, 연령이 증가할수록, 비만도가 증가할수록 대사증후군의 유병률이 높아지는 경향을 나타냈다. 남자에서는 연령, 고소득, 비만, 과다 음주. 과다 흡연이 대사증후군의 관련 요인으로, 여자에서는 연령, 무직, 비만, 심혈관 질환의 가족력, 중등도의 스트레스가 관련 요인으로 나타났다. 결론: 대사증후군은 일차의료에 내원하는 성인 중 비교적 흔하게 나타나는 건강 문제로 약 30%의 유병률을 보였다. 일차의료에서 무증상 성인에게도 허리둘레 측정, 심혈관 위험인자 검사 등 대사증루군의선별검사에 의한 조기 발견과 예방적 차원의 관리가 필요하다고 하겠다 Backgroud: Cardiovascular disease is becoming an important national health issue since its recent increase in incidence and mortality. Despite the significant increase in mortality rate of cardio-vascular disease in Korea, there have been no specific studies concerning metabolic syndrome. The aim of this study was to assess the prevalence of metabolic syndrome and to evaluate the associated factors among adults who visited the primary care. Methods: A total of 2,134 subjects aged 20-79y were recruited from nine primary care clinic. The metabolic syndrome was defined by NCEP ATPⅢ criteria, however, abdominal obesity was assessed by ≥90cm in men and ≥80 cm in women. Anthro-pometric variables and cardiovascular risk factors were measured, and lifestyle factors were assessed through a questionnaire. Results: The prevalence of metabolic syndrome was 31.3% and 29.5% in men and women, respectively. The risk factors associated with metabolic syndrome, in common for both genders, were found to be age, and obesity. Excessive alcohol intake, and heavy smoking were also found to be risk factors of metabolic syndrome in men whereas moderate stress and family history of cardiovascular disease served as risk factors in women. For both genders, greater increase in body weight correlated with higher risk of metabolic syndrome. Conclusion: The prevalence of metabolic syndrome is presumed to be high considering the fact that it is commonly encountered in primary care, therefore a screening program for prevention and management of metabolic syndrome is required.

p-Anisaldehyde가 조골세포 분화에 미치는 영향

김경민 ․ 이도원 ․ 김현준 ․ 김아랑 ․ 장원구 대구대학교 산업기술연구소 2018 産業技術硏究 Vol.29 No.2

p-Anisaldehyde is a natural fragrance extracted from Pimpinella anisum L., and used as a preservative. This study examined the effect of p-anisaldehyde on osteoblast differentiation. First, cytotoxicity tests were carried out after examining the concentrations that did not show toxicity to the cells. The expression of osteoblast differentiation marker gene was confirmed by RT-PCR and was not effective in the treatment with p-anisaldehyde alone. However, p-anisaldehyde decreased the expression levels of inhibitor of differentiation-1 (Id1), distalless related homeobox (Dlx5), and runt-related transcription factor 2 (Runx2), which are osteogenic differentiation marker genes, which are increased in osteogenic condition. alkaline phosphatase (ALP) activity was also confirmed by ALP staining that p-anisaldehyde reduced ALP activity. These results show that p-anisaldehyde is effective in reducing osteoblast differentiation.

ABSTRACTS ; Posters : Purification of the cis , 9- cis , 12- octadecadienate isomerase produced by Butyrivibrio fibrisolvens A38

Sook J . Park,Kyeong A . Park,Jung M . Lee,Jae I . Byon,Yeong L . Ha 생화학분자생물학회(구 한국생화학분자생물학회) 1995 추계학술대회집 Vol.- No.-

스마트폰에 접속 가능한 소형 혈당 모듈

김경아, 이인광, 허아롱, 김경옥, 차은종 충북대학교 의과대학 충북대학교 의학연구소 2014 忠北醫大學術誌 Vol.24 No.1

연구목적: 스마트폰에 접속하여 혈당을 측정할 수 있는 소형 혈당 모듈을 개발하여 그 유용성을 실험 적으로 검증하고자 하였다. 대상 및 방법: 혈액이 전극에 주입되어 생성되는 전류가 전압의 형태로 변환되어 혈당값으로 변환되는 전기화학적 측정 원리를 적용하여 소형 혈당 모듈을 개발하였다. 혈당 모듈의 최소한의 측정 혈액 양은 0.5 μL이며, 5초 이내로 측정이 가능하도록 설계 및 제작하였다. 스마트폰과의 통신은 frequencyshift keying(FSK) 모뎀 방식을 적용하였다. 혈당 모듈의 정확도 실험을 위해 시판되는 혈당계와 인 공혈액으로 비교 실험을 수행하였다. 결과: 시판되는 제품과의 성능 비교 실험에서 시판 제품은 391 mg/dL를 나타내었으며, 소형 혈당 모 듈은 401 mg/dL를 나타내었다. 혈당 모듈의 크기는 50×30×7 mm로서 휴대의 편리성을 높였다. 결론: 스마트폰 기반의 소형 혈당 모듈을 개발하였으며, 기존 제품과의 혈당 측정 상대오차가 약 2.6%로서 정확한 혈당 측정이 가능함을 실험적으로 검증하였다.

A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of YH4808, a novel K⁺-competitive acid blocker

Lee, Hyun A.,Lee, Kyeong-Ryoon,Jang, Seong Bok,Chung, Soo Yong,Yu, Kyung-Sang,Lee, Howard Elsevier 2019 European journal of pharmaceutical sciences Vol.130 No.-

<P><B>Abstract</B></P> <P>A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans. The pharmacokinetic profiles of YH4808 after multiple oral administrations were predicted using a refined PBPK model. The ratios of model-predicted to observed C<SUB>max</SUB>, AUC<SUB>inf</SUB> and AUC<SUB>τ</SUB> values on Day 1 and Day 7 at 100 mg were 0.7–1.0. However, the model failed to predict a decreased exposure after multiple oral administration particularly at higher doses of 200 and 400 mg. The reduced solubility of YH4808 at higher pH was hypothesized as the main cause of the reduction in exposure such that absorption was decreased as pH was increased. This hypothesis was confirmed by PBPK modeling and simulation, where intragastric pH was increased by YH4808.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A case report of a young girl with mucinous borderline tumor of the ovary

( Hyun-mi Lee ),( Kyeong A So ),( Mi Kyung Kim ),( Yoo Kyung Lee ),( In-ho Lee ),( Tae-jin Kim ),( Ki Heon Lee ) 대한산부인과학회 2016 Obstetrics & Gynecology Science Vol.59 No.4

Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient’s life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor.

GO-20 : Human papillomavirus (HPV) prevalence and HPV type distribution in 968 healthy Korean women

( Kyeong A So ),( Young Taek Ouh ),( Jin Hwa Hong ),( Jae Yun Song ),( Nak Woo Lee ),( Jae Kwan Lee ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

To characterize the prevalence and distribution of human papillomavirus (HPV) types among healthy women in South Korea, and to explore risk factors associated with HPV infection. This was a cross-sectional study at a health promotion center of the Korea University Guro hospital for January-June 2013. The basic set included 968 sexually-active women. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the AnyplexTM II HPV 28 Detection (Seegene, Seoul, Korea). Anyplex™ II HPV28 Detection simultaneously detects 19 high-risk HPVs(16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, 82) and 9 low-risk HPVs(6,11, 40, 42, 43, 44, 54, 61, 70). Women with ASC-US+ and /or positive HPV test were referred to colposcopy. Of the 968 women, mean age was 48.8 years. Overall high risk HPV prevalence was 33.7%. Single infection was found in 225 women (23.2%) and co-infections were found in 101 women (10.4%). HPV types 16/18 were found in 61 women (6.3%). The most frequently occurring high risk-HPV types were: 53 (6.5%); 52 (6.1%); 46 (4.8%); 16 (4.5%); 68 (4.2%); 51 (3.5%); 39 and 56 (2.5%); 35 and 66 (2.1%); 18 (1.8%); 82 (1.0%). The most frequently occurring low risk-HPV types were: 54 (5.4%); 70 (3.8%); 42 (3.6%); 61 (3.4%); 44 (3.1%); 43 (2.8%); 40 (2.1%); 6 (1.0%). Prevalence of HPV 16 (16.4%) was most common in women with CIN1+. HPV 16 was most strongly associated with a diagnosis of CIN2+ (odds ratio=18.46, 95% CI: 3.60-94.9, p<0.0001). High-risk HPV prevalence was associated with low parity (1.7 vs 1.9, p=0.034), young age at first delivery (21.7 vs 24.0 p=0.001). Our study indicates that 53, 52, 46, 16 and 68 are common high-risk HPV type. HPV 16 is the most common in the high grade CIN lesions, as in most studies worldwide. The information for regional HPV prevalence can be useful to establish a strategy for cervical cancer prevention in South Korea.