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Hae Won Kim,Yong Sun Cho,Yun Song Lee,Eun Hee Lee,Hee Ran Lee 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.2
<P> In the present study, the underlying mechanisms for diabetic functional derangement and insulin effect on diabetic cardiomyopathy were investigated with respect to sarcoplasmic reticulum (SR) Ca<SUP>2</SUP>-ATPase and phospholamban at the transcriptional and translational levels. The maximal Ca<SUP>2</SUP> uptake and the affinity of Ca<SUP>2</SUP>-ATPase for Ca<SUP>2</SUP> were decreased in streptozotocin-induced diabetic rat cardiac SR, however, even minimal amount of insulin could reverse both parameters. Levels of both mRNA and protein of phospholamban were significantly increased in diabetic rat hearts, whereas the mRNA and protein levels of SR Ca<SUP>2</SUP>-ATPase were significantly decreased. In case of phospholamban, insulin treatment reverses these parameters to normal levels. Minimal amount of insulin could reverse the protein levels; however, it could not reverse the mRNA level of SR Ca<SUP>2</SUP>-ATPase at all. Thus, the decreased SR Ca<SUP>2</SUP> uptake appear to be largely attributed to the decreased SR Ca<SUP>2</SUP>-ATPase level, which is further impaired due to the inhibition by the increased level of phospholamban. These results indicate that insulin is involved in the control of intracellular Ca<SUP>2</SUP> in the cardiomyocyte through multiple target proteins via multiple mechanisms for the decrease in the mRNA for both SR Ca<SUP>2</SUP>-ATPase and phospholamban which are unknown and needs further study.
Lee, Hae Won,Lim, Mi-sun,Seong, Sook Jin,Lee, Joomi,Park, Jeonghyeon,Seo, Jeong Ju,Yun, Hwi-yeol,Baek, In-hwan,Kwon, Kwang-il,Yoon, Young-Ran Informa UK, Ltd. 2011 Expert opinion on drug metabolism & toxicology Vol.7 No.12
<P><B><I>Objectives:</I></B> An enteric-coated formulation of triflusal (triflusal EC), an antiplatelet agent, was developed to reduce the high incidence of gastrointestinal adverse events (AEs). The aim of this study is to compare the pharmacokinetics, pharmacodynamics and safety of triflusal EC with triflusal in healthy Korean male subjects to determine bioequivalence and non-inferiority for the purposes of marketing approval.</P><P><B><I>Methods:</I></B> A randomized, open-label, two-period, crossover study was conducted in 38 subjects. Either triflusal EC or triflusal was administered orally as a single 900 mg loading dose (day 1) followed by eight 600 mg/day maintenance doses on days 2 - 9, with a 13-day washout period. The plasma concentrations of 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), the predominant active metabolite of triflusal, were assessed after administration of the loading dose, using HPLC/MS/MS. The platelet aggregation response to arachidonic acid was determined using turbidimetric aggregometry. </P><P><B><I>Results:</I></B> The 90% CIs, for the geometric mean ratios of the log-transformed AUC<SUB>τ</SUB> and C<SUB>max</SUB> of HTB were seen to be within the predetermined range of 0.8 - 1.25. Triflusal EC was also shown to be non-inferior in its anti-aggregatory effect. No serious AEs were reported during this study.</P><P><B><I>Conclusions:</I></B> The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated.</P>
백작약 조다당분획에 의한 대식세포 활성화를 통한 암세포 증식 억제
박혜란(Hae-Ran Park),정우희(Uhee Jung),정일윤(Ill-Yun Jeong),이성태(Sung-Tae Yee),조성기(Sung-Kee Jo) 한국식품영양과학회 2003 한국식품영양과학회지 Vol.32 No.1
백작약은 한의학에서 보기ㆍ보혈을 위한 탕제에 이용되는 구성 생약재 중의 하나로서 본 연구에서는 백작약이 면역세포를 활성화시켜 암세포의 생장을 억제할 수 있는 능력이 있는지를 확인하고자 하였다. 그 결과 백작약 조다당분획(PJ-P)는 대식세포를 활성화시켜 그 고유기능인 탐식기능을 항진시켰다. 또한 암세포를 저해하는데 중요한 작용을 하는 NO와 TNF-α, IL-1 그리고 IL-6의 분비를 향상시켰다. 이렇게 PJ-P에 의해 활성화된 대식세포는 cytokine들과 NO를 생산함으로써 시험관 내에서 암세포를 살해하였으며, 또한 PJ-P는 암세포를 이식한 마우스의 생존기간을 연장시켰다. 이 같은 실험결과는 백작약의 조다당분획이 항암보조제 및 면역반응조절제로 활용될 가능성이 있음을 시사한다. The immunomodulatory activity of PJ-P, a polysaccharide fraction extracted from Paeonia japonica, were reported in our previous paper. In the present study, we investigated that PJ-P inhibited cancer growth through activation of macrophages. The activities of peritoneal macrophage to induce tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, interleukin-6 (IL-6) and interleukin-12 (IL-12) as well as to ingest fluorescence-latex microbeads were enhanced by treatment of PJ-P. Direct cytocidal activity of PJ-P against cancer cells was not shown. However, in vitro, peritoneal macrophages treated with PJ-P had an activity to kill cancer cells. Furthermore, PJ-P significantly prolonged the survival of mice implanted intraperitoneally with B16F0 mel-anoma cells. These results suggest that PJ-P could be a useful immunomodulator and assistant of anti-tumor agent.
감마선 조사 황기, 백출 및 승마 열수 추출물의 in vitro 유전독성학적 안전성 평가
박혜란(Hae-Ran Park),함연호(Yeon-Ho Ham),정우희(Uhee Jung),정일윤(Ill-Yun Jeong),조성기(Sung-Kee Jo) 한국식품영양과학회 2002 한국식품영양과학회지 Vol.31 No.5
생약재의 식품ㆍ생물 산업적 이용 증대에 따라 생약재의 안전한 위생화 기술이 요구되고 있다. 본 연구에서는 생약재의 위생화 기술로서 방사선 조사기법의 활용 가능성을 검토하기 위하여, 감마선을 조사한 생약재 3종에 대한 유전독성학적 안전성을 평가하고자 하였다. 공시 재료는 오염유기체 완전 구제선량인 10 kGy의 감마선을 조사시킨 황기, 백출 및 승마로 하였으며, 각각의 열수 추출물의 유전독성을 in vitro 시험으로 평가하였다. 유전독성 평가는 Salmonella typhimurium TA98 및 TA100 균주를 이용한 복귀 돌연변이 시험(Ames test)과 Chinese hamster ovary(CHO) 세포를 이용한 in vitro 소핵 유발시험으로 시행하였다. 각각의 시험은 S9 mix를 첨가한 대사활성화 시스템과 첨가하지 않은 비활성화 시스템으로 구분하여 실시하였으며, 시료의 최고 처리 농도는 복귀돌연변이 시험에서는 5 mg/plate로, 소핵유발시험에서는 50%의 세포증식 억제를 나타내는 농도(1 mg/mL)로 하였다. 복귀 돌연변이 시험 결과 대사 활성화 및 비활성화의 경우 모두에서 각 시료에 의한 복귀변이 집락수의 증가를 인정할 수 없었으며, 각 용량단계에서 감마선 조사군과 비조사군 간의 차이도 볼 수 없었으므로 음성으로 판정하였다. 소핵 유발시험에서도 음성대조군 및 감마선 조사군과 비조사군 모두 각 용량 단계에서 세포 내에 생성된 소핵의 빈도가 3% 이하로 나타남에 따라, 시료에 의한 소핵의 유발을 인정할 수 없었으므로 음성으로 판정하였다. 따라서 감마선이 조사된 각각의 시료는 직접 및 간접 돌연변이원으로 작용하지 않으며 세포유전 독성을 나타내지 않음을 확인할 수 있었다. 향후, 생체 내 유전독성시험, 만성독성시험 및 생식독성 시험 등의 추가적인 in vivo 실험이 행하여진다면 감마선 조사 생약재의 안전성을 보다 명확히 밝힐 수 있을 것으로 생각된다. As the utilization of medicinal herbs in food and bio-industry increases, safe hygienic technologies for them are demanded. To consider the possibility of application of radiation technology for this purpose, the genotoxicological safety of three γ-irradiated medicinal herbs were studied. Astragali Radix, Atractylodes Rhizoma and Cimicifugae Rhizoma were irradiated at 10 kGy, and then were extracted with hot water. The genotoxicity of the extracts was examined in two short-term in vitro tests: (1) Salmonella reversion assay (Ames test) in strains of TA98 and TA100; (2) Micronucleus test in cultured Chinese hamster ovary (CHO) cells. The extract was treated at maximum doses of 5 mg/plate in Salmonella reversion assay, and 1 mg/mL in micronucleus test where growth of CHO cells was inhibited by 50%. In Salmonella reversion assay with or without metabolic activation, both extracts of irradiated and non-irradiated herbs showed no significant differences in formation of revertant colonies compared with the negative control. And also in micronucleus test, the incidences of micronucleus in CHO cells cultured with extracts of irradiated herbs were almost same as negative control in less than 3%. These results of two in vitro tests suggest that γ-irradiated herbs do not show mutagenicity and cytogenetic toxicity. Further tests of in vivo genotoxicity and chronic toxicity are needed to ascertain the safety of γ-irradiated herbs.