• Title/Summary/Keyword: Receptor model

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A Feasibility Study for Decision-Making Support of a Radioactive Contamination Model in an Urban Environment (METRO-K) (도시환경 방사능오염 평가모델 METRO-K의 대응행위 결정지원을 위한 실용성 연구)

  • Hwang, Won-Tae;Han, Moon-Hee;Jeong, Hyo-Joon;Kim, Eun-Han;Lee, Chang-Woo
    • Journal of Radiation Protection and Research
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    • v.33 no.1
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    • pp.27-34
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    • 2008
  • A Korean urban contamination model METRO-K (${\underline{M}}odel$ for ${\underline{E}}stimates$ the ${\underline{T}}ransient$ Behavior of ${\underline{R}}adi{\underline{O}}active$ Materials in the ${\underline{K}}orean$ Urban Environment, which is capable of calculating the exposure doses resulting from radioactive contamination in an urban environment, is taking part in a model testing program EMRAS (${\underline{E}}nvironmental$ ${\underline{M}}odelling$ for ${\underline{RA}}diation$ ${\underline{S}}afety$) oragnized by the IAEA (${\underline{I}}nternational$ ${\underline{A}}tomic$ ${\underline{E}}nergy$ ${\underline{A}}gency$). For radioactive contamination scenarios of Pripyat districts and a hypothetical RDD (${\underline{R}}adiological$ ${\underline{D}}ispersal$ ${\underline{D}}evice$), the predicted results using METRO-K were submitted to the EMRAS's Urban Contamination Working Group. In this paper, the predicted results for the contamination scenarios of a Pripyat district were shown in case of both without remediation measures and with ones. Comparing with the predictied results of the models that have taken part in EMRAS program, a feasibility for decision-making support of METRO-K was investigated. As a predicted result of METRO-K, to take immediately remediation measures following a radioactive contamination, if possible, might be one of the best ways to reduce exposure dose. It was found that the discrepancies of predicted results among the models are resulted from 1) modeling approaches and applied parameter values, 2) exposure pathways which are considered in models, 3) assumptions of assessor such as contamination surfaces which might affect to an exposure receptor and their sizes, 4) parameter values which are related with remediation measures applied through literature survey. It was indentified that a Korean urban contamination model METRO-K is a useful tool for dicision-making support through the participation of EMRAS program.

Prognostic Impact of Elevation of Vascular Endothelial Growth Factor Family Expression in Patients with Non-small Cell lung Cancer: an Updated Meta-analysis

  • Zheng, Chun-Long;Qiu, Chen;Shen, Mei-Xiao;Qu, Xiao;Zhang, Tie-Hong;Zhang, Ji-Hong;Du, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1881-1895
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    • 2015
  • Background: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/VEGFR co-expression, in patients with non-small lung cancer remains controversial. Materials and Methods: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. Results: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. Conclusions: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.

Development of bombesin peptide kit for prostate cancer diagnosis and treatment using 64Cu/177Lu.

  • Kim, Mi Hyun;Kim, Min Hwan;Kim, Kwang Il;Kim, Jung Young;Lee, Tae Sup;Kang, Joo Hyun;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.59-64
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    • 2017
  • It has been reported that $^{64}Cu$ was radiolabeled with bombesin (BBN) peptide binding to the gastrin releasing peptide receptor expressed in human prostate cancer cells (PC3), confirming tumor target efficacy in mouse model. In this study, we developed the kit for the diagnosis and treatment of prostate cancer that can be used clinically using bombesin peptide available of $^{64}Cu$ and $^{177}Lu$ radioisotope labeling. The NODAGA-galacto-BBN peptide containing the NODAGA chelator and galactose was dispensed into a sterilized glass vial and lyophilized to prepare a kit. The stability of the kit after long-term storage in the $4^{\circ}C$ cold chamber and the radiolabeling efficiency after $^{64}Cu$ or $^{177}Lu$ labeling were confirmed by thin layer chromatography. When labeling with $^{64}Cu$ at the initial stage of storage, labeling efficiency of NODAGA-galacto-BBN peptide kit was over 96%, labeling efficiency was over 90% when $^{177}Lu$ was labeled. At 11 months after storage, the radiolabeling efficiency of kit against $^{64}Cu$ and $^{177}Lu$ was each over 95% and 90%. The cell viability was significantly reduced in the $^{177}Lu$-NODAGA-galacto-BBN treated group compared with the control and $^{177}Lu$ alone treated group in clonogenic assay. In conclusion, the NODAGA-galacto-BBN kit prepared by the lyophilization showed high stability over time and high yield of radioisotope labeling. Also $^{177}Lu$-NODAGA-galacto-BBN confirmed high cytotoxicity to prostate cancer cells. Therefore, the NODAGA-galacto-bombesin kit is expected to be useful for the diagnosis and treatment of prostate cancer patients.

A Promoter SNP (rs1800682, -670C/T) of FAS Is Associated with Stroke in a Korean Population

  • Kang, Sung-Wook;Chung, Joo-Ho;Kim, Dong-Hwan;Yun, Dong-Hwan;Yoo, Seung-Don;Kim, Hee-Sang;Seo, Wan;Yoon, Jee-Sang;Baik, Hyung-Hwan
    • Genomics & Informatics
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    • v.8 no.4
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    • pp.206-211
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    • 2010
  • The Fas (TNF receptor superfamily, member 6) (FAS)/FAS ligand (FASLG) interaction plays a central role in the regulation of programmed cell death. FAS and FASLG polymorphisms in promoter regions affect transcriptional activities. To investigate whether FAS and FASLG polymorphisms are associated with the development and clinical phenotypes of stroke, 2 promoter single nucleotide polymorphisms (SNPs) in FAS (rs1800682, -670C/T) and FASLG (rs763110, -844C/T) were selected and genotyped by direct sequencing in 220 stroke patients [107 ischemic stroke (IS), 77 intracerebral hemorrhage (ICH), and 36 subarachnoid hemorrhage (SAH)] and 369 control subjects. For the analysis of clinical symptoms, all stroke patients were divided into 3 clinical phenotypes according to the respective results of the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index (MBI) and the presence or absence of complex regional pain syndrome (CRPS). The SNPStats, SNPAnalyzer, and Helixtree programs were used to analyze the genetic data. Multiple logistic regression models (codominant, dominant, and recessive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. The promoter SNP rs1800682 was associated with stroke in the codominant (OR=0.48, 95% CI=0.25-0.94, p=0.04) and dominant models (OR=0.51, 95% CI=0.30-0.87, p=0.011). However, a FASLG SNP (rs763110) was not in Hardy-Weinberg equilibrium (p<0.05). In the analysis of stroke types, rs1800682 was associated with IS in the codominant (OR=0.30, 95% CI=0.12-0.74, p=0.025), dominant (OR=0.44, 95% CI=0.23-0.88, p=0.018), and recessive models (OR=0.45, 95% CI=0.21-0.99, p=0.042). The genotype frequencies of rs1800682 were different between ICH and controls in the dominant model (OR=0.49, 95% CI=0.26-0.94, p=0.031) but not between SAH and controls. In the analysis of clinical symptoms, however, rs1800682 was not related to the 3 clinical phenotypes (NIHSS, MBI, and CRPS). These results suggest that a promoter SNP (rs1800682, -670C/T) in FAS may be associated with the development of stroke in the Korean population.

Anti-obesity Effect of Salsola collina Ethanol Extract (솔장다리 추출물의 항비만 효과)

  • Jin, Kyong-Suk;Lee, Su Hyeon;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.27 no.8
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    • pp.888-895
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    • 2017
  • Salsola collina (S. collina) is an annual plant widely distributed in drought and semi-drought areas, which has been used for a long time as a kind of folk remedy in traditional Chinese medicine for the treatment of hypertension. Previously, the anti-oxidative and anti-cancer activities of S. collina were elucidated in our research group. In this study, the anti-obesity activities of S. collina ethanol extract (SCEE) were evaluated using a pancreatic lipase enzyme inhibition assay and cell culture model. The results showed that SCEE effectively suppressed pancreatic lipase enzyme activity in a dose-dependent manner. Furthermore, SCEE significantly suppressed adipocyte differentiation, lipid accumulation, and triglyceride (TG) content, and triggered lipolysis on insulin, dexamethasone, and 3-isobutyl-l-methylxanthine-treated 3T3-L1 preadipocytes in a dose-dependent manner without cytotoxicity. Its anti-obesity effect was modulated by cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and the peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) gene, as well as protein expressions. Taken together, these results offer the important new insight that S. collina possesses anti-obesity properties, such as pancreatic lipase inhibition and anti-adipogenic and lipolysis effects through the modulation of their upstream signaling pathway. It could become a promising source in the field of nutraceuticals, and the identification of active compounds that confer the biological activities of SCEE may be needed.

The Effects of Supungsunki-hwan on High Fat, High Carbohydrate Diet-induced Obese Type 2 Diabetic Mouse Model (수풍순기환 투여가 고지방, 고탄수화물 식이로 유발된 비만형 제2형 당뇨병 동물모델에 미치는 영향)

  • Park, Jong-Seol;Lee, Byung-Cheol;Doo, Ho-Kyung;Ahn, Young-Min;Ahn, Se-Young
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.257-269
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    • 2009
  • Objective : Obesity is an important cause of diabetes, and lipotoxicity causes insulin resistance. Recently a lot of research is being done on PPAR-${\alpha}$. TNF-${\alpha}$. adiponectin, and leptin, which are important obesity related factors. In this study, we investigated the effects of Supungsunki-hwan on high fat. high carbohydrate diet-induced obese type 2 diabetic mouse models. Methods: Diabetes was induced in ICR male mouse (30${\pm}$5g) with Surwit's high fat, high sucrose diet. Mice were divided into 4 groups(n=10) of Normal. Control. Supungsunkj-hwan group. and acarbose group. The Supungsunki-hwsn group was given 10% Supungsunkj-hwan in their diet. and the acarbose group was given 0.5% acarbose in their diet. After 6 weeks. body weight. food intake, FBS and OGTT. lipid profile and liver enzymes, epididymal fat weight, and gene expression of leptin, adiponectin, TNF-${\alpha}$ and PPAR-${\alpha}$ were measured. Leptin. adiponectin. tumor necrosis factor(TNF)-${\alpha}$ and peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ were evaluated by reverse transcription-polymerase chain reaction. Results : Supungsunkj-hwan increased the gene expression of PPAR-${\alpha}$, which reduces lipotoxicity and insulin resistance. Supungsunkj-hwan also significantly reduced triglyceride. AST. ALT serum levels. and 1 hour oral glucose tolerance levels. Conclusion : These results show that Supungsunkj-hwan improves insulin resistance in the liver and muscles, by reducing triglyceride levels and lipotoxicity through increased PPAR-${\alpha}$ gene expression. This is supported by the fact that Supungsunkj-hwan significantly reduces 1 hour oral glucose tolerance levels. Therefore we suggest that Supungsunkj-hwan would be an effective treatment for obese type 2 diabetic patients.

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Long-Range Transported SO2 Inflow fromAsian Continent to Korea Peninsula Using OMI SO2 Data and HYSPLIT Backward Trajectory Calculations (OMI 이산화황자료와 HYSPLIT 역궤적 계산을 이용한 동북아지역의 장거리 수송되는 이산화황 유입량 산출)

  • Park, Junsung;Hong, Hyunkee;Choi, Wonei;Lee, Hanlim
    • Korean Journal of Remote Sensing
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    • v.30 no.6
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    • pp.743-754
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    • 2014
  • In this present paper, we, for the first time, calculated $SO_2$ inflow from China to Korea peninsula based on OMI $SO_2$ products and HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) backward trajectory calculations. The major factors used to estimate $SO_2$ flux are long range transported $SO_2$ concentration, transport speed of air mass, and thickness of transported air mass layer. The mean and maximum $SO_2$ fluxes are estimated to be 0.81 and $2.11g{\cdot}m^{-2}{\cdot}h^{-1}$, respectively based on OMI products while, those of $SO_2$ fluxes are 0.50 and $1.18g{\cdot}m^{-2}{\cdot}h^{-1}$ respectively using insitu data obtained at the surface. For most cases, larger $SO_2$ inflow values were found at the surface than those estimated for the air mass layer which extends from surface up to 1.5 km. However, increased transport speed of air mass leads to the enhanced $SO_2$ flux at the altitude up to 1.5 km at the receptor sites. Additionally, we calculate uncertainties of $SO_2$ flux using error propagation method.

Anti-obese Effects and Signaling Mechanisms of Chaenomeles sinensis extracts in 3T3-L1 Preadipocytes and Obese Mice Fed a High-fat Diet (3T3L-1 지방전구세포와 고지방식이로 유도된 비만 마우스 모델에서 모과 추출물의 항비만 효과와 억제 기전)

  • Kim, Da-Hye;Kwon, Bora;Kim, Sang Jun;Kim, HongJun;Jeong, Seung-Il;Yu, Kang-Yeol;Kim, Seon-Young
    • Herbal Formula Science
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    • v.25 no.4
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    • pp.457-469
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    • 2017
  • Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

Inhibitory Effect of KIOM-79, a New Herbal Prescription, on AGEs Formation and Expressions of Type IV Collagen and $TGF-{\beta}1$ in STZ-induced Diabetic Rats (복합한약제제 KIOM-79으I STZ 유도 당뇨 모델에서의 최종당화산물 생성 및 Type IV Collagen 및 $TGF-{\beta}1$ 발현 억제 효과)

  • Kim, Young-Sook;Lee, Yun-Mee;Kim, Chan-Sik;Sohn, Eun-Jin;Jang, Dae-Sik;Kim, Jin-Sook
    • Korean Journal of Pharmacognosy
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    • v.37 no.2 s.145
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    • pp.103-109
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    • 2006
  • Advanced glycation end products (AGEs) formation plays an important role in the progression of diabetic complications. To develop effective herbal formulations with suppression of diabetic nephropathy, a common complication in diabetic patients, we evaluated inhibitory activities of KIOM-79, a new herbal prescription, on the formation of AGEs using in vitro and in vivo model systems. Effects of KIOM-79 on the expression of AGEs, RAGEs (receptor for Advanced glycation end products), type IV collagen and renal $TGF-{\beta}1$ mRNA was also examined in streptozotocon (STZ)-induced diabetic rats. STZ-induced diabetic rats were treated orally with KIOM-79 (250 and $500\;kg^{-1}$ once a day for 13 weeks). In vitro system KIOM-79 suppressed the formation of AGEs $(18.12\;{\mu}g/ml)$. In STZ-induced diabetic rats showing accumulation of AGE and RAGE, pathological examination revealed that KIOM-79 prevented AGE and RAGE deposition in the kidney. In STZ induced diabetic rats, the expansion of mesangial matrix and the glomerular tufts seemed to be larger than those in normal rats. Howεver, after administration with KIOM-79, mesangial metrix and glomerular volume were decreased, and overexpression of type IV collagen was also decreased. Overexpression of renal $TGF-{\beta}1$ mRNA was inhibited significantly. These results suggest that the KIOM-79 might be an effective herbal prescription to prevent or alleviate the progression of diabetic nephropathy.

Attenuation of Reperfusion Injury with Angiotension $AT_1$ Receptor Blockade in Rat Myocardial Ischemic Model (백서 심근 허혈 모델에서 angiotension $AT_1$수용체 차단제의 재관류 손상 감소 효과)

  • Choi, Jun-Young;Choi, Dong-Ju;Ahn, Hyuk
    • Journal of Chest Surgery
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    • v.34 no.3
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    • pp.203-211
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    • 2001
  • 배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

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