• KSBB Journal
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• 제25권3호
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• pp.265-270
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• 2010

본 연구에서는 simvastatin에 의한 U-373-MG 세포의 이동 및 침윤에 미치는 효과와 그 가능한 기작에 대해 조사하였다. U-373-MG 세포의 이동에 미치는 simvastatin의 효과를 확인한 결과, $0.01\;{\mu}M$의 simvastatin에서는 U-373-MG 세포의 이동이 약 43% 증가되었으나 $1\;{\mu}M$과 $20\;{\mu}M$에서는 세포의 이동이 각각 28%와 35% 억제되었다. 세포의 침윤 역시 $0.001\;{\mu}M$의 simvastatin에서는 23%, $0.01\;{\mu}M$에서는 26%의 침윤 증가가 관찰되었으나, $1\;{\mu}M$과 $10\;{\mu}M$에서는 세포의 침윤이 각각 45%와 54%가 억제되었다. $0.001\;{\mu}M$ 과 $0.01\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량이 각각 30%와 59% 증가되었으나, $10\;{\mu}M$과 $20\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량은 각각 31%와 60% 감소되었다. MMP-9 및 플라스민의 분비에 미치는 simvastatin의 효과도 MMP-2에 미치는 효과와 유사하였다. Simvastatin이 MMP-2와 MMP-9 단백질의 생성에 미치는 효과를 조사한 결과, $0.001{\sim}1\;{\mu}M$의 simvastatin에서는 MMP-2와 MMP-9 생성이 증가되었으나 $10{\sim}20\;{\mu}M$에서는 MMP-2와 MMP-9의 생성이 감소되었다. 이러한 결과는 낮은 농도의 simvastatin은 혈관신생을 유도하고 높은 농도의 simvastatin은 혈관신생을 억제한다는 것을 보여주는 것이다.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.353-361
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• 2009

Recent in vitro and in vivo animal studies have reported that statin, a cholesterol-lowering drug, stimulate osteogenic differentiation. In the present study, we investigated the effect of simvastatin on osteogenic and adipogenic differentiation in primarily cultured human adipose-derived stem cells (hADSCs). The simvastatin treatment significantly increased the positive cell numbers in alkaline phosphatase and von Kossa staining, and enhanced the expression levels of bone morphogenic protein (BMP)-2, core binding factor alpha 1 (cbfa1), collgen type I and osteonectin mRNAs. Lastly, hADSCs were cultured in the adipogenic media with or without simvastatin to examine the effect of simvastatin on adipogenic differentiation. In the RT-PCR analysis, there were notable decreases in mRNA expression of aP1, C/EBP-$\alpha$ and PPAR-$\gamma$ in hADSCs cultivated in simvastatin-added medium, compared to those in simvastatin-free medium. It suggests that the adipogenic differentiation was significantly inhibited by simvastatin treatment. These observations indicate that simvastatin induces osteogenic differentiation and suppresses adipogenic differentiation in hADSCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제39권4호
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• pp.150-155
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• 2013

Objectives: The objective of this study is to determine the adequate concentration and to evaluate the osteogenic potential of simvastatin in human maxillary sinus membrane-derived stem cells (hSMSC). Materials and Methods: Mesenchymal stem cells derived from the human maxillary sinus membrane were treated with various concentrations of simvastatin. The adequate concentration of simvastatin for osteogenic induction was determined using bone morphogenetic protein (BMP-2). The efficacy of osteogenic differentiation of simavastatin was verified using osteocalcin mRNA, and the mineralization efficacy of hSMSCs and simvastatin treatment was compared with alkaline phosphatase and von Kossa staining. Results: Expression of BMP-2 mRNA and protein was observed after three days and was dependent on the concentration of simvastatin. Expression of osteocalcin mRNA was observed after three days in the $1.0{\mu}M$ simvastatin-treated group. Mineralization was observed after three days in the simvastatin-treated group. Conclusion: These results suggest that simvastatin induces the osteogenic potential of mesenchymal stem cells derived from the human maxillary sinus membrane mucosa.

• Journal of Yeungnam Medical Science
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• 제20권2호
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• pp.152-159
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• 2003

고지혈증이 관상동맥 죽상 동맥경화증의 가장 중요한 위험 인자이며 또한 고지혈증을 치료할 경우 관상동맥 질환의 발생이 감소한다고 인정되고 있다. 이러한 고지혈증 치료제로 새로 개발된 simvastatin($Zocor^{(R)}$)의 단기사용 시 효과와 안정성을 알아보기 위해 저자들은 simvastatin을 12주 사용하여 연구를 시행하였다. 대상 환자는 원발성 고콜레스테롤 혈증으로 진단받은 환자로서 첫(0주)방문일 기준으로 측정한 혈중 콜레스테롤 농도가 240 mg/dl이상이거나 220 mg/dl이상이면서 병력이 있는 환자를 대상으로 하였으며 HMG-CoA reductase 억제제인 simvastatin을 저녁에 1일 20 mg씩 경구투여하였다. 12주 후 시행한 혈액검사소견상 혈청 총 콜레스테롤치, 저비중 지단백 콜레스테롤치 및 중성지방은 치료전에 비하여 치료후에 의미있게 감소하였고(p<0.05) 고비중 지단백 콜레스테롤치는 변화가 없었으며 simvastatin 투여기간중 약물 부작용은 없었다. 이상의 결과로 보아 simvastatin은 고지혈증 환자의 치료에 단기간 사용할 경우 그 효과가 확실하고 안전한 치료제라 생각된다.

• 청정기술
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• 제13권1호
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• pp.34-45
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• 2007

고지혈증 치료제로 잘 알려져 있는 난용성 약물인 심바스타틴(simvastatin)을 대상으로 디클로로메탄을 용매로 사용하고 초임계 이산화탄소를 역용매로 사용하는 초임계 역용매 재결정법에 의해 약물 미세입자를 제조할 때, 운전 조건을 설정하는데 활용될 수 있는 가이드 라인을 제공하기 위하여 simvastatin/디클로로메탄/초임계 이산화탄소 3성분계 혼합물의 상거동을 연구하였다. 가변부피 투시 셀이 장착된 고압 상평형 장치를 사용하여 여러 가지 조건에서 3성분계 혼합물의 구름점(cloud point)을 측정함으로서 디클로로메탄과 초임계 이산화탄소의 혼합용매에서 simvastatin의 용해도를 온도, 압력, 용매 조성의 함수로 결정하였다. 주어진 온도에서 Simvastatin 약물의 용해도는 디클로로메탄의 조성과 압력이 증가할수록 온도가 감소할수록 증가하였다. 상거동 데이터를 바탕으로 교반기가 설치된 실린더 모양의 고압 용기에서 초임계 역용매 재결정 공정을 이용하여 simvastatin 약물을 미세입자로 제조하는 연구를 수행하였다. 운전 조건인 압력 ($8{\sim}12\;MPa$), 온도(303.15 K, 313.15 K), 이산화탄소 공급 속도, 교반 속도 (최대 3,000 rpm)를 변화시키면서 simvastatin 미세입자를 제조함으로써 재결정되는 약물 입자의 크기와 모양에 미치는 공정 변수들의 영향을 관찰하였다.

• 한국임상약학회지
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• 제19권1호
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• pp.32-36
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• 2009

The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with simvastatin (0.3 and 1.0 mg/kg). Compared with the control (given nicardipine alone), coadministration of simvastatin (1.0 mg/kg) significantly (p<0.05) increased the area under the plasma concentration (AUC) and peak plasma concentration ($C_{max}$) of nicardipine. The relative bioavailability (RB%) of nicardipine increased from 1.19- to 1.48-fold. However there were no significant changes in $t_{max}$, and $t_{1/2}$ of nicardipine. The enhanced oral bioavailability of nicardipine might be due to an inbition of cytochrom P450 3A mediated-metabolism of nicardipine in the intestine and in the liver by simvastatin. Based on these results, the concurrent use of simvastatin significantly enhanced the oral exposure of nicardipine in rats. The dosage regimen of nicardipine should be taken into consideration for potential drug interaction when combined with simvastatin in clinics.

• 한국가금학회지
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• 제49권4호
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• pp.265-272
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• 2022

Many studies on poultry have been conducted in the poultry industry to improve their important economic traits, such as egg production, meat quality, and carcass yield. Environmental changes affect the poultry's economic traits, including muscle growth. The purpose of this study is to investigate the mechanisms by which simvastatin causes muscle injury in quail muscle cells. Following treatment with various doses of simvastatin, LD50 in the quail myoblast cells was determined using a cell viability test; cell death was caused by apoptosis and/or necrosis. Thereafter, the expression patterns of the atrophy marker genes were examined via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The results showed that the transcriptional levels of the muscle atrophy marker genes (Atrogin-1, TRIM63) and the upstream genes in their signaling cascade were increased by simvastatin treatment. This indicated that simvastatin induced myogenic cell death and muscle injury via protein degradation through muscle atrophy signaling. Further studies should focus on identifying the mechanism by which simvastatin induces the protein degradation signaling pathway in quail muscle..

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.531-538
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• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• 한국임상약학회지
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• 제12권1호
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• pp.39-50
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• 2002

Hypercholesterolemia is one of main causes of coronary heart disease(CHD). Clinical trials demonstrated that lowering serum cholesterol levels would reduce incidence of new cardiovascular events and mortality by primary or secondary preventions. The objective of this retrospective study was to compare efficacy and side effects of lovartatin and simvastatin in treatement of hypercholesterolemia. In Boramae Hospital, patients were included when they have taken lovastatin 20 mg or simvastatin 10 mg for 52 weeks with laboratory monitoring for cholesterol at baseline, 3, 6 and 12 month period. As results, total 128 outpatients were included with their total cholesterol level <240 mg/dl and triglyceride level <400 mg/dl at baseline. Total cholesterol and LDL cholesterol of lovastatin group (n=60) and simvastatin group (n=68) were significantly reduced from baseline (p=0.001). Lovastatin maximally reduced total cholesterol by $23.9\%,\;triglyceride\;by\;12.3\%$, LDL cholesterol by $36.1\;\%$ and increased HDL cholerterol by $7.8\%$ and simvastatin reduced by $24.1\%,\;20.5\%,\;34.3\%\;respectively$ and HDL increased by $11.2\%$. There were no significant differences between lovastatin and simvastatin in mean percent change of lipid levels at 12, 24 and 52 weeks from baseline. Cumulative percentage of patients reaching the target LDL cholesterol concentration by 24 weeks was $61.7\%$ in lovastatin and $64.7\%$ in simvastatin. Average time to reach the target LDL goal was 100.1 days in lovastatin and 99.8 days in simvastatin. Both lovastatin and simvastatin also significantly reduced total cholesterol and LDL cholesterol in all subgroups (diabetes mellitus, hypertension, and coronary heart disease). In this study, treatment efficacy in patients with coronary heart disease was lower than other patients. Considering clinical importance of secondary prevention, more intensive treatment is necessary to decrease LDL cholesterol level of 100 mg/dl or lower in patients with coronary heart disease or other clinical atherosclerotic disease. There were no serious side effects during the study period. Digestive side effects were most frequently reported (lovastatin $8.3\%\;vs\;simvastatin\;8.8\%$). In conclusion, both lovastatin and simvastatin were similar in lipid lowering effects and there was no difference in incidence of side effects.

• 한국임상약학회지
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• 제21권3호
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• pp.270-275
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• 2011

이 증례는 드물게 보는 경우로 simvastatin과 gemfibrozil을 오랫동안 함께 복용했음에도, 특이한 문제가 발현되지 않았지만, 이들을 warfarin와 함께 치료하는 경우, 아주 높은 alanine aminotransferase (ALT), aspartate aminotransferase(AST) 혈중 농도, rhabdomyolysis, 급성 신장 장애가 발생하였다. 그 후, Simvastatin와 gemfibrozil을 복용 중단시켰더니, ALT/AST는 빠르게 정상수치로 돌아온 경우이다. 이 증례 보고서는 의료인들에게 simvastatin과 gemfibrozil을 함께 혹은 따로 warfarin과 함께 복용시켜 치료할 경우, creatine phosphokinase (CPK) 와 creatinine 혈중 수치들을 포함하여 ALT/AST 농도들을 주의 깊게 모니터하도록 경각심을 주고자 한다.