• KSBB Journal
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• v.25 no.3
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• pp.265-270
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• 2010

Simvastatins are widely used to reduce endogenous cholesterol synthesis and improve hypercholesterolemia. Also, simvastatin have been shown to induce both angiogenic and angiostatic responses. In this study, It was attempted to resolve this controversy by studying the effects of simvastatin on the cell migration and invasion with the proteinases secretion and expression pattern. U-373-MG cells treated with low dose of simvastatin ($0.001{\sim}0.5\;{\mu}M$) showed the induction of migration and invasion compared with the addition of a control buffer. On the contrary, high dose of simvastatin ($1{\sim}20\;{\mu}M$) showed the reduction of migration and invasion compared with the addition of a control buffer. It was also showed that simvastatin-regulated migrative and invasive phenotypes were consistent with the secretion and expression pattern of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasmin.

• Biomolecules & Therapeutics
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• v.17 no.4
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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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• v.39 no.4
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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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• v.20 no.2
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• pp.152-159
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• 2003

Background : Hyperlipidemia is the one of the major risk factors causing the atherosclerosis of coronary arteries. Treatment of hyperlipidemia with drugs has been confirmed the effects of therapy showing a decreased incidence of coronary artery disease. Simvastatin is a new drug of HMG-CoA reductase inhibitors and the short-term hypolipidemic effects and safety of simvastatin is evaluated in patients with hyperlipidemia. Methods: We studied 63 patients (39 males and 24 females, mean age 58) for 12 weeks whose plasma levels of total cholesterol were higher than 240 mg/dL or higher than 220 mg/dL with ischemic heart disease. Simvastatin was administered 20 mg/day and measured lipid profile at 12 week interval. Result: 1) Simvastatin significantly reduced the level of the plasma total cholesterol(-29.3%), LDL-cholesterol(-36.9%) and triglyceride(-13%)(p<0.05) but the level of HDL-cholesterol was not changed after 12 weeks simvastatin therapy. 2) the clinical symptoms and laboratory examination before and after simvastatin treatment showed no particular abnormal findings in short term follow up. Conclusion: These results suggested that short-term simvastatin therapy in patients with hyperlipidemia seeems to be very effective and safe.

• Clean Technology
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• v.13 no.1 s.36
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• pp.34-45
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• 2007

Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-solvent recrystallization process utilizing dichloromethane as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of dichloromethane and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the dichloromethane composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. The second half of this work is focused on the particle formation of the simvastatin drug by a supercritical anti-solvent recrystallization process in a cylindrical high-pressure vessel equipped with an impeller. Microparticles of the simvastatin drug were prepared as functions of pressure (8 MPa to 12 MPa), temperature (303.15 K, 313,15 K), feed flow rate of carbon dioxide, and stirring speed (up to 3000 rpm), in order to observe the effect of those process parameters on the size and shape of the drug microparticles recrystallized.

• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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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.

• Korean Journal of Poultry Science
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• v.49 no.4
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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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• v.23 no.6
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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.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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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.

• Korean Journal of Clinical Pharmacy
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• v.21 no.3
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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.