• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.293-299
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• 2018

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ${\leq}75$ with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40-75 with ${\geq}7.5%$ estimated 10-year ASCVD risk and LDL-C ${\geq}190mg/dL$. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. Methods: Adults (${\geq}18years$) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Center criteria were analyzed. Results: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to low-intensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG ($67{\pm}14$ vs $62{\pm}12$). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). Conclusion: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.

• Development and Reproduction
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• v.11 no.2
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• pp.59-66
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• 2007

Understanding molecular mechanisms that control embryonic stem cell (ESC) self-renewal and differentiation is important for the development of ESC-based therapies. Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), potently reduce cholesterol level. As well as inhibiting cholesterol synthesis, statins inhibit other intermediates in the mevalonate pathway such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), major substrates for protein isoprenylation. Studies showed that pleiotropic effects of statins beyond cholesterol lowering property arise from inhibition of protein isoprenylation that is involved in various cellular functions including proliferation and differentiation. It has been determined that statins have inhibitory effect on ESC self-renewal and stimulatory effect on ESC differentiation into adipogenic/osteogenic lineages. Importantly, statins mediate downregulation of ESC self-renewal by inhibiting RhoA-dependent signaling, independently of their choresterol-lowering properties. Understanding statin's actions on ESCs may provide important insights into the molecular mechanisms that regulate self-renewal or differentiation of ESCs.

• Archives of Plastic Surgery
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• v.36 no.5
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• pp.525-530
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• 2009

Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.