• 약학회지
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• 제53권4호
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• pp.206-216
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• 2009

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (Statins) are potent inhibitors of cholesterol biosynthesis. Cholesterol-lowering therapy using statins significantly reduces the risk of coronary heart disease. Various discovery of statins as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Clinical and animal test results of statins focusing on the prevention and treatment of bone fractures was collected. Three independent literature searches were performed by using from January 1, 2002 to September 2008 for clinical and animal test results. Search term included statins, HMG-CoA reductase inhibitors, pleiotropic effects, fracture, osteoporosis and clinical and animal test. No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. Experimental use of statins as stimulators of bone formation suggests that they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In conclusion, The use of statins in the prevention and treatment of bone fractures requires further study. But observational studies suggest that statins for decreasing bone fractures including osteoporosis have to be considered local direct administration like transdermal or subcutaneous type over oral adminstration.

• Mass Spectrometry Letters
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• 제9권4호
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• pp.95-99
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• 2018

An innovative, simple, and rapid assay method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of eight statin drugs in human urine. A simple sample clean-up procedure using the "dilute and shoot" (DAS) approach enabled a fast and reliable analysis. The influence of the dilution factor was investigated to ensure detectability and reduce the matrix effect. Chromatographic separation was performed on a Phenomenex Kinetex C18 column ($50{\times}3.0mm$ i.d., $2.6{\mu}m$) using an elution gradient of mobile phase A composed of 0.1% acetic acid, and mobile phase B composed of acetonitrile, at a flow rate of 0.35 mL/min. Quantitation was performed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode using electrospray ionization in positive ion mode. The total chromatographic run time was 15 min. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy, precision, and stability. The present method was successfully applied to the analysis of Rosuvastatin in urine samples after oral administration to healthy human subjects.

• Journal of Microbiology and Biotechnology
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• 제29권3호
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• pp.473-481
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• 2019

Statins are a class of lipid-lowering drugs commonly used in the prevention of cardiovascular diseases. However, statin therapy presents many limitations, which have led to an increased interest in non-drug therapies, such as probiotics, to improve blood cholesterol levels. Indeed, probiotic strains such as Lactobacillus acidophilus have been found to improve blood lipid profiles, especially in reducing total cholesterol and LDL-C levels. In this study, we established a high-cholesterol rat model and studied the effect of Lactobacillus acidophilus administration alone or in combination with rosuvastatin. We were able to show that Lactobacillus exerts a cholesterol-lowering effect. Additionally, we observed that when administered together, rosuvastin and Lactobacillus exert a combined cholesterol-lowering effect. Altogether, our data advocate for the possibility of establishing probiotics as non-drug supplements for the treatment of hypercholesterolemia.

• 비만대사연구학술지
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• 제2권1호
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• pp.29-35
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• 2023

Familial hypercholesterolemia (FH) is a genetic disease that is not well known or diagnosed in Korea. This disease is associated with persistently high levels of low-density lipoprotein cholesterol (LDL-C), which increase the risk of coronary artery disease at a young age. Therefore, early diagnosis and treatment are important; however, there are no global consensus diagnostic criteria. In Korea, the Dutch Lipid Clinic Network diagnostic criteria, and the Simon Broome diagnostic criteria were used for diagnosis of FH according to the agreement announced at the Korean Society of Lipid and Atherosclerosis (KSoLA) in 2022. Recently, the absence of coronary artery calcification has been considered a good prognostic factor, even among patients with very high LDL-C levels who are considered to be at high risk for atherosclerotic cardiovascular disease. We describe throughout this paper the diagnosis and treatment of FH in a young male without coronary artery calcification.

• 보건행정학회지
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• 제23권2호
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• pp.112-123
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• 2013

Background: Under the risk of financial sustainability of National Health Insurance, Korean government attempted a series of regulations over pharmaceutical prices. The first price-cut was implemented to the hyperlipidemial treatments, and the prices of statins were reduced on 15th, April in 2009. The purposes of this study are 1) to investigate the impact of this price-cut on pharmaceutical expenditure, and 2) to identify the factors associated with drug-switch among statins. Methods: Using the national patients sample data, this study conducted time series analysis on the expenditures, prices, and volumes of statin drugs. To understand the factors associated with drug-switch, the multinomial logit model was analyzed at the patients level. Results: The results of time series analysis demonstrated that the price-cut of hyperlipidemic medicines did not lead to the reduced expenditure, suggesting the increased volume was the major cause. The multinomial logit analysis identified the switch of healthcare provider as the significant factor that was highly associated with drug-switch, implying the physicians' preference was the major motivation of drug-switch. Conclusion: Without control of utilization, price regulation itself could not reduce pharmaceutical expenditure. This suggests that the pharmaceutical regulations should be implemented on the basis of understanding of provider behaviors. The findings of this study will form the first step for further empirical studies.

• 동의생리병리학회지
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• 제16권2호
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• pp.226-232
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• 2002

This study was carried out to investigate the effect of mixture of Gastrodiae rhizoma (GM) on blood amelioration in high cholesterol-diet rats. Sprague-Dawley male rats were randomly assigned to one normal diet and three high cholesterol-diet groups which contained 1 % (w/w) cholesterol diet. The groups of high cholesterol-diet were classified to control (high cholesterol-diet only), GM-1 (high cholesterol-diet and GM) and ST-1 (high cholesterol-diet and Statin drug). The body and organs weight were not significantly changed among the tested groups. Contents of serum total cholesterol and LDL-cholesterol were significantly increased in cholesterol-diet groups compared with normal diet group but significantly decreased in the group of GM-1. Morphology of red blood cell in GM-1 group was similar to normal diet group but the control group had many crystals of cholesterol. Hepatic xanthine oxidase activity in the rats of high cholesterol-diet was decreased up to the levels of normal diet group according to oral administration of GM. The results of the present study demonstrate that the orally injection of GM can ameliorate the status of total cholesterol and LDL-cholesterol, and repress xanthine oxidase in liver in high cholesterol-diet rats. These finding suggest that GM is expected to be an effective tea for the blood amelioration in high cholesterol-diet rats.

• Journal of Korean Neurosurgical Society
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• 제58권4호
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• pp.328-333
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• 2015

Objective : The goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients. Methods : This study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis. Results : Ninety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups. Conclusion : This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.

• 대한암한의학회지
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• 제25권1호
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• pp.11-24
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• 2020

Objective : Radiodermatitis is a common sequelae in 95% of patients receiving radiation therapy, which is important to be well managed as it can affect the patient's quality of life as well as the cancer treatment schedule. The aim of this study is to review and summarize the interventions available for the treatment of acute radiodermatitis, including traditional Korean medicine, and to propose treatment algorithms for clinicians. Methods : To collect studies about managements for radiodermatitis, domestic and foreign database were used such as Korean journal of traditional knowledge portal (KTKP), Korean studies information service system (KISS), national discovery or science leaders (NDSL), and oriental medicine advance searching integrated system (OASIS), Pubmed, Google scholar and Scopus. Results : Thirty-two studies were selected. There were nine studies on usual care and dressing, eleven studies on chemical agents, two studies on biological preparations, and ten studies on herbal medicines. Conclusion : Hygienic options and dressings have proved to be useful in the management of radiodermatitis. Chemical agents such as corticosteroid, statin, and topical antibiotic agent have proved to alleviate symptoms and severity, regenerate damaged skin, and prevent secondary infection. In biological preparations, EGF (epidermal growth factor) and GM-CSF (granulocyte-macrophage colony-stimulating factor) could be used to protect skin and prevent radiodermatitis. For herbal medicines, Calendula, catechin, β-sitosterol, and Jaungo (紫雲膏) may be effective for symptoms including pain, itching, and burning sensation induced by radiation therapy. Because of some research with conflicting results, further studies are needed to propose an algorithm for more optimal treatments.

• Journal of Microbiology and Biotechnology
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• 제27권5호
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• pp.956-964
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• 2017

Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from Streptomyces avermitilis can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steady-state kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The $k_m$ and $k_{cat}$ values for compactin were $39.1{\pm}8.8{\mu}M$ and $1.12{\pm}0.09min^{-1}$, respectively. The $k_{cat}/K_m$ value for compactin ($0.029min^{-1}{\cdot}{\mu}M^{-1}$) was lower than that for diclofenac ($0.114min^{-1}{\cdot}{\mu}M^{-1}$). Spectroscopic analysis showed that CYP105D7 binds to compactin with a $K_d$ value of $17.5{\pm}3.6{\mu}M$. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.

• 대한한방내과학회지
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• 제40권6호
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• pp.1026-1034
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• 2019

Objective: This study was conducted to investigate the lipid-lowering effect and safety of Daeshiho-tang in patients with uncontrolled lipid levels by statins. Methods: We investigated patients who had an abnormal lipid profile even when taking statins and who were administered Daeshiho-tang at Kyung-Hee University Korean Medical Hospital for at least one day between January 2008 and December 2018. Their basal characteristics and examinations were reviewed retrospectively with respect to lipid profile, AST, ALT, GGT, BUN, and creatinine. The lipid profile was composed of total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. Subgroup analysis was performed on each component of dyslipidemia. Results: Among 20 participants, there were 10 males and 10 females. The mean BMI was 23.52. Eighty five percent of the participants were diagnosed as having cerebral infarction. After the administration of Daeshiho-tang, total cholesterol and LDL cholesterol were significantly reduced, to 41.3 mg/dl and 33.95 mg/dl, respectively. In subgroup analyses, total cholesterol and LDL cholesterol were significantly decreased, to 63 mg/dl and 54.6 mg/dl, respectively. Liver and kidney function showed no significant difference after taking Daeshiho-tang. Conclusions: Daeshiho-tang as a decoction or powder had significant lipid-lowering effects on total cholesterol and LDL cholesterol in patients with dyslipidemia. The lipid-lowering effect on total and LDL cholesterol increased in patients with hypercholesterolemia and hyper-LDL-cholesterolemia, respectively. Based on the minimal changes in the liver and kidney function test, Daeshiho-tang would be safe enough to be used in clinics.