• Journal of Microbiology and Biotechnology
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• v.11 no.6
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• pp.1011-1017
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• 2001

Streptomyces sp. Y-110 cytochrome P-450, induced by the addition of compactin -Na into the culture medium, was purified from the cell extract to apparent homogeniety, mainly by DEAE-Sepharose, hydroxyapatite, and Mono Q column chromatyography. The sepcific activity of purified enzyme on its substrate, compactin-Na, was determined to be 15 nmol of pravastatin per mg protein. The molecular mass of this enzyme on SDS-PAGE was $37{\pm}0.5$ kDa, pI was 4.5, and its CO difference spectrum showed maximum absorption peaks at 452 and 550nm, respectively. The N-terminal amino acid sequence was determined to be Met>Thr>Cys>Thr>Pro>Val>Thr>Val>The>Gly>Ala>Ala>Gly>Gln>Ile>Gly>Tyr>Ala>Leu. Its apparent $K_m$ on compactin-Na was $1.294{\mu}M{\cdot}min^-1,\;and\;V_{max}\;was\;1.028{\mu}M{\cdot}min^-1$. The maximum substrate concentration ($K_s$) for reaction was $270 {\mu}M$and thus $1/[K_s]$ was $3.7{\mu}M$. These physicochemical characteristics and kinetic behavior of this enzyme were compared and shown to be different from those of Streptomyces cytochrome P-450 enzymes reported, suggesting that this enzyme may be an additional member of the Streptomyces cytochrome P-450 family.

• Health Policy and Management
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• v.9 no.3
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• pp.70-94
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• 1999

This paper was performed for a cost-effectiveness analysis of pharmacologic treatment of hypercholesterolemia. Agents modeled were cholestyramine, gemfibrozil. bezafibrate, lovastatin, pravastatin, simvastatin. Pharmacologic effectiveness was estimated by regression from reported clinical trials. Pharmacologic effects were expressed as the percent change of blood cholesterol level. Cost estimates included patients' travel expenses and time loss as well as resource consumption in the health care sector. Bezafibrate was the most efficient agent for reducing total cholesterol levels, having an cost over 1 year of ￦31.400 per percent reduction in total cholesterol. Simvastatin (10mg/d) was also efficient(￦33,100 per percent reduction). Chole styramine(8g/d) was least efficient at ￦90,200. For low-density lipoprotein cholesterol. simvastatin(10mg/d) was most efficient, at ￦23,200 per percent reduction, followed by lovastatin(20mg/d) at ￦28,000. Gemfibrozil was least efficient at ￦77,800 per percent reduction. For high-density lipoprotein cholesterol. bezafibrate(400mg/d) was most efficient at ￦39,300 per percent increase of high-density lipoprotein cholesterol. Cholestyramine was least efficient at ￦514,700. Analyses combining low-density lipoprotein cholesterol and high-density cholesterol effects suggest that bezafibrate(600mg/d) and simvastatin (10mg/d) were most efficient for reducing cardiovascular risk. The cost-effectiveness analysis results show that both simvastatin and bezafibrate could be efficient treatment. Simvastatin provide more effective treatment at higher cost, whereas bezafibrate is more cost-effective, as it may be less effective, at lower cost. Therefore, clinicians should choose reasonable treatment according to the patient's needs This pharmacoeconimc analysis will provide a guideline for efficient pharmacologic treatment and also be reference data for pricing new drugs.

• Journal of Microbiology
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• v.40 no.3
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• pp.211-218
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• 2002

A 4.8-kb DNA fragment encoding the P-450 type hydroxylase and ferredoxin genes was cloned from Pseudonocardia autotrophica IFO 12743 that can convert vitamin D$\_$3/ into its hydroxylated active forms. In order to isolate the P-450 gene cluster in this organism, we designed PCR primers on the basis of the regions of an oxygen binding site and a heme ligand pocket that are general characteristics of the P-450 hydroxylase. Sequencing analysis of the BamHI fragment revealed the presence of four complete and one incomplete ORFs, named PauA, PauB, PauC, and PauD, respectively. As a result of computer-based analyses, PauA and PauB have homology with enoyl-CoA hydratase from several organisms and the positive regulators belonging to the tetR family, respectively. PauC and PauD show similarity with SuaB/C proteins and ferredoxins, respectively, which are composed of P-450 monooxygenase systems for metabolizing two sulfonylurea herbicides in Streptomyces griseolus PauC shows the highest similarity with another CytP-450$\_$Sca2/ protein that is responsible for production of a specific HMG-CoA reductase inhibitor, pravastatin, in S. carbophilus. Cultures of Steptomyces lividans transformant, containing the P-450 gene cluster on the pWHM3 plasmid, was unable to convert vitamin D$\_$3/ to its hydroxylated forms.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.86-91
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• 2006

There are 3 different hypotheses on how statins may affect bones, through promoting bone formation, inhibiting bone resorption or through anti-inflammatory effect. In the 3 cross-sectional studies above, one showed increase BMD at hip and spine, one showed increase BMD only at mid-forearm and one showed that the risk reduction in fractures is not explained by the changes in BMD however, all 3 studies showed a decrease in risk of fracture associated with statins. In the 2 prospective cohort studies, one showed the use of statins was not associated with BMD at any skeletal site or decreasing the risk of fracture, and the other showed statins except pravastatin decreased in risk of vertebrate fracture but not affecting lumbar spine BMD. All of case-control studies indicated reduction in fracture risk but did not provide any data regarding BMD. 2 of the randomized, controlled studies showed no significant reduction in fracture risk as well as statins' effects on BMD. Finally, one longitudinal study showed statin use reduced fracture risk and increased BMD. Among the conflicting results shown above, even when statin use was shown to increase BMD, it does not seem to account for the reduction in fracture risk. There may be different ways that statins affect bone other than those hypotheses proposed above. Many studies seem to agree that pravastatin does not have any effect on bone. Some studies suggested that the reason statins did not achieve clinically significant increases in BMD in some studies, is due to the low affinity of statins on bone; statins are designed to act in the liver therefore their effective concentration in extrahepatic tissue is low. The limitations to those studies discussed above. Many studies did not account for the change of lifestyle while subjects' were on statins. Increases in weight bearing exercise and changes in diet might affect BMD and thus reduce risk of fractures. Mental alertness and vision acuity might prevent falls from occurring; many statin-users in the studies were young so the risk of fractures from falls would be decreased. Almost all of the studies failed exclude patients with neurological problems. During study periods, many subjects may have been started on drugs for diseases that usually occur with aging which could cause drowsiness and lead to falls. The sample sizes used in some of the trials were small and the duration of treatment and follow up might not have been long enough to see clinically relevant results.

• Journal of Life Science
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• v.29 no.12
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• pp.1337-1344
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• 2019

Osteoporosis is characterized by a reduction in bone mass and typically manifests as an increase in fractures. Because this disease is common in elderly populations and lifespans are rapidly increasing, the incidence of osteoporosis has also grown. Most drugs currently used for osteoporosis treatment target osteoclasts in the bone tissue to prevent absorption. However, these medications also cause certain side effects and, furthermore, cannot increase bone mass. Thus, in order to control osteoporosis, regenerative medicine that utilizes adult stem cells and osteoblasts has been extensively studied. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are cholesterol-lowering drugs that have been widely prescribed for cardiovascular diseases. Interestingly, recent studies have reported the beneficial effects of various statins on bone formation via the activation of osteoblasts. Thus, the current study investigated the effects of seven statin-family drugs on osteoblast activity during osteogenic differentiation using adult stem cells from human periosteal tissue. Specifically, statin effects on alkaline phosphatase activity, an early marker of bone cell differentiation, and on calcium deposit, a late marker of bone cell differentiation, were assessed. The results demonstrate that some statins (for example, pitavastatin and pravastatin) have a weak but positive effect on bone formation, and the findings therefore suggest that statin treatments can be a novel modulator for osteogenic differentiation and regenerative medicine using periosteal stem cells.

• Journal of Life Science
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• v.28 no.2
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• pp.247-256
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• 2018

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.