• Proceedings of the Korean Nutrition Society Conference
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• 2003.05a
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• pp.232.2-232.2
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• 2003

• Journal of Environmental Science International
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• v.22 no.12
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• pp.1615-1624
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• 2013

The aims of this study were to investigate and confirm the occurrence and distribution patterns of blood lipid lower agents (BLLAs) in Nakdong river basin (mainstream and its tributaries). 4 (atorvastatin, lovastatin, mevastatin and simvastatin) out of 5 statins and 2 (clofibric acid and zemfibrozil) out of 3 fibrates were detected in 29 sampling sites and simvastatin (>50%) was predominant compound followed by atorvastatin, lovastatin and clofibric acid. The total concentration levels of BLLAs on April, August and November 2009 in surface water samples ranged from ND~25.7 ng/L, ND~18.8 and ND to 38.8 ng/L, respectively. The highest concentration level of BLLAs in the mainstream and tributaries in Nakdong river were Goryeong and Jincheon-cheon, respectively. The sewage treatment plants (STPs) along the river affect the BLLAs levels in river and the BLLAs levels decreased with downstream because of dilution effects.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.97-106
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• 2009

Although lovastatin (LS) is widely used in the treatment of hypercholesterolemia, its bioavailability is known to be around 5%. This study was aimed to increase the solubility and dissolution-permeation rates of LS using solid dispersions (SDs) with bile salts. The solubilities of LS in water, aqueous bile salt solutions and non-aqueous vehicles were determined, and effects of bile salts on the cellulose or duodenal permeation of LS from SDs were evaluated using a horizontal permeation system. SDs were prepared at various ratios of LS to carriers, such as sodium deoxycholate (SDC), sodium glycocholate (SGC) and/or 2-hydroxypropyl-$\beta$-cyclodextrin (HPCD). The addition of bile salts (25 mM) in water increased markedly the solubility of LS by the micellar solubilization. Some non-aqueous vehicles were effective in solubilizing LS. From differential scanning calorimetric studies, it was found that the crystallinity of LS in SDs disappeared, indicating a formation of amorphous state. The SDs showed markedly enhanced dissolution compared with those of their physical mixtures (PMs) and drug alone. In the dissolution-permeation studies using a cellulose membrane, the donor and receptor solutions were maintained as a sink condition using pH 7.0 phosphate buffer containing 0.05% sodium lauryl sulfate (SLS). The flux of LS alone was nearly same as that of LS-SDC-HPCD (1:3:6) PM. However, the flux of LS-SDC-HPCD (1:3:6) SD slightly increased compared with drug alone and PM, suggesting that entrapment of LS in micelles does not significantly hinder the permeation across cellulose membrane. In the dissolution-duodenal permeation studies using a LS-HPCD-SDC (1:3:6) SD, the addition of various bile salts in donor solutions (25 mM) enhanced the permeation of LS markedly, and the fluxes were found to be $0.69{\pm}0.41$, $0.87{\pm}0.51$, $0.84{\pm}0.46$, $0.47{\pm}0.17$ and $0.68{\pm}0.32{\mu}g/cm^2/hr$ for sodium cholate (SC), SDC, SGC, sodium taurodeoxycholate (STDC) and sodium taurocholate (STC), respectively. The stepwise increase of donor SGC concentration increased the flux dose-dependently. From the relationship of donor SGC concentration and flux, the concentration of SGC initiating the permeation across the duodenal mucosa was calculated to be 11.1 mM, which is nearly same as the critical micelle concentration (CMC, 11.6 mM) of SGC. However, with no addition of bile salts and below CMC, the permeation was very limited and irratic, indicating that LS itself is very poor permeable. Higher protions of bile salt in SD such as LS-SDC or LS-SGC (1 : 49 and 1 : 69) showed highly promoted fluxes. In conclusion, SD systems with bile salts, which may form their micelles in intestinal fluids, might be a promising means for providing enhanced dissolution and intestinal permeation of practically insoluble and non-absorbable LS.

• Journal of Life Science
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• v.25 no.1
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• pp.1-7
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• 2015

Cyclin D is a member of the cyclin protein family, which plays a critical role as a core member of the mammalian cell cycle machinery. D-type cyclins (D1, D2, and D3) bind to and activate the cyclin-dependent kinases 4 and 6, which can then phosphorylate the retinoblastoma tumor suppressor gene products. This phosphorylation in turn leads to release or derepression of E2F transcription factors that promote progression from the G1 to S phase of the cell cycle. Among the D-type cyclins, cyclin D3 encoded by the CCND3 gene is one of the least well studied. In the present study, we have investigated the biochemistry of the proteolytic mechanism that leads to loss of cyclin D3 protein. Treatment of human prostate carcinoma PC-3-M cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. Additionally, using inhibitors for various proteolytic systems, we show that degradation of cyclin D3 protein involves the $Ca^{2+}$-activated neutral protease calpain. Moreover, the half-life of cyclin D3 protein half-life increased by at least 10-fold in PC-3M cells in response to the calpain inhibitor. We have also demonstrated that the transient expression of the calpain inhibitor calpastatin increased cyclin D3 protein in serum-starved NIH 3T3 cells. These data suggested that the function of cyclin D3 is regulated by $Ca^{2+}$-dependent protease calpain.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.412.2-413
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• 2002

Purpose. To prepare polymer based physical mixtures or solid dispersions containing solubilizing compositions using a spray-dryer. Methods. Lovastatin.simvastatin.aceclofenac and cisapride were selected as poorly water-soluble drugs. Dextrin. poly(vinylalcohol). poly(vinylpyrrolidone)and polyethylene glycol were chosen as solubilizing carriers for solid dispersions. The solid dispersions containing solubilizing compositions without drug were prepared without using organic solvents or tedious changes of formulation compositions. (omitted)

• Archives of Pharmacal Research
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• v.20 no.2
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• pp.158-170
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• 1997

New HMG-CoA reductase inhibitors, in which 3-substituted 4, 5-polymethylenepyrazoles are employed as a hydrophobic anchor connected to tetrahydro-4-hydroxy-2H-pyran-2-one by a two-carbon bridge, were designed and synthesized to exhibit significant inhibitory activity comparable to mevinolin. The most potent enzyme inhibitor $(11cc, IC_{50}=0.01{\mu}M)$ is 4-fold more potent than lovastatin.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.412.1-412.1
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• 2002

Purpose. To prepare PVP-based solid dispersions containing lovastatin (LOS) and solubilizers (sodium lauryl sulfate. Tween80. oleic acid) to enhance dissolution of practically insoluble LOS. Methods. Solid dispersions containing LOS were prepared by dissolving two different organic solvent systems (acetone/ethanol or acetonitrile/ethanol). Results. The stickiness and flowability of solid dispersion powders were dependent on the composition and ratio of the solubilizers. (omitted)

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.282.2-282.2
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• 2001

• Nutritional Sciences
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• v.6 no.3
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• pp.141-147
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• 2003

Fruits and vegetables reportedly have a protective effect against hyperlipidemia and oxidative disease. Accordingly, this study aimed to investigate the lipid-lowering effect and antioxidative capacity of persimmon leaf extract (PLE) in rats fed a high-cholesterol diet. Male rats were fed a high-cholesterol (1% wt/wt) or high-cholesterol diet supplemented with Lovastatin (0.02% wt/wt) or PLE (0.2% wt/wt) for 5 weeks. The concentration of plasma total cholesterol was significantly lower in the PLE group than in the lovastatin group. However, the concentration of plasma HDL-cholesterol and the ratio of HDL-cholesterol/total-cholesterol (%) were significantly higher in the PLE group than in the control group. The PLE supplement also significantly lowered the contents of hepatic cholesterol and triglyceride. In comparing fecal sterol contents, the PLE group saw a significant increase of both neutral and acidic sterol compared to the other groups. The PLE supplement significantly lowered plasma GOT and GPT activity, which ave indices of hepatic toxicity. Plasma TBARS concentration was significantly lower in the PLE group than in the control group, while hepatic TBARS level was not significantly different between the groups. In a comparison of hepatic antioxidant parameters, SOD, catalase and GSH-Px activity were significantly higher in the PLE group than in the control group. However, the PLE supplement significantly towered antioxidant enzyme activity in the erythrocyte. Furthermore, these results suggest that supplementation of PLE promoted the excretion of fecal sterols, thereby leading to decreased absorption of dietary cholesterol. In addition, PLE may play an important role in regulating antioxidative capacities by altering SOD and ChT activity.

• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.7-14
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• 2003

The PVP-based solid dispersion systems (SDs) containing lovastatin (LOS) and solubilizers (sodium lauryl sulfate, tween 80 and oleic acid) were prepared to enhance dissolution rate of practically water insoluble LOS using solvent evaporation method. Two different organic cosolvents either acetone/ethanol or acetonitrile/ethanol were used for the preparation of SDs. The LOS contents were highly decreased when acetone/ethanol cosolvents were used. The decrease of LOS contents was not caused by acetonitrile or acetone, based on HPLC data. The surface morphology as investigated by scanning electron microscope (SEM) and angle of repose as an index of flowability of SDs were highly dependent on the type and amount of solubilizers used. Based on differential scanning calorimetry (DSC) and X-ray powder diffraction data, the SDs made crystalline LOS into amorphous structure or partially eutectic mixtures. The simultaneous use of the solubilizers in SDs was also useful to increase dissolution rate of LOS in gastric or intestinal fluid. The SDs containing solubilizers reached 76% and 60% in gastric and intestinal fluid, respectively but the commercial tablet gave only less than 4%. These solubilizers in SDs could be also applicable for enhancing dissolution and bioavailability of poorly water-soluble drugs.