• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.6
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• pp.474-484
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• 2007

Purpose: The effect of platelet-rich plasma(PRP) on osteogenesis of marrow-derived osteoblasts on histomorphometric analysis in the mandible of rabbit was assessed. Materials and Method: Bone marrow cells were obtained from iliac bone of rabbits and were cultured in a Dulbecco's Modified Eagle's Medium(DMEM) with Dexamethasone, L-Ascortic acid, ${\beta}$-Glycerophosphate to proliferate and differentiate into osteoblasts for $4{\sim}5$ weeks. The expression of osteogenic mar-kers was detected by reverse transcription-polymerase chain reaction(RT-PCR) and silver nitrate stain. Then we prepared bony defects in the mandible of rabbit, 10.0mm in diameter and 4.0mm deep, by trephine bur. In the control group, the defects were filled with autogenous bone and cultured osteoblasts. In the experimental group, the defects were filled with autogenous bone, cultured osteoblasts and PRP. 2 weeks, 4 weeks, 8 weeks later, each group was evaluated with histological and histomorphometric analyses. Results: In vitro, osteoblasts were identified on RT-PCR and silver nitrate stain. According to histological observation, at 2 weeks well-developed anasto-mosing newly-formed woven bone was observed, at 4 weeks anastomosing newly-formed woven bone having osteoblastic activation was observed, and at 8 weeks thick newly-formed woven bone was observed in both control and experimental groups. According to histomorphometric analysis, there were 1.5% more newly-formed bone volume in experimental group than control group at 2 weeks, 28.4% more at 4 weeks, 4.3% more at 8 weeks. Particularly there were significant differences in bone volume at 4 weeks and 8 weeks new bone. Conclusion: Our results demonstrated PRP may enhance osteogenesis of marrow-derived osteoblasts at 4 weeks, 8 weeks.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.5
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• pp.394-404
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• 2007

Oral squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its high metastasis and recurrent rates and poor prognosis. Taxol is an anticancer agent which is microbial products extracted from jew tree. It combines with the tubulin and induces apoptosis by inhibiting mitosis of cell with microtubule stabilization. Recently, it was reported to be effective in various solid tumors, but only very slight effect has been seen in oral squamous cell carcinomas due to its cell-specific potencies. Cyclosporin A is used as immune suppressant and is being applied in anticancer therapy as its mechanism of induction of change of apoptotic process in various cells have been known. In this study, oral squamous cell carcinoma HN22 cell line was used for in vitro experiment and as for the experimental group taxol and cyclosporin A were applied alone and to observe the synergistic effect of apoptosis, Taxol and cyclosporin A were coadministered with different concentration of taxol for comparison. The results were obtained as follow: 1. There was no difference in Bcl-2, Bax, caspase 3, 8, 9 mRNA expression when cyclosprin A or taxol was applied alone to HN 22 cell line. 2. Caspase 3, 9 mRNA expression was prominently increased when cyclosprin A and taxol were applied together to cancer cell. 3. No significant difference was observed when cyclosporin A and taxol($1{\mu}g/ml$ and $3{\mu}g/ml$) were applied together to cancer cell line. 4. No significant difference was seen in Bcl-2, Bax, and caspase 8 mRNA expression in all the groups of in vitro experiments. 5. When cyclosporin A was applied alone in vivo study on the nude mice, histopathologi cal findings was similar to those of the control group. Oral squamous cell carcinoma induced by inoculation of HN 22 cell line was not reduced after treatment of cyclosporin A. 6. When taxol was applied alone, the islands of squamous cell carcinoma still remained, which meant insignificant healing effect. There was a lesser volume increase compared with the cyclosporin A alone. 7. When taxol and cyclosporin A were applied together, the connective tissue and calcification were seen in the histopathologic findings. Oral squamous cell carcinoma was decreased and cancer cell was disappeared. In observing the tumor mass change with time, there was a gradual decreased size and healing features. As the results of the in vitro experiment, it could conclud that only when the two agents are applied together, mitochondria-mediated apoptosis occurred by considerable increase of caspase 3, 9 mRNA expression, irrespectable of the concentration of taxol. In vivo experiment, there was a discrete synergistic effect when the two agents were applied together. But single use of cyclosporin A was not effective in this study. Based on the results of this experiment, if further clinical studies are done, taxol and cyclosporin A could be effectively used in treatment of oral squamous cell carcinomas.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.295-307
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• 2006

Styela clava, called non-native tunicate or sea squirt, is habitat which include bays and harbors in Korea and several sites in the sea faced world. We fabricate cellulose membrane nerve conduit (CMNC) from this native sea squirt skin, and evaluate the capacity of promoting peripheral nerve regeneration in the rat sciatic nerve defect model. After processing the pure cellulose membrane from the sea squirt skin as we already published before, CMNC was designed as a non-tubular sheet with 14 mm length and 4 mm width. Total eleven male Spraque-Dawley rats (12 weeks, weighing 250 to 300g) were divided into sham group (n=2), silicone tube grafted control group (n=3) and experimental group (n=6). Each CMNC grafted nerve was evaluated after 4, 8 and 12 weeks in the experimental group, and after 12 weeks, sciatic function was evaluated with sciatic function index (SFI) and gait analysis, and histomorphology of nerve conduit and the innervated tissues of sciatic nerve were all examined using image analyzer and electromicroscopic methods in the all groups. The regenerated axon and nerve sheath were found only in the inner surface of the CMNC after 4 weeks and became more thicker after 8 and 12 weeks. In the TEM study, CMNC grafted group showed more abundant organized myelinated nerve fibers with thickened extracellular matrix than silicone conduit grafted group after 12 weeks. The sciatic function index (SFI) and ankle stance angle (ASA) in the functional evaluation were $-47.2{\pm}3.9$, $35.5^{\circ}{\pm}4.9^{\circ}$ in CMNC grafted group (n=2) and $-80.4{\pm}7.4$, $29.2^{\circ}{\pm}5.3^{\circ}$ in silicone conduit grafted group (n=3), respectively. And the myelinated axon was 41.59% in CMNC group and 9.51% in silicone conduit group to the sham group. The development of a bioactive CMNC to replace autogenous nerve grafts offers a potential and available approach to improved peripheral nerve regeneration. As we already published before, small peptide fragment derived from the basement membrane matrix proteins of squirt skin, which is a kind of anchoring protein composed of glycocalyx, induced the effective axonal regeneration with rapid growth of Schwann cells beneath the inner surface of CMNC. So the possibilities of clinical application as a peripheral nerve regeneration will be able to be suggested.

• Korean Journal of Ichthyology
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• v.25 no.1
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• pp.1-8
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• 2013

Rockfish, Sebastes schlegeli (total length; $10.36{\pm}0.49cm$, total weight; $16.28{\pm}1.86g$, N; 290) were exposed to various concentrations of naphthalene for 28 days. Exposure concentrations of naphthalene established control, ethanol (solvent) control, 0.5, 1.0, 1.5 and 2.0 mg Nap $L^{-1}$. After exposure, We observed survival rate, and degree of tissue change (DTC) in gill under optical microscopy. Survival rate of the rockfish was more than 90% in control, ethanol control, 0.5 and 1.0 mg Nap $L^{-1}$, whereas it decreased in 1.5 and 2.0 mg Nap $L^{-1}$ (respectively 80%, 62.2%). In histological observation of gill, hyperplasia of epithelial cells observed in all exposure groups. But no showed increase of DTC which was related to concentration. Whereas, DTC at fusion of gill lamellar, lamellar telangiectasia, stasis, aneurysm and necrosis showed dose dependent increase. Especially, fusion of gill lamellar, lamellar telangiectasia and stasis observed at more 1.0 mg Nap $L^{-1}$, and aneurysm and necrosis at more 1.5 mg Nap $L^{-1}$. These results showed naphthalene caused survival and severe change to the gill of the rockfish which was related to exposure concentration.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.89-94
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• 2013

Layered $Li_{1+x}(Mn_{0.4}Ni_{0.4}Fe_{0.2})_{1-x}O_2$ (0 < x < 0.3) solid solutions were synthesized using solgel method with adipic acid as chelating agent. Structural and electrochemical properties of the prepared powders were examined by means of X-ray diffraction, Scanning electron microscopy and galvanostatic charge/discharge cycling. All powders had a phase-pure layered structure with $R\bar{3}m$ space group. The morphological studies confirmed that the size of the particles increased at higher x content. The charge-discharge profiles of the solid solution against lithium using 1 M $LiPF_6$ in EC/DMC as electrolyte revealed that the discharge capacity increases with increasing lithium content at the 3a sites. Among the cells, $Li_{1.2}(Mn_{0.32}Ni_{0.32}Fe_{0.16})O_2$ (x = 0.2)/$Li^+$ exhibits a good electrochemical property with maximum initial capacity of 160 $mAhg^{-1}$ between 2-4.5 V at 0.1 $mAcm^{-2}$ current density and the capacity retention after 25 cycles was 92%. Whereas, the cell fabricated with x = 0.3 sample showed continuous capacity fading due to the formation of spinel like structure during the subsequent cycling. The preparation of solid solutions based on $LiNiO_2-LiFeO_2-Li_2MnO_3$ has improved the properties of its end members.

• The Journal of Advanced Prosthodontics
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• v.7 no.2
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• pp.172-177
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• 2015

PURPOSE. The purpose of this study was to evaluate cell toxicity due to ion release caused by galvanic corrosion as a result of contact between base metal and titanium. MATERIALS AND METHODS. It was hypothesized that Nickel (Ni)-Chromium (Cr) alloys with different compositions possess different corrosion resistances when contacted with titanium abutment, and therefore in this study, specimens ($10{\times}10{\times}1.5mm$) were fabricated using commercial pure titanium and 3 different types of Ni-Cr alloys (T3, Tilite, Bella bond plus) commonly used for metal ceramic restorations. The specimens were divided into 6 groups according to the composition of Ni-Cr alloy and contact with titanium. The experimental groups were in direct contact with titanium and the control groups were not. After the samples were immersed in the culture medium - Dulbecco's modified Eagle's medium[DMEM] for 48 hours, the released metal ions were detected using inductively coupled plasma mass spectrometer (ICP-MS) and analyzed by the Kruskal-Wallis and Mann-Whitney test (P<.05). Mouse L-929 fibroblast cells were used for cell toxicity evaluation. The cell toxicity of specimens was measured by the 3-{4,5-dimethylthiazol-2yl}-2,5-diphenyltetrazolium bromide (MTT) test. Results of MTT assay were statistically analyzed by the two-way ANOVA test (P<.05). Post-hoc multiple comparisons were conducted using Tukey's tests. RESULTS. The amount of metal ions released by galvanic corrosion due to contact between the base metal alloy and titanium was increased in all of the specimens. In the cytotoxicity test, the two-way ANOVA showed a significant effect of the alloy type and galvanic corrosion for cytotoxicity (P<.001). The relative cell growth rate (RGR) was decreased further on the groups in contact with titanium (P<.05). CONCLUSION. The release of metal ions was increased by galvanic corrosion due to contact between base metal and titanium, and it can cause adverse effects on the tissue around the implant by inducing cytotoxicity.

• Journal of Life Science
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• v.25 no.4
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• pp.406-415
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• 2015

In this study, we investigated the antioxidant activities and compared other physiological properties including anti-cancer and antimicrobial effects of several traditional Korean herb-combined remedies such as Gilgyung-tang (GGT), Daihwangmokdan-tang (DHMDT), Sagan-tang (SGT), Socheonryongtang (SCRT), Sihocheonggan-tang (SHCGT), Sipyukmiyuki-eum (SYMYKE) and Hwangheuk-san (HHS), which were recorded in “Dong-eui-bo-gam” for “Ongjeo”. Total phenolic contents of the herb medicines were in a rich order of GGT ＜ SYMYKE ＜ SCRT ＜ SHCGT ＜ DHMDT ＜ SGT ＜ HHS. Among them, HHS appeared highest in superoxide dismutase-like activity, ferric reducing antioxidant power, scavenging of 2,2’-diphenyl-1-picrylhydrazyl, and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical activity. Interestingly, there was a positive relationship between their total phenolic contents and their antioxidant activities. Although all of them showed anti-proliferative activities in human colon cancer HCT-116 cells, HHS was seven times higher than GGT. Antimicrobial activities against Escherichia coli and Helicobacter pylori were revealed only on SGT, SCRT, SYMYKE and HHS. Taken together, these findings reveal the potential use of traditional Korean herbal formulas as functional ingredients in antioxidant and physiological materials.

• Journal of Life Science
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• v.17 no.11
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• pp.1497-1504
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• 2007

To investigate the function and secretion of human thrombopoietin (TPO) in mammalian cells, hTPO cDNA was cloned using human liver cDNA, and recombinant hTPO (rec-hTPO) was produced in CHO cell lines. In addition, six N-linked glycosylation sites were substituted for Ala to elucidate the role of each carbohydrate chain. To analyze the biological activity, rec-hTPO protein was injected subcutaneously. Blood was withdrawn for platelet determination. The metabolic clearance rate (MCR) was also analyzed at the 1, 4, 10 and 24 hr after tail vein injection. Wild-type TPO (WT) was efficiently secreted into the medium. However, a hTPO mutant with 116 deleted nucleotides detected by PCR cloning was not secreted. The N-linked glycosylation sites had nearly the same expression quantity as rec-hTPO WT apart from mutants 3 and 4. The glycosylation site of mutant 4 appeared to be an indispensable site for hTPO secretion. Also characterized was the biological activity through an injection with rec-hTPO (10 ng) to ICR mice (7 weeks). The result of the blood analysis showed a considerable increase in the platelet number six days after He injection. To analyze the pharmacokinetics, rec-hTPO was injected into the tail vein (5 ng). The result was 200 pg/ml 1hr after this injection. Following this, it dramatically decreased and virtually disappeared 10 hours after the injection. Thus, rec-hTPO may be a treatment for thrombopenia by the production of the high active rec-hTPO. In addition, hTPO can permit the development of potent new analogues that stimulate the platelet value.

• Journal of Life Science
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• v.21 no.9
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• pp.1219-1225
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• 2011

Phytochemicals, non-nutrient chemicals derived from plants, have been shown to have anti-inflammation, anti-oxidation, and chemopreventive effects. In the current study, we investigated whether five different phytochemicals (resveratrol, genistein, epicatechin gallate, diallyl disulfide, and caffeic acid phenethyl ester) alter cell growth and gene expression in human colorectal cancer HCT116 cells. Using a cell viability assay, we found that each of the phytochemicals tested inhibited HCT116 cell growth in a dose-dependent manner. Additionally, using human oligo DNA microarray analysis, we found that only six genes were commonly up-regulated and seven genes were commonly down-regulated in response to each phytochemical treatment. For the commonly up-regulated genes, the microarray analysis was confirmed by reverse transcription.PCR using gene-specific primers. In addition, NAG-1 protein was up-regulated by all treated phytochemcials. The results of this study may help to enhance our understanding of the general molecular mechanisms of chemoprevention that are mediated by phytochemicals in human colorectal cancer.