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Lee, Joo H.,Lee, Myung G. WILEY PUBLISHERS 2007 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.28 No.4
<P>It was reported that the expression of CYP3A1 increased in rats with acute renal failure induced by uranyl nitrate (rat model of U-ARF) compared with controls. It was shown that telithromycin was mainly metabolized via CYP3A1/2 in rats in this study. Hence, the pharmacokinetic parameters of telithromycin were compared after both intravenous and oral administration at a dose of 50 mg/kg to control rats and a rat model of U-ARF. After intravenous administration of telithromycin to rats with U-ARF, the AUC and renal clearance (Cl<SUB>r</SUB>) were significantly greater (35.0% increase) and slower (99.1% decrease), respectively, than the controls. Unexpectedly, the nonrenal clearance (Cl<SUB>nr</SUB>) of telithromycin was comparable between the two groups of rats, suggesting that CYP3A isozyme responsible for the metabolism of telithromycin seemed not to be expressed considerably in the rat model of U-ARF. After oral administration of telithromycin to rats with U-ARF, the AUC was also significantly greater (127% increase) than the controls and the value, 127%, was considerably greater than 35.0% after intravenous administration of telithromycin. This may be due mainly to the decrease in the intestinal first-pass effect of telithromycin compared with controls in addition to significantly slower Cl<SUB>r</SUB> than controls. Copyright © 2007 John Wiley & Sons, Ltd.</P>
Lee, Dongwoo,Park, Kwang‐,Sook,Yoon, Gook Jin,Lee, Hyun Jung,Lee, Jue‐,Yeon,Park, Yoon Shin,Park, Joo‐,Cheol,Lee, Gene,Chung, Chong Pyoung,Park, Yoon Jeong Wiley Publishers 2019 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Vol.107 No.11
<P><B>Abstract</B></P><P>Peptide and proteins are recognized as highly selective and therapeutically active biomaterials, as well as relatively safe in clinical application. A calcium phospholipid‐binding protein, copine 7 (CPNE7), has been recently identified to induce hard tissue regeneration, including bone and dentin by internalizing into the cells. However, the clinical application of the full length of CPNE7 has limited due to its large size with short half‐life. Herein, as an alternative to CPNE7, six bioactive synthetic peptides are designed from CPNE7 (CPNE7‐derived peptides, CDP1–CDP6) and investigated their osteogenic potential. Among the CDPs, CDP4 have the highest level of cell‐penetrating activity as well as osteogenic efficiency in dental pulp stem cells (DPSCs). CDP4 increased the expression of osteogenesis‐related genes and proteins, which was comparable to that by BMP‐2. The cell penetration capacity of CDP4 may synergistically induce the osteogenic potential of DPSCs. Moreover, the implantation of the mixture of CDP4 with injectable collagen gel increased bone formation with recovery in the mouse calvarial defect model, comparable to full‐length CPNE7 and even BMP‐2. In conclusion, these results suggest that our synthetic peptide, CDP4, can be applied in combination with biomaterial to provide high osteogenic efficacy in the field of bone tissue engineering.</P>
Choi, Sung‐,Min,Park, Jin‐,Woo Wiley Publishers 2018 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Vol.106 No.12
<P><B>Abstract</B></P><P>This study investigated the effects of surface modification of clinically available sandblasted/acid‐etched (SLA) titanium oral implants with strontium (Sr)‐containing nanostructures on both early immunoinflammatory macrophage cell functions and osteogenic stem cell functions. The goal was to provide insight for future surface engineering of titanium implants with multifunctional effects, that is, tissue healing capacity at both the nonosteogenic cell centered initial stage and the subsequent osteogenic cell‐governed later stage‐osseointegration process. The Sr‐containing nanostructure was prepared in on the SLA‐type implant surface by wet chemical treatment. The results showed that Sr modification is favorable for early macrophage cell functions and increases osteogenic capacity of the SLA surface. Surface Sr modification notably upregulated regenerative macrophage phenotype expression and anti‐inflammatory cytokine IL10 production while suppressing inflammatory cytokine TNFα. Sr incorporation enhanced certain early cellular events of ST2 stem cells such as early cellular spreading and critical integrin gene expression, which in turn notably increased osteogenic differentiation (osteogenesis‐related phenotype gene expression and osteocalcin production) when combined with the microstructured SLA implant surface. Surface modification of SLA‐type implants with Sr‐containing nanostructures demonstrated the ability to favorably influence early immunoinflammatory macrophage cell functions and the functionality of osteogenesis cells, resulting in an enhanced osseointegration outcome. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3009–3020, 2018.</P>
Kim, Su‐,Hyang,Choi, Yon Rak,Park, Min Sung,Shin, Jung Woog,Park, Ki Dong,Kim, Sung‐,Jae,Lee, Jin Woo Wiley Publishers 2007 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Vol.80 No.4
<P><B>Abstract</B></P><P>The aim of this study was to identify the signal transduction pathways and mechano‐transducers that play critical roles in the processes induced by changes in cyclic hydrostatic pressure and fluid shear in 3‐dimensional (3D) culture systems. Mesenchymal stem cells were loaded into a polymeric scaffold and divided into three groups according to the stress treatment: static, fluid shear, and hydrostatic pressure with fluid shear. Cells were exposed daily to a hydrostatic pressure of 0.2 MPa for 1 min followed by 14 min rest with fluid flow at 30 rpm. Protein extracts were analyzed by Western blot for extracellular signal‐regulated kinase 1/2 (ERK1/2). The complexes were cultured under the mechanical stimuli for 21 days with or without phospho‐ERK1/2 inhibitor (U0126) and evaluated by RT‐PCR, calcium contents, and immunohistochemistry. Under conditions of mechanical stimulation, the activation of ERK1/2 was sustained or increased with time. U0126 suppressed mechanical stimuli‐induced expression of osteocalcin. In addition, calcium contents and the degrees of osteocalcin and osteopontin staining were decreased by this inhibitor. These results demonstrate that mechanical stimuli, particularly hydrostatic pressure with fluid shear, enhance osteogenesis in 3D culture systems via ERK1/2 activation. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006</P>
Microrough titanium surface affects biologic response in MG63 osteoblast-like cells
Kim, Myung-Joo,Kim, Chang-Whe,Lim, Young-Jun,Heo, Seong-Joo Wiley Publishers 2006 Journal of Biomedical Materials Research Part A Vol. No.
<P>The purpose of this study was to define the surface properties of prepared titanium (Ti) disks, which served as a model system, and to contrast the biologic response of MG63 cells exposed to Ti disks with different levels of surface roughness. The surface properties interact with each other, resulting in a change of other surface qualities in addition to roughness due to the surface roughening procedure. The machined Ti disks were roughened by sandblasting and electric glow discharging. The surface properties of the Ti specimens were inspected through a comprehensive surface analysis. MG63 cell behaviors were compared along with cell number, alkaline phosphatase (ALP) activity, Runx2 gene expression, and type I collagen production. Statistics were evaluated, using analysis of variance (ANOVA). The sandblasted Ti disks demonstrated well-controlled surface roughness features and meaningful average roughness ranges, including the surface roughness of the “modern” microrough implant, used clinically. With increasing Ti surface roughness, the cell number decreased, while the ALP activity, type I collagen production, and Runx2 gene expression increased significantly. The rougher the Ti surface was, the sooner the Runx2 gene was expressed. Based on these results, we suggest that the microrough Ti surfaces of the 1–3 μm range may contribute effectively to osteogenic differentiation and proliferation in MG63 cells. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006</P>
Chitosan-coated poly(vinyl alcohol) nanofibers for wound dressings
Kang, Yun Ok,Yoon, In-Soo,Lee, So Young,Kim, Dae-Duk,Lee, Seung Jin,Park, Won Ho,Hudson, Samuel M. Wiley Publishers 2010 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B Vol.b92 No.2
<P>A PVA nanofibrous matrix was prepared by electrospinning an aqueous 10 wt % PVA solution. The mean diameter of the PVA nanofibers electrospun from the PVA aqueous solution was 240 nm. The water resistance of the as-spun PVA nanofibrous matrix was improved by physically crosslinking the PVA nanofibers by heat treatment at 150°C for 10 min, which were found to be the optimal heat treatment conditions determined from chemical and morphological considerations. In addition, the heat-treated PVA (H-PVA) nanofibrous matrix was coated with a chitosan solution to construct biomimetic nanofibrous wound dressings. The chitosan-coated PVA (C-PVA) nanofibrous matrix showed less hydrophilic and better tensile properties than the H-PVA nanofibrous matrix. The effect of the chitosan coating on open wound healing in a mouse was examined. The C-PVA and H-PVA nanofibrous matrices showed faster wound healing than the control. The histological examination and mechanical stability revealed the C-PVA nanofibrous matrix to be more effective as a wound-healing accelerator in the early stages of wound healing than the H-PVA nanofibrous matrix. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010</P>
Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats
Jeong, Dong Won,Kim, Young Hoon,Kim, Hui Hyun,Ji, Hye Young,Yoo, Sun Dong,Choi, Won Rack,Lee, Soo Min,Han, Chang-Kyun,Lee, Hye Suk WILEY PUBLISHERS 2007 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.28 No.2
<P>The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6–33.0 ml/min/kg), V<SUB>ss</SUB> (437–583 ml/kg), dose-normalized AUC (16.0–17.9 µg min/ml based on 1 mg/kg) and t<SUB>1/2</SUB> (41.9–52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, T<SUB>max</SUB>, t<SUB>1/2</SUB>, dose-normalized C<SUB>max</SUB> (66–74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4–5.9 µg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance. Copyright © 2007 John Wiley & Sons, Ltd.</P>