• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1687-1696
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• 2015

Supplementation with probiotics can protect against the development of food allergies by modulating the host immune response; however, the mechanisms are not fully understood. The objective of this study was to investigate the allergy-reducing effects of regulatory dendritic cells (regDCs) induced by Lactobacillus paracasei L9 (L9) in β-lactoglobulin (BLG)-sensitized mice. The L9 supplement suppressed the aberrant balance of Th1/Th2 responses to BLG in mice, via upregulation of the CD4+CD25+Foxp3+Treg cell responses. The amount of CD4+CD25+Foxp3+Treg cells in mesenteric lymph nodes increased by 51.85%. Furthermore, administration of L9 significantly induced the expression of CD103 and reduced the maturation status of DCs in mesenteric lymph nodes, Peyer's patches, and spleen. Bone marrow-derived dendritic cells (BM-DCs) were activated by L9 in vitro, with an approximate 1.31-fold and 19.57-fold increase in expression of CD103 in CD11c+DCs and the level of IL-10 production, respectively, while the expression of CD86 did not change significantly. These data demonstrate that L9 reduced the BLG allergic sensitization, likely through regDCs mediated active suppression.

• Journal of Korean Neurosurgical Society
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• v.44 no.5
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• pp.327-333
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• 2008

Objective: The purpose of this study is to verify the usefulness of the rabbit model for disc degeneration study. Materials: The L1-L2, L2-L3, L3-L4. or L4-L5 lumbar intervertebral disc (IVD) of 9 mature male New Zealand White rabbits were injured by inserting a 16-gauge needle to a depth of 5 mm in the left anterolateral annulus fibrosus while leaving L5-L6 IVD uninjured. Three other rabbits also received intradiscal injections of rabbit disc cells transfected with adenovirus and bone morphogenetic protein-2 (ad-BMP-2) at L4-L5 in addition to injury by 16-gauge needle at the L1-L2 level. Using digitized radiographs, measurements of IVD height were made and analyzed by using the disc height index (DHI). Magnetic resonance imaging (MRI) scans of the injured discs, injected discs, and uninjured L5-L6 discs were performed at 15 weeks post surgery and compared with preoperative MRI scans. Results: All twelve rabbits showed consistent results of disc degeneration within 15 weeks following annular puncture. DHIs of injured discs were significantly lower than that of the uninjured L5-L6 discs (p<0.05). The mean value of disc degeneration grade of injured discs was significantly higher than that of uninjured discs (p<0.05). The injection of disc cell transfected with ad-BMP-2 did not induce disc regeneration at 15 weeks after injection. Conclusion: This study showed that the injured disc had a significant change in DHI on simple lateral radiograph and disc degeneration grade on MRI scans within 15 weeks in all rabbits. Rabbit annular puncture model can be useful as a disc degeneration model in vivo.

• Journal of Veterinary Clinics
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• v.34 no.5
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• pp.370-373
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• 2017

Sacroiliac dislocation is the separation of the iliac wing from the pelvic bone and needs to be repaired by surgery. Corrective surgical methods include open reduction and minimally invasive techniques. In the present study, we used a minimally invasive surgical technique in seven dogs with sacroiliac dislocation. Five cases had unilateral sacroiliac joint luxation and two cases had bilateral sacroiliac joint luxation; all were referred to hospital after being hit by an automobile. All cases were treated with a fluoroscope-assisted, minimally invasive technique. Patients were evaluated by measuring surgery time, postoperative ambulatory time, and calculating pelvic canal diameter ratios. Surgery time was measured from initial incision to completion of skin closure. Mean surgery time was 30.6 minutes in unilateral sacroiliac joint luxation and 68 minutes in bilateral sacroiliac joint luxation. Mean preoperative pelvic canal diameter ratio was 1.22 (${\pm}0.27$), immediate postoperative pelvic canal diameter ratio was 1.26 (${\pm}0.10$), and at 2 weeks after surgery, the pelvic canal diameter ratio was 1.37 (${\pm}0.22$). All cases were ambulatory within 1 week and mean postoperative ambulatory time was 5 days. Based on the results, the use of a minimally invasive technique for correction of sacroiliac dislocation can decrease surgical time, lessen operative and postoperative burdens on patients, and provide owners with a good prognosis.

• Animal cells and systems
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• v.11 no.2
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• pp.147-153
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• 2007

DNA extracted from ancient bones of Cervidae animals was examined to identify the species and to determine the phylogenetic relationships to those from extant cervids. Abundant ancient bones were excavated from Kumsung archaeological site in Jeju Island, Korea, and were identified as Cervidae animals based on morphological features of their antlers and lower mandibles. Their mitochondrial DNA (mtDNA) control region (CR) was partially sequenced and subsequently compared with those previously reported in database. The results confirmed that the ancient sequences are lineage of Cervidae. On the phylogenetic trees constructed using the sequence diversity of the CR sequences of family Cervidae, the ancient DNA sequences were found on distinct clusters. The ancient sequences were located in the subfamily Capreolinae cluster, and six ancient sequences were closely related to those of extant Korean roe deer in Jeju Island and Korean Peninsula. Consequently, the results of this study suggest that the roe deer inhabited Jeju Island in ancient times. However, there is no evidence for the existence of subfamily Cervinae, including Sika deer, while it has been described in several historical records. The results suggest that this finding could contribute to understanding of the origin and phylogenetic relationships of extant and ancient roe deer on Jeju Island.

• The korean journal of orthodontics
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• v.14 no.1
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• pp.53-65
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• 1984

The purpose of this study was to investigate the histopathological change and adaptation process of the mandibular joint of the rat by muscle alteration. For this study, one hundred and twenty eight rats of 25 - and 60 - day old of age were used. Unilateral and bilateral detachment, with anterior positioning of the Masseter muscle, was performed under anesthesia. The animal was sacrified 10, 20, 50, 80 days postoperatively. This alteration in muscle function led to change in neuromuscular activity and demonstrated the adaptive nature of the condyle cartilage to functional demand. The results were as follows : 1. In the right muscle detached group, operated at 25 days of age, marked decrease on the chondroblastic zone was found in the condyle head on the right side of animals examined 10 days postoperatively. Comparing with the control group, no difference was found on the chondroblastic zone in the condylar head of animals examined 20, 50 and 80 days postoperatively. 2. In the bilateral muscle detached group, operated at 25 days of age, the chondroblastic zone was slightly decreased in the anterior parts of condylar head of animals examined 10 days postoperatively. 3. In the unilateral and bilateral muscle detached group, operated at 60 days of age, no significant change was found in the mandibular joint regardless of the post operative experimental periods. 4. Under Toluidine blue staining, slightly decreased metachromasia was found in the condyle head on the right side of unilateral experimental animals, operated at 25 days of age and examined 10 days postoperatively. 5. Under Masson's trichrome staining, increased metachromasia was found in the condyle head on the right side of unilateral experimental animals, operated at 25 days of age and examined 10 days postoperatively. In summary, the condyle of the rat could respond to changes in neuromuscular activity depend on the level of maturation of the tissue, because the endochondral bone formation of the condyle of the rat was almost ended within 3 months.

• The korean journal of orthodontics
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• v.24 no.4 s.47
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• pp.897-916
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• 1994

The biologic potential, which is different from the piezoelectric signals, relates tooth movement at least in part to changes in bone metaboliosm in bioelectric theory. The purpose of this experiment was to determine wheather the application of half sine-wave pulsed electromagnetic fields (HSPEMF) could increase both the rate and amount of orthodontic tooth movement. Forty-three male Hartley guinea pigs, weighting approximately 255g, were utilized in this study. The animals were 35 days old at the start of the study. Laterally directed orthodontic force was applied to the maxillary central incisors of 40 Hartley guinea pigs (20 experimental, 20 control). According to the amount of orthodontic force (6g, 12g), they were divided into two sub-groups (10 experimental I, 10 experimental II, 10 control I, 10 control II). During the experimental period, experimental animals were placed in plastic animal holders with their heads positioned in an area of uniform electromagnetic field. Control animals were placed in similar plastic holders that did not carry the electric apparatus. The results were as follows : 1. The application of a HSPEMF to the experimental groups significantly increase the final amount of orthodontic tooth movement observed over a 10-day experimental period. 2. The application of a HSPEMF to the experimental groups significantly increase the velocity of orthodontic tooth movement observed over a 10-day experimental period. 3. There was no significant difference in the final amount of orthodontic tooth movement at the fourth day to the eighth day, but there was significant difference in the final amount of orthodontic tooth movement at the nineth, tenth day during a 10-day experimental period. 4. After 10 days of HSPEMF exposure & orthodontic force, the experimental groups demonstrated more osteodasts in the pressure side than control groups.

• The korean journal of orthodontics
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• v.47 no.4
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• pp.229-237
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• 2017

Objective: The aim of this study was to compare the initial stability as insertion and removal torque and the clinical applicability of novel orthodontic zirconia micro-implants made using a powder injection molding (PIM) technique with those parameters in conventional titanium micro-implants. Methods: Sixty zirconia and 60 titanium micro-implants of similar design (diameter, 1.6 mm; length, 8.0 mm) were inserted perpendicularly in solid polyurethane foam with varying densities of 20 pounds per cubic foot (pcf), 30 pcf, and 40 pcf. Primary stability was measured as maximum insertion torque (MIT) and maximum removal torque (MRT). To investigate clinical applicability, compressive and tensile forces were recorded at 0.01, 0.02, and 0.03 mm displacement of the implants at angles of $0^{\circ}$, $10^{\circ}$, $20^{\circ}$, $30^{\circ}$, and $40^{\circ}$. The biocompatibility of zirconia micro-implants was assessed via an experimental animal study. Results: There were no statistically significant differences between zirconia micro-implants and titanium alloy implants with regard to MIT, MRT, or the amount of movement in the angulated lateral displacement test. As angulation increased, the mean compressive and tensile forces required to displace both types of micro-implants increased substantially at all distances. The average bone-to-implant contact ratio of prototype zirconia micro-implants was $56.88{\pm}6.72%$. Conclusions: Zirconia micro-implants showed initial stability and clinical applicability for diverse orthodontic treatments comparable to that of titanium micro-implants under compressive and tensile forces.

• BMB Reports
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• v.48 no.11
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• pp.636-641
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• 2015

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H₂O₂), N-acetyl cysteine (NAC), or both. Exposing the cells to H₂O₂ decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H₂O₂ treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H₂O₂ on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H₂O₂ to near normal levels in the cells. Collectively, our findings suggest that H₂O₂-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC.

• Molecules and Cells
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• v.25 no.2
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• pp.265-271
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• 2008

Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Non-synonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the $278^{th}$ amino acid from glutamic acid to lysine (E278K). Uptake of [$3^H$] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were $0.7{\mu}M$ and $1.2{\mu}M$, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis.