• Journal of Periodontal and Implant Science
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• 제29권4호
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• pp.751-765
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• 1999

Several growth factors and polypeptidesare not commonly yet used for regenerators of bone tissue or alveolar bone because of the insufficiency of studies on their side effects, genetic engineering for mass production and stability for clinical application. Recently, many natural medicines, which have advantage of less side effects and possibility of long-term use, have been studied for their capacity and effects of anti-bacterial, anti-inflammatory and regenerative potential of periodontal tissues. Olibanum, Myrrha, Phlomis Radix, and Cimicifugae Rhizoma have been traditionally used as a drug for treatment of bone disease in oriental medicine. The objective of this study was to examine the ability of alkaline phosphatase(ALP) synthesis of rat calvarial osteoblast(MC3T3-E1) when several natural medicines were supplemented. MC3T3-E1 cells were cultured with ${\alpha}$-MEM(negative control), dexamethasone(positive control), and each natural medicines for 3 and 5 days. And then ALP synthesis was measured by spectrophotometer for enzyme activity and by naphthol AS-BI staining for morphometry. All of the natural medicines induced higher activity of ALP synthesis than the negative controls. Especially Olibanumind uced the higher activity than the positive controls (p<0.05). In the aspects of culturing time, except Cimicifugae Rhizoma, the natural medicines induced higher activity of ALP synthesis at 5 days than at 3 days (p<0.05). In morphometry, all of the natural medicines showed statistical significance compared to the negative control (p<0.05). Myrrha a n d Phlomis Radix showed larger positively stained area at 5days than at 3 days, whereas the others did not showed the difference between at 5 and at 3 days(p<0.05). These results indicate that several natural medicines have an inducing ability of ALP synthesis in MC3T3-E1 cells.

• Journal of Periodontal and Implant Science
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• 제29권4호
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• pp.737-749
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• 1999

Recently many researches on plaque removal effect and therapeutic effect of toothpaste containing natural medicines are being studied in early periodontal diseases. The purpose of this study is to examine the clinical and microbiological effect of toothpaste containing natural medicines such as camomile, rhatany, myrrh，sage oil, glycyrrhetinic acid and vitamin E. Sixty three subjects with gingivitis were divided into an experimental group which performed normal oral hygiene procedure with toothpaste containing natural medicines and vitamine E and a control group which also performed normal oral hygiene procedure with Syrinmed? toothpaste without containing herbal extracts and vitamine E. At the baseline, 2 weeks, and 4 weeks, subjects were analyzed for clinical study and microbiological study. After 2 weeks and 4 weeks use of their respective toothpastes, statistically significant decreases of gingival index, plaque index, and bleeding index were shown in both the control and the experimental group. The degree of decrease was more significant in the experimental group than the control group. A statistically significant decrease of pocket depth, and gingival crevicular fluid were shown in both the control and lie experimental group. A statistically significant increase of cocci was shown in both the control and the experimental group, the degree of increase was more significant in the experimental group than control group. A statistically significant decrease ofnon-motile rods, and motile rods were shown in both the control and the experimental group, the degree of decrease was more significant in the experimental group than the control group. Spirochetes increased weakly in both the control and the experimental group but a statistic significance was not shown. A statistically significant decrease of anaerobic bacteria, aerobic bacteria, and black pigmented Bacteroides were shown in both the control and the experimental group. These results indicate that the use of toothpaste containing natural medicines is effective in the prevention and the treatment of periodontal diseases.

• Journal of Periodontal and Implant Science
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• 제30권2호
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• pp.359-374
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• 2000

Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.

• Journal of Periodontal and Implant Science
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• 제35권1호
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• pp.99-109
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• 2005

It has been focused on the importance of the host inflammatory response in periodontal pathogenesis and progression, treatment has been introduced to control the host response and the method, which diminishes production and activity of MMP by doxycycline, has been used in periodontal field. MMP is a proteolytic enzyme which plays a major role in tissue destruction and MMP-1 is secreted in the periodontally healthy tissue, while MMP-8, 9, 13, etc in the inflammatory state. Among these, MMP-13 has been discovered lately and reported to degrade primarily type II collagen. Periodontal ligament (PDL) cell plays a role in destruction of periodontal tissue. This study was to evaluate the effect of doxycycline and mefenamic acid, non-steroidal antiinflammatory drug on MMP-13 mRNA expression in the rat PDL cell. Doxycycline concentration of $1{\sim}100\;{\mu}g/ml$ was added rat PDL cell and cell activity was measured by MIT assay at day 1 and 3. MMP-13 gene expression was evaluated by RT-PCR after PDL cells were pre-treated for 1hour with doxycycline (50 ${\mu}g/ml$) alone or with mefenamic acid ($10^{-6}M$), then added $IL-1{\beta}$(1.0 ng/ml) and incubated for 16-18 hours. The results are as follows: 1. Cell activity decreased Significantly at 24 and 72 hours in 100 ${\mu}g/ml$ (p<0.05). 2. Level of MMP-13 mRNA was in 20.2% increase by $IL-1{\beta}$ and in pre-treating doxycycline group, expression of $IL-1{\beta}$ induced MMP-13 mRNA was inhibited by 31% than $IL-1{\beta}$ treated only. 3. Mefenamic acid did not inhibit on the expression of $IL-1{\beta}$ induced MMP-13 mRNA, while mefenamic acid in combination with doxycycline inhibited the expression by 41% compared to only $IL-1{\beta}$ stimulation. These results suggest that doxycycline synergistically inhibit the expression of $IL-1{\beta}$ induced MMP-13 mRNA in combination with mefenamic acid.

• Reproductive and Developmental Biology
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• 제28권4호
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• pp.211-219
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• 2004

The effects of adenosine 5'-triphosphate (ATP) and ATP analogs, P/sub 2y/ purinoceptor agonists, on growth of normal mouse mammary epithelial cells (NMuMG) were examined. Cells were plated onto 24 well plates in DMEM supplemented with 10 % fetal calf serum. After serum starvation for 24 hours, ATP, P/sub 2y/ purinoceptor agonists (AdoPP[NH]P, ATP-α-S, ATP-γ-S, β, γ-me-ATP and 2me-S-ATP), P/sub 2u/ purinoceptor agonist (UTP) and P/sub 2y/ purinoceptor antagonists (Reactive Blue 2, more selective to P/sub 2y/ receptor than PPADS; PPADS) were added. DNA synthesis was estimated as incorporation of 3H-thymidine into DNA (1 hour pulse with 1 μ Ci/ml, 18～19 hours after treatment). ATP, Adopp[NH]P, ATP-α-S or ATP-γ-S, significantly increased DNA synthesis at 1, 10 and 100 μM concentrations with dose-dependency (P<0.05), and the maximum responses of ATP and ATP analogs were shown at 100 μM concentration (P<0.05). The potency order of DNA synthesis was ATP≥ATP- γ -S>Adopp [NH]P>ATP-α-S. β, γ -me-ATP, 2me-S-ATP and UTP did not increase DNA synthesis. In autoradiographic analysis of percentage of S-phase cells, similar results were observed to those of DNA synthesis. Addition of 1, 10 or 100 μM Reactive Blue 2 or PPADS significantly decreased ATP (100 μM)-induced DNA synthesis, however, PPADS was less effective than Reactive Blue 2. In Elvax 40P implant experiment, ATP directly stimulated mammary endbud growth in situ suggesting the physiological regulator of ATP in mammary growth. ATP 100 μM rapidly increased MAPK activity, reaching a maximum at 5 min and then gradually decreasing to the base level in 30 min. ATP analogs, Adopp[NH]P and ATP-γ-S also increased MAPK activity, however, β, γ-me-ATP and 2me-S-ATP did not. The inhibitor of the upstream MAPK kinase (MEK), PD 98059 (25 μM), effectively reduced ATP (100 μM) or EGF(10 ng/ml, as positive control)-induced MAPK activity and DNA synthesis (P<0.05). These results indicate that ATP-induced DNA synthesis was prevented from the direct inhibition of MAPK kinase pathway. Overall results support the hypothesis that the stimulatory effects of normal mouse mammary epithelial growth by addition of ATP or ATP analogs are mediated through mammary tissue specific P/sub 2y/ purinoceptor subtype, and MAPK activation is necessary for the ATP-induced cell growth.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권2호
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• pp.107-116
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• 2006

Purpose:Maxillay sinus grafting is an effective treatment procedure to improve bone height in the posterior maxillar area for implant installation. Beta-tricalciumphosphate(${\beta}$-TCP) was introduced to be grafting substitute material, providing a reasonable bio-degradation time, no need for harvesting procedure. The purpose of this study is to evaluate bone healing & regeneration phase using histomorphometric and immunohistochemical analysis. Material & Methods:Sixteen rabbits were divided into 4 groups. Bi-lateral maxillary sinus membranes were elevated at each rabbits, ${\beta}$-TCP was augmented in left sinus, autogenous bone was augmented in right sinus. The rabbits were sacrificed at 2, 4, 8 and 12 weeks. We investigated the bone regeneration & growth factor expression. Results: 1. The mean new bone volume formation was 28.99${\pm}$6.55%, 49.54${\pm}$5.47%, 69.09${\pm}$8.90% in autogenous grafted area, and 22.86${\pm}$5.56%, 24.00${\pm}$4.09%, 34.11${\pm}$3.37% in ${\beta}$-TCP area at 4, 8, 12 weeks. Therefore, new bone formation in autogenous bone was significantly higher than ${\beta}$-TCP (p<0.05). 2. The BMP 2/4 expression in autogenous bone grafted area was higher at 4, 8 weeks. 3. There was no difference in expression pattern of BMP-7/PDGF/VEGF during grafted bone regeneration. Conclusion:The authors we conclude that the autogenous bone graft was faster than ${\beta}$-TCP in bone regeneration, and the BMP 2/4 were more important in graft bone regeneration.

• Journal of Periodontal and Implant Science
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• 제32권4호
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• pp.733-744
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• 2002

The fibroblasts are the principal cells in the periodontal ligament of peridontium. As the periodontal ligament fibroblasts (PDLF) show similar phenotype with osteoblasts, the PDLF are thought to play an important role in alveolar bone remodeling. Cell-to-cell contacted signaling is crucial for osteoclast formation. Recently it has been reported that PDLJ enhance the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The aims of this study were to $clarify\;^{1)}$ the mechanism of PDLF-induced osteoclastogenesis $and\;^{2)}$ whether we can use preosteoclast cell line instead of primary hematopoietic preosteoclast cells for studying the mechanism of PDLF-induced osteoclastogenesis. Osteoclastic differentiation of mouse macrophage cell line RAW264.7 was compared with that of mouse bone marrow-derived M-CSF dependent cell (MDBM), a well-known hematopoietic preosteoclast model, by examining, 1) osteoclast-specific gene expression such as calcitonin receptor, M-CSF receptor (c-fms), cathepsin K, receptoractivator nuclear factor kappa B (RANK) ,2) generation of TRAP(+) multinucleated cells (MNCs), and 3) generation of resorption pit on the $OAAS^{TM}$ plate. RAW264.7 cultured in the medium containing of soluble osteoclast differentiation Factor (sODF) showed similar phenotype with MDBM-derived osteoclasts, those are mRNA expression pattern of osteoclast-specific genes, TRAP(+) MNCs generation, and bone resorbing abivity. Formation of resorption pits by osteoclastic MNCs differentiated from sODF-treated RAW264.7, was completely blocked by the addition of osteoprotegerin (OPG), a soluble decoy receptor for ODF, to the sODF-containing culture me야um. The effects of PDLF on differentiation of RAW264.7 into　the TRAP(+) multinucleated osteoclast-like cells were examined using coculture system. PDLF were fxed with paraformaldehyde, followed by coculture with RAW264.7, which induced formation of TRAP(+) MNCs in the absence of additional treatment of sODF. When compared with untreated and fixed PDLF (fPDLF), IL-1 ${\beta}$-treated, or lipopolysaccha-ride-treated and then fixed PDLF showed two-folld increase in the supporting activity of osteoclastogenesis from RAW264.7 coculture system. There were no TRAP(+) MNCs formation in coculture system of RAW264.7 with PDLF of no fixation. These findigs suggested that we can replace the primary hematopoietic preosteoclasts for RAW264. 7 cell line for studying the mechanism of PDLF-induced osteoclastogenesis, and we hypothesize that PDLF control osteoclastogenesis through ODF expression which might be enhanced by inflammatory signals.

• Journal of Periodontal and Implant Science
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• 제28권1호
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• pp.37-56
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• 1998

The purpose of this study was to evaluate the clinical and microbiological outcomes following the use of 30% minocycline-loaded polycaprolacton film and 2% minocycline-loaded gel that was applied locally into pockets combined with scaling and root planing. 25 human subjects who were non-pregnant, non-lactating, aged 20-50 and diagnosed as moderate to advanced adult periodontitis were enrolled. Subjects were excluded if they had a history of severe acute or chronic systemic disease, if they required antibiotic prophylaxis for dental treatment for any reason, or if they reported a history suggestive of hypersensitivity reactions to minocycline or tetracycline. 4quadrants that had several teeth with a 5-8mm probing pocket depth and radiographic evidence of alveolar bone loss for each patient were selected and divided into test sites and control sites according to the split-mouth design. Scaling and root planing was done for each site at baseline(0week). Test sites received the minocycline gel and strip and control sites had saline irrigation. The patients received both treatments simyltaneously. Subgingival irrigation of sterile saline was applied to the control sites for approximately 30 seconds. Minocycline strip and gel was applied into the periodontal pocket at 1, 2, 3, 4 weeks each after scaling and root planing in the test sites. The clinical and microbiological measurements were made at baseline and at the follow-up visits 6, 10, 14, 20 weeks. The results of this study were as follows; 1. The sulcular bleeding index, probing pocket depth and Periocheck test was significantly reduced and the relative proportions of spirochetes and motile rods were significantly reduced and the proportion of cocci was correspondingly increased, in locally delivered minocycline strip group compared to saline irrigation group. 2. In locally delivered minocycline gel group, The effect was the same with minocycline strip group as compared with saline irrigation therapy. 3. There was no significant differences between minocycline strip group and minocycline gelgroup. In conclusion, minocycline HCl local drug delivery combined with scaling and root planing may provide added improvement of clinical and microbiological responses by inhibiting bacterial recolonization of treated sites. It is suggested that the local administration of minocycline-HCl in the periodontal pocket is effective when combined with subgingival mechanical debridement.

• Journal of Periodontal and Implant Science
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• 제36권3호
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• pp.591-600
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• 2006

Purpose: This study assessed the impact of self-reported periodontal health on the oral health-related quality of life among elderly Koreans. Methods: Four hundred twenty one elderly Koreans in Seoul and suburban areas were selected with a cluster (institution) sampling method, and were requested to take oral examinations and finish questionnaires on the Oral Health Impact Profile-14(OHIP-14). and self-reported periodontal health status, such as periodontal symptoms, self-rated periodontal health and periodontal treatment need. As the dependent variable, OHIP-14 showed a positive skewed distribution (skewness: 1.17), we transformed to square-root form to apply parametric analyses. Bivariate analysis by t-test and ANOVA, and multivariate analysis with the two-level regression model accounting clusters were implemented. Results: Mean age of the subjects was 74.6 years and 66.5% were women. Fourteen items of OHIP-14 were summarized to one factor explaining 78.6% of total variance and produced the Chronbach alpha coefficient of 0.92. Results from the multivariate model, adjusting for age, sex, type of institutions, ability to pay, and number of teeth present, showed significantly lower OHIP-14 with reporting less than 3 periodontal symptoms (p(O.OOO1), rating their own periodontal health as above average level (p=O.0144), and thinking they don't need any periodontal treatments in the near future (p=O.0148), than their counterparts. The intraclass-corrrelation estimated by the final model was 0.028. Conclusion: This study demonstrates a significant association between self-reported periodontal health status and the oral health-related quality of life.

• Journal of Periodontal and Implant Science
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• 제24권1호
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• pp.1-14
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• 1994

Dental calculus which is calcifing and/or calcified dental plaque is divided into supragingival calculus and subgingival calculus according to the position of deposit to gingival margin. Subgingival calculus has more important clinical significance in diagnosis and treatment of periodontal disease than supragingival calculus. In order to investigate the deposition pattern of subgingival calculus on each root surface of different tooth type, extracted 192 teeth due to excessive destruction of periodontal tissue were divided according to tooth type and the deposition pattern of subgingival calculus was classified into linear type, veneer type, scattered type, and aggregated type according to the configuration and the extent of deposit. The difference of percentage between each deposition pattern was statistically analyzed by Chi-Square test. Following results were obtained : l. In maxillary incisors, linear type and aggregated type were predominant deposition pattern of subgingival calculus on labial(45.5%, 36.4%) and palatal(36.4%, 36.4%) root surface, aggreated type(72.7%) was on mesial surface, and aggregated type(54.5%) and scattered type(36.4%) was on distal suface. 2. In mandibular incisors, scattered type, linear type and aggregated type were predominant deposition pattern of subgingival calculus on labial(33.3%, 30.6%, 27.8%) and lingual(36.1%, 30.6%, 25.0%) root surface, aggregated type(33.3%), scattered type(27.8% ), and veneer type(27.8%) were on mesial surface, and aggregated type(38.9%) and scattered type(33.3%) on distal surface. 3. In maxillary peremolars, the predominant deposition patterns of subgingival calculus were linear type(28.6%) on buccal root suface, scattered type(35.7%) and linear type(28.6%) on palatal surface, scattered type(39.3%) on mesial surface, aggregated type(46.4%) on distal surface, and aggregated type(53.6%) on furcation area. 4. In mandibular premolars, scattered type was predominant deposition pattern of subgingival calculus on buccal(39.3%) and lingual(50.0%) root surface, scattered type(32.1%) and aggregated type(32.1% ) were on mesial surface, and aggregated type(42.9%) was on distal surface. 5. In maxillary molars, aggregated type(40.0%) and scattered type(32.5%) were predominat deposition pattern of subgingival calculus on buccal root surface, aggregated type was on distal(40.0%) and furcation area(50.0%), but there was no predominat pattern on palatal and mesial root surfaces. 6. In mandibular molars, aggregated type(39.5%) and scattered type(28.9%) were predominant deposition patterns of subgingival calculus on buccal root surface, aggregated type(36.8%) was on lingual surface, linear type(39.5%) and aggregated type(34.2%) were on furcation area, but there was no predominant pattern on mesial and distal root surfaces.