• Archives of Plastic Surgery
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• v.38 no.4
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• pp.485-489
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• 2011

Purpose: Median cleft of upper lip is defined as any congenital vertical cleft through the midline of the upper lip. It is uncommon, its embryological pathogenesis remains unexplained to date. The authors hereby report a rare case of median cleft of the upper lip associated with enlarged frenulum and palatal mass. This case offers some understanding of the possible embryologic development of this anomaly. Methods: A 10-month-old boy born by normal vaginal delivery at full-term had a notch in the midline of the upper lip with widened philtrum along with enlarged median frenulum, alveolar cleft, and mass of the hard palate. We performed en bloc resection of the enlarged frenulum and palatal mass and cheiloplasty under general anesthesia. Results: Histological examination revealed that the frenulum and palatal mass was consisted of fibrous tissue with normal mucous membrane. The postoperative course was satisfactory. Conclusion: A rare case of median cleft of the upper lip with associated enlarged frenulum and palatal mass was presented with proper surgical management. The surgical technique includes marginal excision of the clefted epithelium and reconstruction of orbicularis oris muscle, in addition to en bloc resection of the palatal mass and frenulotomy.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.484-495
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• 2023

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.775-785
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• 1999

Background : The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods : 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. Results : Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methyprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion : These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.662-672
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• 2002

The lungs are frequently the site of adverse drug reactions because of their higher oxygen concentration, the distinctive properties of the pulmonary circulation, and the close proximity of the alveolar epithelium to the blood. Amiodarone, an iodinated benzofuran derivative, is an effective antiarrhythmic drug commonly used for refractory tachyarrhythmia. However, it has a wide range of adverse effects, the most serious of which is lung disease. Most patients present with the insidious onset of dyspnea and a nonproductive cough, and generally recover after withdrawing the drug. We recently experienced four fatal cases of amiodarone pulmonary toxicity. Therefore, we discuss these unusual drug-induced pulmonary toxicity cases with a review of the relevant literature.

• Journal of Periodontal and Implant Science
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• v.28 no.1
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• pp.145-160
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• 1998

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue which has been lost due to destructive periodontal disease, and numerous kinds of materials and techniques have been developed to achieve this goal. Bone grafts include autografts, allografts, xenografts and synthetic grafts. Among the synthetic grafts, bioactive glass has been used in dentistry for more than ten years and Fetner reported improved new bone formation and more amount of new attachment after grafting PerioGlas, a kind of bioactive glass, in 2-wall defects of monkeys in 1994. It Is well known that 1-wall defects have less osteogenic potential and more epithelial migration, so we need to study the erect of bioactive glass in 1-wall dejects in dogs. The present study evaluates the effect of bioactive glass on the epithelial migration, alveolar bone regeneration, cementum formation and gingival connective tissue attachment in intrabony detects of dogs. Four millimeter deep and four millimeter wide 1-wall defects were surgically cheated in the mesial aspects of premolars. The test group received bioactive glass with a flap procedure and the control underwent flap procedure only. Histologic analysis after 8 weeks of healing revealed the following results: 1. The height of gingival margin was 1.30{\pm}0.73mm$ above CEJ in the control and $1.40{\pm}0.78mm$ in the test group. There was no statistically significant difference between the two group. 2. The length of epithelial growth (the distance from CEJ to the apical end of JE) was $1.74{\pm}0.47mm$ in the control and $1.12{\pm}0.36mm$ in the test group. These was a statistically significant difference between the two groups (P<0.01). 3. The length of new cementum was $2.06{\pm}0.73mm$ in the control and $2.62{\pm}0.37mm$ in the test group. There was no statistically significant difference between the two groups. 4. The length of new bone was $1.83{\pm}0.74mm$ in the control and $2.39{\pm}0.59mm$ in the test group. There was no statistically significant difference between the two groups. These results suggest that the use of bioactive glass 1-wall intrabony defects has significant effect on the prevention of junctional epithelium migration, but doesn't have any significant effect on new bone and new cementum formation.

• Journal of Periodontal and Implant Science
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• v.28 no.2
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• pp.219-237
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• 1998

Numerous bone graft materials have been used in Periodontics, in an attempt to reach the main goal of periodontal therapy, i.e. the regeneration of periodontal tissue lost due to destructive periodontal diseases. The present study investigates the effect of composite graft of DFDB and Calcium sulfate with and without Calcium sulfate barrier in Periodontal 1-wall intrabony defects in dogs. Following the initiation of general anesthesia by I.V. administration of 40mg/Kg of Pentobabital, second premolar was extracted and full thickness flap elevated. The crown portion of premolars was removed. Exposed root canals were sealed with Caviton and covered completely with flap. After the healing period of 8 weeks, the surgical sites were re-opened and 1-wall intrabony defects were created, and treated with flap operation alone(control group), with composit graft of 80% DFDB and 20% Calcium sulfate(Experimental group 1), with composite graft of DFDB and calcium sulfate with calcium sulfate membrane( Experimental group 2). Healing response was histologically observed after 8 weeks and the results were as follows : 1. New bone formation was 70 % in the control group, 93 % in the Experimental group I, 89 % in the Experimental group II. There was a no differences between Experimental groups. 2. New cementum formation was not significantly different between control and two Experimental groups. 3. The length of connective tissue adhesion was 30 % in the control, 7% in the Experimental group I and 11 % in the Experimental group II. 4. After 8weeks, calcium sulfate was completely resorbed, while DFDB particle remained. These results suggest that the use of composite graft of allogenic DFDB and Calcium sulfate with and without Calcium sulfate barrier in periodontal 1 wall intrabony defects have little effect on connective tissue adhesion, but has beneficial effect on new alveolar bone and new cementum formation, and prevent downgrowth of epithelium and connective tissue effectively.

• Journal of Periodontal and Implant Science
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• v.27 no.3
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• pp.479-493
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• 1997

There are various treatment methods including barrier membranes in attaining periodontal regeneration and regaining the function of destructed periodontal tissues due to periodontal disease. Barrier membranes consist of non-Resorbable and resorbable types such as Dura mater and $Guidor^{(R)}$ used in the treatment of intrabony defects and classII furcation defects have been shown to be effectively increased the amount of new bone and cementum.In our study we used premolars with class III furcation defects created by removing the bone 4mm apically from CEJ in adult dogs and placed resorbable membrane Dura mater and $Guidor^{(R)}$ for the test group and flap operation was carried out for the control groups. The effect of membrane on junctional epithelium, alveloar bone, cementum, and gingival connective tisssue in the regeneration and healing potential of periodontal tissues was evaluated and healing results were evaluated histologically and histometrically 8 weeks following the surgical procedure. 1. In the clinical observation, there was no exposure of furcation defects in the control group, whereas slight membrane exposure was noted in the test group. 2. New bone was formed up to the level of the notch in the control group, whereas in the test group new bone formation was observed above the level of the notch. 3. New cementum was formed in both groups of the experiment. 4. The connective tissue observed between the new cementum and new bone in the test group were functionally orientated, compared to the irregular formation of connective tissues found in the control group. 5. Root resorption or ankylosis was not observed in any of the groups 6. The mean and median of the control group were 4.31% and 2.23% and for the Dura mater group were 27.85% and 15.57% respectively. There was no significant difference between Dura mater and the control group. 7. The mean and median of the control group were 4.31% and 2.23% and for the $Guidor^{(R)}$ group were 37.27% and 37.19% respectively. There was a significant difference in these two groups(P$Guidor^{(R)}$ were 37.27% and 37.19%. There was no significant difference between the two test groups. Thus, by using Dura mater and Guidor in classIII furcation defects, the predictable amount of periodontal ligament and alveolar bone regeneration may result.

• The Journal of Korean Academy of Prosthodontics
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• v.47 no.3
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• pp.301-311
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• 2009

Statement of problem: Flapless implant surgery using a soft tissue punch device requires a circumferential excision of the mucosa at the implant site. To date, Although there have been several reports on clinical outcomes of flapless implant surgeries, there are no published reports that address the appropriate size of the soft tissue punch for peri-implant tissue healing. Purpose: In an attempt to help produce guidelines for the use of soft tissue punches, this animal study was undertaken to examine the effect of soft tissue punch size on the healing of peri-implant tissue in a canine mandible model. Material and methods: Bilateral, edentulated, flat alveolar ridges were created in the mandibles of six mongrel dogs. After a three month healing period, three fixtures (diameter, 4.0 mm) were placed on each side of the mandible using 3 mm, 4 mm, or 5 mm soft tissue punches. During subsequent healing periods, the peri-implant mucosa was evaluated using clinical, radiological, and histometric parameters, which included Gingival Index, bleeding on probing, probing pocket depth, marginal bone loss, and vertical dimension measurements of the peri-implant tissues. Results: The results showed significant differences (P <0.05) between the 3 mm, 4 mm and 5 mm tissue punch groups for the length of the junctional epithelium, probing depth, and marginal bone loss during healing periods after implant placement. When the mucosa was punched with a 3 mm tissue punch, the length of the junctional epithelium was shorter, the probing depth was shallower, and less crestal bone loss occurred than when using a tissue punch with a diameter $\geq$ 4 mm. Conclusion: Within the limit of this study, the size of the soft tissue punch plays an important role in achieving optimal healing. Our findings support the use of tissue punch that 1 mm smaller than implant itself to obtain better peri-implant tissue healing around flapless implants.