• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

• The Korean Journal of Physiology and Pharmacology
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• 제18권4호
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• pp.333-339
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• 2014

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

• Restorative Dentistry and Endodontics
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• 제13권2호
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• pp.283-294
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• 1988

The purpose of this study was to investigate the characteristic features of the cells and tissues of the chronic periapical lesions using light microscope and electron microscope. Fifteen dental periapical lesions were obtained from the patients undergoing periapical surgery. Each specimen was divided into two parts along the tooth axis. One part was routinely processed for histopathologic examinations. 12 periapical lesions were diagnosed as granuloma and 3 periapical specimens as periapical cyst. The other part was fixed in 2.5% glutaraldehyde in 0.1M sodium cacodylate buffer at pH 7.4 and 1% osmic acid in same buffer. They were embedded in Epon 812. The semithin sections were used for the orientation of the lesions and the ultrathin sections were stained conventionally and examined with AEI Corynth 500 electron microscope. The results were as follows. 1. PMN and macrophages, which were dominant cell type, were scattered in small or large numbers throughout the central destructive area of granuloma. In the granulomatous area, plasma cells and lymphoytes were found in significant number and a lot of new capillary formation were revealed. Clefts caused by cholesterol were often seen in the connective tissue. Occasionally foam cells became collected in groups and epithelial proliferation were present. 2. In both granuloma and cyst, some plasma cells contained narrow cisternae of granular endoplasmic reticulum of which was tightly packed with electron dense materials, and other cells exhibited dilated profiles of granular endoplasmic reticulum. 3. In the area where plasma cells and lymphocytes were collected in groups, lymphocytes with well developed nucleolus and profuse cytoplasm were found and differentiating plasma cells were also present. 4. In the epithelial strands of the granulomatous area, epithelial cells contained enlarged endoplasmic reticulum, tonofilaments and ribosoms. Toward the intercellular space epithelial cells protruded a few microvilli. In the intercellular space, exudate-like electron dense materials, most of which was attached to the plasma membrane, appeared. 5. Some foam cells filled with numerous lipid droplets and others had lipid droplets and crystal-like structures. 6. Cyst epithelium consisted of bright cells and dark cells. The former had bright cytoplasm and small amounts of ribosoms, and the latter dark cytoplasm, many ribosoms, mitochondria and elongated microvilli. 7. Epithelial cells near the cyst lumen protruded a lot of long microvilli toward intercellular space and cyst lumen.

• Journal of Periodontal and Implant Science
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• 제35권4호
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• pp.823-837
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• 2005

The purpose of this study was to study the histopathological correlation between the use of platelet-rich plasma and enamel matrix protein used in conjunction with xenograft. compared to a control group with regards to bone regeneration at the grade III furcation area in beagle dogs. Control group was treated with bovine derived bone $powder(Biocera^{(R)})$, and experimental I group was treated with bovine derived bone powder and Platelet-rich plasma and experimental II group was treated with bovine derived bone powder and Enamel matrix $protein(Emdogain^{(R)})$. The regeneration rate of bone formation was observed and compared histopathologically at 2. 4, and 8 weeks after surgery. The results were as follows: 1. In control group and both experimental groups. inflammatory cells were observed but, new bone formation wasn't. 2. In control group, new cementum on the notch was found in 4 weeks, less mature periodontal ligament when compared to that of experimental group was found and cementum formation was great but, regeneration couldn't be seen in 8 weeks. 3. Experimental I group. new bone formation in the area adjacent to alveolar bone and graft material surrounded by more dense connective tissue were found in 4 weeks. New bone formation up to crown portion was found and periodontal ligament was aligned functionally and cementum more mature. 4. Experimental II group, new bone formation was found under the defect area in 4 weeks and new bone formation around graft material in 8 weeks, too, and there were a number of fibroblasts, blood vessels, acellular cementum, which was less mature when compared to that of experimental I group, and dense collagen fiber like which normal periodontal ligament has in periodontal ligament of experimental II group in 8 weeks. 5. As a result of histologic finding, bone formation rate were 18.0${\pm}$7.87%(control group), 34. 05${pm}$7.25%(experimental I group), 19.33 ${pm}$5.15%(experimental II group) in 4 weeks and 21.89${pm}$1.58%(control group), 38.82${pm}$3.2(experimental I group), 37.65${pm}$9.22%(experimental II group) in 8 weeks. 6. Statistically significant ratio of bone formation was observed in experimental I group in 4 weeks and in experimental II group in 8 weeks. When experimental I group was compared to experimental II group, the ratio of bone formation in experimental I group was higher than that in experimental II group in 4 weeks(p<0.05). This results suggest that platelet-rich plasma showed more new bone formation than enamel matrix protein within 4 weeks. And use of enamel matrix protein in the treatment of periodontal bone defects starts to enhance regeneration after 8 weeks in beagle dogs.

• Journal of Periodontal and Implant Science
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• 제31권3호
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• pp.597-610
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• 2001

Normal gingival fibroblasts functioning is fundamental for the maintenance of periodontal connective tissue as well as wound healing. Nicotine have been found to affect DNA synthesis and cell proliferation, which appear to depend on the type of cells. This in vitro study was done to determine the effects of nicotine, a major component of tobacco, on cell proliferation, viability, activity, cell cycle distribution, and expression of cell cycle regulatory proteins in human gingival fibroblasts. Nicotine has been tested for 2 days or 4 days in 5 different concentrations; $0.1{\mu}g/ml$; $1{\mu}g/ml$; $10{\mu}g/ml$; $100{\mu}g/ml$; $1000{\mu}g/ml$. To assess cell proliferation and viability, viable and non-viable cells were counted by hemocytometer; to evaluate cellular activity, MTT assay was employed; to analyze cell cycle distribution, fluorescent propidium iodide-DNA complex were measured using fluorocytometer; to determine the expression of cell cycle regulatory proteins, western blot analysis was performed. After 2 days and 4 days incubation respectively, at concentrations of $1{\mu}g/ml$ - $1000{\mu}g/ml$, nicotine significantly inhibited proliferation comparing to non-supplemented controls. The cell viability was significantly decreased after 2 days and 4 days at concentrations of $1{\mu}g/ml$ - $1000{\mu}g/ml$ and at $10{\mu}g/ml$ - $1000{\mu}g/ml$ respectively. After 2 days and 4 days, the cellular activity was significantly decreased at concentrations of $10{\mu}g/ml$ - $1000{\mu}g/ml$. Treatment with $100{\mu}g/ml$ nicotine for 48 hours caused an increase in the proportion of G1-phase cells (from 46.41% to 53.46%) and a decrease in the proportion of S-phase cells (from 17.80% to 14.27%). The levels of cyclin $D_1$ and CDK 4 proteins in nicotine-treated fibroblasts were lower than that of controls, whereas the levels of p16 and pRB were higher than that of controls. These results suggest that the decrease of cell proliferation and lengthened Gap phases (G1) by nicotine may due to the increased expression of p16 and pRB as well as decreased expression of cyclin $D_1$ and CDK 4 in human gingival fibroblasts.

• Journal of Periodontal and Implant Science
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• 제34권3호
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• pp.475-487
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• 2004

Purpose: This study was aimed to evaluate the effect of the deproteinated bovine bone powder (DBBP) coated with calcium phosphate (Ca-P) on osseous regeneration in the calvarial bone defect of rat. Materials and Methods : The DBBP (Control group, n=6) and the Ca-P coated DBBP (Experimental group, n=6) were grafted in the critical sized calvarial bone defect (8 mm) of rat weighing 250 g. The animals were sacrificed at 1, 4 week. The biopsy specimens were decalcified with 5%formaldehyde and embedded in paraffin. The rats were sacrificed at 8 week received tetracycline (1 week), calcein blue (4 week), and alizarin red (7 week), and the biopsy specimens were taken. The specimens were embedded in methylmethacrylate and ground to 10 ${\mu}m$ thin sections were made. All of the specimens were stained with H & E and Masson's trichrome and examined under light microscope. The specimens at 8 week were examined under fluorescent microscope. Results : In the Control group, the grafted DBBP was surrounded with connective tissue, and osteoblasts were observed partially around the grafted particles at 1 week. At 4 week, some osteoid was observed and, new bone formation was observed at the periphery of grafted materials at 8 week, In the Experimental group, some osteoid was seen at the periphery of the grafted Ca-P coated DBBP at 1 week, and osteoblast and newly formed bone were observed around the grafted materials. At 8 week, newly formed bone was observed at the periphery of the grafted materials. Conclusion: These results suggest that Ca-P coated DBBP group was more and faster than DBBP group in new bone formation and Ca-P could contribute to enhance bone formation in the critical sized calvarial bone defect of rat.

• Journal of Periodontal and Implant Science
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• 제38권1호
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• pp.75-82
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• 2008

Purpose: The purpose of this study was to evaluate exophytically vertical bone formation in the mandibular premolar area of beagle dogs by the concept of guided bone regeneration with a titanium reinforced e-PTFE membrane combined with human demineralized freeze-dried bone. Materials and Methods: Four one-year old beagle dogs were divided into control and experimental group. All mandibular premolars were extracted and surgical vertical defects of 5 mm in height were created in the extracted sockets. At 8 weeks after the extraction, TR e-PTFE membrane sized with 8 mm in length, 5 mm in width, and 4 mm in height was placed on the decorticated mandible, fixed with metal pins and covered with full-thickness flap and assigned as control group. In experimental group, decorticated mandibule was treated with TR e-PTFE membrane and human demineralized freeze-dried bone. The animals were sacrificed at 16 weeks after the regenerative surgery, and new bone formation was assessed by histomorphometric as well as statistical analysis. Results: Average of new bone formation was 38% in the control group, whereas was 25% in the experimental group (p<0.05). Average of connective tissue formation was 42% in the experimental group, whereas was 30% in the control group (p<0.05). The lamellar bone formation with haversian canals was observed in the both groups. In the experimental group, the particles of human demineralized freeze-dried bone were observed after 16 weeks and complete resorption of graft was not observed. Conclusion: On the basis of these findings, we conclude that titanium reinforced e-PTFE membrane may be used alone for vertical guided bone regeneration, but demineralized freeze-dried bone has no additional effect on vertical guided bone regeneration.

• 대한소아치과학회지
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• 제33권1호
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• pp.109-115
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• 2006

석회화 치성낭은 상악 전치부에 호발하는 발육성 치성낭이나 조직학적 소견이 다양하고 따라서 분류 체계도 다양하다. 악골 내에서 느리게 진행되는 무통성 종창이 일반적이며 24-30%에서 매복치 및 치아종과 연관되어 나타난다. 피복 상피에 나타나는 유령세포는 결합 조직 에 노출되어 석회화 조직을 형성한다. 이 증례는 14세 여아의 상악 견치부에 발생한 치아종을 동반한 석회화 치성낭으로, 매복된 상악 좌측 견치 치관 주위로 경계가 명확한 방사선 투과성 병소와 다발성의 방사선 불투과성 석회화 물질이 혼재된 병소였다. 조직병리학적으로 중층 편평상피로 이장되어있고 상피 내에 유령세포가 관찰되었다. 석회화된 물질은 복합 치아종의 소견을 보여 Preatorius의 조직학적 분류에 의한 석회화 치성낭 Type IB로 진단되었다. 병소의 적출 및 병소에 이환된 견치 발치를 시행하였다. 현재 염증 소견이 관찰되어 병소에 이환된 상악 좌측 제1소구치는 치수치료를 시행하였으며 환아 및 보호자가 포괄적인 교정 치료를 원하여 현재 공간 유지 장치를 장착 중이다.

• 대한소아치과학회지
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• 제29권3호
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• pp.413-417
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• 2002

점액종은 외상으로 인해 구강에서 발생하는 흔한 낭성 병변이다. 하순에 흔히 발생하며 구강저와 순측 점막에도 자주 형성된다. 상순이나 경구개, 후구치대에는 거의 발생하지 않으며 발생빈도에 있어 성차는 없다. 점액종의 일반적인 치료는 낭종을 외과적으로 제거하고 이와 관련된 소타액선을 제거하거나 개창술을 시행하지만 재발할 수 있다. 본 증례는 하순의 물집을 주소로 본 치과 병원에 내원한 환아를 봉합사를 이용한 비외과적 술식으로 치료 후 6개월 동안 재발하지 않은 경우로 환아의 나이가 어리고 행동조절에 문제가 있는 경우 점액종을 비외과적인 방법으로 제거하여 양호한 결과를 얻었기에 보고하는 바이다.

• 대한소아치과학회지
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• 제29권3호
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• pp.371-375
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• 2002

석회화 치성낭은 하나의 독립된 유형의 치성 병소로 인정하고 있지만, 조직학적 소견이 다양하고 분류 체계도 학자들마다 다르다. 또한 석회화 치성낭의 피복상피는 인접한 결합조직에 치성조직을 유도할 수 있는 능력을 갖고 있어 다른 치성 종양과 흔히 동반하여 발생한다. 이 증례는 5세 여아의 상악 전치부에 발생한 치아종을 동반한 석회화 치성낭으로, 매복된 상악 좌측 중절치 및 측절치 치관 주위로 경계가 잘 된 방사선 투과성 병소와 다발성의 방사성 불투과성 석회화 물질이 혼재된 병소였다. 병리조직학적으로 피복상피는 법랑모세포와 유사하였고 상피 내에 유령세포의 군집이 관찰되었다. 석회화된 종괴는 일부 잔존한 범랑기질이 상아질로 둘러싸여 있었고, 퇴축 법랑상피 및 유령세포의 군집이 관찰되어 복잡 치아종이 동반된 석회화 치성낭으로 진단하였다. 이 증례에서와 같이 소아에서도 매복치와 동반하여 방사선 투과 및 불투과상의 혼합 병소가 관찰되면 석회화 치성낭의 가능성을 항상 염두에 두어야 할 필요가 있다. 환자는 수술 1년이 경과한 현재까지 재발의 소견은 없었고, 현재 혼합치열기의 간격조절을 시행 받고 있는 중이다.