Although approximately 200 distinct cell types – including fibroblasts, neurons, and hematopoietic cells – possess the same DNA sequence, they have diverse functions in humans and exhibit considerably different gene expression patterns. It has become increasingly clear that epigenetic regulation plays an important role in gene expression. There are two major forms of epigenetic regulation: posttranslational modification of DNA-associated histone proteins in chromatin and methylation of DNA. These forms are regulated by distinct but coupled pathways. Notably, histone Lys acetylation by histone acetyltransferase and deacetylation by histone deacetylases play a crucial role in on-off regulation of gene expression. It is now understood that epigenetics plays an important role not only in the regulation of gene expression but also in the pathogenesis of a broad range of diseases such as cancer and microbial infections. We have determined that epigenetic regulation is involved in the establishment and maintenance of HIV-1 latency and in the reactivation of HIV-1 by periodontopathic bacteria. In this review, we focus on the effect of histone modification on transcriptional regulation and the contribution thereof to the regulation of HIV-1 gene expression during the lytic and latent stages of HIV-1 infection. Likewise, we discuss the mechanisms by which periodontal diseases may accelerate AIDS progression in infected individuals as a new systemic disease caused by periodontitis and describe potential therapeutic interventions based on epigenetic mechanisms. (J Oral Sci 53, 1-13, 2011)

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The aim of this study was to evaluate the subcutaneous biocompatibility of three root canal sealers in rats. Thirty Wistar rats were divided into three groups according to three time periods (15, 30 and 60 days). Sterilized polyethylene tubes filled with root canal sealers (AH Plus, Epiphany & Grossman), and one empty tube (control) were implanted into four separate dorsal regions in each rat. At the end of each study period, 10 animals were sacrificed, and histologic sections of connective tissue at the open ends of the tubes were prepared. Severity of tissue inflammatory response was assessed. Grossman endodontic sealer had the most severe inflammatory response followed by the AH Plus, Epiphany and control groups. The tissue inflammatory response of the Epiphany and AH Plus sealers was not significantly different. Thus, Epiphany sealer showed acceptable biocompatibility when tested on rat subcutaneous tissue. (J Oral Sci 53, 15-21, 2011)

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There have been a number of attempts to modify the surface of dental implants to improve osseointegration. These modifications include alterations of surface chemistry and roughness. The purpose of this study was to examine the early response of human osteoblast-like cells placed on Ti-6Al-7Nb disks that had a similar grooved surface topography and three different levels of surface roughness (Ra = 0.0374, 0.0911, and 0.2435 μm). Cultures of human osteoblast-like cells revealed no significant difference in initial cell attachment among the various surfaces; however, cell spread was greater on rough surfaces than on glass slides and smoother surfaces. In addition, cell proliferation and Ki-67 expression were increased when cells were cultured on rough surfaces. These results suggest that a greater Ti-6Al-7Nb surface roughness support the initial spread and proliferation of human osteoblast-like cells. Thus, modification of the surface roughness of dental implants might hasten osseointegration. (J Oral Sci 53, 23-30, 2011)

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The purpose of this study was to compare the effects of ultrasonication with ethylenediaminetetraacetic acid (EDTA) and a mixture of tetracycline isomer, an acid, and a detergent (MTAD) as final canal irrigants on the smear layer, debris and erosion scores. Fifty-eight extracted single-rooted human teeth were instrumented with ProTaper rotary files up to size F3. According to the final irrigation regimen, the samples were distributed into the following groups: EDTA, MTAD, EDTA ultrasonicated for 1 min, and MTAD ultrasonicated for 1 min. The smear layer, debris and erosion scores were recorded at the apical, middle, and coronal third of each canal using a scanning electron microscope. Data were subjected to statistical evaluation using the Kruskal-Wallis and Mann-Whitney tests (P < 0.05). There were no significant differences in smear layer or debris removal between the experimental groups. EDTA caused significantly more erosion at the middle level than MTAD. Also EDTA resulted in more erosion at the coronal level than MTAD when subjected to ultrasonication. Ultrasonic activation of EDTA significantly increased its erosive effects at the middle and coronal levels. Based on the present findings, MTAD appears to cause less dentinal erosion while allowing proper removal of the smear layer and debris. (J Oral Sci 53, 31-36, 2011)

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Radiographs of developing teeth are commonly used to assess dental maturity. The method for assessment of dental maturity first described by Demirjian is widely used and accepted. The aim of this study was to assess the accuracy of the Demirjian method in an Iranian population in order to compare the difference in dental maturity between these children with the data obtained in Canadian children and to determine whether there is a correlation between dental maturity and BMI-for-age. In this study, the orthopantomographs of 519 healthy children (264 boys and 255 girls) aged 3.5-13.5 years were reviewed and the dental age was determined by the Demirjian method. The chronological ages of the children were obtained by subtracting their birthdates from the date of taking the radiograph. Height and weight measurements were also recorded and the data were analyzed using SPSS-16 software. The Demirjian method overestimated the age by 0.15 and 0.21 years in boys and girls, respectively. Paired t-test analysis showed that these differences were statistically significant (P = 0.001). The increase in mean age difference initiated from the underweight group towards the overweight group, but this correlation was not statistically significant (P = 0.094). Based on the amount of differences between estimated dental age and chronological age in this investigation, the Demirjian method seems to be clinically applicable in the Iranian population. (J Oral Sci 53, 37-42, 2011)

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A hermetic seal of the root canal space following canal preparation is important in endodontics. This study evaluated the effect of canal curve on adaptation of gutta-percha to dentinal walls of canals obturated using the Herofill system. For this in vitro study, 80 mesial roots of mature human first molars with length of 16 mm, curve between 5° and 45°, and no caries or resorption of the root surface were selected. A cone beam computed tomography system was used to evaluate the presence or absence of a gap in the samples. Photographs were taken in three sections: 2 mm above the curve, at the curve and 2 mm below the curve. The gap area was identified using Photoshop and AutoCAD software. Kruskal Wallis and Mann-Whitney tests were used to analyze the data mounted in a castcurve. There were significant differences between the two lateral condensation groups with various curves; roots with more curve had more gaps. When the Herofill and lateral condensation groups were compared without considering the sections and curve, there was a significant difference between these groups and the Herofill group had less gaps. The Herofill system is an alternative to the lateral condensation technique in severely curved canals. (J Oral Sci 53, 43-50, 2011)

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Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Low-power laser irradiation has a stimulating effect on cells and tissues. Although the carbon dioxide (CO₂) laser is a hard surgical laser, we have attempted to use it at low energy density to achieve biological alterations. To investigate the effects of CO₂ laser irradiation on BSP gene transcription, we used rat osteoblast-like ROS17/2.8 cells. BSP mRNA levels were increased at 12 h after irradiation with the CO₂ laser (2 W, 20 s). Transient transfection assays using various sizes of the rat BSP gene promoter linked to the luciferase reporter gene showed that CO₂ laser irradiation induced luciferase activity of a -116 to +60 BSP promoter construct (pLUC3) at 12 h in the cells. Transcriptional stimulation by CO₂ laser irradiation was abrogated in the pLUC3 construct containing a 2-bp mutation in the fibroblast growth factor 2 response element (FRE). Gel shift analyses showed that CO₂ laser irradiation increased the binding of nuclear protein to FRE. These studies demonstrate that CO₂ laser irradiation increases BSP transcription via FRE in the rat BSP gene promoter. (J Oral Sci 53, 51-59, 2011)

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Lidocaine is an amide local anesthetic and clonidine is an antihypertensive (α2-adrenergic agonist). The use of these two drugs in combination is recommended to enhance the analgesic effect of lidocaine. The aim of this study was to investigate the influence of clonidine co-administration on the extent of lidocaine binding to rat serum, heart and maxillofacial tissues in vivo and in vitro. Thirty-two Wistar rats received either lidocaine alone, or lidocaine and clonidine, in the masseter muscle, and were then sacrificed 15 or 30 min after treatment. Serum, masseter, mandible and heart samples were then isolated and incubated in 0.9% NaCl solution for 12 h at 8°C. The extent of binding in the incubation medium and the serum was estimated by ultrafiltration, and the free lidocaine fraction was determined by the radioscopic method in a β-counter. An in vitro procedure was also performed. Serum, heart, masseter and mandible samples were incubated at 37°C for 15 or 30 min in Ringer's solution containing either lidocaine or lidocaine and clonidine, and the samples were similarly subjected to ultrafiltration. The percentage binding of lidocaine was again estimated by the radioscopic method. Lidocaine levels were found to be increased by clonidine co-administration in vivo and the free lidocaine fraction was enhanced in vitro as well in the examined tissues, obviously through mechanisms related to protein binding alterations. (J Oral Sci 53, 61-66, 2011)

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Podoplanin, a sialomucin-lik e transmembrane glycoprotein, is currently used as a specific marker for lymphatic vessels. However, podoplanin expression has also been linked to tooth development. To investigate the expression of podoplanin in odontomas, 86 tissue samples were classified and then analyzed using immunohistochemical methods. Formalin-fixed, paraffin-embedded specimens were collected and classified, followed by immunohistochemical examination. The majority of the odontomas (66.3%) were the compound type, and the remainder (33.7%) were the complex type. The patients ranged in age from 2 to 89 years (mean, 23.9 years), and 45 (52.3%) of them were male and 41 (47.7%) were female. The most common location for complex odontomas was the molar region of the mandibular bone, and that for compound odontomas was the maxillary incisor region. Immunohistochemistry revealed that developing and mature odontoblasts, Tomes' fibers, and pulp cells near podoplanin-positive odontoblasts were positive for podoplanin. In addition, podoplanin positivity was evident in secretory ameloblasts, but not in mature ameloblasts. The pattern of podoplanin expression in odontomas corresponds to development of the tooth germ, and appears to be influenced by the stage of differentiation of the lesion, suggesting that the protein may participate in the process of differentiation. (J Oral Sci 53, 67-75, 2011)

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Bone sialoprotein (BSP) is a mineralized tissue-specific protein expressed in differentiated osteoblasts that appears to function in the initial mineralization of bone. Calcium hydroxide (Ca(OH)₂) is a basic salt that has been widely used for a variety of applications in dentistry, due to its antimicrobial effects and its capability of inducing hard tissue formation. However, details of the mechanism involved in the mineralization induced by Ca(OH)₂ are still unclear. In the present study, Ca(OH)₂ (0.4 mM) was found to increase the levels of BSP and Runx2 mRNA at 3 h in human osteoblast-like Saos2 cells. Transient transfection assays were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with Ca(OH)₂ (0.4 mM) increased the luciferase activities of the constructs between -60LUC and -927LUC at 12 h. Gel shift analysis showed that Ca(OH)₂ (0.4 mM) increased the binding of nuclear protein to CRE1, CRE2 and FRE. Antibodies against CREB1, c-Fos, c-Jun, JunD, Fra2 and P300 disrupted the formation of the CRE1- and CRE2-protein complexes, and antibodies against Dlx5, Msx2, Runx2 and Smad1 disrupted the formation of the FRE-protein complex. These findings demonstrate that Ca(OH)₂ stimulates BSP transcription by targeting the CRE1, CRE2 and FRE elements in the human BSP gene promoter. (J Oral Sci 53, 77-86, 2011)

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This study examined how interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6r) influence osteoclastic differentiation through the function of chondrocytes. Chondrocytes were cultured with or without IL-6 and/or sIL-6r in the presence or absence of NS398, a specific inhibitor of cyclooxygenase (COX)-2, for up to 28 days. Chondrocytes were also cultured with or without IL-6 and sIL-6r for 28 days, and the conditioned medium from cells cultured without IL-6 and sIL-6r was used to induce differentiation of RAW264.7 cells into osteoclast precursors. Osteoclastic differentiation was assessed by tartrate-resistant acid phosphatase (TRAP) staining. Expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), COX-2, and prostaglandin E₂ (PGE₂) increased in cells exposed to IL-6 and sIL-6r, whereas expression of macrophage colony-stimulating factor (M-CSF) and bone resorption-related enzymes decreased. NS398 blocked the stimulatory/suppressive effects of IL-6 and sIL-6r on the expression of OPG, RANKL, and M-CSF. Fewer TRAP-positive multinucleated cells were detected after treatment with conditioned medium from IL-6- and sIL-6r-treated chondrocytes than after treatment with conditioned medium from untreated chondrocytes. These results suggest that IL-6 and sIL-6r interfere with osteoclast function through the involvement of chondrocytes. Specifically, they appear to suppress the differentiation of osteoclast precursors into osteoclasts by inducing chondrocytic PGE₂ production, which, in turn, increases OPG secretion and decreases M-CSF secretion by chondrocytes. (J Oral Sci 53, 87-96, 2011)

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Oral submucous fibrosis (OSMF) is a disabling, potentially malignant condition of the oral cavity. The aetiology of OSMF is multifactorial but remains obscure. Although arecanut is considered to be the most important causative agent, responses observed in individuals using arecanut vary in relation to quantity and duration. It is considered that an immunological process is responsible for the pathogenesis of disease. We correlated salivary immunoglobulin A (IgA), salivary immunoglobulin G (IgG) and serum immunoglobulin A (IgA), serum immunoglobulin G (IgG), levels by turbidometric immunoassay. We estimated the levels of total serum protein (TSP) and haemoglobin (Hb) to determine the role of nutritional deficiency. The study population comprised 30 cases of OSMF and 10 controls. Five milliliters of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethaemoglobin methods, respectively. All patients showed significant (P < 0.01) increase in serum and salivary IgG, IgA levels as compared to controls. TSP patients showed significant (P < 0.01) decrease as compared to controls. Results of Hb in patients were not significant. The estimation of immunoglobulin levels is important to support the concept of autoimmune basis. Estimation of TSP and Hb suggests that nutrition has a definite role in OSMF. (J Oral Sci 53, 97-102, 2011)

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Spaceflight occurs in an environment of temperature extremes, microgravity, solar and galactic cosmic radiation, lack of atmospheric pressure, and high-speed micrometeorites. Exposure to microgravity and the space environment during space missions of short and long duration has important medical and health implications for astronauts. Psychological well-being is of increasing importance in planned spaceflights and interplanetary missions of long duration. The 6° head-down tilt (HDT) is an established method of mimicking low gravity on earth. The aim of the present study was to determine the effects of 21 days of HDT on psychological stress in 12 healthy male volunteers. Psychological state was assessed by the current stress test, and chromogranin-A (CgA), cortisol, alpha-amylase, and beta-endorphin were measured in saliva. After one week of HDT, all volunteers developed psychological stress, and secretion of CgA, cortisol, alpha-amylase, and beta-endorphin were all significantly higher. Thus, 6° HDT appears to be a valid model to induce psychological stress changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during both a short stay in space, such as that required while orbiting a space station, and in longer spaceflights. (J Oral Sci 53, 103-107, 2011)

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This study evaluated the wear characteristics and bonding to silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy of an acrylic resin that was filled with pre-polymerized composite particles and initiated with tri-n-butylborane (TBB) derivative (Bondfill). Three methyl methacrylate (MMA)-based resins (Bondfill, Super-Bond, and Multi-Bond II) and a microfilled composite restorative material (Metafil C) were assessed. Disk specimens were cast from the alloy and were air-abraded with alumina. The disks were bonded with nine bonding systems selected from two priming and three luting agents. Shear bond strengths were measured before and after thermocycling. Bond strength varied from 2.2 MPa to 28.2 MPa. Three systems based on thione primers (Metaltite and V-Primer) and TBB-initiated resins (Bondfill and Super-Bond) had the highest bond strength after thermocycling (15.9-20.4 MPa). The toothbrush-dentifrice abrasion test showed that the Metafil C material was the most wear-resistant, followed by Bondfill and Super-Bond. In conclusion, Bondfill resin is an alternative to Super-Bond resin for luting metallic restorations and for restoring tooth defects. However, care is required in selecting appropriate clinical cases. (J Oral Sci 53, 109-116, 2011)

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Cemento-osseous dysplasia is a disorder typically found in middle-aged black women. However, the present report describes a case in a 61-year-old Vietnamese male. Without proper pulp testing and diagnosis, the radiographic presentation can easily be misdiagnosed as periapical periodontitis. On the basis of pulp vitality, lack of clinical symptoms and radiographic features, the diagnosis in this case was periapical cemento-osseous dysplasia at the mixed stage, which generally requires no treatment. At the 18-month follow-up, the patient was still asymptomatic and none of the clinical signs had changed. This case highlights the importance of careful clinical examination, including a pulp vitality test, and of having an unbiased view of age, gender, and ethnicity when diagnosing this condition. (J Oral Sci 53, 117-120, 2011)

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We describe the dental and craniofacial anomalies of 2 ethnically distinct patients with Goldenhar syndrome, which is characterized by hemifacial microsomia, facial asymmetry, and ear and dental abnormalities. A 7-year-old Japanese girl and 12-year-old Turkish boy with Goldenhar syndrome were examined clinically and radiographically; both had symptoms of hemifacial microsomia. Multiple organ involvement can limit surgical correction of deformities and affect patient management. Therefore, long-term regular follow-up by a multidisciplinary team is important to monitor the growth and development of patients. (J Oral Sci 53, 121-124, 2011)

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Cluster headache is a neurovascular disorder characterized by attacks of severe and strictly unilateral pain presenting in and around the orbit and temporal area. Attacks occur in series lasting for weeks or months separated by remission periods. An individual attack lasts 15-180 min with a frequency of once every other day to as often as 8 times per day. Ipsilateral radiation of the headache to orofacial regions, including the teeth, is not unusual. The area of involvement may obscure the diagnosis and lead to irreversible and unnecessary dental treatment. A case in which cluster attacks occurred immediately after a dental procedure is described. (J Oral Sci 53, 125-127, 2011)

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Myopathy and muscular pseudohypertrophy associated with severe congenital hypothyroidism has been described as Kocher Debre Semelaigne syndrome, which is a rare disorder with only a few previously published reports. However, none of these reports have described the orofacial aspects of this syndrome. Here we report one such case, which may provide valuable information to specialists in oral healthcare regarding the associated orofacial aspects. (J Oral Sci 53, 129-132, 2011)

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Acromegaly is an acquired disorder related to excessive production of growth hormone after epiphyseal closure of bones. It is characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000-250,000. Although acromegaly rarely manifests in the orofacial regions, it must be considered in patients who develop malocclusion after adolescence. Here, we present a case of acromegaly with brief review of the literature. (J Oral Sci 53, 133-136, 2011)

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