FAK is overexpressed in keratocystic odontogenic tumor: a preliminary study.

BACKGROUND: Focal adhesion kinase (FAK) is an important mediator of cell adhesion, growth proliferation, survival, angiogenesis, and migration. FAK is overexpressed in many locally invasive and malignant lesions including oral cancer. Looking at the tumorigenic nature of keratocystic odontogenic tumor (KCOT), which involves local invasion, proliferation, and recurrence, we hypothesized strong expression of FAK in the epithelial lining of KCOT. MATERIALS AND METHODS: 34 KCOTs, 11 orthokeratinized odontogenic cysts (OOCs), 25 radicular cysts (RCs), 17 dentigerous cysts (DCs), and 25 dental follicles (DFs) were retrieved from archives and subjected to the immunohistochemical analysis using FAK antibody. RESULTS: In KCOT, strong expression was observed in 22 (62.8%) cases followed by weak and negative expression in 9 (25.71%) and 4 (11.4%) cases, respectively. Negative expression was seen in 7 (63.63%) cases of OOC, while 4 (36.36%) showed weak expression. In case of RC, 20 (80%) cases displayed negative expression and 4 (16%) and 1 (4%) cases showed weak and strong expressions, respectively. In case of DC, negative expression was seen in 14 (82.35%) cases and weak expression in 3 (17.64%) cases. DF was characterized by negative [21 (84%)] and weak expression [4 (16%)]. Nuclear expression of FAK was seen only in KCOT (11 cases). There was statistically significant higher FAK expression in KCOT as compared to OOC, RC, DC, and DF (P < 0.00001). CONCLUSION: FAK molecule could be an important player in tumorigenesis of KCOT and thus is a potential target for future drug development.

Immunohistochemical expression of alpha-smooth muscle actin and glucocorticoid and calcitonin receptors in central giant-cell lesions.

BACKGROUND: Central giant-cell lesions (CGCLs) are reactive lesions that consist histologically of spindle-shaped stromal cells, (fibroblasts and myofibroblasts) loosely arranged in a fibrous stroma, multinucleated giant cells and mononuclear cells with haemorrhagic areas. This study identified the immunoexpression of alpha-smooth muscle actin in spindle-shaped stromal cells, and glucocorticoid and calcitonin receptors in multinucleated giant cells and mononuclear cells. Their association with the clinical and radiographic characteristics of these lesions was identified. METHODS: Thirty-five cases of CGCLs were studied. Expression of alpha-smooth muscle actin, glucocorticoid and calcitonin was evaluated by immunohistochemistry. The labelling index was 100 times the quotient of the number of positive cells divided by the total number of cells of each type. Logistic regression analysis was applied. RESULTS: Alpha-smooth muscle actin was positive (54%) for spindle stromal cells (myofibroblasts). A significant association was observed with root resorption (P = 0.004) and cortical bone destruction (P = 0.024). Glucocorticoid immunoexpression was positive for 99% of the giant cells and 86.7% of the mononuclear cells. Glucocorticoid immunoexpression in the mononuclear cells was associated with root resorption (P = 0.031). A longer evolution time was associated with lower immunoexpression of glucocorticoid (OR 12.4: P = 0.047). Calcitonin immunoexpression was positive in 86% of the giant cells. Immunoexpression of calcitonin was associated with age (P = 0.040). CONCLUSIONS: Myofibroblasts are important components of CGCLs, stromal cells and alpha-smooth muscle. Actin immunoexpression was associated with root and cortical bone resorption.

[THE ROLE OF ANTIHYPOXANTS AND ANTIOXIDANT IN TREATMENT OF ODONTOGENIC OF MAXILLOFACIAL AREA].

The aim of this work is the systematization of the literature data for the most clearly defined directions of study of the effectiveness of antioxidant and antihypoxant drugs in complex treatment of patients with purulent inflammatory diseases of the maxillofacial area. The authors attempt to analyze the results of the use of antioxidant and antihypoxant therapy at pyoinflammatory pro- cesses of different localization. Areas of research of the impact of antioxidant and antihypoxants therapy on physical and biochemical parameters of the maxillofacial area and the organism of the patient as a whole are defined.

Porphyromonas gingivalis infection-associated periodontal bone resorption is dependent on receptor activator of NF-κB ligand.

Porphyromonas gingivalis is one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) in P. gingivalis infection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 10(9) P. gingivalis bacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition to P. gingivalis infection. Robust serum IgG and salivary IgA antibody (P < 0.01) and T cell proliferation (P < 0.05) responses to P. gingivalis were detected at day 7 and peaked at day 28 in P. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P < 0.01) and periodontal bone resorption (P < 0.05) were significantly elevated at day 28 in the P. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in the P. gingivalis-infected group compared to the levels in the uninfected group (P < 0.01). Injection of anti-RANKL antibody (P < 0.05) or OPG-Fc (P < 0.01), but not L6-Fc, into rat gingival papillae after P. gingivalis infection resulted in significantly reduced periodontal bone resorption. This study suggests that P. gingivalis infection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.

Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases.

OBJECTIVE: The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. MATERIALS AND METHODS: Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. RESULTS: Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. CONCLUSIONS: Two possible histopathogenesis of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele.

Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis.

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague-Dawley (SD) rats (n = 30) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice.

Inflammatory immune reactions in response to periodontopathogens trigger periodontal destruction, but their role to protect the host against infection remains unknown. Thus, we examined the mechanisms by which IFN-gamma modulates the outcome of Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice. Our results showed that IFN-gamma deficient mice developed less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significant lower alveolar bone loss and inflammatory reaction. However, the absence of IFN-gamma results in increased bacterial load in periodontal tissues and higher acute phase reaction, followed by a disseminated bacterial infection and mice death during the course of the disease. Such impaired host response was found to be associated with a reduction in the levels of inflammatory cytokines and chemokines and in the number of GR1+, F4/80+, CD4+ and CD8+ leukocytes in the diseased periodontium of IFN-gamma deficient mice. In addition, the levels of both antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase were also found to be reduced in IFN-KO mice. Our results demonstrate for the first time that a periodontal infection may be lethal in an immunocompromised host. In addition, the mechanisms involved in IFN-gamma mediated cell migration to diseased periodontal tissues, and its essential role to control A. actinomycetemcomitans infection were clarified.

Profiling of radicular cyst and odontogenic keratocyst cytokine production suggests common growth mechanisms.

The aim of this study was to compare the cytokine expression profiles of cyst fluids (CFs) and tissue culture supernatants (SUPs) from 7 radicular cysts (RCs) and 7 odontogenic keratocysts (OKCs) by using Human Cytokine Antibody Array to identify the specific cytokines involved in formation and expansion of RCs and OKCs, respectively. There were significant differences in relative expression levels of IL-1 beta, MCP1, MIP1 beta, FGF-9, GDNF, HGF, IGFBP-3, Ang, IP-10, MIF, OPG, and TGF-beta2 between RC-CF and OKC-CF (P < .05). On the other hand, the cytokine expression patterns of RC-SUP (HGF, IL-8, NAP-2, IL-6, TIMP-1 and 2, GRO, IP-10, and Ang) were similar to those of OKC-SUP. Only the relative expression level of GRO differed between RC-SUP and OKC-SUP (P < .05). The similarities of cytokine production by tissue cultures derived from RC and OKC indicate that the expansion mechanisms of RC and OKC might involve similar biologic mechanisms other than infection.

Expression of Bcl-2 in Primary and Recurrent Odontogenic Keratocysts in Comparison with Other Odontogenic Lesions.

PURPOSE: To determine the biological behaviour of common odontogenic cystic lesions by analysing and comparing bcl-2 expression amongst them. MATERIALS AND METHODS: Our study covered 90 formalin fixed paraffin embedded tissue samples: 26 primary cases each of radicular cysts (RC), dentigerous cysts (DC) and odontogenic keratocysts (OKC) and 12 of recurrent OKCs. Bcl-2 expression was analysed immunohistochemically and data analysis was accomplished using SPSS version 17.0. Means were taken for age while for gender and site of the lesions frequencies and percentages were determined. The Chi-square test was applied to evaluate any statistically significant difference of bcl-2 expression in these lesions and p value of ≤0.05 was taken as significant. RESULTS: All the recurrent OKCs showed a strong positivity for bcl-2 that was absent in all of its primary cases (p value<0.05). Although variation in expression of bcl-2 was not found to be statistically significant between RC and DC, however, it became significant when all primary cases of these common odontogenic lesions were compared. CONCLUSIONS: Recurrent OKC showed comparatively a more aggressive behaviour than their primary counterparts and also from RC and DC. Bcl-2 proved to be a valuable adjunct in determining aggressive biological behaviour of odontogenic lesions.

p53 protein in odontogenic cysts: increased expression in some odontogenic keratocysts.

AIMS: To assess p53 protein expression in a range of odontogenic cysts arising in the mouth, including those of developmental and inflammatory origin. METHODS: p53 protein was identified using the polyclonal antibody CM-1, together with a standard immunoperoxidase technique. A total of 36 cystic lesions were examined, all of which were histologically benign. RESULTS: Expression of p53 protein was identified within the lining of five of 12 odontogenic keratocysts but was not detected in the other cystic lesions in the series. CONCLUSIONS: This is believed to be the first report that identifies increased expression of p53 protein in benign cystic epithelium. The increased expression of p53 protein in the nucleus is usually associated with malignant disease. These findings are relevant to the management of odontogenic keratocysts which have a tendency to recur, and also to Gorlin Goltz syndrome in which keratocysts and multiple basal cell carcinomas are features.

Influences of ovariectomy on experimental tooth movement in the rat.

Estrogen withdrawal, which is important in the pathogenesis of post-menopausal osteoporosis, accelerates bone metabolism with a negative calcium balance. Therefore, it is hypothesized that estrogen deficiency could affect the rate of experimental tooth movement and alveolar bone remodeling. Six-week-old rats received a bilateral ovariectomy (OVX) or sham operation. Fourteen days later, rats were subjected to lateral tooth movement in the upper molar with nickel-titanium wire of 10 g of force. OVX significantly increased the rate of experimental tooth movement from 12 days after experimental tooth movement (p < 0.001). Eighteen days after the start of tooth movement, bone histomorphometry demonstrated that OVX significantly elevated the osteoblast surface, osteoclast surface, and number of osteoclasts (p < 0.05) in the alveolar bone. These findings indicated that estrogen deficiency caused significantly rapid orthodontic tooth movement, and that the acceleration of tooth movement could be due to the further activation of alveolar bone turnover.

Cytokeratin expression in central mucoepidermoid carcinoma and glandular odontogenic cyst.

Central mucoepidermoid carcinoma (MEC) is an entity whose origin is still controversial. Glandular odontogenic cyst (GOC) is a recently described lesion whose relationship to low-grade central MEC has been reported in the literature. Our aim was to assess the cytokeratin (CK) profile of central MEC and GOC, and compare the results with CK expression in salivary gland MEC and odontogenic cysts and tumors. Eighty-five cases, including 6 central MECs, 23 salivary gland MECs, 10 GOCs, 34 odontogenic cysts and 12 ameloblastomas, were studied through immunohistochemistry using eleven monoclonal anti-CK antibodies. All central MECs expressed CKs 5, 7, 8, 14, and 18 and all GOCs expressed CKs 5, 7, 8, 13, 14, and 19. Comparing CK expression from GOC and central MEC we found differences in CKs 18 (30% vs 100%) and 19 (100% vs 50%). Central MEC and GOC are probably distinct entities with CK profiles similar to lesions of glandular and odontogenic origins, respectively, and expression of CKs 18 and 19 could be useful in their differential diagnosis.

A biochemical study on the nature of jaw cysts (III). Instrumental analysis of the viscous component of fluids in ciliated cysts of the maxilla.

Cyst fluids are composed of electrolytes, proteins, lipids and viscous components. These substances affect the state of jaw cysts. Jaw cysts whose inner wall layer is ciliated epithelium contain high-viscosity fluids. This study comprised 30 cases of the following types of jaw cysts: nasopalatine, mucosal and ciliated cysts of the maxilla. And the author chiefly investigated ciliated cysts of the maxilla. Their fluid contents were extracted and pre-treated for analysis. It was concluded that hyaluronidase in cyst fluids causes cyst walls to decompose hyaluronic acid in the cellular interstitium of cyst walls or in the basement membrane of the cellular layer and convert it into cyst fluid, hence it is confirmed that the main component of viscous cyst fluid is hyaluronic acid.

Comparative study of biochemical characteristics of the fluids in otitis media with effusion and postoperative maxillary cysts.

The biochemical characteristics and smears of the fluids in M-OME, S-OME, AOM, POMC, and AMS were studied. The fluids in S-OME and POMC had the character of transudate rather than exudate. On the other hand, M-OME, AOM, and AMS showed a more exudative or secretive nature. The character of the product from the inflammatory process of the specific condition was particularly seen in M-OME, AOM, and AMS. Thus we speculate that the chronic inflammatory process has a close relationship to the pathogenesis of OME, especially in mucoid types.

[Cefotiam passage into the maxillary sinus tissues].

Clinical study was made on cefotiam (CTM) and the following results were obtained. Tissue concentrations of CTM were determined 1 hour after intravenous injection (CTM 1 g) in chronic sinusitis and maxillary cyst. Concentrations of CTM were 16.53 micrograms/g, 13.26 micrograms/g in mucosa of the maxillary sinus, maxillary cyst, respectively. Antibacterial activity of CTM was measured on Escherichia coli, Staphylococcus epidermidis, Aerococcus, Acidaminococcus fermentans, Peptostreptococcus anaerobius; that were isolated from pus of maxillary sinus. The highest MIC on them was 3.13 micrograms/ml.

[Diagnostic value of osteotropic bone scintigraphy in maxillary sinus diseases]. / Wartosc badan scyntygraficznych znacznikiem osteotropowym w diagnostyce chorób zatok przynosowych.

The authors described the application of facial bone scintigraphy in 6 patients with acute and 47 patients with chronic sinusitis, 4 patients with cyst of maxillary sinus, 4 patients with sinus maxillary neoplasm and 4 patients with pyocele of frontal sinus. Facial bone scintigraphy was performed by gamma-camera Siemens Gammasonics ZLC-750 after intravenous administration of 15 mCi of 99mTcMDP in anteroposterior projection. The index of accumulation of the tracer (JAT) in maxillary sinus region was counted separately in men and in women in the reference group. In patients with purulent sinusitis marked JAT was predominated. Correlation between JAT and symptoms and rhinological signs has been shown in patients with chronic purulent sinusitis. In patients with sinus maxillary neoplasm high JAT was predominated.

[Silicon of the medium in the postoperative maxillary cyst].

As part of a study on chronic inflammatory disease of the mucous membrane, silicon of the medium in postoperative maxillary cysts and in other cysts was measured, and following results were obtained. Silicon concentrations of the medium in the postoperative maxillary cysts and in the postoperative ethmoidal cysts were 34.5 ppm and 42.9 ppm (geometrical mean) respectively, and they were higher than in other primary cysts such as frontal cyst, nasal vestibular cyst, and dental cyst. The silicon content of the medium in the postoperative maxillary cyst varied with the water content of the medium; the lower the water content the higher was the silicon content and the relationship was expressed by the following equation. log S = 7.43 + 7.14 log d-6.14 log w, where S = Si (mcg), d = dry weight (g.) and w = wet weight (g.). The high concentration of silicon in the postoperative cyst was considered to be due to the large amount of silicon transudate from the surrounding fibrous tissue through a highly damaged or missing epithelial wall of the cyst.

Endogenous opioids regulate alveolar bone loss in a periodontal disease model.

AIM: The anti-inflammatory effects of exogenous opioid compounds have been demonstrated in several conditions. Nevertheless, the function of endogenous opioid peptides released by the host during inflammatory processes deserves further characterization. The aim of this study was to verify whether endogenous opioids are involved in the progression of the inflammatory alveolar bone loss induced by ligature in rats. MAIN METHODS: The experimental model of periodontal disease (PD) induced by ligature in rats was used throughout the study. A silk ligature was placed around the 2nd upper molar of male Holtzman rats, for 7 days. Rats received different doses of either the non-selective opioid antagonist naloxone or vehicle, locally into the afflicted gingival tissue, from the 3rd to the 5th day after ligature placement. In the 7th experimental day, rats were euthanized and their maxillae were collected for evaluation of alveolar bone and fiber attachment loss, presence of neutrophils (myeloperoxidase assay), osteoclast amount, and levels of cytokines IL-6, TNF-α, IL-8 and IL-10 in periodontal tissues. KEY FINDINGS: Naloxone increased alveolar bone loss significantly, in a dose-dependent manner, in relation to vehicle-treated rats. In contrast, the opioid antagonist did not affect the loss of fiber attachment. The treatment with naloxone also induced a significant increase in myeloperoxidase levels, osteoclast number and cytokines in periodontal tissues of rats with ligature-induced PD. SIGNIFICANCE: Endogenous opioids protect the host from the progression of inflammatory alveolar bone loss that occurs in chronic periodontitis.

Peripheral cementifying fibroma: a clinical diagnostic dilemma.

The peripheral ossifying fibroma (POF) is a reactive gingival overgrowth occurring frequently in the anterior maxilla. It originates in the cells of the periodontal ligament and is more common in children and young adults. In the current article a case of gingival over growth, which was thought to be puberty-induced gingivitis was seen in the lower anterior maxillary gingiva. Histology of the excised tissue showed cellular, fibrous connective tissue stroma with calcified osseous calcifications indicative of POF. The definitive diagnosis is established only by histological examination, which revealed the presence of highly cellular connective tissue with focal calcifications. Surgery is the treatment of choice, though the recurrence rate can reach 20% in case of POF. After histological confirmation the recall and clinical evaluation protocol of POF varies due to its increased recurrence rate, which the general dentist should be aware of.

Comparative immunohistochemical expression of RANK, RANKL and OPG in radicular and dentigerous cysts.

OBJECTIVE: Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) are members of the superfamily of ligands and receptors of tumour necrosis factor family involved in bone metabolism. The formation, differentiation and activity of osteoclasts are regulated by these proteins. To clarify the roles of osteoclast regulatory factors in cystic expansion of odontogenic cysts, expression of these proteins were analysed in radicular and dentigerous cysts. DESIGN: The immunohistochemistry expression of these biomarkers were evaluated and measured in lining epithelium and fibrous capsule of the radicular (n=20) and dentigerous cysts (n=20). RESULTS: A similar expression in lining epithelium was observed in the lesions. The fibrous capsule of dentigerous cyst showed a higher content of RANK-positive and RANKL-positive cells than fibrous capsule of radicular cyst. In the lining epithelium the RANKL/OPG ratio showed higher numbers of OPG-positive than RANKL-positive cells, whereas fibrous capsule of the cysts had a tendency to present a similar expression (OPG=RANKL). CONCLUSION: Ours findings indicate the presence of RANK, RANKL and OPG in cysts. Moreover, increased expression of OPG compared to RANKL in the lining epithelium could contribute to the differential bone resorption activity in theses lesions.