39 resultados para Epitélio olfatório


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Odontogenic cysts are pathologic cavities covered by odontogenic epithelium and filled by liquid, desquamated cells or other materials. The intraosseous lesions, such as radicular cyst and dentigerous cyst, present a potential of expansion capable of promoting the destruction of the surrounding osseous tissue. The mechanisms related to this process of expansion are the proliferation of cystic epithelium, the increase of the osmolarity of the cystic fluid and the synthesis of reabsorption factors such as IFN-γ and TGF-β1. The aim of this study was to evaluate and compare the immunohistochemical expression of IFN-γ and TGF-β1 between radicular cysts and dentigerous cysts in order to understand the role and behavior of these proteins in the expansion of these cysts. We selected 20 cases of radicular cyst and 20 cases of dentigerous cyst chosen from the files of UFRN s Laboratory of Oral Pathology. After analyzing the clinical data, the cases underwent the routine staining technique (HE) and immunohistochemistry for the appearance of IFN-γ and TGF-β1 in the epithelium and capsule of these cysts. The statistical analysis using the Mann-Whitney test revealed no statistically significant difference in immunoexpression of IFN-γ between the epithelium (p = 0.565) and capsules (p = 0.414) of radicular cysts and dentigerous cysts. Moreover, there was no statistically significant difference of immunoexpression of TGF-β1 between the epithelium (p = 0.620) and capsules (p = 0.056) of radicular cysts and dentigerous cysts. The Wilcoxon test revealed no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.225) and capsules (p = 0.370) of radicular cysts. There was no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.361) of dentigerous cysts. However, there was a statistically significant difference between IFN-γ and TGF-β1 immunoexpressions in the capsule (p = 0.001) of dentigerous cysts, being TGF-β1 the factor which presented the most significant immunoexpression. Given these results, we conclude that there was no difference in immunohistochemical expression of IFN-γ and TGF-β1 between radicular and dentigerous cysts and that TGF-β1 was more significant than the IFN-γ in the capsule of dentigerous cysts

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Conselho Nacional de Desenvolvimento Científico e Tecnológico

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The radicular cysts (RCs) and dentigerous (DCs), despite having different etiologies, form a pathological cavity lined by epithelium, which grows due to the buildup of fluid inside, as the surrounding bone is reabsorbed and the epithelium will being induced to proliferate. The epithelial proliferation, which has been identified as one of the key processes in the growth of odontogenic cystic lesions, is influenced by growth factors such as EGFR (epidermal growth receptor factor) and podoplanin (PDPN), many of which may have its production stimulated mainly during inflammatory processes. The objective of this research was to evaluate and compare the immunohistochemical expression of EGFR and PDPN in 30 cases of RCs and 30 cases of DCs, semiquantitatively, in light microscopy, associating it with the degree of inflammation, cellular localization of immunostaining and with the immunostained epithelial layers. Data were statistically analyzed by Chi-square test and Fisher exact test, considering a significance level of 5 %. The results showed high immunoreactivity of both proteins in the lesions studied, only statistically significant difference was observed in immunostaining of PDPN (p=0.033), which proved higher in RCs. The other analyzed parameters showed no relevant significant differences. We conclude that, as EGFR and PDPN showed high immunoreactivity in cystic lesions analyzed, these proteins participate the pathogenesis of these lesions through the epithelial stimulation process, despite having different etiologies. Furthermore, it can infer that the higher immunostaining of PDNP in RCs that DCs showed no distinction indicator between the two lesions, regarding their etiologies, once this protein also showed a considerable expression in DCs, independent of the intensity of the inflammatory infiltrate

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Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs

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Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity, accounting for more than 90% of all malignancies in this location. Cyclooxygenases (COX s) are key enzymes on arachidonic acid metabolism and prostaglandin synthesis, being expressed basically in two forms: the constitutive (COX-1) and the inducible (COX-2). Increased levels on the expression of COX-2 have been implicated in the pathogenesis tumor progression of various forms of human cancer, including oral squamous cell carcinoma, some of what suggesting a possible interaction between COX-2 and the protein expressed by the tumor suppressor gene p53, mutated in more than 50% of all human cancers. The mean of the present research consisted in analyze the correlation between the expression of COX-2 and p53, at the protein level, as well as evaluate the difference on the expression of these two proteins with the histological grading of malignancy. 34 cases of oral squamous cell carcinoma were selected and graded according to the histological grading system proposed by Bryne (1998) and the labeling indexes (LI s) for COX-2 and p53 evaluated using immunohistochemistry method. The results revealed that COX-2 was expressed in increased levels in most of the specimens, although there was no statistic significant correlation between LI s from COX-2 and p53 (p>0.05), and there were no statistical differences on the expression of these proteins between tumors of high and low grade of malignancy (p>0.05). Interestingly, the expression of COX-2 and p53 was detected in fragments of dysplastic oral epithelium adjacent to tumor areas, on basal and suprabasal layers. The absence of statistical correlation between the expression of COX-2 and p53 proteins do not rule ot the existence of a relation between them, were it may reflect the diversity of regulatory pathways between both, different direct and indirect inhibitory effects of COX-2 over p53, as well as the wide range of activation macheenisms for COX-2 and mutational status of the p53 gene Another conclusion point that the increased expression of COX-2 observed in oral squamous cell carcinomas suggest a role for this protein in the processes of pathogenesis and tumoral evolution of this malignant neoplasm

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The expression of bone morphogenetic proteins (BMPs) is altered in a variety of human canceres. The BMP-2/4 and BMPR-IA were recently shown to be overexpressed in high-risk premalignant and malignant lesions of oral epithelium. The present study analysed the expression of BMP-2/4 and BMPR-IA in Oral Squamous Cell Carcinoma (OSCC) such as their implications in disease prognostic using munohistochemistry. Ten cases of Oral Fibroepithelial Hiperplasia were selected as a control group. The experimental group included 16 cases of OSCC without metastases and 7 cases of OSCC metastatic. The presence or absence of nodal metastases was used as parameter to evaluated the disease prognostic. The results demonstrated weak immunoreactivity for BMP-2/4 and BMPR-IA in every case of the control group. In the cases of OSCC with metastases an overexpression of BMP-2/4 (71,4%) was observed while the BMPR-IA showed weak expression (85,7%). In the cases of OSCC without metastases BMP-2/4 (62,5%) and BMPR-IA showed strong immunostaining standing out an overexpression of the receptor in all the specimens. Observed statistical significance for correlation between the oral cancer prognostic and the staining intensity of the BMP-2/4 (p=0,002). There wasn t statistical significance for association between the staining intensity of the BMPR-IA and the disease prognostic (p<0,001). In conclusion, this findings suggest that the overexpression of BMP-2/4 associated with the loss of expression of the BMPR-IA in OSCC metastatic has prognostic relevance, as the loss of sensitivity to BMPs can be an indicative of metastases development in OSCC

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The tissular destruction found in periodontal diseases is caused mainly by components of the host that have its production stimulated by the products of the microorganisms present on the plaque. Matrix Metalloproteinases (MMPs), a class of enzymes involved both in physiologic and pathologic extracellular matrix degradation are considered the main responsible for the characteristic tissular loss in periodontal disease, and the understanding of how this happens can have a series of beneficial implications for prevention, diagnosis and treatment of this illness. The aim of this work was to study the immunohistochemical expression of MMP-1, MMP-2, and MMP-9 in fragments of gingival biopsies with clinical diagnose of periodontal disease. MMP-1 has expressed significantly more than the others MMPs in gingivitis both in the epithelium (p=0,0008) and connective tissue (p=0,0049). In periodontitis, both MMP-1 and MMP-9 has expressed significantly more than MMP-2 in the epithelium (p<0,0001) and in the connective tissue (p=0,0002). MMP-1 and MMP-9 presented more expression in periodontitis than in gingivitis but MMP-1 only in the connective tissue (p=0,03) and MMP-9 in the epithelium (p=0,003) and in the connective tissue (p=0,04). In conclusion, these results indicate that the MMP-1 presents high expression in every stages of the periodontal diseases, and increases its expression in the connective tissue when the gingivitis evolves to periodontitis. Therefore, it may have an important role in connective tissue degradation and bone loss observed in disease, since early, in gingivitis, until late stages, in periodontitis, of the periodontal disease. MMP-9 has expressed more in periodontitis than in gingivitis, both in epithelium and in connective tissue. It means that this enzyme may have some importance in the progression of gingivitis to periodontitis by acting in bone resorption observed in this desease

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The odontogenic keratocysts are distinguished from other odontogenic cystic lesions by their potentially aggressive clinical behavior and association, in some cases, with Gorlin syndrome. Studies have suggested that syndrome keratocysts, in comparison with sporadic lesions, have higher growth and infiltration capacity and higher recurrence tendency. The aim of this study was to analyze, by means of immunohistochemistry, the expressions of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), the angiogenic index (CD34) and the presence of myofibroblasts (α-SMA) in primary and recurrent sporadic keratocysts and in keratocysts associated with Gorlin syndrome. The sample was composed by 30 sporadic keratocysts (22 primary and 8 recurrent) and 22 syndrome keratocysts. In the epithelium and in the fibrous capsule of the lesions, the immunoexpression of RANKL and OPG was evaluated by determination of the percentage of positive cells, according to the following scores: 0 (less than 10% of positive cells), 1 (11% - 50% of positive cells), 2 (51% - 75% of positive cells) and 3 (more than 76% of positive cells). In addition, cases were classified according to the RANKL score/ OPG score ratio, as follows: RANKL > OPG, RANKL < OPG, and RANKL = OPG. The angiogenic index was analyzed by counting the microvessels immunoreactive to anti-CD34 antibody in 5 fields (200). The analysis of myofibroblasts was performed by counting the cells immunoreactive to anti-α-SMA antibody in 10 fields (400). The analysis of the expressions of RANKL and OPG in the epithelial lining and in the fibrous capsule did not reveal significant differences between groups (p > 0.05). Regarding the RANKL/ OPG ratio in the epithelial lining, most sporadic primary (54.5%) and syndrome lesions (59.1%) showed RANKL < OPG ratio and RANKL = OPG ratio, respectively (p > 0.05). With respect to the RANKL/ OPG ratio in the fibrous capsule, the majority of sporadic primary (81.8%) and sporadic recurrent lesions (75.0%) and most syndrome lesions (45.5%) showed RANKL = OPG ratio (p > 0.05). The mean number of microvessels was 69.2 in sporadic primary lesions, 67.6 in recurrent lesions, and 71.6 in syndrome lesions, with no significant differences between groups (p > 0.05). The mean number of myofibroblasts was 34.4 in sporadic primary lesions, 29.3 in recurrent lesions, and 33.7 in syndrome lesions, with no significant differences between groups (p > 0.05). In conclusion, the results of the present study suggest that the differences in the biological behavior between sporadic keratocysts and keratocysts associated with Gorlin syndrome may not be related to the expressions of RANKL and OPG, the RANKL/ OPG ratio, the angiogenic index or the number of myofibroblasts in these lesions

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The aim of this study was determine whether an association exists in the gum tissue between the expression of markers of tissue hypoxia (HIF-1α and GLUT-1) with a marker of inflammatory activity (COX-2) and a marker of collagen degradation (EMMPRIN). Was performed immunohistochemistry with antibodies specific for these markers on 60 samples of gingival tissue divided into two groups: gums (n = 26) and gingivitis (n = 34) and expression was analyzed in the epithelial tissue and connective tissue . The reactivity epithelial for COX-2 was observed in only two cases as the HIF-1α, GLUT-1 and EMMPRIN was strongly expressed in the epithelial basal layer and the immunostaining was gradually decreased as the cells away from this layer, and negative in the region suprabasal in most specimens. In connective tissue, and HIF-1α EMMPRIN were strongly positive for most cases analyzed as GLUT-1 was negative in most cases. Immunostaining for COX-2 showed an association with gingival inflammatory infiltrate. The expression of EMMPRIN, HIF-1α and GLUT-1 in normal gums confirms the physiological role of these markers, however there was no association with tissue inflammation. Given the findings we can conclude that the inflammatory changes installed in frames of chronic gingivitis may not be sufficient to activate the factors of hypoxia to levels that can be quantified by immunohistochemical analysis, in addition, the findings are not conclusive in relationship to involvement of EMMPRIN in the secretion of MMPs to degrade collagen in the frames of gingivitis. We suggest the use of technical analysis and quantification of RNA of EMMPRIN and MMPs in order to determine whether collagen degradation observed in gingivitis suffers or not, significant influence of EMMPRIN for secretion and activation of MMPs

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

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The objective of this study was perform by the streptoavidin-biotin technique an immunohistochemical analysis of α2β1, α3β1e α5β1 integrins in 11 normal oral mucosa (NOM), 16 oral inflammatory fibroepithelial hyperplasia (OIFH) and 25 oral epithelial dysplasia (OED) (16 mild, 2 moderates and 7 severe), to determine if exists qualitative alteration in the expression of these integrins and if this guard relation with the oral epithelial modifications. It was observed that for the α2β1 integrin the majority of the sample showed a predominantly intense labeling diffusely distributed in the intercellular contacts and the cytoplasm of cells of the basal and suprabasal layers, without difference of this profile between the different types of specimens, however with a trend to weak or loss of expression in 21.1% of the OEDs, being all the specimens that had not expressed this heterodimer, severe OEDs. For the α3β1 integrin the majority of the sample showed a weak or absent labeling in basal layer. The α5β1 integrin showed a predominant strong diffuse labeling in the intercellular contacts and cytoplasm in the suprabasal layer, with difference only in the labeling intensity between the types of specimens, inhabiting this difference in the OEDs, where 12 (48%) specimens had shown a weak labeling. It was concluded that the evaluated integrins can be involved in the cell-cell, cell-ECM interactions modulating the cellular differentiation and maintenance of the epithelial structural arrangement. The variable expression of the α5β1 integrin in the OEDs, could suggest, respectively, a role of this molecule in the cellular survival, with intention to perpetuate the modified phenotype in these lesions, or a suppressor role on the modified phenotype due to lack of interaction of this molecule with the fibronectina of the MEC

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The development and progression of odontogenic tumors have been associated with an imbalance in the activity of growth factors, adhesion molecules, extracellular matrix proteins and their degradation enzymes, angiogenic factors and osteolytic. Some studies have shown that interaction relationships inductive epithelial / mesenchymal determinants of Odontogenesis are mimicked by these tumors. The objective of this research was to investigate the immunolocalization of growth factors (BMP-4 and FGF-8) and Sindecan-1 structural protein in a series of odontogenic tumors presenting different biological behaviors, to contribute to a better understanding of the role of these proteins in tumor development. The sample consisted of 21 of the solid ameloblastoma, odontogenic keratocysts 19 and 14 odontogenic adenomatoid tumors. Increased Sindecan-1 immunostaining was seen in the epithelium of the lesions when compared with mesenchyme. In ameloblastoma and odontogenic keratocysts, this expression was higher than in AOT. Epithelial expression of BMP4 showed quantitatively similar in the three studied lesions; however, when anlisada mesenchymal immunoreactivity, was detected significant higher expression when compared to the ameloblastoma keratocysts. In ameloblastoma, mesenchymal expression was predominantly (p = 0.008), while in keratocyst higher expression in the epithelium was observed (p = 0.046). In all injuries, strong or moderate correlation was observed in the BMP-4 immunoreactivity in the epithelium and mesenchyme. FGF-8, no injury was observed difference between the immunoreactivity in the epithelium or mesenchyme, however in ameloblastoma positive correlation was found (Spearman correlation, rho = 0.857, p <0.001). The results of this study suggest that the three evaluated biomarkers actively involved in the pathogenesis of lesions, especially the expression of ameloblastomas indicating a strong interaction between parenchymal and stromal cells which may contribute to its marked aggressiveness.

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Kidney transplantation is the best treatment for patients who have lost kidney function. Renal transplant patients require accurate immunosuppressive drugs to prevent rejection. In this process T helper cells of the immune system perform key role in the immune response to the graft, and recently the Th17 cells has been investigated by production of IL-17 potent proinflammatory cytokine whose role in the rejection has also been described. Increased of Th17 cell expression has an important association with the development of rejection in renal microenvironment, however the likely mechanism is not well understood. This study aimed to evaluate the Th17 response from the influence of the chemotactic axis CCR6/CCL20 and genetic variants in IL-17 and IL-17RA. We conducted a case-control study involving 148 patients transplanted at the University Hospital Onofre Lopes/UFRN in which assessed by immunohistochemistry protein expression of IL-17 and chemokines CCR6/CCL20 and by PCR-RFLP genetic variants in IL17A and IL17RA. Our results showed no influence of genetic polymorphisms on the outcome of the graft or the protein expression of IL-17. In renal graft microenvironment found several sources producing IL-17: tubular epithelial cells, glomerular cells, neutrophils and cell interstitial infiltration, in turn the expression of chemotactic axis CCR6/CCL20 was restricted to the tubular epithelium cells. There was a slight positive linear correlation between the presence of IL-17 and expression of chemotactic axis CCR6/CCL20 in the microenvironment of renal graft. Therefore, we believe that, combined with our results, further studies with increased "n" sample and greater control over the variables involved in obtaining the renal specimen, can determine more clearly the influence of chemotactic axis CCR6 / CCL20 and polymorphisms in cytokines related to Th17 profile on the control of this cell subtype response in rejection processes to renal allograft.

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Candidiasis is a major oral manifestation in kidney transplant patients. Candida spp. possess essential virulence factors which contribute for the infectious process, including the ability to adhere to epithelial cells and biofilm formation. The extract obtained from the leaves of Eugenia uniflora [acetone: water (7:3, v/v)] has demonstrated antifungal activity against Candida spp. This study evaluated the influence of the extract of E. uniflora in adhesion to human buccal epithelial cells (HBEC) and biofilm formation of 42 strains of Candida spp. isolated from the oral cavity of kidney transplant patients. Candida spp. strains belonging to a culture collection were reactivated and phenotypically re-identified by classical and molecular methods (genotyping ABC and RAPD), when necessary, to complete the identification to the species level. For the virulence tests evaluated in vitro, yeasts were grown in the presence and absence of 1000 g/mL of the extract. A ratio of 10: 1 (Candida spp. cells x HBECs) was incubated for 1 hour at 37 ° C, 200 rpm, fixed with 10% formalin and the number of Candida cells adhered to 150 HBEC determined by optical microscope. Biofilms were formed on polystyrene microplates in the presence or absence of the extract. The quantification was performed with crystal violet staining at 570 nm. All isolates were viable and exhibited phenotypic characteristics suggestive of each species identified. Two strains presumptively identified as Candida dubliniensis belonged to this species as determined with genotyping ABC, while strains identified as belonging to the Candida parapsilosis species complex were differentiated by RAPD genotyping. Candida albicans was found to be the most adherent species to the buccal epithelia, while C. tropicalis showed remarkable biofilm formation.We could detect that the extract of E. uniflora was able to reduce adhesion to HBEC for both Candida albicans and non-Candida albicans Candida species. On the other hand, only 16 Candida spp. strains (36 %) showed reduced biofilm formation. However, two highly biofilm producer strains of C. tropicalis had an expressive reduction in biofilm formation. This study reinforces the idea that besides growth inhibition, E. uniflora may interfere with the expression of some virulence factors of Candida spp., and may be possibly applied in the future as a novel antifungal agent.

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benign epithelial odontogenic lesions are great clinical importance entities that develop in the jaws from the tissues that form teeth. It has been shown that in benign and malignant tumors, are present in a large number of tumor stem cells, which has great implications in the development of these lesions. Oct-4 and CD44 have been demos as important markers for tumoral stem cells. The objective of this study was to identify epithelial cells expressing stem cell markers by immunohistochemical expression of Oct-4 and CD44 in a series of cases of benign epithelial odontogenic lesions. The sample was comprised of 20 cases of odontogenic keratocyst (OKC), 20 cases of solid/multicystic ameloblastoma and 20 cases of adenomatoid odontogenic tumor (AOT). The expression of Oct-4 and CD44 was evaluated in epithelial lesions using the percentage of positive cells (PP) and the intensity of expression (IE), being realized the sum of these scores, resulting in Total Immunostaining Score (TIS) ranging 0 to 7. The results were submitted to the appropriate statistical test (nonparametric Kruskal-Wallis and Spearman correlation coefficient). All cases were positive for both markers and most showed high expression of both markers. The analysis of Oct-4 expression revealed no statistically significant differences (p = 0.406) among the studied lesions. Regarding the CD44 expression, there was a statistically significant difference between the cases of ameloblastoma and TOA in relation to the CCO, with the latter show more cases in the score 7 (p = 0.034). In the correlation analysis of the immunoreactivity of both markers in the three lesions studied, there was no statistically significant correlation. The results of this study identified the presence of cells with stemness characteristics arranged at various sites in the epithelial component of the studied lesions suggesting their possible role in the histogenesis and differentiation in benign epithelial odontogenic lesions, thus contributing to the development of these lesions.