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ResumoA paracoccidioidomicose (PCM) é uma doença fúngica limitante com ocorrência em países latino‐americanos. Lesões secundárias em mucosa e pele são observadas em sua forma crónica. Um homem leucoderma de 60 anos, etilista, hipertenso, fumante e ex‐garimpeiro apresentou‐se cancerofóbico e com a queixa principal de dor do lado direito da boca. Ao exame intraoral, observou‐se uma úlcera extensa com bordas irregulares, endurecida e edemaciada. Foi realizada biópsia incisional e, por meio de exame histopatológico após coloração por hematoxina e eosina e Gomori‐Grocott, concluiu‐se que o referente caso clínico era de PCM. O paciente foi encaminhado a um infectologista e foi tratado com itraconazol 200mg. Assim, objetivamos relatar um caso clínico de PCM com sinais e sintomas intraorais.AbstractParacoccidioidomycosis (PCM) is a fungal disease with occurrence in Latin America. Secondary lesions in mucosa and skin are observed in chronic presentation. One man, caucasian, 60 years old, alcoholic, hypertensive, smoke and ex‐miner, cancer‐phobia and with main complain of pain in the right side of the mouth. At intraoral exam, was observed a large ulcer with irregular borders, hard and edematous. It was made a incisional biopsy and through histopathologic exam, after Hematoxin and Eosin and Gomori‐Groccot, the final diagnosis was PCM. The patient was referred to a infectologist and the treatment was Itraconazol 200mg. We aimed report a case of PCM with intraoral signs and symptoms.

Purpose: Candida albicansis known to produce secreted aspartyl proteinases (SAPs) to aid adhesion, invasion, and host tissue destruction. SAPs may contribute to denture stomatitis (DS) pathogenesis. The aim of this study was to develop an in vivo experimental model for Candida-associated DS that allows the analysis of SAP2, SAP5 ,a nd SAP9 expression by C. albicans from biofilm induced on the denture surface. MaterialsandMethods: Thirty-fivemaleWistarratswere dividedintothree groups: control, denture, and denture/Candida group. The last two groups remained with dentures for 2, 4, and 6 days, with or without induced biofilm. SAP expression was concomitant with leukocyte counts as well as clinical and histological changes shown by animal palate. Results: The signs observed at 4 days in the denture/Candida group were clinically closer to the Candida-associated DS, showing a significant increase of neutrophils and decrease of lymphocytes in peripheral blood, presence of inflammation signs on the palate similar to DS Newton type I, and fungal invasion in the epithelial layer. Accordingly, the denture/Candida group at 4 days presented the highest relative expression of all SAPs studied. Conclusion: The results showed a coincidence between SAP expression and clinical, microscopic, and blood data. Finally, the molecular findings were consistent with the virulence capacities of C. albicans from biofilm formed on the denture resin, which possibly allowed epithelial invasion by the fungus.

Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p

Made available in DSpace on 2015-12-07T15:34:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2015-12-07T15:52:49Z : No. of bitstreams: 1 PMC4531177.pdf: 2455935 bytes, checksum: f43a0355a37eee2d18dbbb1909e90828 (MD5) Equisetum giganteum L. (E. giganteum), Equisetaceae, commonly called giant horsetail, is an endemic plant of Central and South America and is used in traditional medicine as diuretic and hemostatic in urinary disorders and in inflammatory conditions among other applications. The chemical composition of the extract EtOH 70% of E. giganteum has shown a clear presence of phenolic compounds derived from caffeic and ferulic acids and flavonoid heterosides derived from quercitin and kaempferol, in addition to styrylpyrones. E. giganteum, mainly at the highest concentrations, showed antimicrobial activity against the relevant microorganisms tested: Escherichia coli, Staphylococcus aureus, and Candida albicans. It also demonstrated antiadherent activity on C. albicans biofilms in an experimental model that is similar to dentures. Moreover, all concentrations tested showed anti-inflammatory activity. The extract did not show cytotoxicity in contact with human cells. These properties might qualify E. giganteum extract to be a promising alternative for the topic treatment and prevention of oral candidiasis and denture stomatitis. Department of Stomatology (Pathology), Bauru School of Dentistry, University of São Paulo (USP), Alameda Doutor Octávio Pinheiro Brisolla 9-75, 17012-901 Bauru, SP, Brazil. Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP, Brazil. Department of Prosthodontics, Bauru School of Dentistry, University of São Paulo (USP), Alameda Doutor Octávio Pinheiro Brisolla 9-75, 17012-901 Bauru, SP, Brazil. Department of Biological Sciences, Faculty of Sciences, São Paulo State University (UNESP), Bauru, SP, Brazil. Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP, Brazil. Department of Biological Sciences, Faculty of Sciences, São Paulo State University (UNESP), Bauru, SP, Brazil.

Existem poucos estudos a respeito da presença de constituintes fúngicos na circulação sanguínea de indivíduos com estomatite por dentadura (ED) (AHMAD et al., 2002), considerada uma forma localizada de candidose; o que poderia caracterizar o poder de invasão sistêmica do fungo nesta condição local, bem como um prévio reconhecimento desses antígenos por células presentes na circulação sanguínea do hospedeiro, o que poderia explicar aspectos específicos da resposta imune localizada e sistêmica. Assim sendo, este trabalho teve por objetivo avaliar a presença do fungo Candida albicans (C. albicans) no palato, na superfície interna das próteses totais superiores e no sangue de pacientes com ED, em dois momentos distintos. A população de estudo foi composta por indivíduos usuários de prótese total superior (PTS), com e sem estomatite por dentadura, avaliados e selecionados nas clínicas de graduação e pós-graduação da Disciplina de Prótese, do Departamento de Prótese, da Faculdade de Odontologia de Bauru da Universidade de São Paulo (FOB USP). Indivíduos não usuários de próteses removíveis constituíram o grupo controle. Assim o trabalho foi constituído por três grupos, cada um com 14 pacientes. As lesões de estomatite por dentadura foram diagnosticadas clinicamente e por meio de confirmação microbiológica em CHROMAgar Candida, a partir de material biológico coletado da mucosa palatal e da superfície interna da PTS. A PCR foi realizada quando da ocorrência do crescimento de colônias verdes para diferenciação das espécies C. albicans e C. dubliniensis. As amostras de sangue foram analisadas para a detecção de fragmentos de DNA responsáveis pela codificação da proteína da parede da hifa1(Hwp1) de C. albicans, utilizando a técnica da PCR. Os resultados demonstraram que nem os usuários de PTS, independentemente da presença de ED, nem os voluntários não usuários apresentaram a proteína Hwp1 no sangue, em nenhuma das amostras coletadas. A presença de fungos do gênero Candida foi mais frequente (p 0,005) entre os usuários de PTS com ED quando comparado com os outros indivíduos. Além disso, pudemos constatar que os pacientes com diagnóstico clínico e microbiológico de ED não apresentaram distribuição sanguínea de C. albicans. There are few studies about the presence of yeast constituents in the bloodstream of patients with denture stomatitis (DE), a localizated kind of candidiasis; what could characterize the yeast systemic invasion power in this local condidition, and also previous acknowledgement of these antigens by cells of the entertainer bloodstream, and explain specific features of the immune located and systemic answer. So being, this work had as a goal to evaluate the presence of the yeast Candida albicans (C. albicans) at the palate, at the internal surface of the upper denture and in the blood of patients with DE, at two different moments. The population of study was composed by individuals both with and without upper denture, with and without stomatitis, assessed and selected in the clinics of graduation and postgraduation of the Discipline of Prosthesis, of the Department of Prosthesis, of the Faculdade de Odontologia de Bauru of the University of São Paulo (FOB USP). Individuals who are not users of removable dentures constituted the group control. So the work was constituted by three groups, each one with 14 patients. The injuries of stomatitis were diagnosed clinically and through microbiological confirmation in CHROMAgar Candida, from biological collected material of the palatal mucosa and of the internal surface of the upper denture. The PCR was carried out when the growth of green colonies for differentiation of the stain C. albicans and C. dubliniensis happened. The samples of blood were analyzed for the detection of fragments of DNA responsible for the codification of the hyphal wall protein (Hwp1) of C. albicans. The results demonstrated that not even the users of upper denture, independently of the presence of the DE, not even the volunteers who are not users presented the protein Hwp1 in the blood, in none of the collected samples. The yeast Candida presence was more frequent (p 0,005) in the group 1 when compared with the other groups. Morever, we can conclude that patients with clinic and microbiologic diagnostic have not presented bloodstream distribution of C. albicans.

Lipomas are very common benign slow-growing soft tissue neoplasms composed of mature adipose tissue mostly diagnosed in the fifth decade of life. These tumors rarely present in the oral cavity, representing less than approximately 5% of all benign mouth tumors. They are usually less than 2cm in size and etiology remains unclear. We report a young male patient presenting with a giant lipoma in the buccal mucosa. Histopathology revealed a large area of mature fat cells consistent with conventional lipoma and an area of the mucosal lining of the lesion suggestive of morsicatio buccarum. In the present article, we emphasize the clinicopathological features and differential diagnosis of the disease.

O objetivo deste trabalho foi avaliar, in vitro, se a incorporacao de extratos hidroalcoolicos de Equisetum giganteum (Eg) e de Punica granatum (Pg) a um adesivo protetico influencia no desenvolvimento do biofilme de Candida albicans sobre a superficie de resina acrilica termopolimerizavel. Apos identificacao dos compostos por HPLC-PAD, foi selecionada a fracao e a concentracao de interesse por meio da concentracao inibitoria minima (CIM). Os biofilmes de C. albicans foram induzidos durante 3, 6 ou 12 horas sobre corpos de prova de resina acrilica, previamente submetidos ao tratamento com o adesivo associado aos fitoterapicos (AD/Eg ou AD/Pg). Como controles, corpos de prova foram tratados apenas com adesivo (AD), ou com a associacao adesivo/nistatina (AD/Nt) ou nao recebam tratamento (PBS), n=2 por grupo, em cada experimento. A atividade antimicrobiana foi avaliada por meio das unidades formadoras de colonias (UFC/mL), e pelo percentual de reducao da atividade metabolica pelo ensaio colorimetrico - XTT. Os resultados foram expressos como media ± desvio padrao, e submetidos ao teste de Kruscal-Wallis e Mann-Whitney (UFC/mL); e ANOVA-2 seguido do teste de Tukey HSD e o teste de Dunnett (XTT), com significância quando p˂ 0,05. Foi possivel identificar compostos derivados de kaempferol e quercetina em Eg e punicalina, em Pg. A associacao de ambos os fitoterapicos ao adesivo (AD/Eg ou AD/Pg) reduziram significativamente o biofilme de C. albicans sobre a superficie da resina, em comparacao ao grupo AD. Em acordo, houve aumento do percentual de reducao da atividade metabolica do biofilme em todos os periodos, na presenca dos fitoterapicos. Por fim, sugerimos que a associacao destes fitoterapicos ao adesivo protetico podera constituir uma alternativa temporaria, viavel e inovadora para auxiliar no tratamento e/ou prevencao da Estomatite Protetica. Apoio Financeiro: FAPESP #2014/07012-7 Descritores: Estomatite sob Protese; Adesivos Teciduais; Fitoterapia.

Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5- and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25−CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment. Mol Cancer Ther; 16(12); 2871–80. ©2017 AACR.

Purpose The aim of this study was to evaluate the effect of 1% sodium hypochlorite (H1%) and 4% chlorhexidine gluconate (CG4%) on the adhesion of Candida albicans to denture base acrylic resins, as well as to verify the effect of the acquired salivary pellicle (ASP) formation on this process. Materials and Methods A total of 300 acrylic specimens were immersed in distilled water (control) (n = 100), H1% (n = 100), or CG4% (n = 100) for 30 days. Twenty specimens were used in each experimental period (0, 1, 7, 15, 30 days). At the end of disinfection testing periods, 10 specimens of each group were exposed to human whole saliva to simulate ASP formation, and then all specimens were incubated with C. albicans ATTC 90028. Microorganism adhesion was analyzed by fluorescence microscopy, after staining with Acridine orange. Results In the 30th disinfection cycle in relation to baseline, the H1% or CG4%, without ASP formation, reduced the C. albicans adhesion by approximately 80%; however, with ASP, this reduction after disinfection with H1% was higher (88%). The presence of ASP resulted in higher reduction of adhered fungal cells in comparison to resin without ASP, at the 1st H1% or CG4% disinfection cycle, as well as at 30th H1% disinfection cycles. Conclusions Our results suggest that the presence of saliva might influence the adhesion of C. albicans and improve the effectiveness of methods to reduce fungal adhesion.

Nodularna leukoplakija je nehomogeni oblik oralne leukoplakije obično s bijelom bradavičastom, nodularnom, ulceriranom ili eritematoznom (crvenkastom) površinom s velikim rizikom od pretvorbe u malignu tvorbu u usporedbi s homogenim oblikom. Najčešće zahvaća komisure usnica, obraznu sluznicu i meko nepce. Često je povezana s epitelnom displazijom ili karcinomom, pa je prijeko potrebna detaljna mikroskopska procjena, a poslije redovite kontrole. Temelj za postavljanje točne dijagnoze jest odabrati pravo mjesto za biopsiju, ali i bliska suradnja liječnika dentalne medicine i oralnog patologa., Nodular leukoplakia is a non-homogeneous type of oral leukoplakia presenting a white surface with verrucous, nodular, ulcerated or erythematous features with a greater risk of malignant transformation when compared to the homogeneous type. Common sites of involvement include lip commissures, buccal mucosa and soft palate. It is often associated with epithelial dysplasia or carcinoma and requires detailed microscopic assessment and regular follow-up. The importance of a proper selection of the area to be biopsied and the close teamwork between a dentist and oral pathologist is the basis of providing an accurate final diagnosis.

Research on cancer stem cells (CSCs) has greatly increased in the field of medicine and pathology; however, some conceptual misunderstandings are still present among the public as well as within the general scientific community that is not yet familiar with the subject. The very first problem is the misinterpretation of CSCs as a synonym of their normal counterparts, the well-known stem cells (SCs). Particularly in Dentistry, another common mistake is the misinterpretation of oral CSCs as normal tooth-derived SCs. The present review aims to clarify important concepts related to normal SCs and CSCs, as well as discuss the relevance of CSCs to the development, metastasis and therapy resistance of oral squamous cell carcinoma.

A presença de Candida albicans nos biofilmes microbianos aderidos na superfície interna das próteses removíveis, principalmente totais superiores, está relacionada com uma doença inflamatória no palato, conhecida como estomatite protética (EP). Assim, torna-se fundamental a realização de novos estudos sobre alternativas terapêuticas, direcionados à prótese e não somente à mucosa, que sejam simultaneamente antimicrobianas, anti-inflamatórias, não tóxicas para os tecidos bucais e que produzam menos danos à prótese que os métodos convencionais. Os fitoterápicos podem representar uma destas alternativas. Objetivos: O objetivo deste trabalho foi estudar a ação fitoterápica do Equisetum giganteum, nas concentrações de 50, 25, 16, 8 e 4 mg/mL, sobre C. albicans e descartar sua ação citotóxica sobre o palato humano bem como sobre monócitos humanos. Material e Métodos: Após coleta, obtenção e identificação de compostos por espectrometria de massas do extrato hidroalcoólico de E. giganteum, sua atividade antimicrobiana foi determinada pela concentração inibitória mínima em meio líquido, contra as cepas clínicas Candida albicans SC 5314 e Escherichia coli O:124, e a cepa padrão Staphylococcus aureus ATCC 6538. Propriedades antiaderentes do extrato, sobre biofilmes de C. albicans induzidos sobre corpos de prova de resina acrílica, foram determinadas por imunofluorescência (LIVE/DEAD) e pela análise em microscópio de varredura confocal a laser. A atividade anti-inflamatória do fitoterápico foi averiguada através da análise da produção de espécies reativas de oxigênio (ROS) por monócitos humanos estimulados por C. albicans e LPS, por meio da marcação fluorescente utilizando o reagente Cell Rox Deep Red®. Avaliação de citotoxicidade foi realizada in vitro com células epiteliais de palato humano e monócitos humanos, por meio do ensaio colorimétrico MTT. Os resultados foram expressos como média ± desvio padrão e submetidos aos testes estatísticos Teste de Kruskal-Wallis; ANOVA one-Way; ANOVA two-Way, Teste de Miller; Teste de Tukey e Dunnet; Teste de Fisher, sendo p

Background: Antifungal agents incorporated into temporary denture resilient liners as drug carriers and delivery have been suggested as an alternative treatment for denture stomatitis. However, to test the in vivo biocompatibility of this protocol, standardization of an intraoral device for optimal drug delivery is required. Objective: Standardized criteria were produced to adjust an acrylic intraoral device (IOD) for rats feasible for denture stomatitis treatment by sustained drug-delivery based on minimal inhibitory drug concentrations (MICs) of antifungals for Candida albicans biofilm. Method: Adjustments methodological involved diet, impression technique, type of retention device to the palate and histopathological analysis. 115 Wistar rats were tested without IOD, with devices without relining or relined with temporary resilient material (Trusoft) modified or not by drugs at MICs (nystatin- 0.032g/mL; chlorhexidine diacetate-0.064g/mL; ketoconazole-0.128g/mL). The animals were sacrificed after 7 or 14 days from the IOD installation. Results: Paste diet enabled the best animal survival conditions. The IODs that most satisfactorily remained in position were those designed only to the posterior palatal mucosa and cement-retained in molars, being all obtained from impressions highly detained and individual. In both periods, Trusoft without/with drugs showed good performance. Only histological samples from hard/soft tissues were considered appropriate for region of interest-RI determination (n=12), which corresponded to the area restricted to the first molars between the palatal neurovascular bundles. Final samples of all groups allowed a standardized descriptive histopathological analysis in both periods. Conclusion: The methodological standardization of this rat model resulted in IODs for optimal antifungal delivery for denture stomatitis treatment.

Introduction Denture stomatitis is the most common pathology affecting denture wearers and its main cause is colonisation of dentures with Candida albicans. Objective This study investigated the effectiveness of two commercial composite surface sealants (Biscover® LV and Surface Coat®) to reduce C. albicans biofilm colonisation on denture resin, as well as their surface integrity after disinfection cycles with 1% sodium hypochlorite solution. Methods Heat-cured acrylic resin specimens were manufactured (10 mm × 10 mm × 1 mm). The specimen surfaces were mechanically polished to simulate rough or smooth denture surfaces. Four surface-treatment groups were tested: smooth surfaces [0.3 μm of mean roughness (Ra)]; rough surfaces (3 μm of Ra); rough surfaces treated with Biscover® LV; and rough surfaces treated with Surface Coat®. Specimens of each group were randomly divided to undergo immersion in distilled water or 1% sodium hypochlorite for 30 or 90 cycles each. Specimens of all groups in each immersion solution were tested using a crystal violet (CV) staining assay for biofilm quantification and by scanning electron microscopy for visual analyses of surface integrity and biofilm structure. CV assay data were analysed using one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test (P < 0.05). Results The effectiveness and surface integrity of Biscover® LV-treated surfaces were similar to those of smooth surfaces, whereas Surface Coat®-treated surfaces presented a similar performance to rough surfaces in all solutions and cycles. Conclusion These results suggest the possibility of clinical use of Biscover® LV for denture coating on surfaces in which mechanical polish is not indicated, such as the fitting surface.

Candida-associated denture stomatitis (DS) is the most frequent lesion among denture wearers, especially the elderly. DS is strongly associated with Candida albicans, as well as local and systemic factors, such as impaired immune response. Monocytes are important in the protective immune response against the fungus by the production of cytokines that recruit and activate leukocytes. There are functional changes in these cells with age, and individual alterations involving monocyte response may predispose the host to developing infections by Candida spp. In this study, our aim was to evaluate the production of TNF-α, IL-6, CXCL8, IL-1β, MCP-1 and IL-10 by monocytes from elderly denture wearers with/without DS and elderly or young non-denture wearers. We detected that monocytes from elderly denture wearers with Candida-related denture stomatitis produced lower levels of CXCL-8, IL-6 and MCP-1. This imbalance in cytokine levels was observed in spontaneous or LPS-stimulated production. Therefore, our data suggested that inherent aspects of the host, such as changes in cytokine production by monocytes, might be associated with the development and the persistence of DS irrespective of aging.

Candida albicans (C. albicans) is a fungus commonly found in the human mucosa, which may cause superficial and systemic infections, especially in immunosuppression. Until now, the main actors in the defense against this fungus are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells. However, mast cells are strategically located to play a first line of anti-Candida defense and it has appropriate mechanisms to do it. As with other cells, the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC-labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The intracellular production of NO and ROS was measured by DAF-FM diacetate and CellROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide release were analyzed by Griess reaction and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C. albicans with production of intracellular NO, but not ROS. Moreover, increased levels of nitrite were also observed. The absence and/or blockade of TLR2/Dectin-1 caused significant decreased in C. albicans phagocytosis and NO production. Our results showed that mast cells are able to phagocytose and produce NO against C. albicans via TLR2/Dectin-1. Therefore, mast cells could be important during the course of Candida infection and as a therapeutic target.

Juvenile ossifying fibroma (JOF) is a rare fibro-osseous neoplasm, defined as a variant of the ossifying fibroma that arises within the craniofacial bones. Two subgroups, juvenile psammomatoid ossifying fibroma (PsJOF) and juvenile trabecular ossifying fibroma, have been delineated by their histology. PsJOF occurs predominantly in the sinonasal and orbital bones. This work reports on 2 cases of extensive PsJOF in the body of the right mandible as well as reviews the literature regarding the radiographic and histologic features, treatment, and prognosis of PsJOF of the jaws.

We have identified impaired neutrophils in elderly individuals which could be involved with Candida-related denture stomatitis (DS), an oral infection predominantly caused by Candida albicans, affecting especially elderly individuals using dental prosthesis. However, specific mechanisms performed by neutrophil contributing to the susceptibility of the elderly to DS are not fully understood. This study evaluated activation features of blood neutrophils from elderly and young individuals with DS. Blood neutrophils cultured with C. albicans from elderly subjects secreted decreased levels of CXCL8. However, C. albicans challenged-neutrophils from DS patients produced high IL-4 and IL-10, and low GM-CSF levels, regardless of age. Additional elastase activity of neutrophils from both elderly groups was detected after incubation with C. albicans, but only neutrophils from elderly DS demonstrated high myeloperoxidase activity. Therefore, DS patients have affected neutrophils, and the advance of age intensifies these damages. In summary, individuals with Candida-related denture stomatitis presented variation in the neutrophil phenotype and activation. Such alterations were more intense in neutrophils from infected elderly individuals.

doi: 10.1111/j.1741-2358.2011.00476.x Salivary immunity in elderly individuals presented with Candida-related denture stomatitis Objectives: Elderly individuals with Candida-related denture stomatitis (DS) present with a reduced defence against Candida albicans. This study evaluated levels of antimicrobial mediators in the elderly DS saliva and salivary neutrophils’ activation characteristics compared with elderly and young without DS. Methods: Salivary peroxidases (SPO) and elastase activities (ELA), nitric oxide (NO), transforming growth factor beta (TGF-β), IL-6 and CCL3 production were determined in saliva from elderly with or without DS, and young control individuals. TLR4, CXCR1, CD11b, CD16 and CD32 expression on salivary neutrophils were evaluated. Correlations between number and apoptosis rate of salivary neutrophils, enzymatic activities and cytokine levels were determined. Results: Elderly DS individuals exhibited the lowest SPO and ELA activities. Also, the activity of both enzymes was low in elderly without DS. Although both elderly groups showed higher salivary NO and TGF-β levels compared to young control groups, elderly DS presented the highest salivary NO, TGF-β, IL-6 and CCL3 levels. Decreased percentages of salivary TLR4+ and CD16+ neutrophils were detected in both elderly groups. Although these damages could influence the establishment and persistence of DS, the highest levels of salivary IL-6 and CCL3 in elderly DS could be preventing more serious complications.

Studies investigating the immunopathological aspects of Jorge Lobo ' s disease have shown that the infl ammatory infi ltrate consists mainly of histiocytes and multinucleated giant cells involving numerous yeast-like cells of Lacazia loboi , with the T lymphocytes more common than B lymphocytes and plasma cells. The quantifi cation of cytokines in peripheral blood mononuclear cells culture supernatant has revealed alterations in the cytokines profi le, characterized by predominance of a Th2 profi le. In view of these fi ndings and of the role of cytokines in cell interactions, the objective of the present study was to investigate the presence of the cytokines IL-10, TGF- s 1 and TNF- α , as well as iNOS enzyme in granulomas induced by L. loboi . Histological sections obtained from skin lesions of 16 patients were analyzed by immunohistochemistry for the pres- ence of these cytokines and iNOS. The results showed that TGF- s 1 was the cytokine most frequently expressed by cells present in the infl ammatory infi ltrate, followed by IL-10. There was a minimum to discrete positivity of cells expressing TNF- α and iNOS. The results suggest that the presence of immunosuppressive cytokines in skin lesions of patients with the mycosis might be responsible for the lack of containment of the patho- gen as demonstrated by the presence of numerous fungi in the granuloma.

Summary We previously showed that neutrophils from patients with Candida-related denture stomatitis exhibited damaged function, and the advance in age intensified this condition. Because such alterations had been determined in elderly people that were not denture wearers, the purpose of this study was to clarify functional and phenotypic characteristics of neutrophils from elderly denture wearers (EDW) and young denture wearers (YDW) without oral lesion. We enrolled 20 denture wearers (12 EDW and 8 YDW) and determined the positivity of Candida species on maxillary prosthesis and palate. Additionally, blood and salivary neutrophils were evaluated. Furthermore, cytokines and chemokines salivary levels were detected. YDW presented higher positivity of Candida albicans than elderly ones. However, blood neutrophils from EDW expressed less CXCR1, CD62L and CD11b and had lower C. albicans phagocytosis than YDW. Although myeloperoxidase and elastase activity was significantly higher in C. albicans-stimulated blood neutrophils from elderly, they produced high levels of IL-10 and low levels of Granulocyte macrophage-colony stimulating factor (GM-CSF). Despite apoptosis rate of salivary neutrophils was enhanced, these cells were at a high number in YDW. GM-CSF and IL10 were lower in saliva from elderly group. These data confirmed that ageing affects blood and salivary neutrophils and could predispose elderly to persistent oral infections.

Candida albicans is considered the most important Candida species able to cause oral infections in denture wearers. In recent years, Candida dubliniensis has emerged as a pathogenic yeast in humans. The close phenotypic similarities of C. albicans and C. dubliniensis have led to the misidentification of these species. In this work, our aim was to verify through PCR the presence of C. dubliniensis in palate and maxillary denture samples from 112 denture wearers presenting with or without denture-related stomatitis (DRS). C. dubliniensis was isolated at low rates from both palate (5.3 % and 10.7 %) and maxillary denture (5.3 % and 8.9 %) samples from wearers regardless of the presence of the disease. However, when C. dubliniensis was detected in individuals with DRS, it was always associated with C. albicans. In addition, our results showed that C. albicans was the most commonly identified candidal species in maxillary denture and hard palate samples from DRS patients (78.5 % and 89.2 %, respectively) as well as from controls (31.2 % and 28.5 %, respectively). In conclusion, C. dubliniensis was detected in the oral environment of denture wearers. The association of C. dubliniensis with C. albicans occurred in approximately 10 % of the DRS cases.

Background: The Langerhans cells (LCs) are scattered throughout the epithelium of skin and mucosa and have been associated with the graft-vs.-host disease (GVHD), which is the highest cause of morbidity and mortality in patients who underwent bone marrow transplant (BMT). This study aims at quantifying the LCs in the oral chronic GVHD (cGVHD). Methods: Microscopic sections from biopsies carried out in the buccal mucosa of 40 patients who underwent allogenic BMT and developed (20) or not (20) oral cGVHD (Groups 1 and 2, respectively) were utilised. For the control group, free surgical margins of 20 biopsies of non-inflammatory lesions in the buccal mucosa (Group 3) were used. The sections were studied in routine colouration and immunostained for CD1a. Results: Group 1 (with cGVHD) presented a greater number of Langerhans’ cells/mm2 (50.6 ± 37.2) when compared with the other groups (Group 2, 23.11 ± 19.7; Group 3, 16.6 ± 17.3). Conclusion: Our results suggest a greater recruitment of LCs in patients transplanted with cGVHD, probably as a result of cytokines secreted by the inflammatory cells.

The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident, inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction.

It is becoming accepted that multiple cell types in stromal microenvironment are involved in tumorigenesis. In this setting, mast cells (MC) display a diversity of roles that may contribute to the defense against tumors or tumor progression. Thus, the aim of this study was to evaluate density and migration of MCs in OSCC (oral squamous cell carcinoma) and pre-malignant oral hyperkeratosis (leukoplakia) as well as their relationship with clinical and microscopic parameters. The tryptase and c-kit expression was analyzed in 38 cases of OSCC, 26 cases of leukoplakia, and 12 cases of clinically healthy oral mucosa (control) by means of immunohistochemistry. The tryptase(+) cell numbers were decreased in OSCC (P=0.0003) and leukoplakia (P=0.03) compared with control. Similar numbers of tryptase(+) cells were observed in leukoplakia and OSCC (P=0.31). The density of c-kit(+) MCs was also significantly lower in OSCC and leukoplakia in relation to control resulting in a reduced c-kit(+)/tryptase(+) relationship in OSCC (19%) in comparison with leukoplakia (59%) and control (63%). No correlation was observed between MC populations with clinical and microscopic characteristics of OSCC. Our findings suggest that the decrease in MC numbers in pre-malignant and malignant oral lesions may be related to the migration failure of these cells, possibly reflecting an important modification in the microenvironment during tumor initiation and progression.

Objective To evaluate the presence of cytolytic T lymphocytes (CD8+), memory T cells (CD45RO+), helper T lymphocytes (CD4+), and mast cells in pulps from healthy and carious human teeth. Study design The teeth were separated into groups: I = unerupted; II = partially erupted, without caries; III = erupted, without caries; IV = erupted with shallow dentine caries; and V = teeth with pulp polyps. The immunoperoxidase staining procedure was used to detect CD8, CD45RO, CD4, and tryptase (mast cell marker) antigens. The number of each cell type was obtained by counting the number of cells per mm2. Results Mast cells were only present in pulp polyps. Pulps from carious teeth contained more CD4+ and CD8+cells than from noncarious teeth. There was a significant decrease in the number of lymphocytes in pulp polyps in comparison to the other groups. Conclusions Mast cells probably do not contribute to the early vascular or specific immune responses in the initial dental pulp pathosis, although they may be involved in a chronic phase of pulp inflammation such as pulp polyps. On the other hand, CD4+ and CD8+T cells participate mainly in initial phenomena of the immune response to incipient caries and seem not to substantially contribute to the response in pulp polyps.

Papillary cystadenoma is a rare, benign salivary gland tumor which is well-circumscribed, containing cystic cavities with intraluminal papillary projections. Only 19 cases arising within minor salivary glands (MnSG) from the oral cavity sites have been reported in the English literature (PubMed 1958–2014). We report 11 new cases of MnSG papillary cystadenomas in conjunction with a review of the literature. Demographic information, clinical and histologic features, treatment and prognosis are compiled and discussed for all 30 cases reported in the English literature.

Background: Periapical lesions are thought to be the result of a local inflammatory response mediated by inflammatory cell infiltration and production of inflammatory mediators. Although chemokines are strongly implicated in the migration and activation of leukocytes in different inflammatory diseases and experimental models, little is known regarding the expression of chemokines and their receptors in human apical periodontitis. Objective and methods: The objective of this study was to determine the expression of chemokines and their receptors by real-time polymerase chain reaction in samples obtained from healthy gingiva, periapical granulomas, and inflammatory periradicular cysts. The inflammatory infiltrate was characterized by immunohistochemistry. Results: Comparing cysts and granulomas, an increase in CD4+ and CD8+ cells was observed in granulomas, despite the similar numbers of CD45RO-positive cells detected in both lesions. The analysis of mRNA expression revealed increased levels of CCR1, CCR2, CCR3, CCR5, CXCR1, and CXCR3 in both types of lesion compared with controls. Cysts exhibited a higher expression of CCR3, CCR5, CXCR1, and CXCR3 compared to granulomas. A significantly higher expression of RANTES, IP-10, and MCP-1 was detected in cysts compared with controls or granulomas. The expression of interleukin-8, MIP-1α, and MIP-1β was not different in the three experimental groups. Conclusions: The increase in Th1 type (CCR1, CCR5, and CXCR3) and Th2 type (CCR2 and CCR3) receptors in both periapical lesions suggests the concomitant occurrence of Th1 and Th2 responses. Furthermore, the prevalent expression of the receptors CCR3, CCR5, CXCR1, and CXCR3 and of the chemokines RANTES, IP-10, and MCP-1 in cysts may point to a role in the progression of granulomas to cysts.

To analyse age- and gender-related microscopic changes in sublingual glands obtained from human cadavers.One hundred eighty six human sublingual glands were obtained from 93 autopsies. Approximately five individuals of each gender per decade of life were allocated to three age groups: group I (0-30 years, n=26); group II (31-60 years, n=32) and group III (61-90 years, n=35). The specimens were fixed in 10% formalin and submitted to routine histological processing, and sections were stained with hematoxylin and eosin.Significant differences with increasing age were observed for the following microscopic aspects: acinar atrophy (r=0.26, p=0.0115); replacement of parenchyma by fibrous tissue (r=0.79, p0.0001) and/or adipose tissue (r=0.63, p0.0001); oncocytosis (r=0.61, p0.0001); duct-like structures (chi(2)=14.68, p=0.0006) and congested blood vessels (chi(2)=7.18, p=0.0276). The mononuclear infiltrate changed from focal to diffuse with age (H=8.47, p=0.0144). No significant differences were observed between genders.The aging process starts with acinar atrophy, followed by the presence of duct-like structures and ends with the replacement of the parenchyma by fibrous and/or adipose tissue. The mononuclear infiltrate changes from focal to diffuse. No difference in the aging of the sublingual glands is observed between men and women.

OBJECTIVE: The aim of this study was to characterize the effects of dentin extracts on cytokine, chemokine and nitric oxide (NO) production by primary rat bone cells. STUDY DESIGN: Osteoblastic bone marrow cultures were exposed to particulate (D-part), non-particulate (Dn-part) and demineralized dentin extracts and evaluated for proliferative activity, cell morphology, alkaline phosphatase activity and bone-like nodule formation. Cytokine production was assessed by enzyme-linked immunosorbent assay and NO release by the Griess method. RESULTS: The dentin extracts did not affect osteoblast numbering. Conversely, they up regulated in a dosedependent manner the production by the osteoblasts of the pro-inflammatory interleukin-1b (IL-1b), tumor necrosis factor-a, IL-6, cytokine-induced neutrophil chemoattractant-1, and of the anti-inflammatory cytokine, IL-10. The NO production was stimulated only by D-n-part. CONCLUSION: These results demonstrate that dentin induces the production of inflammatory cytokines by osteoblasts and suggest that pro-resorptive pathways might be stimulated when dentin molecules come into contact with bone cells during pathological processes associated with dentin and bone matrix dissolution. Oral Diseases (2004) 10, 258–264

Dentin is a reservoir of several potentially active molecules, and dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) are the two major non-collagenous proteins. It has been established that dentin molecules are released as a consequence of osteoclast action during the resorption process. Along with osteoclasts, inflammatory cells seem to play an important role at sites of root resorption. Although the role of dentin molecules in dentinogenesis is well known, their role in pathological processes associated with dentin matrix dissolution is unclear. Recent studies have suggested that dentin components may function as chemotactic and activator signals for inflammatory cells at these sites. Herein we present evidence that demineralized dentin crude extract, DSP, and DPP induced doseand time-dependent neutrophil migration into the peritoneal cavity of mice and that this activity was inhibited by dexamethasone, but not by indomethacin or MK886. The blockade of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) receptors inhibited neutrophil accumulation. The neutrophil migration was also diminished in the absence of the chemokines cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein-2 (MIP-2), but not in the absence of macrophage inflammatory protein-1alpha (MIP-1alpha). These results demonstrate that dentin induces neutrophil migration via the synthesis of IL-1beta, TNF-alpha, and chemokines and they suggest that dentin matrix proteins may have an active role in inflammatory cell recruitment during pathological processes associated with dentin and bone matrix dissolution.

Dentin contains numerous polypeptides and signaling molecules sequestered in a mineralized matrix. The exposure and release of these molecules occur as a consequence of injury to the pulp and periodontal ligament, which may result from luxation, orthodontic movement or infections of tooth and periodontal structures. When released at these sites, dentin constituents have the potential to act on different surrounding cells, including periodontal cells, osteoblasts, osteoclasts and inflammatory cells, and to affect the course of dental disease. Experimental studies have highlighted the interactions between dentin and cells from tooth and periodontal tissues and reveal dentin to be a cell adhesive, signaling and migratory stimulus for various mesenchymal and inflammatory cells. These results support the hypothesis that dentin molecules might function as regulatory signals for the healing and resorption of dental and periodontal tissues. Data from recent and classical investigations are summarized, many open questions are discussed, and current hypotheses concerning the mechanisms of tooth resorption and periodontal healing are outlined. Many questions regarding the importance of dentin as a source of multifunctional molecules remain unanswered and provide important directions for future studies.

Cells other than macrophages and lymphocytes have recently been shown capable of producing cytokines and mediators. Among these are mast cells, a cell population now recognized for its immunoregulatory properties. Little is known about the complex interactions between cells, cytokines, and other inflammatory elements in periapical lesions. The objective of this investigation was to determine the immunohistochemical pattern of expression of mast cells tryptase in periapical lesions based on study of 20 apical granulomas and 20 periapical cysts. Microscopic analysis revealed mast cells to be present in greater numbers in periapical cysts than in apical granulomas, and in cysts were more numerous in regions of active inflammation. Mast cells tended to be more common in the peripheral regions of both periapical lesions, and were often found in close proximity to lymphocytes. These findings lead us to propose a functional relationship between these two cell populations that may facilitate elicitation of an immune response contributory to the pathogenesis of periapical lesions.

The activation of inflammatory cells and consequent release of mediators play an important role in the resorption of mineralized tissues. In the present study, we examined the ability of dentin extracts to induce inflammatory cell recruitment and activation. We showed here that dentin extracts triggered an intense cell migration and progressive cell maturation, in a time- and dose-dependent manner. Expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and hydrogen peroxide (H2O2) was also up-regulated by dentin extracts. These results show that inflammatory events can be elicited in response to dentin, which may suggest a possible involvement of dentin molecules in the inflammatory events, coupled with their release at the root resorption sites.

A distinctive form of paradental cyst can occur on the buccal and apical aspects of erupted mandibular molars. This cyst has peculiar clinical and radiographic features, although the microscopic findings are the same as those of odontogenic inflammatory cysts. Diagnostic and therapeutic problems can occur when this lesion is misinterpreted as a radicular cyst. The purpose of this paper is to present an additional case of a paradental cyst in the buccal and mesial aspects of a mandibular second molar involving the apical area of a mandibular first molar. The difficulty of diagnosis, treatment, and controversies regarding terminology are also discussed.

Pilomatricomas are relatively rare tumors of ectodermal origin from the outer root sheath cell of the hair follicle. They are usually asymptomatic, solitary, firm or hard, freely mobile, dermal or subcutaneous nodules. The purpose of this article is to present a case that illustrates the diagnostic difficulty encountered by oral surgeons and pathologists and to review the literature regarding pilomatricomas of the auricular region. Pilomatricomas são tumores relativamente raros de origem ectodérmica a partir das células da bainha externa do folículo piloso. Estes se apresentam geralmente como nódulos dérmicos ou subcutâneos, usualmente assintomáticos, solitários, firmes ou duros e extremamente móveis. O objetivo deste artigo é apresentar um caso que ilustra a dificuldade de diagnóstico encontrada pelos cirurgiões e patologistas bucais e apresentar uma revisão da literatura relativa aos pilomatricomas da região auricular.

The expression of the inducible nitric oxide synthase enzyme (iNOS) is a response to an inflammatory stimulus and produces a large amount of nitric oxide (NO), which may act as a cytotoxic molecule against the invading microorganism and may be related to both harmful and beneficial effects to tissues. OBJECTIVE AND MATERIAL AND METHODS: Inorder to further characterize the presence of NO in human periodontal disease, we undertook a quantitative study of iNOS positive cells in samples of clinically healthy gingival tissues, plaque-induced gingivitis and localized chronic periodontitis using immunohistochemistry. RESULTS: A significant increase in the number of iNOS+ cells mm−2 was found in the samples of the gingivitis and periodontitis compared with those of the control. In all groups most of the polymorphonuclear cells showed intense immunoreactivity for iNOS independent of the disease stage, and the percentage of iNOS+ polymorphonuclear cells increased significantly in periodontal disease when compared with the control. CONCLUSION: Our results indicate that iNOS increases in the presence of periodontal disease. In addition, our findings suggest that polymorphonuclear cells present anadditional activation pathway in periodontal disease, expressing significant iNOS and probably representing an important source of NO in human periodontal disease that has not been previously reported.

Candida albicans is known to produce secreted aspartyl proteinases (SAPs) to aid adhesion, invasion, and host tissue destruction. SAPs may contribute to denture stomatitis (DS) pathogenesis. The aim of this study was to develop an in vivo experimental model for Candida-associated DS that allows the analysis of SAP2, SAP5, and SAP9 expression by C. albicans from biofilm induced on the denture surface.Thirty-five male Wistar rats were divided into three groups: control, denture, and denture/Candida group. The last two groups remained with dentures for 2, 4, and 6 days, with or without induced biofilm. SAP expression was concomitant with leukocyte counts as well as clinical and histological changes shown by animal palate.The signs observed at 4 days in the denture/Candida group were clinically closer to the Candida-associated DS, showing a significant increase of neutrophils and decrease of lymphocytes in peripheral blood, presence of inflammation signs on the palate similar to DS Newton type I, and fungal invasion in the epithelial layer. Accordingly, the denture/Candida group at 4 days presented the highest relative expression of all SAPs studied.The results showed a coincidence between SAP expression and clinical, microscopic, and blood data. Finally, the molecular findings were consistent with the virulence capacities of C. albicans from biofilm formed on the denture resin, which possibly allowed epithelial invasion by the fungus.

Dendritic cells (DCs) are the most potent antigen-presenting cells, playing a key role in induction of both innate and adaptive immunity. Immunosenescence refers to age-associated changes in the immune system, which may be associated with susceptibility to infections and their clinical complications. The precise effects of aging on DCs in immunity to infections are not well understood. Among the common pathogenic microorganisms, the fungus Candida albicans is an important pathogen for the development of invasive infections, especially in immunocompromised individuals, as well as during aging. To make a comparative in vitro evaluation of the immunomodulatory function of DCs challenged with C. albicans, by phagocytosis of the fungal cells, and determine the involvement of TLR2 and TLR4 receptors. For this purpose, DCs were generated with the use of peripheral blood monocytes from healthy young and aged subjects. The phagocytosis of C. albicans is developed by DCs in TLR2- and TLR4-dependent way. This mechanism is not affected by aging. Given the important role of the DCs in responses against the fungus, it is evident that if changes in phagocytosis occurred with aging, impairment in the elderly could develop. However, the evidence that phagocytosis of this fungus by DCs is not impaired with aging, brings us to the question of which are the mechanisms truly associated with the prevalence of certain diseases in the elderly.