Falha na produção de óxido nítrico pelos macrófagos e diminuição de células T CD4+ na paracoccidioidomicose bucal: possíveis mecanismos que permitem a multiplicação fúngica local

Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO), a product of the inducible nitric oxide synthase enzyme (iNOS), as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP), we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm². Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN) cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues). Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.A paracoccidioidomicose é uma doença granulomatosa crônica que induz resposta inflamatória e imune específica. A participação do óxido nítrico (NO), produto da enzima óxido nítrico sintase induzível (iNOS), como uma importante molécula fungicida contra o fungo Paracoccidioides brasiliensis tem sido demonstrada. Com o objetivo de melhor caracterizar as lesões orais da paracoccidioidomicose (OP), propusemos estudo imunohistoquímico das células iNOS+ e das células CD45RO+, CD3+, CD8+, CD20+, CD68+ e mastócitos. As amostras foram distribuídas em grupos de acordo com o número de fungos viáveis por mm². Nossos resultados demonstraram leve imunomarcação para iNOS nas células gigantes multinucleadas (MNGC) e na maioria das células mononucleares (MN), e a proporção de células MN/MNGC iNOS+ na OP foi comparável a do grupo Controle (tecido bucal clinicamente saudável). Adicionalmente, nossa análise revelou similaridade no número de células CD4+ entre o Controle e o grupo de OP com elevado número de fungos. Estes achados sugerem que a baixa expressão de iNOS e a diminuição de células CD4+ na OP podem representar possíveis mecanismos que permitiram a multiplicação local do fungo e a manutenção das lesões bucais ativas

Oral cancer stem cells - properties and consequences

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

Phagocytosis and nitric oxide production by peritoneal adherent cells in response to Candida albicans in aging: a collaboration to elucidate the pathogenesis of denture stomatitis

Elderly denture wearers are commonly affected by Candida-associated denture stomatitis (DS), an inflammatory process of the oral mucosa strongly associated with Candida spp and other microorganisms, as well as local and systemic factors. The impaired immune response against pathogens is among the inherent host factors that have been also associated with the pathogenesis of DS. Mononuclear phagocytes respond to the pathogens through phagocytosis followed by the production of several substances inside the phagosomes, among them are the reactive nitrogen species (RNS). A failure in these mechanisms may contribute to the DS development. Objective The aim of this study was to investigate the influence of aging on the internalization and the production of nitric oxide (NO) by peritoneal adherent cells (PAC), in response to Candida albicans (C. albicans). Material and methods PAC obtained from young and aged mice were challenged with dead or viable C. albicans by using predetermined proportions (cells:yeast) for 30 and 120 minutes. Phagocytosis was analyzed by acridine orange dye, and NO production by the Griess reaction. Results C. albicans phagocytosis by PAC from aged mice was similar to that of young mice, although the cells from older mice cells present more internalized fungi compared with matched control. In addition, a tendency towards impaired NO production by peritoneal mononuclear phagocytes from aged mice was observed. Conclusions PAC from aged mice may capture and store many fungi, which in turn may mean that these cells are effectively unable to eliminate fungi, probably due to impaired NO production. Therefore, considering the important role of C. albicans overgrowth in the pathogenesis of DS and the aspects observed in this study, aging may favor the onset and severity of local candidosis such as DS and its systemic forms

Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence

Background: Aging is associated with complex and constant remodeling of the immune function, resulting in an increasing susceptibility to infection and others diseases. The infections caused by Gram-negative microorganisms, present in nursing homes and hospitals, constitute one of the most common infections in the elderly, and are mainly combated by innate immune cells. Although the functions of innate immunity seem more preserved during aging than of adaptive immune mechanisms, two systems operate in an integrated way in the body, so that injury in one part of the immune system inevitably affects the other as they are part of a defensive network. The aim of this study was to investigate the in vitro production of proinflammatory (TNF-α, IL-6, IL-1α, CXCL-8 and MCP-1) and antiinflammatory (TGF-α and IL-10) cytokines by monocytes, stimulated or not (basal) with lipopolysaccharide, from healthy young and elderly subjects. By means of PBMCs, we also studied if cytokine profile is altered in these different patient groups, in the presence of lymphocytes, under the same experimental conditions. Results: The monocytes from elderly presented higher basal production of TNF-α, MCP-1 and lower of TGF-α than young monocytes. PBMC showed similar cytokines production, irrespective age or stimulation presence. In the presence of lymphocytes, the spontaneous production of IL-10 was higher and of TGF-α was lower than monocytes, regardless of age. After LPS-stimulation, the presence of lymphocytes resulted in increased IL-6, IL-1α, MCP-1 and IL-10 and decreased CXCL-8 and TGF-α in comparison to pure culture of monocytes from young patients. With age, the same differences were observed, except for CXCL-8 and TGF-α which production was the same between monocytes and PBMC stimulated with LPS.Conclusion: These findings reinforce the systemic state of inflamm-aging frequently reported in elderly and considered a factor of susceptibility to numerous diseases. Still, the cytokine production from just monocytes of the elderly showed alterations, while in the lymphocyte presence not, suggesting an immunomodulator role of lymphocytes on monocytes. In addition, the differences between the production patterns by LPS-stimulated PBMC between young and elderly volunteers can be related with an imbalance in response against Gram-negative bacteria in throughout life

Pleomorphic adenoma with extensive squamous metaplasia and keratin cyst formations in minor salivary gland: a case report

Pleomorphic adenoma (PA), the most common salivary gland tumor, accounts for 54 to 65% of all salivary gland neoplasias and 80% of the benign salivary gland tumors. It most frequently affects the parotid gland, followed by the submandibular and the minor salivary glands. Microscopically, mucous, sebaceous, oncocytic and squamous metaplasia, sometimes with the formation of keratin pearls, may be present, but the latter rarely results in the formation of extensive keratin-flled cysts lined by squamous epithelium. Extensive squamous metaplasia can be mistaken for malignancy, including mucoepidermoid carcinoma and squamous cell carcinoma. Here, we present an unusual case of PA with extensive squamous metaplasia and keratin cyst formations in a minor salivary gland, and discuss its microscopic features, including the immunohistochemical characteristics, and differential diagnosis of this uncommon presentation

Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

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 (

Fcγ receptors on aging neutrophils

Objective: Neutrophils are key effector cells of the innate immune system. They recognize antigens through membrane receptors, which are expressed during their maturation and activation. Neutrophils express FcγRII (CD32), FcγRIII (CD16), and FcγRI (CD64) after being activated by different factors such as cytokines and bacterial products. These receptors are involved with phagocytosis of IgG-opsonized microbes and enhance defense mechanisms. Based on that, our study seeks to compare the expression of FcγRII, FcγRIII, FcγRI, and CD11b on neutrophils from elderly and young subjects and their expression after in vitro activation with cytokines and LPS. Methodology: Neutrophils were isolated from human peripheral blood and from mice bone marrow by density gradient. After isolation, FCγRs expression was immediately analyzed by flow cytometry or after in vitro stimulation. Results: In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed. Exposure to CXCL8 and LPS resulted in a higher percentage of FcγRIa+ neutrophils on elderly individuals’ samples but lower when compared with neutrophils from young donors. We observed that LPS caused an increase in FcγRIIa expression on aging human neutrophils. In contrast, FcγRIIIb expression in response to CXCL8 and LPS stimulation was not altered in the four groups. CD11b expression was lower in neutrophils from elderly individuals even in response to LPS and CXCL8. In mice, we observed differences only regarding CD11b expression, which was increased on aged neutrophils. LPS exposure caused an increase in all FcγRs. Conclusions: Our results suggest that, in humans, the overall pattern of FcγR expression and integrin CD11b are altered during aging and immunosenescence might contribute to age-related infection

The Importance of a Proper Selection Area to be Biopsied in Nodular Leukoplakia: a Case Report

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