Neurofibromin expression by normal salivary glands.

INTRODUCTION: Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated. AIM: To investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1. MATERIAL AND METHOD: Ten samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method. RESULTS: Neurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34). CONCLUSION: Neurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.

Increased extracellular matrix deposition during chondrogenic differentiation of dental pulp stem cells from individuals with neurofibromatosis type 1: an in vitro 2D and 3D study.

BACKGROUND: Neurofibromatosis 1 (NF1) presents a wide range of clinical manifestations, including bone alterations. Studies that seek to understand cellular and molecular mechanisms underlying NF1 orthopedic problems are of great importance to better understand the pathogenesis and the development of new therapies. Dental pulp stem cells (DPSCs) are being used as an in vitro model for several diseases and appear as a suitable model for NF1. The aim of this study was to evaluate in vitro chondrogenic differentiation of DPSCs from individuals with NF1 using two-dimensional (2D) and three-dimensional (3D) cultures. RESULTS: To fulfill the criteria of the International Society for Cellular Therapy, DPSCs were characterized by surface antigen expression and by their multipotentiality, being induced to differentiate towards adipogenic, osteogenic, and chondrogenic lineages in 2D cultures. Both DPSCs from individuals with NF1 (NF1 DPSCs) and control cultures were positive for CD90, CD105, CD146 and negative for CD13, CD14, CD45 and CD271, and successfully differentiated after the protocols. Chondrogenic differentiation was evaluated in 2D and in 3D (pellet) cultures, which were further evaluated by optical microscopy and transmission electron microscopy (TEM). 2D cultures showed greater extracellular matrix deposition in NF1 DPSCs comparing with controls during chondrogenic differentiation. In semithin sections, control pellets hadhomogenous-sized intra and extracelullar matrix vesicles, whereas NF1 cultures had matrix vesicles of different sizes. TEM analysis showed higher amount of collagen fibers in NF1 cultures compared with control cultures. CONCLUSION: NF1 DPSCs presented increased extracellular matrix deposition during chondrogenic differentiation, which could be related to skeletal changes in individuals with NF1.

Craniomaxillofacial morphology alterations in children, adolescents and adults with neurofibromatosis 1: A cone beam computed tomography analysis of a Brazilian sample

Background: Oral manifestations are common in neurofibromatosis 1 (NF1), and include jaws and teeth alterations. Our aim was to investigate the craniomaxillofacial morphology of Brazilian children, adolescents and adults with NF1 using cone beam computed tomography. Material and Methods: This study was conducted with 36 Brazilian individuals with NF1 with ages ranging from 4 to 75. The participants were submitted to anamnesis, extra and intraoral exam and cephalometric analysis using cone beam computed tomography. Height of the NF1 individuals was compared to the length of jaws and skull base. The results of the cephalometric measurements of the NF1 group were compared with a control group paired by age, gender and skin color. Results: Individuals with NF1 had lower maxillary length (p<0.0001), lower mandibular length (p<0.0001), lower skull base length (p<0.0001. In children and adolescents, the mandible was more posteriorly positioned (p=0.01), when compared with the control group. There was no association between jaws and skull base length with the height of the individuals with NF1. Conclusions: Brazilian children, adolescents and adults with NF1 have short mandible, maxilla and skull base. Moreover, children and adolescents present mandibular retrusion (AU)

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High prevalence of hyposalivation in individuals with neurofibromatosis 1: a case-control study.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and has widely variable expressivity. Oral manifestations are common, but there are no studies that investigated functional alterations in salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1 individuals, comparing to a control group, and to investigate the possible causes and some consequences of salivary gland alteration. METHODS: This is a case-control study that evaluated the salivary flow rate of NF1 individuals (n = 49) and compared to an age and sex-matched control group. We have also investigated the possible causes and consequences of hyposalivation in NF1 individuals through anamnesis, a specific questionnaire, physical examination, tongue coating evaluation and cytopathological exam to assess the prevalence of oral candidiasis. RESULTS: Hyposalivation at rest was present in 59% (29/49) of NF1 individuals in contrast to 22% (11/49) in the control group, being statistically significant (P <0.0001; Wilcoxon rank-sum test). The analysis of the adjusted residual showed that the prevalence of hyposalivation in NF1 individuals (46.9%) was 4-fold higher than in controls (10.2%). None of the possible causes of hyposalivation (medications, low liquid intake, caffeinated or stimulant drink use, mouth breathers, alcohol, smoke and plexiform neurofibroma close to or involving major salivary glands areas) had important impact on the salivary flow rate in NF1 individuals. CONCLUSIONS: Hyposalivation may be a consequence of NF1, as occurs in other genetic diseases. More studies are necessary to understand if there is and what is the relationship between NF1 and hyposalivation.

Aspectos anatômicos e patológicos da neuralgia do trigêmeo: uma revisão da literatura para estudantes e profissionais da saúde / Anatomic and pathologic aspects of the trigeminal neuralgia: a literature review for students and health professionals

O nervo trigêmeo é considerado um nervo misto, com fibras aferentes (sensitivas) e eferentes(motoras). As fibras sensitivas são responsáveis por um quadro neurológico, conhecido como neuralgia do trigêmeo. O objetivo deste trabalho é relacionar aspectos anatômicos do nervo trigêmeo com os sinais e sintomas da neuralgia, esclarecendo sua incidência, etiologia e terapêutica, além de relatar casos incomuns dessa doença. Foi realizada uma ampla revisão da literatura e identificadas as características da neuralgia do nervo trigêmeo, os casos mais incidentes, levando em consideração idade e sexo do paciente, além da sua causa e tratamento indicado. A neuralgia trigeminal é caracterizada por dores intensas e repentinas, semelhantes a choques elétricos, sendo no início confinadas a uma divisão, embora ela possa se irradiar sobre os ramos das outras divisões do nervo trigêmeo. Essas dores são desencadeadas por leves toques em pontos específicos na pele da face. Geralmente é unilateral e mais freqüente nas mulheres, a partir da quarta década de vida. A neuralgia acomete com mais freqüência o nervo mandibular, em seguida o nervo maxilar e menos comum no ramo oftálmico. Uma condição muito rara é o acometimento simultâneo dos três ramos do nervo trigêmeo. A causa, geralmentedesconhecida, também pode estar relacionada com variações anatômicas, tanto do próprio nervo quanto de estruturas adjacentes, ou neoplasias. O tratamento é complexo devido à dificuldade de identificação dos mecanismos desencadeantes. Em conclusão, o conhecimento da anatomia do nervo trigêmeo, associado à anamnese do paciente, sinais e sintomas da doença, é indispensável para o seu diagnóstico diferencial e terapêutica adequada.

The trigeminal nerve has afferent (sensory) and efferent (motor) fibers, however the sensory ones are responsible for a disorder called trigeminal neuralgia. The purposed of this study is to correlate the anatomical aspects of the trigeminal nerve with the neuralgia’s signs and symptoms, explaining its incidence, etiology and therapeutic management, besides relating unusual cases of this disease. It was performed a wide revision of the literature and it was identified the characteristics of the trigeminal neuralgia, regarding age and sex of the patient, besides its cause andappropriate treatment. The trigeminal neuralgia is characterized by hard and sudden pains, similar to electric discharges, being in the beginning confined to a branch, although it can irradiate to along the other divisions of the trigeminal nerve. These pains are begun by a quick touch in specific point in the skin of face. Generally is unilateral and more prevalent inthe woman, starting from the fourth decade of life. The neuralgia attacks more frequently the mandibular nerve, soon afterwards the maxillary and less common the ophthalmic branch. A very rare condition is the simultaneous attack of the three trigeminal nerve branches. The cause is always unknown, however it can be related for anatomical variations, as much the own nerve as the adjacent structures, even neoplasias. Treatment is complex due to the difficulty of identification of the carrying mechanisms. In conclusion, the knowledge of the trigeminal nerve anatomy associated to the patient’sanamnesis, signs and symptoms of the pathology, is indispensable to its differential diagnosis and appropriate therapeutic management.