RESUMEN
Considering the side effects in the oral cavity and dental structures of radiotherapy (RDT) for head and neck cancer, this study aimed to evaluate the effects of RDT on the root dentin concerning the obliteration of dentinal tubules, the inorganic composition of intra-radicular dentin, and the integrity of collagen fibers. Thirty human canines were selected from a biobank and randomly divided into two groups (n=15). The samples were sectioned buccolingually, and a hemisection was used for structural analysis by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Low-vacuum SEM images were obtained at 2000-x magnification to observe the obliteration of the dentinal tubules. Moreover, compositional evaluation was performed using EDS. After RDT, the SEM and EDS analyses were repeated using the same methodology. RDT was applied fractionally at 2 Gy per day, 5 days per week, for 7 weeks, resulting in a total dose of 70 Gy. The collagen integrity of the irradiated and non-irradiated samples was analyzed using Masson's trichrome and picrosirius red staining polarization microscopy. Samples subjected to RDT exhibited dentinal tubule obliteration (p < 0.001); low integrity of type I and III collagen fibers (p < 0.05); compositional reduction of calcium (p = 0.012), phosphorus (p = 0.001), and magnesium (p < 0.001); an increased Ca/P ratio (p < 0.001). RDT affects the structure of dentinal tubules, the inorganic composition of intra-radicular dentin, and the collagen fiber integrity in the root dentin, which may interfere with the effectiveness and durability of dental procedures.
Asunto(s)
Calcio , Dentina , Humanos , Colágeno , Dentina/química , Microscopía Electrónica de Rastreo , Fósforo/análisis , Fósforo/farmacología , Raíz del DienteRESUMEN
Abstract Considering the side effects in the oral cavity and dental structures of radiotherapy (RDT) for head and neck cancer, this study aimed to evaluate the effects of RDT on the root dentin concerning the obliteration of dentinal tubules, the inorganic composition of intra-radicular dentin, and the integrity of collagen fibers. Thirty human canines were selected from a biobank and randomly divided into two groups (n=15). The samples were sectioned buccolingually, and a hemisection was used for structural analysis by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Low-vacuum SEM images were obtained at 2000-x magnification to observe the obliteration of the dentinal tubules. Moreover, compositional evaluation was performed using EDS. After RDT, the SEM and EDS analyses were repeated using the same methodology. RDT was applied fractionally at 2 Gy per day, 5 days per week, for 7 weeks, resulting in a total dose of 70 Gy. The collagen integrity of the irradiated and non-irradiated samples was analyzed using Masson's trichrome and picrosirius red staining polarization microscopy. Samples subjected to RDT exhibited dentinal tubule obliteration (p < 0.001); low integrity of type I and III collagen fibers (p < 0.05); compositional reduction of calcium (p = 0.012), phosphorus (p = 0.001), and magnesium (p < 0.001); an increased Ca/P ratio (p < 0.001). RDT affects the structure of dentinal tubules, the inorganic composition of intra-radicular dentin, and the collagen fiber integrity in the root dentin, which may interfere with the effectiveness and durability of dental procedures.
Resumo Considerando os efeitos colaterais na cavidade oral e estruturas dentárias da radioterapia (RDT) para o câncer de cabeça e pescoço, este estudo teve como objetivo avaliar os efeitos da RDT sobre a dentina radicular quanto à obliteração dos túbulos dentinários, a composição inorgânica da dentina intra-radicular e a integridade das fibras colágenas. Trinta caninos humanos foram selecionados de um biobanco e divididos aleatoriamente em dois grupos (n=15). As amostras foram seccionadas no sentido vestíbulo-lingual, e uma hemissecção foi utilizada para análise estrutural por microscopia eletrônica de varredura (MEV) e espectrômetro de raios X de dispersão de energia (EDS). Imagens de MEV de baixo vácuo foram obtidas com aumento de 2500x para observar a obliteração dos túbulos dentinários. Além disso, a avaliação composicional foi realizada usando EDS. Após a RDT, as análises em MEV e EDS foram repetidas usando a mesma metodologia. A RDT foi aplicada fracionada a 2 Gy por dia, 5 dias por semana, durante 7 semanas, resultando em uma dose total de 70 Gy. A integridade do colágeno das amostras irradiadas e não irradiadas foi analisada usando microscopia de polarização de coloração com tricrômio de Masson e picrosirius red. As amostras submetidas a RDT apresentaram obliteração dos túbulos dentinários (p < 0,001); baixa integridade das fibras colágenas tipo I e III (p < 0,05); redução composicional de cálcio (p = 0,012), fósforo (p = 0,001) e magnésio (p < 0,001); e uma relação Ca/P aumentada (p < 0,001). A RDT afeta a estrutura dos túbulos dentinários, a composição inorgânica da dentina intra-radicular e a integridade das fibras colágenas na dentina radicular, o que pode interferir na eficácia e durabilidade dos procedimentos odontológicos.
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We propose the use of a tool recently introduced by Gayer (2010), known as the "economic climate tracer", to analyze and monitor the cyclical evolution of tourism source markets to Portugal. Considering the period 1987-2015, we evaluate how tourism to Portugal has been affected by economic cycles. This tool is useful as it clearly illustrates the evolutionary patterns of different markets, and allows us to identify close relationships with economic fluctuations. We found that German tourism plays a leading role, since its movements are followed with delays by tourism flows from other countries, and exhibits higher resilience to shocks. Also, domestic and Spanish tourism have both displayed less irregular behaviors than tourism from other source markets. On the contrary, tourism from the Netherlands and the UK, have displayed irregular patterns, which demonstrates the urgency to diversify tourism source markets to reduce the country's vulnerability to external shocks and economic cycles.
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Myc protooncogenes play important roles in the regulation of cell proliferation, growth, differentiation and survival during development. In various developing organs, c-myc has been shown to control the expression of cell cycle regulators and its misregulated expression is detected in many human tumors. Here, we show that c-myc gene (Myc) is highly expressed in developing mouse lens. Targeted deletion of c-myc gene from head surface ectoderm dramatically impaired ocular organogenesis, resulting in severe microphtalmia, defective anterior segment development, formation of a lens stalk and/or aphakia. In particular, lenses lacking c-myc presented thinner epithelial cell layer and growth impairment that was detectable soon after its inactivation. Defective development of c-myc-null lens was not caused by increased cell death of lens progenitor cells. Instead, c-myc loss reduced cell proliferation, what was associated with an ectopic expression of Prox1 and p27(Kip1) proteins within epithelial cells. Interestingly, a sharp decrease in the expression of the forkhead box transcription factor Foxe3 was also observed following c-myc inactivation. These data represent the first description of the physiological roles played by a Myc family member in mouse lens development. Our findings support the conclusion that c-myc regulates the proliferation of lens epithelial cells in vivo and may, directly or indirectly, modulate the expression of classical cell cycle regulators in developing mouse lens.
Asunto(s)
Cristalino/citología , Cristalino/embriología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Animales , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Cristalinas/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Ectodermo/citología , Ectodermo/crecimiento & desarrollo , Células Epiteliales/citología , Factores de Transcripción Forkhead/metabolismo , Regulación del Desarrollo de la Expresión Génica , Silenciador del Gen , Proteínas de Homeodominio/metabolismo , Ratones , Fenotipo , Proteínas Proto-Oncogénicas c-myc/deficiencia , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Nibrin (NBN or NBS1) and ATM are key factors for DNA Double Strand Break (DSB) signaling and repair. Mutations in NBN or ATM result in Nijmegen Breakage Syndrome and Ataxia telangiectasia. These syndromes share common features such as radiosensitivity, neurological developmental defects and cancer predisposition. However, the functional synergy of Nbn and Atm in different tissues and developmental stages is not yet understood. Here, we show in vivo consequences of conditional inactivation of both genes in neural stem/progenitor cells using Nestin-Cre mice. Genetic inactivation of Atm in the central nervous system of Nbn-deficient mice led to reduced life span and increased DSBs, resulting in increased apoptosis during neural development. Surprisingly, the increase of DSBs and apoptosis was found only in few tissues including cerebellum, ganglionic eminences and lens. In sharp contrast, we showed that apoptosis associated with Nbn deletion was prevented by simultaneous inactivation of Atm in developing retina. Therefore, we propose that Nbn and Atm collaborate to prevent DSB accumulation and apoptosis during development in a tissue- and developmental stage-specific manner.