AIMS: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. MATERIALS & METHODS: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition, tyrosine phosphorylation events were investigated. RESULTS & CONCLUSION: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic.

Os doentes transplantados renais têm alto risco para desenvolver queratoses actínicas e câncer de pele. Para verificar o efeito quimioprofilático da acitretina estudamos a evolução de 13 doentes transplantados renais com queratoses actínicas múltiplas e história de carcinomas cutâneos submetidos a tratamento por 12 meses (20mg/dia). Fez-se a avaliação clínica e laboratorial regularmente em todo o período do estudo. Realizou-se exame histopatológico, demonstração imuno-histoquímica de sub-populações de linfócitos T (CD4, CD8), células natural killer e células de Langerhans, sua quantificação e comparação em biopsias de pele, sem lesão, de área exposta e protegida do sol antes, após seis e 12 meses de tratamento. Observou-se melhora das lesões cutâneas e ausência de aparecimento de novos tumores em 12 dos 13 pacientes. Não ocorreram alterações laboratoriais relacionadas a função renal, hepatotoxicicidade e hiperlipidemia. Não houve diferenças significativas histopatológicas e da população de linfócitos T e células natural killer da pele exposta e protegida do sol com o tratamento. Verificou-se aumento numérico de células de Langerhans epidérmicas aos 12 meses quando comparado aos da pele antes e após seis meses de tratamento (p = 0,002 e p = 0,003). Em nossa casuística o uso de acitretina em doses baixas foi útil para melhorar o aspecto cutâneo e prevenir lesões cutâneas pré-cancerosas e carcinomas. O aumento das células de Langerhans epidérmicas estaria relacionado ao efeito imunomodular da acitretina. / Renal transplant recipients have an increased incidence of actinic keratosis and skin cancer. In order to examine the chemoprophylatic effects of low-dose acitretin on skin cancer development we submitted 13 renal transplanted patients to acitretin therapy (20 mg/day) for 12 month. The patients were assessed at monthly intervals during the first 6 months and every two months until the 12th month for new skin lesions and for acitretin toxicity. Normal skin biopsies of sun exposed and sun protected area were taken for histopathological exam and submitted to immunohistochemistry technique to demonstrate CD4+ and CD8+ T lymphocytes, natural killer cells and Langerhans cells wich were counted and compared in the beginning, after 6th month and 12th month of the treatment. There was an improvement of actinic keratosis and all patients but one did not develop new skin cancer. Side-effects were well-tolerated and no significant biochemical effects were observed. Although there were no differences in the microscopic aspects of the skin and in the number of CD4+ and CD8+ T lymphocytes and natural killer cells, there was a significant increase in the number of epidermal Langerhans cells after 12 months of acitretin therapy. The data obtained permit us to conclude that low dose acitretin therapy is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients. The increase in epidermal Langerhans cells observed may be an expression of the immunomodulatory effect of acitretin.

Indiana University-Purdue University Indianapolis (IUPUI) / Endodontic regeneration (ERP) has been successfully used in the treatment of traumatized immature teeth. The procedure has three essential steps: disinfecting the root canal (i.e. triple antibiotic paste (TAP) or double antibiotic paste (DAP)), provoking bleeding inside the canal to form a scaffold upon which pulp stem cells will be deposited and continue root growth, and creating a good coronal seal. Previous research has reported that antibiotic pastes (TAP and DAP) are cytotoxic to stem cells in the concentrations commonly used in endodontic regeneration (1000 mg/mL). To decrease the adverse effects on stem cells and increase the rate of success of the regeneration, defining appropriate antibiotic concentrations for ERP is critical. In this project, five in-vitro experiments were conducted to determine the breakpoint dilutions of both TAP and DAP medicaments, and to prepare a suitable novel pastes containing diluted TAP or DAP medicaments for ERP. In the first experiment, we compared the antibacterial effect of TAP, and DAP against early biofilm formation of Enterococcus faecalis (E. faecalis) and Porphyromonas gingivalis bacteria. In the second study, we investigated the antibacterial effect of various dilutions of TAP and DAP antibiotic medicaments against established E. faecalis biofilm. In the third experiment, we investigated longitudinally the residual antibacterial activity of human radicular dentin treated with 1000, 1 or 0.5 mg/ml of TAP and DAP. In the fourth study, we investigated the cytotoxic effect of various dilutions of TAP and DAP antibiotic medicaments on the survival of human dental pulp stem cells (DPSC). And in the fifth experiment, we investigated the antibacterial and cytotoxic effect of novel intracanal medicaments consisting of methylcellulose (MC) and/or propylene glycol (PG) mixed with 1mg/ml of TAP or DAP. 1 mg/ml of DAP or TAP medicaments had a significant antibacterial effect against early bacterial biofilm formation, and established bacterial biofilm. Furthermore, 1 mg/ml had a residual antibacterial activity comparable to 1000 mg/ml. The novel intracanal medicaments had comparable antibacterial effect to currently used medicaments (1000 mg/ml). Additionally, the novel intracanal medicaments significantly enhanced DPSC metabolic activity, compared to currently used medicaments in endodontic regeneration procedures.

Mast cells play pivotal roles in immunoglobulin (Ig) E-mediated airway inflammation, expressing interleukin (IL)-13 and monocyte chemoattractant protein-1 (MCP-1), which in turn regulate IgE synthesis and/or inflammatory cell recruitment. The molecular effects of IL-1beta on cytokine expression by human mast cells (HMC) have not been studied well. In this report, we provide evidence that human umbilical cord blood-derived mast cells (CBDMC) and HMC-1 cells express the type 1 receptor for IL-1. We also demonstrate that IL-1beta and tumor necrosis factor-alpha are able to induce, individually or additively, dose-dependent expression of IL-13 and MCP-1 in these cells. The induction of IL-13 and MCP-1 gene expression by IL-1beta was accompanied by the activation of IL-1 receptor-associated kinase and translocation of the transcription factor, nuclear factor (NF) kappaB into the nucleus. Accordingly, Bay-11 7082, an inhibitor of NF-kappaB activation, inhibited IL-1beta-induced IL-13 and MCP-1 expression. IL-1beta also induced IL-13 promoter activity while enhancing the stability of IL-13 messenger RNA transcripts. Dexamethasone, a glucocorticoid, inhibited IL-1beta-induced nuclear translocation of NF-kappaB and also the secretion of IL-13 from mast cells. Our data suggest that IL-1beta can serve as a pivotal costimulus of inflammatory cytokine synthesis in human mast cells, and this may be partly mediated by IL-1 receptor-binding and subsequent signaling via nuclear translocation of NF-kappaB. Because IL-1beta is a ubiquitously expressed cytokine, these findings have important implications for non-IgE-mediated signaling in airway mast cells as well as for innate immunity and airway inflammatory responses, such as observed in extrinsic and intrinsic asthma.