Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis.

AimTo evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis.Materials & methodsMale albino Wistar rats were divided randomly into five groups of twenty-one rats each, and given the following treatments for 10 days: (1) no ligature + water, (2) ligature + water, (3) ligature + 50 mg/kg Met, (4) ligature + 100 mg/kg Met, and (5) ligature + 200 mg/kg Met. Water or Met was administered orally. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantitate linear and bone volume/tissue volume (BV/TV) volumetric bone loss. Histopathological characteristics were assessed through immunohistochemical staining for MMP-9, COX-2, the RANKL/RANK/OPG pathway, SOD-1, and GPx-1. Additionally, confocal microscopy was used to analyze osteocalcin fluorescence. UV-VIS analysis was used to examine the levels of malondialdehyde, glutathione, IL-1β and TNF-α from gingival tissues. Quantitative RT-PCR reaction was used to gene expression of AMPK, NF-κB (p65), and Hmgb1 from gingival tissues. Significance among groups were analysed using a one-way ANOVA. A p-value of p<0.05 indicated a significant difference.ResultsTreatment with 50 mg/kg Met significantly reduced concentrations of malondialdehyde, IL-1β, and TNF-α (p < 0.05). Additionally, weak staining was observed for COX-2, MMP-9, RANK, RANKL, SOD-1, and GPx-1 after 50 mg/kg Met. OPG and Osteocalcin showed strong staining in the same group. Radiographically, linear measurements showed a statistically significant reduction in bone loss after 50 mg/kg Met compared to the ligature and Met 200 mg/kg groups. The same pattern was observed volumetrically in BV/TV and decreased osteoclast number (p<0.05). RT-PCR showed increased AMPK expression and decreased expression of NF-κB (p65) and HMGB1 after 50 mg/kg Met.ConclusionsMetformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats

Gliclazide Prevents 5-FU-Induced Oral Mucositis by Reducing Oxidative Stress, Inflammation, and P-Selectin Adhesion Molecules

Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1β and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1–2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1–1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters

Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica

BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985 and 2007. RESULTS: There were still many unanswered questions regarding the pharmacology of ecstasy and the pathophysiology of its toxic effects. The fundamental mechanism of action is insufficient to explain all effects induced by the drug. The exact mechanism responsible for mediating the toxic effects of MDMA on 5-HT neurons remain to be elucidated. DISCUSSION: There is limited information in published literature about the underlying pharmacology and mechanism of action that could account for the neurotoxic and other phathophysiological effect of MDMA.CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase) é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável

Perceção docente da supervisão pedagógica

Dissertação apresentada para a obtenção do grau de Mestre em Ciências da Educação na área de Supervisão e Orientação PedagógicaNa escola de hoje, a supervisão pedagógica pode desempenhar um papel importante na construção de uma cultura de equipa docente, baseada na partilha de experiências e saberes, em que o envolvimento de cada indivíduo se torna essencial para a identidade coletiva do grupo. O presente trabalho pretendeu conhecer a perceção docente da supervisão pedagógica através de um estudo de caso numa escola onde a investigadora exerceu a profissão docente durante vários anos. A finalidade do mesmo consistiu em perceber a existência ou não de relação entre a realidade supervisiva atual e a que se pretenderia que existisse por parte dos docentes. Os dados foram recolhidos primeiramente através de entrevistas semiestruturadas e, posteriormente, por questionários elaborados com base naquelas. Para além da análise de conteúdo, procedeu-se também à análise documental baseada em autores reconhecidos da vasta bibliografia relativa ao tema em estudo. Os resultados obtidos permitiram-nos concluir que, efetivamente, existe um desfasamento entre perceções da realidade supervisiva e perceções do que seria desejável no desempenho dessa mesma função. Com base no presente estudo empírico, pudemos apurar que a supervisão pedagógica deve sofrer alterações na sua génese. Essas alterações deverão visar um trabalho de equipa não hierarquizado, em que são fundamentais os comportamentos colaborativos numa perspetiva dialógica de trabalho. O supervisor deverá ser alguém dotado de competências sociais e cognitivas que lhe permitam fomentar a cooperação, revelando um espírito de liderança e promovendo a consecução de objetivos comuns, o que permitirá o desenvolvimento da identidade profissional docente baseada num espírito que se deseja de equipa.In nowadays school, pedagogical supervision can play an important role in the construction of teachers’ team culture based on sharing out experience and knowledge in which the involvement of each individual becomes essential for the collective group identity. The present work intended to realize the teachers’ perception concerning the pedagogical supervision troughout a case study research performed at a school where the researcher taught for several years. Its goal consisted in being aware if there was a relation between nowadays pedagogical supervising reality and the one that teachers would like to see accomplished. Data were collected, first by semi-structural interviews and then, through questionnaires which were built based on the interviews. Beyond a data content analysis, a documental analysis based on recognized authors on these matters was accomplished. The achieved results allowed us to conclude that there is a really imbalance between the perceptions of the supervising reality and the perceptions of what it would be desirable in the supervising fulfilment. According to this empirical study, we could establish that pedagogical supervision must be changed on its basis. Those changes shall aim at a non-hierarchical team work, in which collaborative behaviours are essential in a working dialogical perspective. The supervisor shall be endowed with social and cognitive competences that will allow him/her to promote cooperation, revealing leadership and promoting the achievement of common goals that will permit the development of the teaching professional identity, based on a desired team spirit. Perceção docente da Supervisão Pedagógicainfo:eu-repo/semantics/publishedVersio

Chitosan Membrane Modified With a New Zinc(II)-Vanillin Complex Improves Skin Wound Healing in Diabetic Rats

The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we evaluated the healing effects of a new zinc complex, [Zn(phen)(van)2], identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 μmol cm-2 (CS-ZPV1) and 1.22 μmol cm-2 (CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in Wistar rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1β, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-β and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1β as well as increased IL-10 and gene expression of TGF-β and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds

Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.

Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters

Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model.

Oral mucositis (OM) is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT), an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60 mg/Kg) and 2 (40 mg/Kg). Animals were pretreated with oral AZT (1, 5, or 10 mg/kg) or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012) of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO), Malonyldialdehyde (MDA), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-α) were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA). Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), and transforming growth factor (TGF)-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni's test was used to calculate the means of intergroup differences (p ≤ 0.05). Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01), MDA (p<0.5) and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05) and IL-1β (p<0.05) levels, increased the cheek pouch levels of IL-10 (p<0.01), and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg) did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair