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

Criptococcose: revisão sistemática dos casos ocorridos no Brasil entre 1995-2005

The paper performs a systematic revision of clinical cases of patients with cryptococcosis in Brazil. We selected 13 papers printed in PUBMED, from 1995 to 2005. Nine papers refer to clinical cases in regions Central-East, South and Southeast, and three in regions North and Northeast. We studied the several authors, year, locality, number of clinical cases, agent, signals and symptoms, correlated diseases, immune response and outcome. The major cases of cryptococcosis in regions South, Southwest and Central-East occurred in patients with Aids. The cases of Criptococcus neoformans gattii occurred mainly in Northeast. The signals and symptoms of the infection are related to problems in central nervous system and lungs. The outcome of cryptococcosis cases described in the literature is reduced probably due to co-infection with Aids.Neste artigo, apresenta-se uma revisão sistemática da literatura científica a respeito dos casos clínicos de criptococose ocorridos no Brasil. Foram selecionados trabalhos publicados na PUBMED, entre os anos de 1995 e 2005, totalizando 13 publicações, nas quais se encontram casos clínicos em pacientes com ou sem AIDS. Nove desses estudos ocorreram nas regiões Centro-Oeste, Sul e Sudeste, e três deles envolvem a região Norte e Nordeste. Foram verificadas as seguintes variáveis: autor (es), ano, localidade, número de casos investigados, agente(s) etiológico(s), sinais e sintomas, doença isolada ou associada, resposta imune e desfecho. Pôde-se constatar que a maior parte dos casos relatados ocorreu como co-infecção associada a Aids, sendo o agente etiológico mais freqüente o Cryptococcus neoformans var. neoformans (sorotipos A e D). Esses casos foram encontrados com maior prevalência nas regiões Sul, Sudeste e Centro-Oeste. A ocorrência de C neoformans var. gattii (sorotipos B e C) está relacionada com áreas endêmicas, localizadas na região Norte e Nordeste. Os sinais e sintomas afetam, principalmente, o Sistema Nervoso Central e os pulmões. Os casos relatados na literatura apresentam limitações quanto ao desfecho da criptococose, possivelmente, devido ao fato de a patologia se desenvolver, principalmente, como uma co-infecção relacionada à Aids

Representações sociais sobre o risco ocupacional na perspectiva do trabalhador da saúde

Objetivou-se identificar os sentidos construídos sobre risco ocupacional por trabalhadores da saúde, através da abordagem estrutural das representações sociais. Participaram 220 profissionais de saúde de um hospital público de Natal, Rio Grande do Norte. Utilizou-se a técnica de evocação livre de palavras e os dados foram tratados analisando-se de forma articulada as médias de frequência e ordem de evocação. Os resultados mostram que os sistemas centrais têm composições diferentes nos três grupos: doença e morte nos médicos, perfurocortante e perigo nos enfermeiros e contaminação, doença, infecção e perigo nos odontólogos. A complexidade dos vínculos entre trabalho e risco sugere que estratégias e alternativas de ação sejam operacionalizadas, com a integração das diferentes categorias profissionais e ramos de conhecimento em torno de um objetivo comum, a partir de um espaço interdisciplinar, ampliando o nível de conscientização desses profissionais referente às consequências de suas práticas para a saúde

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

Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.

AIM:To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury. METHODS:Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed. RESULTS:CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1β and NF-κB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI), procollagen type III (PCIII), and NF-κB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group. CONCLUSIONS:CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs) through suppression of inflammatory cytokines