Molecular mechanism and health effects of 1,2-Naphtoquinone

Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death. Many signal transduction pathways act as a vulnerable target for 1,2-NQ, including kappaB kinase b (IKKbeta) and protein tyrosine phosphatase 1B (PTP1B). Antioxidant molecules act in defense against ROS/RNS-mediated 1,2-NQ responses to injury. Nonetheless, its inhibitory effects at PTP1B, altering the insulin signaling pathway, represents a new therapeutic target to treat diabetes type 2. Questions exist whether exposure to 1,2-NQ may promote arylation of the Keap1 factor, a negative regulator of Nrf2, as well as acting on the sepiapterin reductase activity, an NADPH-dependent enzyme which catalyzes the formation of critical cofactors in aromatic amino acid metabolism and nitric oxide biosynthesis. Exposure to 1,2-NQ is linked to neurologic, behavioral, and developmental disturbances as well as increased susceptibility to asthma. Limited new knowledge exists on molecular modeling of quinones molecules as antitumoral and anti-microorganism agents. Altogether, these studies suggest that 1,2-NQ and its intermediate compounds can initiate a number of pathological pathways as AP in living organisms but it can be used to better understand molecular pathways

Pain assessment in surgical patients with impaired cognition

Pain is considered the 5th vital sign and its measurement/assessment and records are required and must be systematic. Ineffective pain management involves complications in clinical status of patients, longer hospitalization times and higher costs with health. In the surgical patient with impaired cognition, hetero measurements should be made, based on behavioural and physiological indicators. We used to determine the efficacy and efficiency of the Observer Scale, the Abbey Pain Scale and Pain Assessment in Advanced Dementia (PAINAD). Our study is an applied, non-experimental, quantitative, descriptive and analytical research. The data collection instrument consisted of patients’ sociodemographic and clinical data, the Observer Scale, the Abbey Pain Scale (Rodrigues, 2013) and PAINAD (Batalha et al., 2012). We assessed pain at an early phase and 45 minutes after an intervention for its relief. The sample is non-probabilistic for convenience, consisting of 76 surgical patients with impaired cognition, admitted to the surgery services of a central hospital, aged between 38 and 96 years. There was a positive correlation between the results of the three scales, most evident in the initial evaluation. Pain intensity in the same patient is higher when assessed with PAINAD (OM = 2.16) and lower when assessed with the Observer Scale (OM = 1.78). The most effective and efficient scale is PAINAD. Due to the small sample size, we suggest confirmatory studies so that the results can be generalized

Determinantes de saúde em crianças dos 3 aos 10 anos

RESUMO 1: Introdução: Os estilos de vida atuais sugerem comportamentos de risco que estão na base do perfil de saúde do país. Objetivo: Avaliar os estilos de vida e sua associação com dados sociodemográficos numa amostra de crianças portuguesas dos 3 aos 10 anos de idade. Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: Constatou-se que as crianças com mais idade apresentavam uma menor adesão a comportamentos alimentares saudáveis, uma maior prevalência de atividade física (49,2%), no entanto, foram, também aquelas que apresentaram um maior índice de atividades sedentárias (27,1%). Os rapazes apresentaram maiores níveis de atividade física (51,6%) e índices mais elevados de comportamentos sedentários (28,6%). Relativamente à zona de residência, existiu uma maior prevalência de consumo de legumes (73,2%) e fastfood (24,0%) e de comportamentos sedentários (26,1%) em zonas urbanas. As crianças que pertenciam a agregados familares de rendimentos mais favoráveis e com maior nível de habilitações literárias consumiam mais leite e derivados, legumes e praticavam mais atividade física. No entanto, apresentaram maior prevalência de consumo de fastfood e comportamentos sedentários. Conclusões:Torna-se perceptível a necessidade de se intervir nos grupos mais vulneráveis no sentido de uma mais eficaz equidade em saúde. Palavras-chave: Crianças; estilos de vida; dados sociodemográficos; escolas.ABSTRACT 1: Introduction: The current lifestyles suggests risk behaviors that are the basis of a country's health profile. Objective: Assess the lifestyles and its association with sociodemographic variables among a sample of Portuguese children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: It was found that the older children had a lower adherence to healthy eating habits and a higher prevalence of physical activity (49.2%). However, there were also those with higher rate of sedentary activities (27.1%). The boys had higher levels of physical activity (51.6%) and higher rates of sedentary behaviors (28.6%). With regard to residence area, there was a higher prevalence of consumption of vegetables (73.2%), fastfood (24.0%) and sedentary behaviors (26.1%) in urban areas. Children belonging to households of more favorable monthly earnings and a higher level of educational qualifications consumed more dairy product, vegetables and practiced more physical activity. However, they had a higher prevalence of fastfood consumption and sedentary behaviors. Conclusions: It becomes noticeable the need to make an intervention on the most vulnerable groups to obtain more effective health equity. Keywords: Children; lifestyles; sociodemographic data; schools.RESUMO 2: Introdução: As iniquidades de género na distribuição de recursos estão ainda profundamente associadas à saúde precária e à diminuição do bem-estar das mulheres e das crianças. Objetivo: Analisar a influência dos fatores materno-fetais nos estilos de vida numa amostra de crianças portuguesas dos 3 aos 10 anos de idade Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: As crianças que habitam em meio rural apresentavam um peso à nascença superior comparativamente às do meio urbano (93,7%). As grávidas com mais idade obtiveram uma prevalência de antecipação da primeira consulta de gravidez mais elevada (96,5%) assim como uma prevalência mais elevada de consultas de vigilância durante a gravidez (97,2%) quando comparadas com as grávidas mais novas. As mães com habilitações literárias superiores ao 9.º ano de escolaridade apresentavam uma prevalência de amamentação superior (58,0%) e os seus filhos uma prevalência de consumo de fastfood superior (64,9%) quando comparadas com as mães com habilitações literárias inferiores. Conclusões: Denota-se a importância da maturidade, formação e capacitação das mães para os cuidados maternos e neonatais. Palavras-chave: crianças; estilos de vida; fatores materno-fetais.ABSTRACT 2: Introduction: Gender inequalities in the distribution of resources is still deeply associated with poor health and reduced welfare of women and children. Objective: To analyze the influence of maternal and fetal factors in lifestyles of children, in a sample of children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: Children who live in rural areas presented a higher birth weight compared to those who live in urban areas (93.7%). Older pregnant women obtained a higher prevalence of the first medical appointment antecipation (96.5%) as well as a higher prevalence of medical appointments during pregnancy (97.2%) when compared with younger pregnant women. Mothers with qualifications higher than the 9th grade showed a higher prevalence of breastfeeding (58.0%) and their children presented a higher prevalence of fastfood consumption (64.9%) when compared with mothers with lower educational qualifications. Conclusion: To denote the importance of maturity and training of mothers in maternal and neonatal care. Keywords: children; lifestyles; maternal fetal factors

Conversion of immunosuppressive monotherapy from cyclosporin A to tacrolimus reverses bone loss in rats

Tacrolimus is used for transplant patients with refractory graft rejection and those with intolerance to cyclosporin (CsA), without the disfiguring adverse effects frequently attributed to CsA therapy. Since we have shown that CsA-associated bone loss can also affect alveolar bone, the purpose of this study was to evaluate the effects of conversion of monotherapy from CsA to tacrolimus on alveolar bone loss in rats. Groups of rats were treated with either CsA (10 mg/kg/day, s.c.), tacrolimus (I mg/kg/day, s.c.), or drug vehicle for 60 and 120 days, and an additional group received CsA for 60 days followed by conversion to tacrolimus for a further 60-day period. Bone-specific alkaline phosphatase (BALP), tartrate-resistent acid phosphatase (TRAP-5b), calcium (Ca2+), interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) concentrations were evaluated in the serum. Analyses of bone volume, bone surface, number of osteblasts, and osteoclasts were performed. Treatment with CsA for either 60 or 120 days was associated with bone resorption, represented by lower bone volume and increased number of osteoclasts; serum BALP, TRAP-5b, IL-1 beta, IL-6, and TNF-alpha were also higher in these animals. After conversion from CsA to tacrolimus, all the altered serum markers returned to control values in addition to a significant increase of bone volume and a lower number of osteoclasts. This study shows that conversion from CsA to tacrolimus therapy leads to a reversal of the CsA-induced bone loss, which can probably be mediated by downregulation of IL-1 beta, IL-6, and TNF-alpha production

Abdominal hyperalgesia in secretory phospholipase A(2)-induced rat pancreatitis: Distinct roles of NK1 receptors

We investigated the potential of secretory phospholipase A(2) (sPLA(2))-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA(2) from Crotalus durissus terrificus (sPLA(2) Cdt, 300 mu g kg(-1)) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK1 receptor antagonist. Injection of sPLA(2) Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4 h, which returned to normality by 24 h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA(2) exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4 h, but not 24 h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA(2) Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA(2) Cdt nor sPLA(2) from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK1 receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA(2)-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA(2)s do not directly depolarize sensory fibres in vitro. (C) 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Proposta de acompanhamento tutorial : um projecto de acção em contexto escolar

No presente estudo, analisam-se os principais problemas diagnosticados num Agrupamento de Escolas, identificando as principais necessidades, fragilidades, assim como os recursos vigentes no mesmo. Nesse sequência é apresentada uma Proposta de Acompanhamento Tutorial de forma a dotar o Agrupamento de meios que possam servir as exigências, colocadas no âmbito do domínio da acção socioeducativa. A proposta de acompanhamento tutorial que se apresenta, assenta neste propósito, enquadrando e reflectindo o papel fundamental de uma equipa multidisciplinar permanente, constituída pelos seguintes técnicos: Psicólogo, Professor Tutor e Director de Turma, que em conjunto elaboram um Plano Individual de Acompanhamento Tutorial (PIAT). No PIAT são mencionadas as áreas onde o aluno requer um acompanhamento técnico e definidas as estratégias a serem desenvolvidas por cada ano lectivo, durante todo o seu percurso escolar. Após a definição dos possíveis técnicos a intervir e recursos necessários, para a sua implementação, é definida nomeadamente a duração da mesma e a articulação com a família e redes sociais envolventes.In this study, we analyze the main problems diagnosed in a Group of Schools, identifying key needs, weaknesses, and resources existing in it. Following this is a Proposal Monitoring Tutorial in order to provide the grouping of resources which can serve the demands placed within the field of socio-educational action. The proposed follow tutorial that shows, based on this point, framing and reflecting the fundamental role of a permanent multi-disciplinary team, consisting of the following technicians: Psychologist, Teacher and Director of Tutor Team, which together draw up an Individual Plan Monitoring Tutorial (PIAT). PIAT are mentioned in the areas where the student requires a technical monitoring and defined strategies to be developed for each academic year throughout their school careers. After defining the technical potential to intervene and resources necessary for its implementation, is defined including its duration and interaction with the surrounding family and social networks

Neurofilament heavy subunit in cerebrospinal fluid: A biomarker of amyotrophic lateral sclerosis?

The objectives of this study were to investigate the presence of the three neurofilament subunits, ubiquitin, proteasome and 3-nitrotyrosine, in CSF samples of ALS patients. CSF samples were obtained by lumbar puncture from 10 ALS patients and six controls. All samples were analysed by Western blotting. Results revealed that neurofilament heavy subunit was identified in 70% of ALS cases and we conclude that this subunit may be a promising biomarker for clinical diagnosis of ALS.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)FAPERJCNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FUJBFUJ

Participation of peripheral tachykinin NK(1) receptors in the carrageenan-induced inflammation of the rat temporomandibular joint

Temporomandibular disorders represent one of the major challenges in dentistry therapeutics. This study was undertaken to evaluate the time course of carrageenan-induced inflammation in the rat temporomandibular joint (TMJ) and to investigate the role of tachykinin NK(1) receptors. Inflammation was induced by a single intra-articular (i.art.) injection of carrageenan into the left TMJ (control group received sterile saline). Inflammatory parameters such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold) and TNF alpha and IL-1 beta concentrations were measured in the TMJ lavages at selected time-points. The carrageenan-induced responses were also evaluated after treatment with the NK(1) receptor antagonist SR140333. The i.art. injection of carrageenan into the TMJ caused a time-dependent plasma extravasation associated with mechanical allodynia, and a marked neutrophil accumulation between 4 and 24 h. Treatment with SR140333 substantially inhibited the increase in plasma extravasation and leukocyte influx at 4 and 24 h, as well as the production of TNF alpha and IL-1 beta into the joint cavity, but failed to affect changes in head-withdrawal threshold. The results obtained from the present TMJ-arthritis model provide, for the first time, information regarding the time course of this experimental inflammatory process. In addition, our data show that peripheral NK(1) receptors mediate the production of both TNF alpha and IL-1 beta in the TMJ as well as some of the inflammatory signs, such as plasma extravasation and leukocyte influx, but not the nociceptive component. 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[02/00300-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/07853-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Sanofi-Aventis(Sanofi-Aventis, France)[SR140333

Hydrogen Sulfide: An Endogenous Mediator of Resolution of Inflammation and Injury

Significance: Hydrogen sulfide is emerging as an important mediator of many aspects of inflammation, and perhaps most importantly as a factor promoting the resolution of inflammation and repair of injury. Recent Advances: In the gastrointestinal tract, H2S has been shown to promote healing of ulcers and the resolution of mucosal inflammation. On the other hand, suppression of endogenous H2S synthesis impairs mucosal defense and leads to increased granulocyte infiltration. H2S has been exploited in the design of more effective and safe anti-inflammatory drugs. Critical Issues: Enteric bacteria can be a significant source of H2S, which could affect mucosal integrity; indeed, luminal H2S can serve as an alternative to oxygen as a metabolic substrate for mitochondrial respiration in epithelial cells. Enterocytes and colonocytes thereby represent a “metabolic barrier” to the diffusion of bacteria-derived H2S into the subepithelial space. A compromise of this barrier could result in modulation of mucosal function and integrity by bacterial H2S. Future Directions: Improvements in methods for measurement of H2S and development of more selective inhibitors are crucial for gaining a better understanding of the pathophysiological importance of this mediator. Results from animal studies suggest that H2S-releasing agents are promising therapeutic agents for many indications, but these compounds need to be assessed in a clinical setting. Antioxid. Redox Signal. 17, 58–67