Classification and management of mild head trauma

Mild head trauma had been defined in patients with direct impact or deceleration effect admitted with a Glasgow Coma Scale score of 13–15. It is one of the most frequent causes of morbidity in emergency medicine. Although common, several controversies persist about its clinical management. In this paper, we describe the Brazilian guidelines for mild head trauma, based on a critical review of the relevant literature

Diclofenac and caffeine inhibit hepatic antioxidant enzymes in the freshwater fish Astyanax altiparanae (Teleostei: Characiformes)

Although concentrations of pharmaceutical compounds in aquatic ecosystems are low, they can cause toxic effects on organisms. The aim of this study was to evaluate the effects of diclofenac (DCF), a non-steroidal anti-inflammatory drug, and caffeine (CAF), a central nervous system stimulant, both alone or combined, in Astyanax altiparanae males under acute exposure (96 h), measuring neurotoxicity biomarkers, antioxidant response and damage at biochemical and cellular levels. DCF concentration in water, separated and combined, was 3.08 mg L−1 and that of CAF was 9.59 mg L−1. To assess neurotoxicity, brain and muscle acetylcholinesterase (AChE) activities were measured. To evaluate oxidative stress, the enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione S-transferase (GST), as well as lipoperoxidation (LPO), were analyzed in liver and gills. Activity of hepatic cyclooxygenase (COX) was also evaluated. Genotoxicity was assessed in blood using comet assay and micronucleus test, as well as nuclear abnormalities. DCF and CAF, alone or combined, had neither effect on AChE activity, nor in the activity of SOD, CAT, GPx and GST in gills. In liver, DCF inhibited SOD and GPx activity, CAF inhibited CAT activity, the mixture inhibited SOD and GST activity; although only fish exposed to CAF showed increased hepatic LPO. Under these experimental conditions, no effect on COX activity was observed, nor cytotoxic and genotoxic damage. The most pronounced effects were caused by the drugs separately, since both compounds altered the enzymes, but only CAF triggered LPO, showing more harmful effects.Fil: Muñoz Peñuela, Marcela. Universidade de Sao Paulo; BrasilFil: Lo Nostro, Fabiana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Dal'Olio Gomes, Aline. Universidade de Sao Paulo; BrasilFil: Tolussi, Carlos Eduardo. Universidade Anhembi Morumbi; BrasilFil: Branco, Giovana Souza. Universidade de Sao Paulo; BrasilFil: Pinheiro, João Paulo Silva. Universidade de Sao Paulo; BrasilFil: Godoi, Filipe Guilherme Andrade de. Universidade de Sao Paulo; BrasilFil: Moreira, Renata Guimarães. Universidade de Sao Paulo; Brasi

Influence of Polymeric Restorative Materials on the Stress Distribution in Posterior Fixed Partial Dentures: 3D Finite Element Analysis

This study evaluated the effect of interim restorative materials (acrylic resin (AR), resin composite (RC) or polyetheretherketone (PEEK) for dental computer-aided design/computer-aided manufacturing (CAD/CAM)) on the stress distribution of a posterior three-unit fixed partial denture

Elaboração e validação de instrumento avaliador da adesão ao tratamento da hipertensão

OBJETIVO Elaborar e validar instrumento de avaliação da adesão ao tratamento da hipertensão arterial sistêmica, com base na teoria da resposta ao item. MÉTODOS O desenvolvimento do instrumento envolveu procedimentos teóricos, empíricos e analíticos. Os procedimentos teóricos compreenderam a definição do constructo adesão ao tratamento da hipertensão arterial sistêmica, identificação dos domínios intervenientes e a elaboração do instrumento, seguida da análise semântica e conceitual por peritos. O procedimento empírico englobou a aplicação do instrumento a 1.000 usuários com hipertensão arterial sistêmica, atendidos em um centro de referência em Fortaleza, CE, em 2012. A etapa analítica validou o instrumento por meio da análise psicométrica e dos procedimentos estatísticos. O modelo da teoria da resposta ao item usado na análise foi o da resposta gradual de Samejima. RESULTADOS Doze dos 23 itens do instrumento inicial foram calibrados e permaneceram na versão final. O coeficiente alfa (α) de Cronbach foi de 0,81. Os itens referentes ao uso da medicação quando apresenta algum sintoma e o uso de gordura apresentaram bom desempenho, pois tiveram melhor poder de discriminar os indivíduos que aderem ao tratamento. Deixar de tomar a medicação alguma vez e o consumo de carnes brancas apresentaram menor poder de discriminação. Itens referentes à realização de exercício físico e ser rotina seguir o tratamento não medicamentoso tiveram maior dificuldade de resposta. O instrumento mostrou-se mais apropriado para medir a baixa adesão ao tratamento da hipertensão arterial sistêmica do que a alta adesão. CONCLUSÕES O instrumento mostrou-se adequado para avaliar a adesão ao tratamento da hipertensão arterial sistêmica, pois consegue diferenciar os indivíduos com alta adesão daqueles com baixa adesão. Sua utilização pode facilitar a identificação e aferição do cumprimento à terapêutica prescrita, além de viabilizar o estabelecimento de metas a serem alcançadas

Grape skin extracts from winemaking by-products as a source of trapping agents for reactive carbonyl species

BACKGROUND Clinical evidence supports the relationship between carbonyl stress and type II diabetes and its related pathologies. Methylglyoxal (MGO) is the major dicarbonyl compound involved in carbonyl stress. Efforts are therefore being made to find dietary compounds from natural sources that could exert an MGO trapping response. RESULTS The in vitro MGO trapping capacity of six red and seven white grape skin extracts (GSE) obtained from winemaking by-products was investigated. Methanolic GSE exhibited a promising MGO trapping capacity that was higher in red GSE (IC50 2.8 mg mL−1) when compared with white GSE (IC50 3.2 mg mL−1). The trapping ability for red GSE correlated significantly with total phenolic content and antioxidant capacity. However, no correlations were observed for white GSE, which suggests that other compounds were involved in the trapping activity. CONCLUSION GSE may be considered a natural source of carbonyl stress inhibitors, thus opening up its possible utilization as a nutraceutical ingredient. Further investigations are required to understand the mechanism involved in the carbonyl trapping ability of red and white grape skin samples and their relationship with glycation. © 2015 Society of Chemical Industry.PSC Sri Harsha would like to thank the University of Milan for providing additional funding through the ERASMUS student network program. This work was partly funded by projects CSIC-201370E027, AGER (project number 2010–2222) and S2013/ABI-3028-AVANSECAL.Peer reviewe

Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis

BACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. AIMS: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. METHODS: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. RESULTS: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. CONCLUSIONS: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH

Global update on the susceptibility of humam influenza viruses to neuraminidase inhibitors 2012-2013

Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) is sporadic, often follows exposure to NAIs, but occasionally occurs in the absence of NAI pressure. The emergence and global spread in 2007/2008 of A(H1N1) influenza viruses showing clinical resistance to oseltamivir due to neuraminidase (NA) H275Y substitution, in the absence of drug pressure, warrants continued vigilance and monitoring for similar viruses. Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 11,387 viruses collected by WHO-recognized National Influenza Centres (NIC) between May 2012 and May 2013 to determine 50% inhibitory concentration (IC50) data for oseltamivir, zanamivir, peramivir and laninamivir. The data were evaluated using normalized IC50 fold-changes rather than raw IC50 data. Nearly 90% of the 11,387 viruses were from three WHO regions: Western Pacific, the Americas and Europe. Only 0.2% (n=27) showed highly reduced inhibition (HRI) against at least one of the four NAIs, usually oseltamivir, while 0.3% (n=39) showed reduced inhibition (RI). NA sequence data, available from the WHO CCs and from sequence databases (n=3661), were screened for amino acid substitutions associated with reduced NAI susceptibility. Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=18), A(H3N2) with NA E119V (n=3) or NA R292K (n=1) and B/Victoria-lineage with NA H273Y (n=2); amino acid position numbering is A subtype and B type specific. Overall, approximately 99% of circulating viruses tested during the 2012-2013 period were sensitive to all four NAIs. Consequently, these drugs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections

Silencing cytokeratin 18 gene inhibits intracellular replication of Trypanosoma cruzi in HeLa cells but not binding and invasion of trypanosomes

<p>Abstract</p> <p>Background</p> <p>As an obligatory intracellular parasite, <it>Trypanosoma cruzi</it>, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during <it>T. cruzi</it>-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle <it>in vitro</it>. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence.</p> <p>Results</p> <p>CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different <it>T. cruzi </it>strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18.</p> <p>Conclusion</p> <p>The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of <it>T. cruzi </it>in HeLa cells, but not trypanosome binding and invasion.</p

Malária em usuários de drogas de administração endovenosa associada à soropositividade para HIV

Cases of induced malaria have been notified in S. Paulo State, Brazil, in recent years. At the same time the number of cases imported from endemic regions of Brazil has been increasing. One case of induced malaria by Plasmodium vivax was registered in Presidente Prudente, located in the west of the State, in 1988 and a further eleven cases in 1989. This city is considered to be one of the main transit ports for people who come into the State from the Amazonian region. The patients declared that they had not been to any possible transmission area of malaria. All of them had, however, taken cocaine, sharing the same contaminated needle and syringe. Previously, one person with imported malaria was detected, who had transmitted the disease to the first case in 1988 and also to a further group of 3 people in 1989. One of these three latter cases then transmitted the disease to two other people. As the group of people continued to use the drug among themselve, 2 new cases arose. Afterwards, they re-infected themselves again (one of the was re-infected twice). The test for Humam Immunodeficiency Vírus was positive for 5 individuals, of whom one had a negative result and 2 others did not undergo the test. This information is discussed within the present context.Infecções induzidas de malária têm sido verificadas nos últimos anos no Estado de São Paulo, Brasil concomitantemente com o aumento de casos importados procedentes da região endêmica do país. Destaca-se o registro de um caso em 1988 e onze casos em 1989 de malária induzida por Plasmodium vivax, em indivíduos residentes na cidade de Presidente Prudente, situada a oeste do Estado e considerada uma das "portas de entrada" de pessoas procedentes da Região Amazônica. Os pacientes afirmaram não terem se deslocado recentemente ou negaram deslocamentos para áreas com possibilidade de transmissão de malária. Todos fizeram uso de drogas injetáveis, participando de círculos de conhecidos afins e geralmente dividiam a mesma agulha e seringa no uso da cocaína. Foi detectado o doente de malária que transmitiu inicialmente a doença ao caso de 1988, e a um primeiro grupo de três indivíduos em 1989. Destes três casos, um transmitiu a doença a outro grupo de dois indivíduos em 1989. A partir destas primeiras infecções e do uso continuado das drogas injetáveis entre grupos, surgiram dois novos casos e houve reinfecção em dois indivíduos (um destes apresentou duas reinfecções). O exame para detecção de HIV foi positivo em cinco indivíduos, um apresentou resultado negativo e não foi realizado em outros três indivíduos. São analisadas as informações desses casos e discutida a importância de sua ocorrência no momento atual

Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection

A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice