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Guilherme Carneiro,1 Elton Luiz Silva,1 Layssa Alves Pacheco,1 Elaine Maria de Souza-Fagundes,2 Natássia Caroline Resende Corrêa,3 Alfredo Miranda de Goes,3 Mônica Cristina de Oliveira,1 Lucas Antônio Miranda Ferreira11Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; 2Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil; 3Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilAbstract: This work aims to develop solid lipid nanoparticles (SLNs) loaded with retinoic acid (RA) to evaluate the influence of two lipophilic amines, stearylamine (SA) and benethamine (BA), and one hydrophilic, triethylamine (TA), on drug-encapsulation efficiency (EE) and cytotoxicity in cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without amine) to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively. SA-RA-loaded SLNs resulted in positively charged particles, whereas those with TA and BA were negatively charged. The EEs were significantly improved with the addition of the amines, and they increased from 36% ± 6% (without amine) to 97% ± 2%, 90% ± 2%, and 100% ± 1% for SA, TA, and BA, respectively. However, stability studies showed higher EE for BA-RA-loaded SLNs than TA-RA-loaded SLNs after 30 days. The formulations containing SA loaded or unloaded (blank SLNs) with RA were cytotoxic in normal and cancer cell lines. In contrast, the blank SLNs containing TA or BA did not show cytotoxicity in human breast adenocarcinoma cells (MCF-7), while RA-loaded SLNs with the respective amines were significantly more cytotoxic than free RA. Furthermore, the cytotoxicity of BA-RA-loaded SLNs was significantly higher than TA-RA-loaded SLNs. These findings are in agreement with the data obtained in the evaluation of subdiploid DNA content and cell-cycle analysis, which showed better anticancer activity for BA-RA-loaded SLNs than TA-RA-loaded SLNs and free RA. Taken together, these findings suggest that the BA-RA-loaded SLN formulation is a promising alternative for the intravenous administration of RA in the treatment of cancer.Keywords: solid lipid nanoparticles, all-trans retinoic acid, cancer, treatment, antitumor activity, ion pairing

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia–reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase–MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.

The 12 principles of green chemistry were stated to pursue good practices and techniques that minimize the use of hazardous substances in the production and application of chemicals. To minimize the risks and the pollution generated using chemicals, new methodologies must be developed that avoid the application of dangerous products or its amount. Considering the principle of pollution prevention, this work proposes the development and application of a different methodology for the quantification of humic substances (HS), applying a spectrophotometric methodology that reduces the quantity of hazardous reagents (sodium dichromate and sulfuric acid) and minimizes the waste production. To deeply acknowledge the method, a validation of the methodology was done to allow the evaluation of its effectiveness to report reliable results. It was done by the evaluation of the parameters often used for this purpose (analytical limits, precision, accuracy, selectivity, robustness, and method working range). The detection limit attained was 0.03 g glucose/L and the quantification limit was 0.09 g glucose/L. The precision and accuracy were also evaluated using the repeatability limit and through performance testing, respectively, with a repeatability limit of 0.045 g/L and a Z-score less than 2. For selectivity and robustness, differences in variances were not significant, and the working range is well adjusted, with no differences regarding the precision of the lower and higher standard. The results obtained showed that the method under study, adapted to the green chemistry principles, can be applied to quantify HS in impure and complex samples.

Analytical or hybrid numerical-analytical solutions based on the Generalized Integral Transform Technique (GITT) are obtained for the transient three-dimensional pumping problem of aquifers with a fully penetrating vertical well between two parallel streams. The problem formulation for confined and leaky aquifers allows for achieving exact analytical solutions through integral transforms, while the unconfined aquifer case introduces a fourth kind boundary condition which leads to a coupled transformed head ordinary differential system, that can be solved either analytically or numerically. A convergence analysis is performed to illustrate the consistency of the numerical results achieved for the head distribution, as well as for the related pumping rates. Results are obtained for selected cases and comparisons with literature results are performed. A solution verification confirms the agreement of the integral transform solutions with available simulations and provides additional confidence for the analysis of a few physical parameters that influence the hydrological behavior.

Cátia Cristina Silva Sousa Vergara Palma,1 Pablo Moura Lopes,2 Eliete Leão Clemente Silva,1 Maria de Fátima da Matta Bevilaqua,1 Alfredo de Souza Bomfim,2 Marilia Brito Gomes1 1Department of Internal Medicine, Diabetes Unit, State University Hospital of Rio de Janeiro, Rio de Janeiro, Brasil; 2Department of Internal Medicine, Cardiology Unit, State University Hospital of Rio de Janeiro, Rio de Janeiro, BrasilCorrespondence: Cátia Cristina Silva Sousa Vergara PalmaDepartment of Internal Medicine,Diabetes Unit, Rio de Janeiro State University (UERJ), Boulevard 28 de Setembro, 77- 3º Andar - Vila Isabel, Rio de Janeiro, RJ 20551-030, BrazilTel +55 212 868 8224Email catiasousapalma@gmail.comAim: There is a wide variety of cardiovascular outcomes in patients with type 2 diabetes (T2DM), even in asymptomatic individuals. Carotid intima-media thickness (CIMT) is a marker of subclinical atherosclerosis and can be considered as a predictor of cardiovascular risk (CVR). The aim of this study was to evaluate the relationship between CIMT-determined vascular age (VA), CVR scores, and thyroid function in asymptomatic patients with T2DM.Patients and Methods: Clinical laboratory and CIMT parameters were measured in 154 asymptomatic patients with T2DM. The Framingham risk score (FRS) was performed with chronological age (CA) and with VA. A multinomial logistic regression model was used to analyze variables related to CVR reclassification.Results: The use of CIMT-determined VA led to the reclassification of 54 (35.52%) out of 152 asymptomatic T2DM patients, being 20 (37.03%) to a lower categorical risk and 34 (62.96%) to a higher categorical risk according to FRS. The variables that were associated to reclassification to a higher categorical risk were positive family history (FH) of premature coronary artery disease (p=0.046), FH of thyroid disease (p=0.010), use of statins (p=0.027), and free T4 levels (p=0.009).Conclusion: VA determined from CIMT allowed the reclassification of the CVR in asymptomatic T2DM patients. FH of premature CAD, FH of known thyroid disease, use of statins, and free T4 levels were associated to a reclassification into a higher risk category. The use of doppler to perform CIMT measure is currently more accessible, especially in a low-middle income country like Brazil. However, further prospective studies must be performed to establish the predictive values of CIMT on atherosclerosis and how thyroid function acts like cardiovascular risk marker on CVR scores.Keywords: vascular age, type 2 diabetes, cardiovascular risk, CIMT

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Without maps blind people are limited to receive information about the geographic space through words and/or need to memorize long descriptive information in order to have access to places. Maps may offer access to spatial information for this group of users to organize their internal spatial images (estimating distances, locating places and objects). As a consequence, this might revert in a greater independence and autonomy in the orientation, mobility and self-assurance of these people. Such facts demonstrate the importance of cartographic education of people with visual impairment (VI), a theme that has been the object of study of the authors of this article. The fi rst part of the text demonstrates how the tactile maps were standardized in the Laboratory of Tactile and School Cartography of Federal University of Santa Catarina and how they are produced. The following section describes the Tactile Model System - Mapavox developed in partnership with São Paulo State University - UNESP, |Rio Claro Campus and Tércio Pacitti Institute of Computer Applications and Research of Federal University of Rio de Janeiro (UFRJ). One last item is dedicated to demonstrate experiences of the authors in the cartographic initiation of blind students, where the importance of pedagogic mediation of tactile pedagogical material in this process is discussed.

INTRODUCTION: Neuroimaging studies of elderly individuals reveal alterations in the white matter that are incompatible with the patient?s parkinsonism, mistakenly classified as vascular parkinsonism (VP). METHOD: This study was conducted on a population composed of 20 patients with Parkinson?s disease (PD) whose neuroimaging exams revealed vascular alterations in the white matter and seven patients with VP in order to compare diagnostic criteria. RESULTS: Age at disease onset of patients with PD was 55±12 years and patients with VP it was 62±13 years. Twelve patients with PD and five patients with VP presented arterial hypertension; three patients with VP and two patients with PD presented gait impairment; all patients with VP presented rigidity and bradykinesia, six of them presented resting tremor; 19 patients with PD presented tremor and 19 of them presented rigidity, while 17 presented bradykinesia. When the symptoms and evolution of both diseases were compared, the vascular alterations in the white matter were considered unspecific. CONCLUSION: Since clinical symptoms are unspecific, a differential diagnosis requires neuroimaging, good response to levodopa and clinical evolution.

Com o objetivo de analisar a variação anatômica ao longo do caule de Terminalia ivorensis, estudaram-se amostras de madeira de três indivíduos, nos planos radial e axial. Para tal, corpos de prova foram obtidos a partir de discos de madeira, de 2 em 2cm, no sentido medula-câmbio. A metodologia usada para desenvolver o trabalho foi aquela tradicionalmente recomendada para estudos em anatomia vegetal. A descrição anatômica realizada seguiu as recomendações do IAWA Committee. No sentido radial do caule, alguns elementos anatômicos apresentaram tendências de variação definidas e significativas estatisticamente quando aplicado o teste Tukey para comparação de médias. São eles: freqüência, diâmetro e comprimento dos elementos de vaso, freqüência de raios/mm linear, comprimento dos raios em número de células, e comprimento e espessura da parede das fibras. Já no sentido axial, todas as variáveis analisadas não se mostraram estatisticamente significativas. Os resultados observados devemse, principalmente, à caracterização bem definida dos lenhos juvenil e adulto na madeira de Terminalia ivorensis.

Com o objetivo de avaliar o comportamento estomático e o potencial da água da folha em plantas jovens de Mimosa caesalpiniifolia, Enterolobium contortisiliquum e Tabebuia aurea submetidas a estresse hídrico, desenvolveu-se um experimento em casa de vegetação no Laboratório de Fisiologia Vegetal da UFRPE. As plântulas foram submetidas a dois tratamentos hídricos (100% da CP e 50% da CP) e aos 5¹, 7, 13 e 22 dias de estresse hídrico, foram avaliadas a transpiração (E), a resistência difusiva (Rs), a temperatura da folha (Tfol), a temperatura do ar (Tar), umidade relativa do ar (UR), a radiação fotossinteticamente ativa (PAR) e o déficit de pressão de vapor (DPV) às 7h, 9h, 12h e 15h. Após 30 dias de estresse, foi medido o potencial da água da folha (Yw) entre 9-10 horas. Os maiores valores de E foram registrados entre 9-12h para todas as espécies, sendo mais baixos nas plantas estressadas. O oposto foi verificado para Rs, com diferenças na magnitude dos valores entre espécies e horários de avaliação. A Rs das plantas estressadas de E. contortisiliquum foi influenciada pela Tar e de M. caesalpiniifolia pela UR e PAR. O Yw decresceu com o estresse, com reduções de até 155%. A Tfol não se mostrou bom indicador dos efeitos do estresse hídrico sobre as espécies.

Apresentamos um caso de linfoangiossarcoma de membro superior esquerdo, em paciente de 52 anos, previamente submetida à mastectomia radical modificada à esquerda, seguida de radioterapia devido ao carcinoma de mama 6 anos antes. Esta rara síndrome está associada a linfedema crônico, após mastectomia radical, seguida de radioterapia. Aproximadamente 400 casos foram relatados na literatura. A ocorrência infreqüente dessa doença e a aparência inócua do tumor, freqüentemente levam a retardo no diagnóstico e tratamento. No caso dessa paciente, o diagnóstico foi obtido por meio de biópsia incisional da lesão, com confirmação pela imuno-histoquímica, utilizando marcadores de células endoteliais, anticorpo anti-CD31, vimentina e actina muscular. A paciente foi submetida à amputação do membro superior, e encontra-se em seguimento sem recorrência local ou à distância há 18 meses.

OBJETIVO: Abelhas africanizadas são mais agressivas, enxameiam várias vezes ao ano e utilizam grande variedade de locais para nidificar, diferentemente das européias. Tal comportamento proporciona maior contato com a população, o que pode aumentar o número de acidentes. Assim, realizou-se estudo com o objetivo de conhecer o comportamento dessas abelhas, assim como a identificação de estratégias mais eficientes de manejo e orientação à população. MÉTODOS: A fonte de dados foi constituída de 3.061 registros de solicitações da população atendidas pelo Centro de Controle de Zoonoses do Município de São Paulo, de 1994 a 1997, para retirada de colméias e enxames. Foram analisados locais mais freqüentes de instalação de colônias e pouso de enxames, além da correlação com variáveis climáticas. Para isso, utilizou-se o coeficiente de Pearson. RESULTADOS: Os valores diários apresentaram correlação positiva com temperatura média e grau de insolação, e negativa com umidade relativa e pluviosidade. As colônias instalaram-se preferencialmente em construções artificiais; os enxames em árvores. CONCLUSÕES: Períodos do ano com altas temperaturas e baixo índice pluviométrico estão relacionados a maior atividade das abelhas e maior número de enxames, propiciando maior contato com a população. Objetos como caixas e tambores não devem ficar expostos; deve-se vedar forros e paredes, pois são abrigos em potencial para colônias e enxames. Áreas arborizadas servem de refúgio para enxames. Deve-se ter atenção em contato com áreas verdes e não se deve manusear enxames.

Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by trauma, shock, sepsis and several complex surgical maneuvers. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, a common cause of death after trauma, sepsis or major surgeries. Monitoring gut perfusion during experiments may provide valuable insights over new interventions and therapies highly needed to reduce trauma and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in clinical and experimental models of trauma, shock and surgical maneuvers associated with abrupt hemodynamic changes, such as aortic occlusion and hepatic vascular exclusion. Next issue we will be presenting our experience with gas tonometry in experimental and clinical sepsis.

Este estudo foi conduzido em uma área localizada no município de Lagoa da Confusão, Estado do Tocantins, com os objetivos de diagnosticar fragmentos florestais naturais, denominados regionalmente de "ipucas", e mapear as diferentes feições fisionômicas e o uso antrópico da área. Para realização deste estudo utilizou-se um sistema de informações geográficas, IDRISI 2.0. O principal resultado obtido foi o histórico de perturbação que se intensificou a partir da criação do Estado do Tocantins e da implantação do Projeto Rio Formoso para o cultivo de arroz irrigado; em relação à classificação fisionômica e ao uso antrópico foram individualizadas 73 "ipucas". A partir das variáveis consideradas verificou-se que, em relação à área, 56,16% dos fragmentos possuem áreas de até 5,00 ha e apenas quatro apresentaram áreas superiores a 100,00 ha. Aproximadamente 50% destas possuem formas alongadas, o que indica alta relação perímetro/área. Apenas três "ipucas" apresentaram índice de circularidade (C) próximo de 1. Foram identificadas oito feições circunvizinhas às "ipucas". Destas, cinco são ambientes naturais (varjão-sujo, varjão-limpo, pastagem natural, corpos d'água e afloramento rochoso) e as demais resultantes de ações antrópicas (área agrícola, pastagem plantada e rede viária).

Panicum maximum e Chloris gayana foram submetidas à chuvas simuladas com soluções de fluoreto de potássio (15mg ml-1) com objetivo de identificar as injúrias causadas pelo flúor (F-), como poluente atmosférico, na estrutura da lâmina foliar e fornecer subsídios para a seleção de características diagnósticas a serem utilizadas na bioindicação. Os principais sintomas foram clorose e necrose, principalmente no ápice e margens das lâminas. Nos cortes transversais, quatro tipos de alterações causadas pelo flúor são relacionadas: redução do número, tamanho e arranjo dos cloroplastos; necrose dos tecidos principalmente nas margens das folhas; erosões na superfície da folha e hipertrofia das células. Em C. gayana, no entanto, não foram observadas as alterações nos cloroplastos e os outros sintomas foram bem mais discretos que em P. maximum. A ocorrência de compostos fenólicos foi registrada pela coloração com fucsina em todas as regiões da lâmina onde foram observadas lesões. Ao microscópio eletrônico de varredura foi observado o achatamento e formação de concavidades nas paredes externas das células. Este experimento confirma a maior sensibilidade de P. maximum ao flúor e revela algumas características anatômicas de C. gayana que, entre outros fatores, podem estar contribuindo para a maior resistência desta espécie a este poluente.

A biotransformation experiment of trachyloban-19-oic acid (2) was carried out with Rhizopus stolonifer. After twenty days of reaction, four metabolites were extracted, isolated and characterized: two trachylobane type compounds, the 7beta (3) and the 17 (5) hydroxyl derivatives, and two rearranged ent-kaur-11-en-19-oic acids, the 16beta (4) and the 9alpha,16beta (6) hydroxylated compounds. Products 4 and 5 were isolated as their methyl esters (4a and 5a) after esterification of a mixture containing their corresponding acids. The rearrangement of a trachylobane diterpene leading to ent-16beta-hydroxy-kaur-11-ene derivatives gives support to the biogenetic proposal based on the occurrence of this rare group of kaurenes only in plants containing trachylobane representatives. By the best of our knowledge, this is the first report on the isolation of compounds 5 and 6.

Desde a década de 70 o sistema de saúde vem se transformando com a redemocratização do Estado Brasileiro. O SUS representou um importante passo para o fortalecimento dos sistemas de administração locais e regionais. Tal situação tem contribuído para o aumento do controle local e para as mudanças no processo de trabalho. Este estudo considera essas mudanças no sistema local de saúde em Campinas, São Paulo, e analisa, quantitativa e qualitativamente, as práticas de 233 enfermeiras da rede municipal em relação às políticas de saúde locais. Cerca de 58% trabalham em serviços locais e 42% em serviços especializados, em níveis distritais e central de administração. Os serviços de enfermagem organizam-se em seis áreas principais: administração, coordenação de recursos humanos, educação de pessoal, informática, administração em saúde e vigilância em saúde. A intervenção das enfermeiras tem se dirigido às diversas áreas, mas continua centrada nas consultas médicas, com pequena ênfase em atividades coletivas e de promoção à saúde. Concluímos que novas práticas de promoção à saúde coletiva precisam ser fomentadas de acordo com os objetivos de desenvolvimento da saúde em âmbito local.

O objetivo deste trabalho foi comparar cafeeiros das espécies Coffea arabica L. cv. Catuaí-Vermelho e C. canephora Pierre cv. Conilon quanto à fotossíntese líquida e a aspectos da anatomia foliar a esta relacionados. Verificaram-se taxas fotossintética líquida, transpiratória e de condutância estomática maiores em plantas de C. canephora. As plantas de C. arabica apresentaram menor eficiência do sistema "antena", e folhas menores, porém mais espessas. As duas espécies diferiram, ainda, quanto ao tipo, dimensões e número dos estômatos presentes na epiderme foliar: paracíticos em C. arabica e actinocíticos em C. canephora, e maiores, mas em menor número, em C. arabica.

A problemática atual da questão ambiental remete-nos à discussão histórica da racionalidade científica, sobretudo nas sociedades ocidentais contemporâneas, onde o conflito entre a relação homem/meio natural fica evidenciado. Pretendendo dar conta deste conflito, a ecologia constituída como disciplina científica destaca-se como um campo problemático da ciência que busca integrar diversas disciplinas em torno de si. Alguns movimentos sociais, orientando-se por uma "visão ecologizada" (ecossistêmica) de mundo, partem para denunciar os impactos ambientais oriundos, dentre outros, do modelo tecno-industrial altamente poluidor, consumidor dos recursos naturais e gerador da atual desordem global da biosfera. Esses movimentos, sendo orientados por éticas diferenciadas, reivindicam mudanças do quadro social e ambiental da sociedade atual a fim de garantir as necessidades das futuras gerações.

El dolor de cuello inducido por cristales a veces ocurre en pacientes con enfermedades por depósitos de hidroxiapatita o pirofosfato de calcio deshidratado. Los depósitos de hidroxiapatita comprometen el ligamento longitudinal cervical, los discos intervertebrales, y los depósitos de CPPD, el ligamento amarillo, las articulaciones interapofisarias y probablemente el ligamento transverso. Esto sugiere que la enfermedad por depósito de CPPD compromete frecuentemente la columna cervical. Aunque pueden ser asintomáticos, estos depósitos se asocian a ataques agudos de cervicalgia con rigidez, fiebre y aumento de la VSG, simulando PMR y/o Arteritis de Células Gigantes o síntomas neurológicos. Nosotros describimos 2 casos con síndrome de la corona de presentación atípica simulando PMR.

Abstract Background Duchenne muscular dystrophy (DMD) is a sex-linked inherited muscle disease characterized by a progressive loss in muscle strength and respiratory muscle involvement. After 12 years of age, lung function declines at a rate of 6 % to 10.7 % per year in patients with DMD. Steroid therapy has been proposed to delay the loss of motor function and also the respiratory involvement. Method In 21 patients with DMD aged between seven and 16 years, the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1) were evaluated at three different times during a period of two years. Results We observed in this period of evaluation the maintenance of the FVC and the FEV1 in this group of patients independently of chronological age, age at onset of steroid therapy, and walking capacity. Conclusion The steroid therapy has the potential to stabilize or delay the loss of lung function in DMD patients even if they are non-ambulant or older than 10 years, and in those in whom the medication was started after 7 years of age.

Abstract Background Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. Findings Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested. Conclusions Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.

Abstract This commentary describes how the Brazilian Ministry of Health's (MoH) research support policy fulfilled the National Agenda of Priorities in Health Research (NAPHR). In 2003, the MoH started a democratic process in order to establish a priority agenda in health research involving investigators, health managers and community leaders. The Agenda was launched in 2004 and is guiding budget allocations in an attempt to reduce the gap between scientific knowledge and health practice and activities, aiming to contribute to improving Brazilian quality of life. Many strategies were developed, for instance: Cooperation Agreements between the Ministry of Health and the Ministry of Science and Technology; the decentralization of research support at state levels with the participation of local Health Secretariats and Science and Technology Institutions; Health Technology Assessment; innovation in neglected diseases; research networks and multicenter studies in adult, women's and children's health; cardiovascular risk in adolescents; clinical research and stem cell therapy. The budget allocated by the Ministry of Health and partners was expressive: US$419 million to support almost 3,600 projects. The three sub-agenda with the higher proportion of resources were "industrial health complex", "clinical research" and "communicable diseases", which are considered strategic for innovation and national development. The Southeast region conducted 40.5% of all projects and detained 59.7% of the resources, attributable to the concentration of the most traditional health research institutes and universities in the states of São Paulo and Rio de Janeiro. The second most granted region was the Northeast, which reflects the result of a governmental policy to integrate and modernize this densely populated area and the poorest region in the country. Although Brazil began the design and implementation of the NAPHR in 2003, it has done so in accordance with the 'good practice principles' recently published: inclusive process, information gathering, careful planning and funding policy, transparency and internal evaluation (an external independent evaluation is underway). The effort in guiding the health research policy has achieved and legitimated an unprecedented developmental spurt to support strategic health research. We believe this experience is valuable and applicable to other countries, but different settings and local political circumstances will determine the best course of action to follow.