A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium bergheistrain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

Phenolic contents of extracts of Syzygium cumini leaves, collected monthly over a one-year period, were quantitatively determined by the modified Folin-Ciocalteau method. Extracts and tannin-free fractions were assayed by their potential to inhibit mouse paw edema induced by C48/80. HPLC showed high molecular weight phenolic species and flavonoids in the active extracts and fractions. The highest total phenolic content corresponded to the most potent degree of inhibition and the flavonoids were supposed to be the main species responsible for the activity, given that the flavonoid-enriched ethyl-acetate fraction maintained its effect down to a dose of 0.01 mg/kg in a dose-response manner.

As atividades de pesquisa e desenvolvimento (P&D) realizadas nos institutos públicos de pesquisa (IPPs) têm como característica uma gestão arraigada nas premissas acadêmicas, que priorizam a geração e difusão do conhecimento. Em contrapartida, a necessidade de competitividade tecnológica no mercado e a pressão pela participação, como instrumentos da política pública do esforço nacional rumo à inovação, têm pressionado os IPPs para a busca por resultados mais concretos. Esse fato acarreta a geração de grandes lacunas nos processos relacionados à gestão, induzindo a uma constante necessidade de aperfeiçoamento gerencial, no sentido de criar e melhorar ferramentas que contribuam para adequá-la à nova realidade. Este artigo propõe uma metodologia de gestão de projetos de P&D, que se baseia no direcionamento dos projetos de pesquisa para a obtenção de produtos, e considera suas características multidisciplinares e interdisciplinares e a incerteza inerentes a esse processo. Essa metodologia foi desenvolvida no Instituto de Tecnologia de Fármacos da Fiocruz e é proposta como um modelo original para instituições semelhantes.

The Research and Development (R&D) activities carried out at public research institutes have a strongly rooted academic-like management which focuses on knowledge improvement. On the other hand, the need for technological competitiveness and contribution in the national effort towards innovation has lead Brazilian organizations to search for more concrete results: products. This fact accounts for huge gaps in management-related processes and a constant need for managerial improvements in order to generate and perfect tools suitable to a new reality. This article proposes a R&D project management methodology focused on research projects that aim at new technological products taking into consideration the multidisciplinary and interdisciplinary aspects and the uncertainty inherent to this process. It presents the case of the Pharmaceutical Technology Institute, a unit of the Oswaldo Cruz Foundation, and proposes an original model for similar institutes.

Mycobacteria, specially Mycobacterium tuberculosis are among the micro-organisms that are increasing dramatically the number of infections with death, all over the world. A great number of animal experimental models have been proposed to investigate the mechanisms involved in the host response against these intracellular parasites. Studies of airway infection in guinea-pigs and rabbits, as well as, in mice intravenously infected with BCG have made an important contribution to our understanding of the virulence, pathogenesis and the immunology of mycobacterial infections. Although, there are few models to study the mechanisms of the initial inflammatory process induced by the first contact with the Mycobacteria, and the relevance of the acute generation of inflammatory mediators, cytokines and leukocyte infiltration to the development of the mycobacterial infection. In this work we reviewed our results obtained with a model of M. bovis BCG-induced pleurisy in mice, describing the mechanisms involved in the leukocyte influx induced by BCG at 24 hr. Different mechanisms appear to be related with the influx of neutrophils, eosinophils and mononuclear cells and distinct inflammatory mediators, cytokines and adhesion molecules are involved in the BCG-induced cell accumulation.