Use of Guanidine Compounds in the Treatment of Neglected Tropical Diseases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Electrochemical, Spectrophotometric and Liquid-Chromatographic Approaches for Analysis of Tropical Disease Drugs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Tele-education environment and didactic iconography in sexual transmitted diseases

The field of advertising has developed techniques of mass communication and rapid transmission of information. Among these techniques are slogans and iconographies. This work used such tools for educational purposes and was divided into three modules. Module 1 evaluated the use of simplified textual communication (slogans) about the subject Sexually Transmitted Diseases. It was applied to third-year medical students, which had not taken the course on this theme. To evaluate the impact of the textual communication form (slogans), long phrases were elaborated in scientific language containing 15 topics. From these long phrases, compact phrases were developed using techniques of the advertising area for elaboration of slogans. Three forms of didactic material about that theme were developed. The first form consisted of long phrases in descriptive topics, using scientific language. The second was constituted exclusively of compact phrases in the form of slogans, and the third was composed of the combination of the two previous forms. Then, 10 multiple-choice questions were elaborated and applied in two phases. In the first phase, application occurred immediately after the reading of didactic texts; in the second phase, it happened 60 days after the reading. For statistical analysis, Snedcor's F test was used for analysis of variance, at 5% significance level. There was an increase in memorization by students who read the material containing the association between long phrases and slogans, which indicates that the latter, when used as an auxiliary model of learning, can bring significant benefits for education. Module 2 consisted of analyzing the elaboration of educational videos produced in graphic computing (called iconographies) for development of dynamic communication means. The theme Hair Cycle was utilized. Viability of high quantities of information in few minutes of animation could be demonstrated together with the advantage of presenting the process in a dynamic form without wasting scientific details. Module 3 presented the inclusion of slogans in educational videos produced in graphic computing about the Hair Cycle, showing a new tool for rapid and efficient transference of data. Slogans and iconographies, when utilized in educational material, can bring significant benefits for the student's learning.

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

Biodiversity Can Help Prevent Malaria Outbreaks in Tropical Forests

Background: Plasmodium vivax is a widely distributed, neglected parasite that can cause malaria and death in tropical areas. It is associated with an estimated 80-300 million cases of malaria worldwide. Brazilian tropical rain forests encompass host- and vector-rich communities, in which two hypothetical mechanisms could play a role in the dynamics of malaria transmission. The first mechanism is the dilution effect caused by presence of wild warm-blooded animals, which can act as dead-end hosts to Plasmodium parasites. The second is diffuse mosquito vector competition, in which vector and non-vector mosquito species compete for blood feeding upon a defensive host. Considering that the World Health Organization Malaria Eradication Research Agenda calls for novel strategies to eliminate malaria transmission locally, we used mathematical modeling to assess those two mechanisms in a pristine tropical rain forest, where the primary vector is present but malaria is absent. Methodology/Principal Findings: The Ross-Macdonald model and a biodiversity-oriented model were parameterized using newly collected data and data from the literature. The basic reproduction number (R0) estimated employing Ross-Macdonald model indicated that malaria cases occur in the study location. However, no malaria cases have been reported since 1980. In contrast, the biodiversity-oriented model corroborated the absence of malaria transmission. In addition, the diffuse competition mechanism was negatively correlated with the risk of malaria transmission, which suggests a protective effect provided by the forest ecosystem. There is a non-linear, unimodal correlation between the mechanism of dead-end transmission of parasites and the risk of malaria transmission, suggesting a protective effect only under certain circumstances (e.g., a high abundance of wild warm-blooded animals). Conclusions/Significance: To achieve biological conservation and to eliminate Plasmodium parasites in human populations, the World Health Organization Malaria Eradication Research Agenda should take biodiversity issues into consideration. © 2013 Laporta et al.

The Genetic Architecture of Climatic Adaptation of Tropical Cattle

Adaptation of global food systems to climate change is essential to feed the world. Tropical cattle production, a mainstay of profitability for farmers in the developing world, is dominated by heat, lack of water, poor quality feedstuffs, parasites, and tropical diseases. In these systems European cattle suffer significant stock loss, and the cross breeding of taurine x indicine cattle is unpredictable due to the dilution of adaptation to heat and tropical diseases. We explored the genetic architecture of ten traits of tropical cattle production using genome wide association studies of 4,662 animals varying from 0% to 100% indicine. We show that nine of the ten have genetic architectures that include genes of major effect, and in one case, a single location that accounted for more than 71% of the genetic variation. One genetic region in particular had effects on parasite resistance, yearling weight, body condition score, coat colour and penile sheath score. This region, extending 20 Mb on BTA5, appeared to be under genetic selection possibly through maintenance of haplotypes by breeders. We found that the amount of genetic variation and the genetic correlations between traits did not depend upon the degree of indicine content in the animals. Climate change is expected to expand some conditions of the tropics to more temperate environments, which may impact negatively on global livestock health and production. Our results point to several important genes that have large effects on adaptation that could be introduced into more temperate cattle without detrimental effects on productivity.

Purification and biological effects of a C-type lectin isolated from Bothrops moojeni

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Renal- and calcium-dependent vascular effects of Polybia paulista wasp venom

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Purification, characterization, crystallization and theoretical molecular modeling of gyroxin fraction from Crotalus durissus terrificus venom (Laurenti, 1768)

The venom of Crotalus durissus terrificus snakes presents various substances, including a serine protease with thrombin-like activity, called gyroxin, that clots plasmatic fibrinogen and promote the fibrin formation. The aim of this study was to purify and structurally characterize the gyroxin enzyme from Crotalus durissus terrificus venom. For isolation and purification, the following methods were employed: gel filtration on Sephadex G75 column and affinity chromatography on benzamidine Sepharose 6B; 12% SDS-PAGE under reducing conditions; N-terminal sequence analysis; cDNA cloning and expression through RT-PCR and crystallization tests. Theoretical molecular modeling was performed using bioinformatics tools based on comparative analysis of other serine proteases deposited in the NCBI (National Center for Biotechnology Information) database. Protein N-terminal sequencing produced a single chain with a molecular mass of similar to 30 kDa while its full-length cDNA had 714 bp which encoded a mature protein containing 238 amino acids. Crystals were obtained from the solutions 2 and 5 of the Crystal Screen Kit (R), two and one respectively, that reveal the protein constitution of the sample. For multiple sequence alignments of gyroxin-like B2.1 with six other serine proteases obtained from snake venoms (SVSPs), the preservation of cysteine residues and their main structural elements (alpha-helices, beta-barrel and loops) was indicated. The localization of the catalytic triad in His57, Asp102 and Ser198 as well as S1 and S2 specific activity sites in Thr193 and Gli215 amino acids was pointed. The area of recognition and cleavage of fibrinogen in SVSPs for modeling gyroxin B2.1 sequence was located at Arg60, Arg72, Gln75, Arg81, Arg82, Lis85, Glu86 and Lis87 residues. Theoretical modeling of gyroxin fraction generated a classical structure consisting of two alpha-helices, two beta-barrel structures, five disulfide bridges and loops in positions 37, 60, 70, 99, 148, 174 and 218. These results provided information about the functional structure of gyroxin allowing its application in the design of new drugs.