The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Ingresos y gastos de gobierno, 1947-1954 = Government income and expenditure, 1947-1954

Incluye Bibliografía

White book of e-government interoperability for Latin America and the Caribbean: version 3.0

Includes bibliography

e-Government architectures, technical and political situation in Latin America

Includes bibliography

Quality management and competitiveness: the diffusion of the ISO 9000 standards in Latin America and recommendations for government strategies

Includes bibliography

Quality management, ISO 9000 and government programmes

Includes bibliography

Macroeconomic volatility and social vulnerability in Brazil: the Cardoso government (1995-2002) and perspectives

Includes bibliography

Structural budget balance: methodology and estimation for the Chilean central government 1987-2001

Includes bibliography

Paradigmas diversos no campo da assistência social e seus estabelecimentos assistenciais típicos

In order to understand what is the situation of entities that serve children and adolescents today, as well as the institutional plot that comprises these institutions, we aimed to formulate a set of paradigmatic possibilities that would allow us to understand the configuration of the dialectical field of various pulses, in which these entities are located. We detected the subjects we associate with counterparts paradigms of Charity, of Human Promotion, of Philanthropy, of assistentialist government patronage, of Social Work as a State Policy, and finally, another set of events that we propose to designate as the paradigm of Citizen Subjects we associate with the ethical perspective of People Education. These paradigmatic possibilities range from the simply various and contrasting ones, including the similar and competing ones, to the dialectically contradictory ones. Its spectrum oscillates between tutelage and citizenship. The characterization of these didactic paradigms can provide us a compass that is required in a highly complex social field, allowing us to understand the variety of ethical effects promoted by these paradigms in the social field.

Planning and government

Includes bibliography

The United States Government's Caribbean Basin Initiative

Includes bibliography

Systemic competitiveness: a new challenge for firms and for government

Includes bibliography

Raúl Prebisch: his years in government

Includes bibliography

Institutional reform and government coordination in Brazil's social protection policy

Includes bibliography

Accountability in government programmes to promote small and medium-sized enterprises

Includes bibliography