Calcium-Independent Membrane Damage by Venom Phospholipases A(2)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

4 '-Aminochalcones As Novel Inhibitors of the Chlorinating Activity of Myeloperoxidase

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

A Validated Stability-Indicating LC Method for Orbifloxacin in the Presence of Degradation Products

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

Anthelmintic effects of condensed tannins on Trichostrongylus colubriformis in experimentally infected sheep

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

Associação micorízica em espécies arbóreas, atividade microbiana e fertilidade do solo em áreas degradadas de cerrado

The recuperation of areas used during the construction of the hydroelectric plant, especially in 'borrowed areas', is a difficult and long process since all vegetation and the fertile layer of soil were removed. Interventions in these degraded areas could accelerate the revegetation process. The objective of this research was to evaluate the association of arbuscular mycorrhizal fungi (AMF) in tree species, microbial activity (basal respiration) and fertility of 'cerrado' degraded areas. Soil from two areas, pasture soil and exposed subsoil, were utilized. Organic and mineral fertilization, and liming, were added to the pit for better seedlings' initial growth, where 50 mL of preserved cerrado soil was applied as inoculum of microorganisms. Seedlings of 11 tree species were planted: Anadenanthera falcata (Benth.) Speg ('angico-preto'), Acacia polyphylla D. C. ('monjoleiro'), Stryphnodendron adstringens (Mart.) Coville ('barbatimao'), Dimorphandra mollis Benth ('faveiro'), Hymenaea stigonocarpa Mart. ex Hayne ('jatoba-de-cerrado'), Dipteryx alata Vog. ('baru'), Machaerium acutifolium Vogel ('jacaranda-do-campo'), Schinus terebinthifolia Raddi ('aroeirapimenteira'), Magonia pubescens St. Hil. ('tingui'), Lafoensia pacari St. Hil. ('dedaleira') and Tabebuia aurea (Manso) Benth. & Hook ('ipe-amarelo'). Twelve months later, root samples were colleted at the depth of 0-0.10 m and used for evaluations. The subsoil, as compared to pasture soil, was poor in organic matter and presented less microbial activity. The highest mycorrhizal colonization was seen in the species Acacia polyphylla D. C. (monjoleiro), Magonia pubescens St. Hil. (tingui), Hymenaea stigonocarpa Mart. ex Hayne (jatoba-de-cerrado) and Schinus terebinthifolia Raddi (aroeira-pimenteira). These species could be indicated in revegetation projects in 'cerrado' degraded areas. Plants from both areas showed seedlings form high mycorrhizal colonization and low numbers of spores.

Growth parameters and nutrient content in four multipurpose tree species with potential characteristics for agroforestry systems in a Cerrado region in Botucatu, São Paulo State, Brazil

In order to evaluate growth characteristics, adaptability, biomass production, nutrient recycling, nutrient distribution and the ability to regenerate degraded land, a trial using four multipurpose tree species (Leucaena leucocephala, Leucaena diversifolia, Acacia melanoxylon and Mimosa scabrella) was undertaken over two years in a distrophic red yellow latosol (oxisol) following a randomized block experimental design with four replications. At the age of two years, A. melanoxylon and L. diversifolia were the tallest species (5.25 and 4.97 m, respectively) and A. melanoxylon and M. scabrella had the largest diameters at 20 cm from tree base. Mimosa scabrella and A. melanoxylon had the highest dry matter production and quantity of nutrients in the above ground biomass. In all species, the highest nutrient contents were found in the leaves, followed by branches and stems. From all species, the highest Nutrient Utilization Efficiency Indexes were obtained for sulphur, phosphorous, and magnesium; L. diversifolia was the most efficient for nitrogen, potassium, calcium, sulphur, and manganese, while A. melanoxylon was the most efficient for phosphorus, magnesium, boron, iron, and zinc. Litter production levels over a three month period were as follows: M. scabrella > A. melanoxylon > L. diversifolia > L. leucocephala. Litter nutrient content was higher in M. scabrella than in the other species.

A review of antifertility folkloric plants tested in laboratory animals

The use of natural active principals is widespread among a great proportion of the rural population, or by people who do not have easy access to medical assistance. These active principles are used as food or medicines, and even for purposes of contraception. It becomes necessary to establish a relationship between the folklore habits and current information on the nature of anti-fertility substances, and knowledge of their mechanisms. Anti-fertility agents may exert their actions in a number of areas, (hypothalamus, anterior pituitary, oviduct, uterus, and vagina), inhibiting synthesis and/or liberation of hormones (follicle-stimulating, luteinizing, and steroid hormones), ovulation, ovum transportation, and implantation process. Therefore, a review of literature was carried out, including of several plants used by women as abortifacient and anti-fertility agents to compare their effects with those obtained among laboratory animals.

Retorno de nutrientes ao solo via deposição de serapilheira de quatro espécies leguminosas arbóreas na região de Botucatu - São Paulo, Brasil

The annual litter fall production and the concentrations of macronutrients of four leguminous tree species were evaluated. The experiment was installed in a distrophic red yellow latosol (Oxisol), derivative of the Bauru sandstone group. The studied species were: Leucaena leucocephala. Acacia melanoxylon, L. diversifolia and Mimosa scabrella. The experimental design was randomized blocks, with four treatments (species) and four replications. The litter fall was collected in boxes measuring 50×50×10 cm, two boxes by treatment in each block. The material was collected monthly and dried, weighed and chemically analyzed. The litter fall deposition occurred in the following order: M. scabrella (7,051 kg ha -1 ano -1), A. melanoxylon (2,789 kg ha -1 ano -1), L. diversifolia (1,576 kg ha -1 ano -1) and L. leucocephala (1,389 kg ha -1 ano -1). The content of nutrients obeyed the following order: N>Ca>K>Mg>P>S, with the exception of L. leucocephala that presented a bigger content of S in relation to the P.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

Molecular modeling databases: A new way in the search of protein targets for drug development

DBMODELING is a relational database of annotated comparative protein structure models and their metabolic, pathway characterization. It is focused on enzymes identified in the genomes of Mycobacterium tuberculosis and Xylella fastidiosa. The main goal of the present database is to provide structural models to be used in docking simulations and drug design. However, since the accuracy of structural models is highly dependent on sequence identity between template and target, it is necessary to make clear to the user that only models which show high structural quality should be used in such efforts. Molecular modeling of these genomes generated a database, in which all structural models were built using alignments presenting more than 30% of sequence identity, generating models with medium and high accuracy. All models in the database are publicly accessible at http://www.biocristalografia.df.ibilce.unesp.br/tools. DBMODELING user interface provides users friendly menus, so that all information can be printed in one stop from any web browser. Furthermore, DBMODELING also provides a docking interface, which allows the user to carry out geometric docking simulation, against the molecular models available in the database. There are three other important homology model databases: MODBASE, SWISSMODEL, and GTOP. The main applications of these databases are described in the present article. © 2007 Bentham Science Publishers Ltd.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

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.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.