The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Regiones del cromosoma 5 asociadas a características de crecimiento en ganado criollo romosinuano / Chromosomal 5 regions associated with growth traits in the romosinuan o creole cattle

El crecimiento es una de las características de naturaleza cuantitativa que influye en la calidad de la canal. En el presente estudio se identificaron las regiones cromosomales responsables para la variación del crecimiento en el cromosoma 5 en una población de ganado criollo romosinuano. Se evaluaron en 72 progenies las características de peso alnacimiento, peso al destete, peso a los 12 meses y a los 16 meses, área de ojo del lomo alos 12 y 16 meses, espesor de grasa dorsal a los 12 y 16 meses, espesor de grasa del anca a los 12 y 16 meses, ganancia diaria predestete y posdestete, al igual que los genotipos de tres polimorfismos de nucleótido simple de los genes MYF5, PDE1B e IGF1 y decuatro microsatélites BM6026, CSSM34, RM500, ETH10, distribuidos a lo largo del cromosoma. Se realizó un análisis de regresión linear el cual mostró el efecto de seis loci de rasgos cuantitativos (QTL) asociados a características de crecimiento. Cinco QTL fueron significativos (p≤0,05) para las características de peso al nacimiento, peso a los16 meses, área del ojo de lomo a los 12 y 16 meses y ganancia diaria posdestete y un QTL se encontró con una significancia de p≤0,01 para la característica ganancia diaria predestete. Los resultados demostraron que los genes MYF5, PDE1B, IGF1 pueden ser genes candidatos posicionales que inciden en la variación del crecimiento para la calidad de la canal en el ganado romosinuano.

Growth is a quantitative trait that influences the carcass quality. In the present study, bovine chromosomal 5 regions responsible for growth variations have been identified in a Romosinuano creole cattle population. The traits birth weight, weaning weight,12 months weight, 16 months weight, the rib eye area at 12 and 16 months, back fatthickness at 12 and 16 months, rump fat thickness at 12 and 16 months, preweaning and postweaning daily gain were evaluated in 72 progenies, as well as the genotypes of 3 SNPs from the MYF5, PDE1B, IGF1 genes and 4 microsatellites (BM6026,CSSM34, RM500, ETH10) distributed along the chromosome. A linear regression analysis showed the six QTL effect associated with growth traits. Five QTL were significant at p≤0.05 for the triait birth weight, weight at 16 months, rib eye area at 12 and 16 months, and preweaning daily gain interval between 45 and 105 cM and aQTL showed a level significance of p ≤ 0.01 for the postweaning daily gain. It was demostrated according to the position of the QTLs identified in the present study, that the MYF5, PDE1B and IGF1 genes might be positional candidate genes affecting the growth variation for carcass quality in Romosinuano cattle.

Propolis: Biological and pharmacological activies. Therapeutic uses of this bee-product

This review aims to present an update of propolis properties, with emphasis on Brazilian samples. It also brings attention to points, such as standardization protocols and scientific evidence, that needed to be further investigated in order to broaden the potential therapeutic use of this bee product. Propolis became a traditional remedy in folk medicine. In recent decades a great interest has arisen in more knowledge a out its composition and therapeutic activities. Its composition is very complex, varying with the geographic region, with more than 300 constituents having been identified to date. The biological activity of propolis is associated mainly with phenolic compounds such as flavonoids and derivatives of hydroxycinnamic acids. In recent years, Brazilian propolis became the subject of increasing interest, due to its unusual chemical composition when compared with samples from other contries. Several compounds isolated presented a variety of biological activities, such as microbicidal, antioxidant and antitumoral. Although there is a huge amount of information about the chemistry and biological activity of propolis, its application in human and veterinary therapies has hardly changed. Propolis is used both in human and veterinary clinics in Eastern Europe countries, Cuba and in Uruguay. Most of the therapeutic effect of this resin is associated with microbicidal properties and the ability to scavenge free radicals. A multidisciplinary study correlating chemical composition, basic plant sources in different geographic regions, as well as and biological and pharmacological activities, open the possibility of a classification of a limited number of "chemical types" of propolis which will be possible only with the combined effort of the national and international scientific communities.

Differential effect of amphotericin B on the three evolutive stages of Trypanosoma cruzi and on the host cell-parasite interaction

1. Amphotericin B (Am.B) was shown to have a direct effect on T. cruzi, with the three forms of the parasite presenting different susceptibilities to the drug in the following order: amastigotes > trypomastigotes > epimastigotes. These differences highlight the importance of using the vertebrate forms of the parasite in tests of new drugs. 2. The treated parasites showed alterations of the plasma membrane, suggesting that, as in fungi, the primary effect of Am.B was probably via formation of complexes with membrane components. 3. When exposed to filipin, another polyene antibiotic, the three parasite forms were observed to present a similar order of susceptibility, with comparable ultrastructural modifications. 4. Higher concentrations of Am.B were required to damage the intracellular parasites in vitro, 2.3 micrograms/ml for parasites inside peritoneal macrophages and 7 micrograms/ml for parasites inside heart muscle cells. 5. Am.B is effective against the parasite, but is also toxic to mammalian cells. Testing of Am.B for the control of Chagas' disease by blood transfusion may be useful, since bloodstream forms are lysed by lower concentrations of the drug than those required to affect intracellular parasites