Biophysical and biological properties of small linear peptides derived from crotamine, a cationic antimicrobial/antitumoral toxin with cell penetrating and cargo delivery abilities.

Crotamine is a natural polypeptide from snake venom which delivers nucleic acid molecules into cells, besides having pronounced affinity for negatively charged membranes and antifungal activity. We previously demonstrated that crotamine derived short linear peptides were not very effective as antifungal, although the non-structured recombinant crotamine was overridingly more potent compared to the native structured crotamine. Aiming to identify the features necessary for the antifungal activity of crotamine, two linear short peptides, each comprising half of the total positively charged amino acid residues of the full-length crotamine were evaluated here to show that these linear peptides keep the ability to interact with lipid membrane model systems with different phospholipid compositions, even after forming complexes with DNA. Interestingly, the presence of cysteine residues in the structure of these linear peptides highly influenced the antifungal activity, which was not associated to the lipid membrane lytic activity. In addition to the importance of the positive charges, the crucial role of cysteine residues was noticed for these linear analogs of crotamine, although the tridimensional structure and lipid membrane lytic activity observed only for native crotamine was not essential for the antifungal activity. As these peptides still keep the ability to form complexes with DNA molecules with no prejudice to their ability to bind to lipid membranes, they may be potentially advantageous as membrane translocation vector, as they do not show lipid membrane lytic activity and may harbor or not antifungal activity, by keeping or not the semi-essential amino acid cysteine in their sequence.

Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom.

We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose-dependent manner [IC50 value of 1.87 µM], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H(+) homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles.

Anthelmintic effects of a cationic toxin from a South American rattlesnake venom.

Despite the unquestionable importance of the highly cationic feature of several small polypeptides with high content of positively charged amino acids for their biological activities, positively charged peptides do not necessarily have the capacity to cross the cell membranes. Interestingly, we found that crotamine, a positively charged amphiphilic peptide from the South American rattlesnake venom, has a unique cell-penetrating property with affinity for acidic vesicles, besides a well-characterized antimicrobial and antitumoral activities. In spite of a remarkable in vitro antifungal activity of crotamine against Candida spp., no significant effect of this peptide could be observed in the course of Candida albicans and Candida krusei infection on Caenorhabditis elegans asssed in vivo. These experiments, in which the nematode C. elegans was used as a living host, suggested, however, the potential anthelmintic activity of crotamine because of its uptake by the worms and accumulation in their acidic compartments. As described in the present work, this lysosomotropic property is consistent with a previously proposed mechanism of toxicity of crotamine on mammalian tumoral cell lines. This study also allowed us to propose the cationic peptides with lysosomotropic property, as crotamine, as a potential new class of anthelmentics with ability to overcome the challenging problems of drug resistance.

Estudos baseados nas técnicas de angiografia / Study based in angiography techniques

Este trabalho baseia-se em levantamentos radiométricos feitos nos modos de fluoroscopia e grafia, considerando medidas de feixe primário e secundário, com o objetivo da avaliação das taxas de exposição a que estão submetidos o paciente, o médico, o anestesista e demais membros da equipe executora de exames de radiologia vascular periférica.

Regimes ideais para exames específicos / Ideal regimes to specific examinations

Este trabalho visa a implantação de uma "tabela de regimes ideais para exames específicos" em radiodiagnóstico, para não só estabelecer um regime para cada tipo de exame, mas também fazer com que haja uma diminuição de filmes rejeitados e uma menor exposição do paciente.

This work has been an implantantion ·' regimes ideal of the table " for especify exams in radiografic, because establish each type of exam but too do which that decrease of films waste and a smaller pacient of exposição.

Diferença de densidade de um filme radiológico / Difference of density of a radiological film

Este trabalho foi realizado com o propósito de verificar a diferença de "densidade conforme Carlaton, Arlene cap.23" em três marcas de filmes diferentes, mostrando que além de fatores relacionados com o paciente, regime usado, processadoras, etc, também o filme em si é uma preocupação no sentido de termos uma boa qualidade de imagem.

This work has the purpose of find out the density difference in three marks of different films, displaying that over there of factors related with the pacient, used regime, processors, etc, too the film is a preocupacion in attention to have a good quality of the image

Controle de rejeitos radioativos em medicina nuclear / Control of radioative waste in medicine nuclear

Esta pesquisa é uma coletânea de dados sobre o controle de rejeitos no setor de Medicina Nuclear do Hospital São Lucas da PUCRS, visando melhores meios de armazenamento, uma redução dos mesmos e uma otimização do serviço.

This research is a collection of data about the control of waste in Medicine Nuclear of Hospital São Lucas of PUCRS. Purpose better means of storing, a decrease of sarnes anda optimizing the service