Antifungal and antitumor models of bioactive protective peptides

Peptides are remarkably reactive molecules produced by a great variety of species and able to display a number of functions in uni-and multicellular organisms as mediators, agonists and regulating substances. Some of them exert cytotoxic effects on cells other than those that produced them, and may have a role in controlling subpopulations and protecting certain species or cell types. Presently, we focus on antifungal and antitumor peptides and discuss a few models in which specific sequences and structures exerted direct inhibitory effects or stimulated a protective immune response. The killer peptide, deduced from an antiidiotypic antibody, with several antimicrobial activities and other Ig-derived peptides with cytotoxic activities including antitumor effects, are models studied in vitro and in vivo. Peptide 10 from gp43 of P. brasiliensis (P10) and the vaccine perspective against paracoccidioidomycosis is another topic illustrating the protective effect in vivo against a pathogenic fungus. The cationic antimicrobial peptides with antitumor activities are mostly reviewed here. Local treatment of murine melanoma by the peptide gomesin is another model studied at the Experimental Oncology Unit of UNIFESP.

Peptídeos são moléculas particularmente reativas produzidas por uma grande variedade de espécies, aptos a exercer um número de funções em organismos uni-e multicelulares como mediadores, agonistas e substâncias regulatórias. Alguns deles exercem efeitos citotóxicos em células outras das que os produzem, e podem ter um papel controlando subpopulações e protegendo certas espécies ou tipos celulares. No presente, focalizamos peptídeos antifúngicos e antitumorais e discutimos alguns modelos nos quais seqüências específicas e estruturas exercem efeitos inibitórios diretos ou estimulam uma resposta imune protetora. O peptídeo letal ("killer"), deduzido de um anticorpo anti-idiotípico, com várias atividades antimicrobianas bem como outros peptídeos derivados de imunoglobulinas com atividades citotóxicas incluindo efeitos antitumorais são modelos estudados in vitro e in vivo. O peptídeo P10 da gp43 de P. brasiliensis e a perspectiva de vacina contra a paracoccidioidomicose é outro tópico ilustrando o efeito protetor in vivo contra um fungo patogênico. Peptídeos antimicrobianos catiônicos com atividades antitumorais são os principais revistos aqui. O tratamento local do melanoma murino com o peptídeo gomesina é outro modelo estudado na Unidade de Oncologia Experimental (UNONEX) da UNIFESP.

Resistance of melanized yeast cells of Paracoccidioides brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18

Paracoccidioides brasiliensis, a thermal dimorphic fungal pathogen, produces a melanin-like pigment in vitro and in vivo. We investigated the involvement of carbohydrates and monoclonal antibody to CD18, on phagocytosis inhibition, involving macrophage receptors and the resistance of melanized fungal cells to chemically generated nitric oxide (NO), reactive oxygen species (ROS), hypochlorite and H2O2. Our results demonstrate that melanized yeast cells were more resistant than nonmelanized yeast cells to chemically generated NO, ROS, hypochlorite and H2O2, in vitro. Phagocytosis of melanized yeast cells was virtually abolished when mannan, N-acetyl glucosamine and anti-CD18 antibody were added together in this system. Intratracheal infection of BALB/c mice, with melanized yeast cells, resulted in higher lung colony forming units, when compared to nonmelanized yeast cells. Therefore, melanin is a virulence factor of P. brasiliensis.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2 percent). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9 percent) appeared at the top of the list, followed by candidiasis (30.2 percent), histoplasmosis (10.1 percent) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Role of parasite surface glycoconjugates on induction/regulation of immune responses and inflammation, elicited during Trypanosoma cruzi infection: potential implications on pathophysiology of Chagas" disease

To understand the interaction of Trypanosoma cruzi and the immune system of the vertebrate host, and therefore the pathophysiology of Chagas' disease, different research groups have focused their attention on the identification and characterization of parasite molecules involved in the activation of either innate or adaptive immune responses. The parasite surface molecules that serve as targets of the vertebrate host immune system have also been studied and identified. These studies have revealed that the quatitatively dominant complex of glycosylphosphatidylinositol (GPI)-anchored molecules (GIPLs, mucins and TS) present on the surface of T. cruzi trypomastigotes are essential to control activation of the innate immune system and promote initiation of acquired immune responses in the vertebrate host. Two major families of surface glycoproteins (mucin-like glycoproteins and transialidases) have also been shown to be important targets of parasite specific humoral and cellular immune responses. They are, thus, important candidates for vaccine development as determined in studies using experimental models. Studies regarding the molecular cloning and/or biochemical characterization of the above mentioned T. cruzi surface molecules, and their ability to influence the outcome of T. cruzi infection in the vertebrate host through the stimulation and/or control of the immune system are presently reviewed. A proposition is made that such molecules may have evolved and been selectively conserved to establish an equilibrium between the parasite and its vertebrate host, limiting parasite replication, but allowing parasite persistence and host survival, thus favoring the maintenance of T. cruzi life cycle.

José Ribeiro do Valle (1908) / José Ribeiro do Valle (1908)

Introduz algumas notas biográficas sobre José Ribeiro do Valle e apresenta a entrevista por ele concedida a Luiz R. Travassos, Neide Iurkiewicz e Vera Rita da Costa, que focaliza sua trajetória profissional a partir do despertar de seu interesse pela ciência, passando por sua experiência como médico sanitarista, professor e pesquisador em farmacologia.(MAM)

Carbohydrate epitopes: structure and presentation and the reactivity of biological ligands: recognition of alpha-D-Galp NAc and alpha-D-Galp conformational structures

Apart from glycolipids and glycoproteins that express A and B blood group antigens which contain terminal nonreducing units of alpha-D-Galp NAc and alpha-D-Galp respectively, there are several other glycoconjugates in nature that contain these units linked to unfucosylated saccharides or protein. They represent normal products of the action of specific glycosyl-transferases in primate and nonprimate mammalian cells, protozoa and a few other microorganisms, end-units of carbohydrate components that have not benn further processed by additional glycosylation, or neo-antigens resulting from deregulation of certain transferases as in tumor cells. Biological ligands recognizing these structures include mono and polyclonal antibodies, bacterial fimbriae and laminin. Binding depends on the linkages and sequence of the carbohydrate chain, but also on the epitope conformation as influenced by adjacent substitution, angling determined by the glycoconjugate-substrate interaction, steric hindrance and other factors. These aspects are discussed in this minireview.