Current Knowledge of Trichosporon spp. and Trichosporonosis

Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Lab Especial Micol, Disciplina Infectol, BR-04023062 São Paulo, BrazilUniv Fed Rio Grande do Norte, Lab Micol Med Mol, Dept Anal Clin Toxicol, BR-59072970 Natal, RN, BrazilUniversidade Federal de São Paulo, Lab Especial Micol, Disciplina Infectol, BR-04023062 São Paulo, BrazilFAPESP: 2005/02006-0FAPESP: 2005/04442-1FAPESP: 2007/08575-1CNPq: 308011/2010-4CAPES: PNPD 02640-09-0Web of Scienc

Towards a Vaccine Against Rheumatic Fever

Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes

Predictive Models for the Diagnostic of Human Visceral Leishmaniasis in Brazil

Visceral leishmaniasis (VL) is a neglected tropical disease endemic to 65 countries, including Brazil, where the disease frequently occurs in remote locations and treatment is often performed on the basis of clinical suspicion. Predictive models based on scoring systems could be a helpful tool for the clinical management of VL. Based on clinical signs and symptoms, and five different serological tests of 213 patients with parasitologically confirmed (cases) and 119 with clinical suspicion of VL but with another confirmed etiology (non-cases), twelve prediction models using logistic regression and classification and regression trees (CART) for VL diagnosis were developed. The model composed of the clinical-laboratory variables and the rk39 rapid test showed the best performance in both logistic regression and CART (Sensitivity of 90.1% and specificity ranging from 97.2–97.4%). The scoring system is simple and based on the clinical-laboratory findings that are easily available in most clinical settings. The results suggest that those models might be useful in locations where access to available diagnostic methods is difficult, contributing to more efficient and more rational allocation of healthcare resources

Efeito de uma competi??o escolar de futebol com jogos em dias consecutivos no estado de recupera??o de jogadores sub-19.

The present study aimed to evaluate the effect of a school soccer competition with consecutive day games on the recovery status of U-19 players. Thirty-one school athletes (17.1?1.1 years) who played a U-19 school soccer competition (composed of two groups of four soccer teams each, followed by semifinals and final) were randomly evaluated. Games lasted 70 min (two periods of 35 min with 15 min rest interval), and they were played on consecutive days with 24 h between each game. Delayed onset muscle soreness (DOMS) and Total Quality Recovery (TQR) were measured before group phase games (n= 31) and semifinals games (n= 18). The internal game load was measured by the session rate of perceived exertion (session-RPE) method. TQR was higher before the first game when compared to the other games (p< 0.001). DOMS increased after the first game and did not return to baseline before the fourth game. Both session-RPE and internal load of the fourth game were higher than in the other games (p< 0.001). In addition, there was no correlation between internal game load and TQR (p> 0.05). The monotony observed during the evaluated period was 3.1?2.0 AU. The results indicate that the 24 h rest period seems to be insufficient for complete recovery of U-19 soccer school athletes, suggesting the organization of U-19 school soccer competitions with higher rest interval between games and search for methods to increase the recovery rate.O presente estudo objetivou analisar o efeito de uma competi??o escolar de futebol com jogos em dias consecutivos no estado de recupera??o f?sica de jogadores sub-19. Foram avaliados, de forma aleat?ria, 31 atletas escolares (17,1?1,1 anos) participantes de uma competi??o escolar de futebol de campo sub-19, composta de duas chaves com quatro equipes cada, seguido de semifinais e final. Os jogos tiveram 70 min de dura??o (dois tempos de 35 min com 15 min de intervalo), e foram realizados em dias consecutivos com intervalo de 24h entre cada jogo. Foi medida a dor muscular de in?cio tardio (DOMS) e Qualidade Total de Recupera??o (QTR) antes de cada jogo da primeira fase (n= 31) e da semifinal (n=18). A carga interna dos jogos foi medida a pelo m?todo da percep??o subjetiva do esfor?o da sess?o (PSE-sess?o). A QTR foi maior antes do primeiro jogo em compara??o com os demais jogos (p< 0.001). A DOMS aumentou ap?s o primeiro jogo e n?o retornou aos valores basais antes do quarto jogo (p< 0.001). A PSE-sess?o e a carga interna do quarto jogo foram maiores que as dos demais jogos (p< 0,001). Em adi??o, n?o houve correla??o entre a carga interna do jogo e a QTR (p> 0,05). A monotonia encontrada no per?odo avaliado foi de 3,1?2.0 UA. Os resultados indicam que o per?odo de 24h parece ser insuficiente para a completa recupera??o de atletas escolares de futebol sub-19, sugerindo a organiza??o de competi??es escolares de futebol sub-19 com maior intervalo entre os jogos e busca por m?todos que acelerem a recupera??o

Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global Expression during Morphogenesis in Candida albicans

Candida albicans is able to switch from yeast to hyphal growth and this is an essential step for tissue invasion and establishment of infection. Due to the limited drug arsenal used to treat fungal infections and the constant emergence of resistant strains, it is important to search for new therapeutic candidates. Therefore, this study aimed to investigate by proteomic analysis the role of a natural product (Eugenia uniflora) in impairing hypha formation in C. albicans. We also tested the potential action of E. uniflora to prevent and treat oral candidiasis induced in a murine model of oral infection and the ability of polymorphonuclear neutrophils to phagocytize C. albicans cells treated with the ethyl acetate fraction of the extract. We found that this fraction greatly reduced hypha formation after morphogenesis induction in the presence of serum. Besides, several proteins were differentially expressed in cells treated with the fraction. Surprisingly, the ethyl acetate fraction significantly reduced phagocytosis in C. albicans (Mean 120.36 ± 36.71 yeasts/100 PMNs vs. 44.68 ± 19.84 yeasts/100 PMNs). Oral candidiasis was attenuated when C. albicans cells were either pre-incubated in the presence of E. uniflora or when the fraction was applied to the surface of the oral cavity after infection. These results were consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml) and attenuation of tissue damage observed with histopathological analysis of animals belonging to treated group. We also observed shorter true hyphae by direct examination and histopathological analysis, when cells were treated with the referred natural product. The E. uniflora ethyl acetate fraction was non-toxic to human cells. E. uniflora may act on essential proteins mainly related to cellular structure, reducing the capacity of filamentation and attenuating infection in a murine model, without causing any toxic effect on human cells, suggesting that it may be a future therapeutic alternative for the treatment of Candida infections

Factors influencing terrestriality in primates of the Americas and Madagascar

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (bodymass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use

Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 11 million people in Latin America. The involvement of the host's immune response on the development of severe forms of Chagas disease has not been fully elucidated. Studies on the immune response against T. cruzi infection show that the immunoregulatory mechanisms are necessary to prevent the deleterious effect of excessive immune response stimulation and consequently the fatal outcome of the disease. A recall response against parasite antigens observed in in vitro peripheral blood cell culture clearly demonstrates that memory response is generated during infection. Memory T cells are heterogeneous and differ in both the ability to migrate and exert their effector function. This heterogeneity is reflected in the definition of central (TCM) and effector memory (TEM) T cells. Our results suggest that a balance between regulatory and effectors T cells may be important for the progression and development of the disease. Furthermore, the high percentage of central memory CD4+ T cells in indeterminate patients after stimulation suggests that these cells may modulate host's inflammatory response by controlling cell migration to tissues and their effector role during chronic phase of the disease