Paracoccidioidomicose intestinal: Relato de caso

The authors report a case of intestinal involvement of paracoccidioidomycosis and discuss the symptoms, diagnosis and treatment in a patient thought to have colonic cancer. The differential diagnosis should be considered with cancer.

Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron

The mechanisms used by Paracoccidioides brasiliensis (Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose-dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocytes and the CHLOR treatment in vitro induces Pb 18 yeast-killing by monocytes by restricting the availability of intracellular iron. Besides, the CHLOR treatment in vivo significantly reduces the number of organisms in the lungs of Pb-infected mice protecting them from several infections. Thus, CHLOR was effective in the treatment of murine paracoccidioidomycosis, suggesting the potential use of this drug in patients' treatment.

Paracoccidioidomycosis: No genetic damage in human peripheral blood cells of patients assessed by single-cell gel (comet) assay

Paracoccidioidomycosis is a systemic fungal infection caused by Paracoccidioides brasiliensis. As infectious diseases can cause DNA damage, the authors aimed at analyzing DNA breakage in peripheral blood cells of patients with paracoccidioidomycosis by using the comet assay. The results suggested that paracoccidioidomycosis does not cause genotoxicity.

Evidence for the role of calcineurin in morphogenesis and calcium homeostasis during mycelium-to-yeast dimorphism of Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is a dimorphic fungus that causes paracoccidioidomycosis, the most prevalent human deep mycosis in Latin America. The dimorphic transition from mycelium to yeast (M-Y) is triggered by a temperature shift from 25°C to 37°C and is critical for pathogenicity. Intracellular Ca 2+ levels increased in hyphae immediately after temperature-induced dimorphism. The chelation of Ca 2+ with extracellular (EGTA) or intracellular (BAPTA) calcium chelators inhibited temperature-induced dimorphism, whereas the addition of extracellular Ca 2+ accelerated dimorphism. The calcineurin inhibitor cyclosporine A (CsA), but not tacrolimus (FK506), effectively decreased cell growth, halted the M-Y transition that is associated with virulence, and caused aberrant growth morphologies for all forms of P. brasiliensis. The difference between CsA and FK506 was ascribed by the higher levels of cyclophilins contrasted to FKBPs, the intracellular drug targets required for calcineurin suppression. Chronic exposure to CsA abolished intracellular Ca 2+ homeostasis and decreased mRNA transcription of the CCH1 gene for the plasma membrane Ca 2+ channel in yeast-form cells. CsA had no detectable effect on multidrug resistance efflux pumps, while the effect of FK506 on rhodamine excretion was not correlated with the transition to yeast form. In this study, we present evidence that Ca 2+/calmodulin-dependent phosphatase calcineurin controls hyphal and yeast morphology, M-Y dimorphism, growth, and Ca 2+ homeostasis in P. brasiliensis and that CsA is an effective chemical block for thermodimorphism in this organism. The effects of calcineurin inhibitors on P. brasiliensis reinforce the therapeutic potential of these drugs in a combinatory approach with antifungal drugs to treat endemic paracoccidioidomycosis. Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Paracoccidioidomicose é esporotricose associada à imunossupressão

Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis, a dimorphic fungus, prevalent in tropical and subtropical America. It is rare in the United States of America, Canada, Asia and Europe and in these countries it is related to immigrants from endemic areas. Paracoccidioidomycosis associated with immunosuppression runs a course with rapid progression and dissemination of the disease, with many cutaneous lesions. The mortality rate is up to 35% when associated with HIV infection or AIDS. The diagnosis depends on visualization of the agent through direct examination, histopathology, or culture. First choice treatment is done with Amphotericin B deoxycholate. Itraconazole is an option for long term treatment. Sporotrichosis is caused by Sporothrix schenckii, the species of reference. Other species have been considered such as: Sporothrix brasiliensis, S.globosa and S.mexicana and the S.schenckii var. lurei. It is a ubiquitous disease although more prevalent in tropical and subtropical areas. Currently, it has been reported as a zoonotic disease of cats and dogs, with transmission to their owners in the city of Rio de Janeiro (Brazil). Sporotrichosis associated to immunosuppression is uncommon or underreported. There were 34 cases in association with HIV infection or AIDS reported so far. Presenting with disseminated disease and non cutaneous lesions including joints, lungs and central nervous system. Amphotericin B deoxycholate is the first choice for treatment and itraconazol considered an alternative.

Paracoccidoides brasiliensis 30 kDa Adhesin: Identification as a 14-3-3 Protein, Cloning and Subcellular Localization in Infection Models

Paracoccidoides brasiliensis adhesion to lung epithelial cells is considered an essential event for the establishment of infection and different proteins participate in this process. One of these proteins is a 30 kDa adhesin, pI 4.9 that was described as a laminin ligand in previous studies, and it was more highly expressed in more virulent P. brasiliensis isolates. This protein may contribute to the virulence of this important fungal pathogen. Using Edman degradation and mass spectrometry analysis, this 30 kDa adhesin was identified as a 14-3-3 protein. These proteins are a conserved group of small acidic proteins involved in a variety of processes in eukaryotic organisms. However, the exact function of these proteins in some processes remains unknown. Thus, the goal of the present study was to characterize the role of this protein during the interaction between the fungus and its host. To achieve this goal, we cloned, expressed the 14-3-3 protein in a heterologous system and determined its subcellular localization in in vitro and in vivo infection models. Immunocytochemical analysis revealed the ubiquitous distribution of this protein in the yeast form of P. brasiliensis, with some concentration in the cytoplasm. Additionally, this 14-3-3 protein was also present in P. brasiliensis cells at the sites of infection in C57BL/6 mice intratracheally infected with P. brasiliensis yeast cells for 72 h (acute infections) and 30 days (chronic infection). An apparent increase in the levels of the 14-3-3 protein in the cell wall of the fungus was also noted during the interaction between P. brasiliensis and A549 cells, suggesting that this protein may be involved in host-parasite interactions, since inhibition assays with the protein and this antibody decreased P. brasiliensis adhesion to A549 epithelial cells. Our data may lead to a better understanding of P. brasiliensis interactions with host tissues and paracoccidioidomycosis pathogenesis. © 2013 Silva et al.

The role of leukotriene B4 in early stages of experimental paracoccidioidomycosis induced in phenotypically selected mouse strains

Paracoccidioidomycosis is a human systemic mycosis caused by the fungus Paracoccidioides brasiliensis. The mechanisms involved in innate immune response to this fungus are not fully elucidated. Leukotrienes are known to be critical for the clearance of various microorganisms, mainly by mediating the microbicidal function of phagocytes. We investigated the involvement of leukotriene B4 in the early stages of experimental paracoccidioidomycosis, which was induced by intratracheal inoculation of the fungus in selected mouse lines. The mouse lines utilized were produced through bi-directional phenotypic selection, endowed with maximal or minimal acute inflammatory reactivity, and designated AIRmax and AIRmin, respectively. AIRmax mice were more resistant to the infection, which was demonstrated by reduced lung fungal loads. However, the two lines produced similar amounts of leukotriene B4, and pharmacological inhibition of this mediator provoked similar fungal load increases in the two lines. The lower fungal load in the AIRmax mice was associated with a more effective inflammatory response, which was characterized by enhanced recruitment and activation of phagocytic cells and an increased production of activator cytokines. This process resulted in an increased release of fungicidal molecules and a diminution of fungal load. In both lines, leukotriene production was associated with a protective response in the lung that was consequent to the effect of this eicosanoid on the influx and activation of phagocytes. © 2013 ISHAM.

Studies of natural killer cells in patients with paracoccidioidomycosis

The number and activity of natural killer (NK) cells were studied in 34 untreated patients with paracoccidioidomycosis, 20 with the chronic form of the disease and 14 with the acute form. NK cells were detected with monoclonal antibody Leu-11c and the cytotoxic activity was measured using a single cell assay against K562 target cells. Both groups of patients had an increased number of circulating NK cells, their cytotoxic activity being significantly lower than in the healthy controls. These findings may be of importance in the immunological disturbances associated with paracoccidioidomycosis since NK cells exert important immune effector functions and may play a role in resistance against Paracoccidioides brasiliensis.

Chromosome aberrations in lymphocyte cultures from paracoccidioidomycosis patients

Blood cell lymphocyte chromosomes from untreated (UT) and clinically-cured (CC) patients with paracoccidioidomycosis and from healthy (control) people (CO) were studied. The frequency of aneuploid cells in the UT patients was higher than in the CC and CO individuals. The frequency of metaphase cells with premature centromere division was significantly higher in the UT than in the CC and CO group. No structural aberration and no statistically significant difference in the frequency of polyploidy was observed in the three groups studied. Our findings are indicative of an aneugenic (aneuploidy-inducing) action of infection by Paracoccidioides brasiliensis.

An old taxonomic dilemma: the identity of the western south Atlantic lebranche mullet (Teleostei: Perciformes: Mugilidae)

The identification of the lebranche mullet in the western south Atlantic has long been problematical. In most recent works either Mugil liza Valenciennes and M. platanus Gunther, 1880 or M. liza and M. cephalus Linnaeus, 1758 were recognized from the region and more rarely the occurrence of only one species has been proposed but without sufficient morphological, biochemical or molecular data to allow the designation of the taxonomically appropriate name. Analysis of meristic and morphometric data taken from samples collected from Venezuela to Argentina, clearly indicates that there is only one species of lebranche mullet in the Caribbean Sea region and the Atlantic coast of South America and that Mugil liza is the appropriate name. The comparison of the combined data from all the samples of M. liza with the data taken from one sample of M. cephalus that originated in the Mediterranean, the possible locality from which type specimens were collected (Eschmeyer and Fricke, 2009), revealed significant differences indicating that they are different species. It is also suggested that individuals from the western north Atlantic identified as M. cephalus might represent a population of M. liza in this region.

Tectonics and sedimentation in the Curitiba Basin, south of Brazil

The Curitiba Basin, Parana, lies parallel to the west side of the Serra do Mar range and is part of a continental rift near the Atlantic coast of southeastern Brazil. It bears unconsolidated and poorly consolidated sediments divided in two formations: the lower Guabirotuba Formation and the overlying Tinguis Formation, both developed over Precambrian basement. Field observations, water well drill cores, and interpretations of satellite images lead to the inference that regional tectonic processes were responsible for the origin of the Basin in the continental rift context and for morphotecatonic evolution through block tilting, dissection, and erosion. The structural framework of the sediments and the basement is characterized by NE-SW-trending normal faults (extensional tectonic D-1 event) reactivated by NE-SW-trending strike-slip and reverse oblique faults (younger transtensional tectonic D-2' to transpressional tectonic D-2, event). This tectonic event, which started in the Paleogene and controlled the basin geometry, began as a halfgraben and was later reactivated as a pull-apart basin. D-2 is a neotectonic event that controls the current morphostructures. The Basin is connected to the structural rearrangement of the South American platform, which underwent a generalized extensional or trantensional process and, in late Oligocene, changed to a compressional to transpressional regime. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

Some constraints on the modeling using the uranium isotopes U-238 and U-234 for dating groundwaters from Guarany aquifer, South America

Groundwaters from the Guarany aquifer located at the South American continent and sampled at four wells with described geological sections in São Paulo State, Brazil, were chemically and isotopically analysed with two aims: to evaluate the quality of this important hydrological resource and to investigate the possibility of using the natural uranium isotopes U-234 and U-238 as a chronological tool, since the U-234/U-238 activity ratio and dissolved U content data in groundwater systems have generated models for dating purposes.

A stratigraphic chart of the Late Carboniferous/Permian succession of the eastern border of the Parana Basin, Brazil, South America

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Some constraints on the modelling using the uranium isotopes 238U and 234U for dating groundwaters from Guarany aquifer, South America

Groundwaters from the Guarany aquifer located at the South American continent and sampled at four wells with described geological sections in São Paulo State, Brazil, were chemically and isotopically analysed with two aims: to evaluate the quality of this important hydrological resource and to investigate the possibility of using the natural uranium isotopes 234U and 238U as a chronological tool, since the 234U/238U activity ratio and dissolved U content data in groundwater systems have generated models for dating purposes.

Recognition of Cretaceous, Paleocene, and Neogene tectonic reactivation through apatite fission-track analysis in Precambrian areas of southeast Brazil: Association with the opening of the south Atlantic Ocean

Apatite fission-track analysis was used for the determination of thermal histories and ages in Precambrian areas of southeast Brazil. Together with geological and geomorphologic information, these ages enable us to quantify the thermal histories and timing of Mesozoic and Cenozoic epirogenic and tectonic processes. The collected samples are from different geomorphologic blocks: the high Mantiqueira mountain range (HMMR) with altitude above 1000 m, the low Mantiqueira mountain range (LMMR) under 1000 m, the Serra do Mar mountain range (SMMR), the Jundiá and Atlantic Plateaus, and the coastline, all of which have distinct thermal histories. During the Aptian (∼120 Ma), there was an uplift of the HMMR, coincident with opening of the south Atlantic Ocean. Its thermal history indicates heating (from ∼60 to∼80 °C) until the Paleocene, when rocks currently exposed in the LMMR reached temperatures of ∼100 °C. In this period, the Serra do Mar rift system and the Japi erosion surface were formed. The relief records the latter. During the Late Cretaceous, the SMMR was uplifted and probably linked to its origin; in the Tertiary, it experienced heating from ∼60 to ∼90 °C, then cooling that extends to the present. The SMMR, LMMR, and HMMR were reactivated mainly in the Paleocene, and the coastline during the Paleogene. These processes are reflected in the sedimentary sequences and discordances of the interior and continental margin basins. © 2002 Elsevier Science Ltd. All rights reserved.