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141.
André Mario Doi Antonio Carlos Campos Pignatari Michael B. Edmond Alexandre Rodrigues Marra Luis Fernando Aranha Camargo Ricardo Andreotti Siqueira Vivian Pereira da Mota Arnaldo Lopes Colombo 《PloS one》2016,11(1)
Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. From June 2007 to March 2010, we studied a total of 2,563 nosocomial bloodstream infection (nBSI) episodes. Candida spp. was the 7th most prevalent agent. Most of the patients were male, with a median age of 56 years. A total of 64 patients (46.7%) were in the ICU when candidemia occurred. Malignancies were the most common underlying condition (32%). The crude mortality rate of candidemia during the hospital admission was 72.2%. Non-albicans species of Candida accounted for 65.7% of the 137 yeast isolates. C. albicans (34.3%), Candida parapsilosis (24.1%), Candida tropicalis (15.3%) and Candida glabrata (10.2%) were the most prevalent species. Only 47 out of 137 Candida isolates were sent to the reference laboratory for antifungal susceptibility testing. All C. albicans, C. tropicalis and C. parapsilosis isolates were susceptible to the 5 antifungal drugs tested. Among 11 C. glabrata isolates, 36% were resistant to fluconazole, and 64% SDD. All of them were susceptible to anidulafungin and amphotericin B. We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil.Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy. 相似文献
142.
Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdig?o-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J. Dick Jr Gene B. Hubbard Jane F. VandeBerg John L. VandeBerg 《PLoS neglected tropical diseases》2016,10(1)
Background
Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.Methods and Findings
Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.Conclusions
Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease. 相似文献143.
144.
Aviva Breuer Christeene G. Haj Manoela V. Foga?a Felipe V. Gomes Nicole Rodrigues Silva Jo?o Francisco Pedrazzi Elaine A. Del Bel Jaime C. Hallak José A. Crippa Antonio W. Zuardi Raphael Mechoulam Francisco S. Guimar?es 《PloS one》2016,11(7)
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4''-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. 相似文献
145.
Balancing economic costs and ecological outcomes of passive and active restoration in agricultural landscapes: the case of Brazil
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Pedro H. S. Brancalion Daniella Schweizer Ulysse Gaudare Julia R. Mangueira Fernando Lamonato Fabiano T. Farah André G. Nave Ricardo R. Rodrigues 《Biotropica》2016,48(6):856-867
Forest restoration requires strategies such as passive restoration to balance financial investments and ecological outcomes. However, the ecological outcomes of passive restoration are traditionally regarded as uncertain. We evaluated technical and legal strategies for balancing economic costs and ecological outcomes of passive versus active restoration in agricultural landscapes. We focused in the case of Brazil, where we assessed the factors driving the proportion of land allocated to passive and active restoration in 42 programs covering 698,398 hectares of farms in the Atlantic Forest, Atlantic Forest/cerrado ecotone and Amazon; the ecological outcomes of passive and active restoration in 2955 monitoring plots placed in six restoration programs; and the legal framework developed by some Brazilian states to balance the different restoration approaches and comply with legal commitments. Active restoration had the highest proportion of land allocated to it (78.4%), followed by passive (14.2%) and mixed restoration (7.4%). Passive restoration was higher in the Amazon, in silviculture, and when remaining forest cover was over 50 percent. Overall, both restoration approaches showed high levels of variation in the ecological outcomes; nevertheless, passively restored areas had a smaller percentage canopy cover, lower species density, and less shrubs and trees (dbh > 5 cm). The studied legal frameworks considered land abandonment for up to 4 years before deciding on a restoration approach, to favor the use of passive restoration. A better understanding of the biophysical and socioeconomic features of areas targeted for restoration is needed to take a better advantage of their natural regeneration potential. 相似文献
146.
Danielly Beraldo dos Santos Silva Luana Mireli Carbonera Rodrigues Adriana Araújo de Almeida Kelly Mari Pires de Oliveira Alexéia Barufatti Grisolia/ 《Memórias do Instituto Oswaldo Cruz》2016,111(3):192-199
The azoles are the class of medications most commonly used to fight infections caused
by Candida sp. Typically, resistance can be attributed to mutations
in ERG11 gene (CYP51) which encodes the cytochrome P450
14α-demethylase, the primary target for the activity of azoles. The objective of this
study was to identify mutations in the coding region of theERG11
gene in clinical isolates of Candidaspecies known to be resistant to
azoles. We identified three new synonymous mutations in the ERG11
gene in the isolates of Candida glabrata (C108G, C423T and A1581G)
and two new nonsynonymous mutations in the isolates of Candida
krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of
these nonsynonymous mutations was predicted using evolutionary conservation scores.
The G524R mutation did not have effect on 14α-demethylase functionality, while the
Y166S mutation was found to affect the enzyme. This observation suggests a possible
link between the mutation and dose-dependent sensitivity to voriconazole in the
clinical isolate of C. krusei. Although the presence of the Y166S in
phenotype of reduced azole sensitivity observed in isolate C.
kruseidemands investigation, it might contribute to the search of new
therapeutic agents against resistant Candida isolates. 相似文献
147.
148.
149.
Rosana S Lopes Marcelo M Cardoso Arthur O Sampaio Mario Santos BarbosaJr Celice C Souza Michelle C da Silva Elane Magno N Ferreira Marco Aurelio M Freire Rafael Rodrigues Lima Walace Gomes-Leal 《Journal of biosciences》2016,41(3):381-394
Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke. 相似文献