The dimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM), a mycosis of high incidence in Brazil. The toxicity of drug treatment and the emergence of resistant organisms have led to research for new candidates for drugs. In this study, we demonstrate that the natural product argentilactone was not cytotoxic or genotoxic to MRC5 cells at the IC50 concentration to the fungus. We also verified the proteomic profile of Paracoccidioides lutzii after incubation with argentilactone using a label free quantitative proteome nanoUPLC-MSE. The results of this study indicated that the fungus has a global metabolic adaptation in the presence of argentilactone. Enzymes of important pathways, such as glycolysis, the Krebs cycle and the glyoxylate cycle, were repressed, which drove the metabolism to the methylcytrate cycle and beta-oxidation. Proteins involved in cell rescue, defense and stress response were induced. In this study, alternative metabolic pathways adopted by the fungi were elucidated, helping to elucidate the course of action of the compound studied.
Preeclampsia is an obstetric disease of unknown cause that affects approximately 5% of pregnant women. The visual system may be affected with variable intensity, being the retinal detachment a rare complication. The retinal detachment in preeclampsia is usually bilateral and serous, and its pathogenesis is related to the choroidal ischemia secondary to an intense arteriolar vasospasm. The majority of patients have complete recovery of vision with clinical management, and surgery is unnecessary. This is a case report of a 27 year old patient who developed the severe form of preeclampsia on her first pregnancy. She had progressive blurred vision, until she could see only shadows. Ophthalmic examination diagnosed spread and bilateral retinal detachment. With blood pressure control at postpartum, the patient had her retina reattached, and recovery of vision.
The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including Paracoccidioides spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did not show inhibitory action on the fungus. The results were supported by in silico experiments.
Introduction:The purpose of this study was to compare respiratory signs and symptoms between patients with and without chest X-ray abnormalities in order to establish the meaning of radiographic findings in pulmonary PCM diagnosis. Methods: The epidemiological, clinical and radiological lung findings of 44 patients with paracoccidiodomycosis (PCM) were evaluated. Patients were divided into two groups of 23 and 21 individuals according to the presence (group 1) or absence (group 2) of chest X-ray abnormalities, respectively, and their clinical data was analyzed with the aid of statistical tools. Results: As a general rule, patients were rural workers, young adult males and smokers -group 1 and 2, respectively: males (91.3% and 66.7%); mean age (44.4 and 27.9 year-old); smoking (34.7% and 71.4 %); acute/subacute presentation (38.1% and 21.7%); chronic presentation (61.9% and 78.3%). The most frequent respiratory manifestations were -group 1 and 2, respectively: cough (25% and 11.4%) and dyspnea (22.7% and 6.8%). No statistical difference was observed in pulmonary signs and symptoms between patients with or without radiographic abnormalities. The most frequent radiological finding was nodular (23.8%) or nodular-fibrous (19%), bilateral (90.5%) and diffuse infiltrates (85.7%). Conclusions: Absence of statistical difference in pulmonary signs and symptoms between these two groups of patients with PCM indicates clinical-radiological dissociation. A simplified classification of radiological lung PCM findings is suggested, based on correlation of these data and current literature review.
Dentre as infecções fúngicas que acometem seres humanos, a candidíase adquire relevância e Candida albicans é o agente etiológico mais comum, porém têm emergido episódios de candidíase causada por outras espécies como Candida parapsilosis. O Cerrado brasileiro possui uma grande diversidade de plantas e a Curcuma longa, planta vastamente encontrada neste bioma, tem sido estudada por sua capacidade tanto antibacteriana quanto antifúngica. O presente trabalho teve como objetivo avaliar a atividade antifúngica de C. longa sobre C. parapsilosis por meio da análise da capacidade inibitória de extratos de diferentes partes da referida planta sobre o fungo. Foi avaliada a atividade antifúngica dos extratos etanólicos de rizoma e folhas de C. longa por meio do método de macrodiluição seriada, determinandose a concentração inibitória mínima (CIM), e por meio do teste de sensibilidade em placas e do método de disco de difusão. Além disso, avaliou-se o sinergismo entre os extratos em associação com antifúngicos tradicionalmente utilizados. C. longa apresentou atividade inibitória sobre o crescimento de C. parapsilosis com valor de CIM (500 ppm) obtido a partir dos extratos etanólicos de rizoma e folha. Foi possível observar atividade sinérgica entre a folha e anfotericina B e atividade antagônica entre rizoma e anfotericina B. Conclui-se que os extratos de folha e rizoma de C. longa apresentam atividade antifúngica sobre C. parapsilosis de maneira dose-dependente, evidenciando o potencial antifúngico da referida planta.
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