BACKGROUND Recent studies showed that essential oils from different pepper species (Piper spp.) have promising leishmanicidal and trypanocidal activities.OBJECTIVES In search for natural compounds against Trypanosoma cruzi, different forms of the parasite were incubated for 24 h at 28ºC or 4ºC with Piper aduncum essential oil (PaEO) or its main constituents linalool and nerolidol.METHODS PaEO chemical composition was obtained by GC-MS. Drug activity assays were based on cell counting, MTT data or infection index values. The effect of PaEO on the T. cruzi cell cycle and mitochondrial membrane potential was evaluated by flow cytometry.FINDINGS PaEO was effective against cell-derived (IC50/24 h: 2.8 μg/mL) and metacyclic (IC50/24 h: 12.1 μg/mL) trypomastigotes, as well as intracellular amastigotes (IC50/24 h: 9 μg/mL). At 4ºC - the temperature of red blood cells (RBCs) storage in blood banks - cell-derived trypomastigotes were more sensitive to PaEO (IC50/24 h = 3.8 μg/mL) than to gentian violet (IC50/24 h = 24.7 mg/mL). Cytotoxicity assays using Vero cells (37ºC) and RBCs (4ºC) showed that PaEO has increased selectivity for cell-derived trypomastigotes. Flow cytometry analysis showed that PaEO does not affect the cell cycle of T. cruzi epimastigotes, but decreases their mitochondrial membrane potential. GC-MS data identified nerolidol and linalool as major components of PaEO, and linalool had trypanocidal effect (IC50/24 h: 306 ng/mL) at 4ºC.MAIN CONCLUSION The trypanocidal effect of PaEO is likely due to the presence of linalool, which may represent an interesting candidate for use in the treatment of potentially contaminated RBCs bags at low temperature.
Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle in which four distinct developmental forms alternate between the insect vector and the mammalian host. It is assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host, a paradigm corroborated by the widely acknowledged fact that only this stage is susceptible to the complement system. In the present work, we establish a T. cruzi in vitro and in vivo epimastigogenesis model to analyze the biological aspects of recently differentiated epimastigotes (rdEpi). We show that both trypomastigote stages of T. cruzi (cell-derived and metacyclic) are able to transform into epimastigotes (processes termed primary and secondary epimastigogenesis, respectively) and that rdEpi have striking properties in comparison to long-term cultured epimastigotes: resistance to complement-mediated lysis and both in vitro (cell culture) and in vivo (mouse) infectivity. Proteomics analysis of all T. cruzi stages reveled a cluster of proteins that were up-regulated only in rdEpi (including ABC transporters and ERO1), suggesting a role for them in rdEpi virulence. The present work introduces a new experimental model for the study of host-parasite interactions, showing that rdEpi can be infective to the mammalian host.
A sonar based device with tactile feedback was developed to improve the mobility and independence of visually impaired individuals. It features a transceiver/receiver, a potentiometer, a microcontroller, a rechargeable polymer lithium ion battery, and a Nokia Cell phone vibrator. All components are commercially available and housed in a custom acrylic package with 86 mm × 34 mm × 12 mm in dimension, and 120 grms in weight. Additionally, the device features an adjustable detection scheme for user customization of distance range, and a tactile feedback system that avoids interference with auditory sensory information. The device was tested for its navigational efficacy in an artificial indoor environment, and in a live outdoor setting. Ten subjects (9 males and 1 female), with a mean age of 35 years-old (range: 17 to 52) were presented with a series of navigational tasks resulting in considerable reduction of head, shoulder, chest, and arms collisions during their locomotion. We conclude that this device greatly improves the mobility and safety of visually impaired individuals.
Several novel quinine analogs with trypanocidal activity have been identified with the para-nitro-substituted derivative displaying a submicromolar IC, which is 83-times lower than quinine and three-times lower than benznidazole. Transmission electron microscopy analysis demonstrated that these compounds induced a marked vacuolization of the kinetoplast of intracellular amastigotes and cell-derived trypomastigotes.
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