38 research outputs found

    Nelfinavir, an HIV-1 Protease Inhibitor, Induces Oxidative Stress–Mediated, Caspase-Independent Apoptosis in Leishmania Amastigotes

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    Visceral leishmaniasis is the most severe form of disease caused by the parasite Leishmania. It is a major concern in South America, Africa, India and the Middle East. Additionally, it has now emerged as an important opportunistic disease in patients coinfected with HIV-1. This is due, in part, to the increasing overlap between urban centers and rural areas endemic for Leishmania. Although more efficient combinatorial antiviral drug regimens for treating HIV-1 infection have been developed, the impact of such therapies on HIV-1/Leishmania coinfection is yet to be explored. In this study, we investigated the effect of nelfinavir, a well-characterized anti-HIV-1 drug, on Leishmania. Treating the parasite with nelfinavir activates events that are hallmarks of programmed cell death (also called apoptosis). Among these are oxidative stress, changes in DNA replication and fragmentation, and release of mitochondrial enzymes. Furthermore, these events occur without the participation of caspases, which are classically linked to apoptosis; however, this atypical apoptosis requires the translocation of endonuclease G from mitochondria to the cytoplasm. These findings provide insights for the design of new anti-parasitic therapies, particularly in the case of Leishmania/HIV-1 coinfections

    X-ray high-resolution vascular network imaging

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    This paper presents the ïŹrst application of high-resolution X-ray synchrotron tomography to the imaging of large micro- vascular networks in biological tissue samples. This technique offers the opportunity of analysing the full three-dimensional vascular network from the micrometre to the millimetre scale. This paper presents the speciïŹc sample preparation method and the X-ray imaging procedure. Either barium or iron was injected as contrast agent in the vascular network. The impact of the composition and concentration of the injected solution on the X-ray synchrotron tomography images has been studied. Two imaging modes, attenuation and phase contrast, are compared. Synchrotron high-resolution computed tomography offers new prospects in the three-dimensional imaging of in situ biological vascular networks
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