Mycobacterium tuberculosis is the main aetiologic agent of tuberculosis, a disease of great concern in less‐developed regions. Apoptosis is a conspicuous event in macrophages infected in vitro with mycobacteria, a phenomenon also observed in vivo in granulomas of patients with tuberculosis. To determine its significance, it is important to define the mycobacterial moieties involved and how they cause apoptosis. Here we show that the 38‐kDa lipoprotein induces macrophage caspase‐dependent apoptosis involving TNF‐α and FasL and, interestingly, with the upregulation of cell‐death receptors TNFR1, TNFR2 and Fas. A role for the Toll‐like receptor 2 was also demonstrated. In conclusion, the ability to induce apoptosis of host cells is another property of the 38‐kDa lipoprotein, a molecule that has focused attention for being an immunodominant antigen that participates in phosphate transport.

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.

No abstract

The present work proposes a new mathematical eye model for ophthalmic brachytherapy dosimetry. This new model includes detailed description of internal structures that were not treated in previous works, allowing dose determination in different regions of the eye for a more adequate clinical analysis. Dose calculations were determined with the MCNP-4C Monte Carlo particle transport code running n parallel environment using PVM. The Amersham CKA4 ophthalmic applicator has been chosen and the depth dose distribution has been determined and compared to those provide by the manufacturer. The results have shown excellent agreement. Besides, absorbed dose values due to both 125I seeds and 60Co plaques were obtained for each one of the different structures which compose the eye model and can give relevant information in eventual clinical analyses.