Tiago Pedrosa

Sulforaphane Induces Oxidative Stress and Death by p53-Independent Mechanism: Implication of Impaired Glutathione Recycling

Sulforaphane (SFN) is a naturally-occurring isothiocyanate best known for its role as an indirect antioxidant. Notwithstanding, in different cancer cell lines, SFN may promote the accumulation of reactive oxygen species (ROS) and cause cell death e.g. by apoptosis. Osteosarcoma often becomes chemoresistant, and new molecular targets to prevent drug resistance are needed. Here, we aimed to determine the effect of SFN on ROS levels and to identify key biomarkers leading to ROS unbalance and apoptosis in the p53-null MG-63 osteosarcoma cell line. MG-63 cells were exposed to SFN for up to 48 h. At 10 μM concentration or higher, SFN decreased cell viability, increased the%early apoptotic cells and increased caspase 3 activity. At these higher doses, SFN increased ROS levels, which correlated with apoptotic endpoints and cell viability decline. In exposed cells, gene expression analysis revealed only partial induction of phase-2 detoxification genes. More importantly, SFN inhibited ROS-scavenging enzymes and impaired glutathione recycling, as evidenced by inhibition of glutathione reductase (GR) activity and combined inhibition of glutathione peroxidase (GPx) gene expression and enzyme activity. In conclusion, SFN induced oxidative stress and apoptosis via a p53-independent mechanism. GPx expression and activity were found associated with ROS accumulation in MG-63 cells and are potential biomarkers for the efficacy of ROS-inducing agents e.g. as co-adjuvant drugs in osteosarcoma.

The Effect of Lycopene Preexposure on UV-B-Irradiated Human Keratinocytes

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV-B-irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h period. Thereafter, several parameters were analyzed by FCM and RT-PCR: genotoxicity/clastogenicity by assessing the cell cycle distribution; apoptosis by performing the Annexin-V assay and analyzing gene expression of apoptosis biomarkers; and oxidative stress by ROS quantification. Lycopene did not significantly affect the profile of apoptotic, necrotic and viable cells in nonirradiated cells neither showed cytostatic effects. However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells. In irradiated cells, lycopene preexposure resulted in overexpression of BAX gene compared to nonexposed irradiated cells. This was accompanied by a cell cycle delay at S-phase transition and consequent decrease of cells in G0/G1 phase. Thus, lycopene seems to play a corrective role in irradiated cells depending on the level of photodamage. Thus, our findings may have implications for the management of skin cancer.

Concepts for a personal health record

Healthcare is about information. It is usually assumed that personal health information exists primarily for professionals use but well informed patients motivate better informed professionals. A longitudinal health record containing a patients medical history has been the holy grail of healthcare. Personal Electronic Health Records (P-EHR) hold the potential to transform healthcare by providing a complete set of patient managed information. We present a portable P-EHRs functionalities from the patients perspective.

An SNMP Filesystem in Userspace

Modern computer networks are constantly increasing in size and complexity. Despite this, data networks are a critical factor for the success of many organizations. Monitoring their health and operation status is fundamental, and usually performed through specific network management architectures, developed and standardized in the last decades. On the other hand, file systems have become one of the best well known paradigms of human-computer interaction, and have been around since early days in the personal computer industry. In this paper we propose a file system interface to network management information, allowing users to open, edit and visualize network and systems operation information.

PROFILING COMPUTER ENERGY CONSUMPTION ON ORGANIZATIONS

Modern organizations depend on computers to work. Text processing, CAD, CAM, simulation, statistical analysis and so on are fundamental for maintaining high degree of productivity and competitiveness. Computers in an organization, consume a considerable percentage of the overall energy and, although a typical computer provides power saving technologies, such as suspending or hibernating components, this feature can be disabled. Moreover, the user can opt for never turning off the workstation. Well defined power saving policies, with appropriate automatic mechanisms to apply them, can provide significant power savings with consequent reduction of the power expense. With several computers in an organization, it is necessary to build the profile of the energy consumption. We propose installing a software probe in each computer to instrument the power comsumption, either diretly, by using a power meter, or indirectly, by measuring the processor performance counters. This distributed architecture, with software probes in every computer and a centralized server for persistence and decision making tries to save energy, by defining and applying organization level power saving policies.