Hepatotoxicity prediction by systems biology modeling of disturbed metabolic pathways using gene expression data.

The present study applies a systems biology approach for the in silico predictive modeling of drug toxicity on the basis of high-quality preclinical drug toxicity data with the aim of increasing the mechanistic understanding of toxic effects of compounds at different levels (pathway, cell, tissue, organ). The model development was carried out using 77 compounds for which gene expression data for treated primary human hepatocytes is available in the LINCS database and for which rodent in vivo hepatotoxicity information is available in the eTOX database. The data from LINCS were used to determine the type and number of pathways disturbed by each compound and to estimate the extent of disturbance (network perturbation elasticity), and were used to analyze the correspondence with the in vivo information from eTOX.

Integrative Modeling Strategies for Predicting Drug Toxicities at the eTOX Project.

Early prediction of safety issues in drug development is at the same time highly desirable and highly challenging. Recent advances emphasize the importance of understanding the whole chain of causal events leading to observable toxic outcomes. Here we describe an integrative modeling strategy based on these ideas that guided the design of eTOXsys, the prediction system used by the eTOX project.

eTOXlab, an open source modeling framework for implementing predictive models in production environments.

Background: Computational models based in Quantitative-Structure Activity Relationship (QSAR) methodologies are widely used tools for predicting the biological properties of new compounds. In many instances, such models are used as a routine in the industry (e.g.

[Usefulness of bispectral index in pharmaceutical cost reduction for anesthesia].

Background: The bispectral index (BIS) is a value derived from an electroencephalograph (EEG); it is correlated with depth of sedation and loss of consciousness. Therefore, it has been considered that its control on sedation depth could influence cost saving in drugs as well as decreased anesthesia costs.

Methods: A total of 175 patients were studied.

[Ketorolac vs metamizol preemptive analgesia in children].

Preventive analgesia produced by ketorolac and metamizol was evaluated during a prospective study randomized in two groups. One hundred twenty children were included aged from 3 to 6 years who underwent surgery by different procedures. Analgesic dose was applied 15 min prior to surgery by intravenous (i.