Few apoptotic cells were found in saline- or MAO-B inhibitor-treated CFTRinh-172 purchase animals but MPTP markedly induced apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) after 1 day. When mice were pretreated with deprenyl or Ro 16-6491, not only nigrostriatal dopamine levels but also NPCs were significantly protected against MPTP. In addition, MPTP-induced apoptosis was found in both juvenile (postnatal 21 days) and older (12 months old) mice, suggesting NPCs to be different from the dopamine system, which has been thought to exhibit age-dependent susceptibility to MPTP. (C) 2008 Elsevier Inc. All rights reserved.”
“The

risk associated with exposure to hepatotoxic drugs is difficult to quantify. Animal experiments to assess their chronic toxicological impact are time consuming. New quantitative approaches

to correlate gene expression changes caused by drug exposure to chronic toxicity are required. This article proposes a mathematical model entitled Toxicologic Prediction Network (TPN) to assess chronic hepatotoxicity based on subchronic hepatic gene expression see more data in rats. A directed graph accounts for the interactions between the drugs, differentially expressed genes and chronic hepatotoxicity. A knowledge-based mathematical model estimates phenotypical exposure risk such as toxic hepatopathy, diffuse fatty change and hepatocellular adenoma for rats. The network’s edges encoding the interaction strength are determined by solving an inversion problem that minimizes the difference between the observed and the predicted relative gene expressions as well as the chronic toxicity data. A realistic case study demonstrates how chronic health risk of three halogenated aromatic hydrocarbons can be inferred from subchronic gene expression data. The advantages of the TPN are further demonstrated through two novel applications: Estimation of toxicological impact of new drugs and drug mixtures

as well as rigorous determination of the optimal drug formulation to achieve maximum potency with minimum side-effects. Prediction of animal toxicity may be relevant for assessing risk for humans in the future. (C) 2008 Elsevier Ltd. All rights reserved.”
“While proper brain function requires the complex interaction of chemicals perpetually occupied in purposeful IPI145 biochemistry, it is well established that certain toxic substances have the potential to disrupt normal brain physiology and to impair neurological homeostasis. As well as headache, cognitive dysfunction, memory disturbance, and other neurological signs and symptoms, disruption of brain function may also manifest as subtle or overt alteration in thoughts, moods, or behaviors. Over the last four decades, there has been the unprecedented development and release of a swelling repertoire of potentially toxic chemicals which have the capability to inflict brain compromise.