Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

Derivation of Ecologically Based Soil Standards for Trace Elements

A comprehensive and practical overview of the state of the science, Soil Quality Standards for Trace Elements: Derivation, Implementation, and Interpretation addresses the derivation of soil quality standards for trace elements and the implementation of these standards within regulatory and risk assessment frameworks. Forty experts from 11 countries across Europe, Asia, and North America—a multidisciplinary group of government policy makers and regulators, academics, industry representatives, and consultants—provide a focused discussion on the science and methods underpinning the derivation of soil quality standards for trace elements. Outlines the supporting science for setting environmental and human health standards Covers the application and practical use of soil quality standards for trace elements Contains recommendations on the development and use of soil quality standards for trace elements Identifies best practices in accounting for (bio)availability and exposure modelling in standard setting for soils The book provides a clear description of how to derive and implement soil quality standards for trace elements in order to assess human and environmental risks. It covers scientific developments useful for resolving discrepancies in the setting and implementation of soil quality standards. It provides useful tips, including do's, and don'ts on how to deal with issues such as variation of the natural background and soil type dependent toxicity