The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles

In vitro studies with particles are a major staple of particle toxicology, generally used to investigate mechanisms and better understand the molecular events underlying cellular effects. However, there is ethical and financial pressure in nanotoxicology, the new sub-specialty of particle toxicology, to avoid using animals. Therefore an increasing amount of studies are being published using in vitro approaches and such studies require careful interpretation. We point out here that 3 different conventional pathogenic particle types, PM10, asbestos and quartz, which cause diverse pathological effects, have been reported to cause very similar oxidative stress effects in cells in culture. We discuss the likely explanation and implications of this apparent paradox, and its relevance for testing in nanotoxicology

Ultrasound characteristics of foot and ankle structures in healthy, coper, and chronically unstable ankles

Objective: Ankle sprains constitute approximately 85% of all ankle injuries and up to 70% of people experience residual symptoms. Whilst the injury to ligaments is well understood the potential role of other foot and ankle structures has not been explored. The objective was to characterise and compare selected ankle structures in participants with and without a history of lateral ankle sprain. Methods: 71 participants were divided into 31 healthy, 20 coper, and 20 chronic ankle instability groups. Ultrasound images of the anterior talofibular and calcaneofibular ligaments, fibularis tendons and muscles, tibialis posterior and Achilles tendon were obtained. Thickness, length, and cross sectional areas were measured and compared between groups. Results: When under tension the anterior talofibular ligament was longer in copers and chronic ankle instability groups compared to healthy participants (p < 0.001 and p = 0.001 respectively). The chronic ankle instability group had the thickest ATFL and CFL among the three groups (p < 0.001). No significant differences (p > 0.05) in tendons and muscles were observed between the three groups. Conclusions: The ultrasound protocol proved reliable and was used to evaluate the length, thickness, and CSA of selected ankle structures. The length of the ATFL and the thickness of the ATFL and CFL were longer and thicker in injured groups compared to healthy

Should hydroxyethyl starch solutions be totally banned?

The choice of which intravenous solution to prescribe remains a matter of considerable debate in intensive care units around the world. Trends have been moving away from using hydroxyethyl starch solutions following concerns about safety. But are the available data sufficient to clearly assess the risk-benefit balance for all patients, and is there enough evidence of harm to justify removing these drugs completely from our hospitals? © 2013 BioMed Central Ltd

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

The WHO checklist: a global tool to prevent errors in surgery

In this article, we welcome the adoption of the WHO surgical checklist to prevent errors in surgical practice. We highlight the scale of the problem and discuss the adoption of this tool in the UK

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.

Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli