Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

Funding This study was funded by the Medical Research Council (Grant number G0800149). Research material from this study is not available. Acknowledgement We are very grateful to Dr Robin A.J. Smith, Department of Chemistry, University of Otago, Dunedin, New Zealand, for the generous gifts of MitoE and MitoQ, without which this work would not have been possible.Peer reviewedPublisher PD

Pharmacological activation of endogenous protective pathways against oxidative stress under conditions of sepsis

Funding The study was funded entirely by institutional funds.Peer reviewedPostprin

Reliability of lithium dilution cardiac output in anaesthetized sheep

Background Cardiac output (CO) measurement with lithium dilution (COLD) has not been fully validated in sheep using precise ultrasonic flow probe technology (COUFP). Sheep generate important cardiovascular research models and the use of COLD has become more popular in experimental settings. Methods Ultrasonic transit-time perivascular flow probes were surgically implanted on the pulmonary artery of 13 sheep. Paired COLD readings were taken at six time points, before and after implantation of a left ventricular assist device (LVAD) and compared with COUFP recorded just after lithium injection. Results The mean COLD was 5.7 litre min−1 (range 3.8-9.6 litre min−1) and mean COUFP 5.9 litre min−1 (range 4.0-9.2 litre min−1). The bias (standard deviation) was 0.3 (1.0) litre min−1 [5.1 (16.9)%] and limits of agreement (LOA) were −1.7 to 2.3 litre min−1 (−28.8 to 39.0%) with a percentage error (PE) of 34.4%. Data to assess trending [rate (95% confidence intervals)] included a 78 (62-93)% concordance rate in the four-quadrant plot (n=27). In the half moon polar plot (n=19), the mean polar angle was +5°, the radial LOA were −49 to +35° and 68 (47-89)% of data points fell within 22.5° of the mean polar angle. Both tests indicated moderate to poor trending ability. Conclusion COLD is not precise when evaluated against COUFP in sheep based on the statistical criteria set, but the results are comparable with previously published animal studie

A no-go theorem on the nature of the gravitational field beyond quantum theory

Recently, table-top experiments involving massive quantum systems have been proposed to test the interface of quantum theory and gravity. In particular, the crucial point of the debate is whether it is possible to conclude anything on the quantum nature of the gravitational field, provided that two quantum systems become entangled due to solely the gravitational interaction. Typically, this question has been addressed by assuming an underlying physical theory to describe the gravitational interaction, but no systematic approach to characterise the set of possible gravitational theories which are compatible with the observation of entanglement has been proposed. Here, we introduce the framework of Generalised Probabilistic Theories (GPTs) to the study of the nature of the gravitational field. This framework has the advantage that it only relies on the set of operationally accessible states, transformations, and measurements, without presupposing an underlying theory. Hence, it provides a framework to systematically study all theories compatible with the detection of entanglement generated via the gravitational interaction between two non-classical systems. Assuming that such entanglement is observed we prove a no-go theorem stating that the following statements are incompatible: i) the two non-classical systems are independent subsystems, ii) the gravitational field is a physical degree of freedom which mediates the interaction and iii) the gravitational field is classical. Moreover we argue that conditions i) and ii) should be met, and hence that the gravitational field is non-classical. Non-classicality does not imply that the gravitational field is quantum, and to illustrate this we provide examples of non-classical and non-quantum theories which are logically consistent with the other conditions.Comment: 12 pages main text; 23 pages Appendices; many diagrams. Improved presentation compared to the first versio

Any consistent coupling between classical gravity and quantum matter is fundamentally irreversible

When gravity is sourced by a quantum system, there is tension between its role as the mediator of a fundamental interaction, which is expected to acquire nonclassical features, and its role in determining the properties of spacetime, which is inherently classical. Fundamentally, this tension should result in breaking one of the fundamental principles of quantum theory or general relativity, but it is usually hard to assess which one without resorting to a specific model. Here, we answer this question in a theory-independent way using General Probabilistic Theories (GPTs). We consider the interactions of the gravitational field with a single matter system, and derive a no-go theorem showing that when gravity is classical at least one of the following assumptions needs to be violated: (i) Matter degrees of freedom are described by fully non-classical degrees of freedom; (ii) Interactions between matter degrees of freedom and the gravitational field are reversible; (iii) Matter degrees of freedom back-react on the gravitational field. We argue that this implies that theories of classical gravity and quantum matter must be fundamentally irreversible, as is the case in the recent model of Oppenheim et al. Conversely if we require that the interaction between quantum matter and the gravitational field are reversible, then the gravitational field must be non-classical.Comment: 5 pages main text; 8 pages Appendices (many diagrams

Volatile anaesthetics reduce neutrophil inflammatory response by interfering with CXC receptor-2 signalling

Background Growing evidence suggests a protective effect of volatile anaesthetics in ischaemia-reperfusion (I/R)-injury, and the accumulation of neutrophils is a crucial event. Pro-inflammatory cytokines carrying the C-X-C-motif including interleukin-8 (IL-8) and CXC-ligand 1 (CXCL1) activate CXC receptor-1 (CXCR1; stimulated by IL-8), CXC receptor-2 (CXCR2; stimulated by IL-8 and CXCL1), or both to induce CD11b-dependent neutrophil transmigration. Inhibition of CXCR1, CXCR2, or both reduces I/R-injury by preventing neutrophil accumulation. We hypothesized that interference with CXCR1/CXCR2 signalling contributes to the well-established beneficial effect of volatile anaesthetics in I/R-injury. Methods Isolated human neutrophils were stimulated with IL-8 or CXCL1 and exposed to volatile anaesthetics (sevoflurane/desflurane). Neutrophil migration was assessed using an adapted Boyden chamber. Expression of CD11b, CXCR1, and CXCR2 was measured by flow cytometry. Blocking antibodies against CXCR1/CXCR2/CD11b and phorbol myristate acetate were used to investigate specific pathways. Results Volatile anaesthetics reduced CD11b-dependent neutrophil transmigration induced by IL-8 by >30% and CD11b expression by 18 and 27% with sevoflurane/desflurane, respectively. This effect was independent of CXCR1/CXCR2 expression and CXCR1/CXCR2 endocytosis. Inhibition of CXCR1 signalling did not affect downregulation of CD11b with volatile anaesthetics. Blocking of CXCR2-signalling neutralized effects by volatile anaesthetics on CD11b expression. Specific stimulation of CXCR2 with CXCL1 was sufficient to induce upregulation of CD11b, which was impaired with volatile anaesthetics. No effect of volatile anaesthetics was observed with direct stimulation of protein kinase C located downstream of CXCR1/CXCR2. Conclusion Volatile anaesthetics attenuate neutrophil inflammatory responses elicited by CXC cytokines through interference with CXCR2 signalling. This might contribute to the beneficial effect of volatile anaesthetics in I/R-injur

Witworld: A generalised probabilistic theory featuring post-quantum steering

We introduce Witworld: a generalised probabilistic theory with strong post-quantum features, which subsumes Boxworld. Witworld is the first theory that features post-quantum steering, and also the first that outperforms quantum theory at the task of remote state preparation. We further show post-quantum steering to be the source of this advantage, and hence present the first instance where post-quantum steering is a stronger-than-quantum resource for information processing.Comment: 9 pages, loads of diagrams. Comments welcom

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

Background The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Methods Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Results Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s−1 (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. Conclusions In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve bloc

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Finite size corrections to the radiation reaction force in classical electrodynamics

We introduce an effective field theory approach that describes the motion of finite size objects under the influence of electromagnetic fields. We prove that leading order effects due to the finite radius $R$ of a spherically symmetric charge is order $R^2$ rather than order $R$ in any physical model, as widely claimed in the literature. This scaling arises as a consequence of Poincar\'e and gauge symmetries, which can be shown to exclude linear corrections. We use the formalism to calculate the leading order finite size correction to the Abraham-Lorentz-Dirac force.Comment: 4 pages, 2 figure