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

The Kinetics of Solvent Reorientation in Hydroxylated Solvents From the Exciting-wavelength Dependence of Chromophore Emission Spectra

The disappearance of the exciting-wavelength dependence of the phosphorescence spectra of polar, aromatic chromophores in supercooled glycol–water mixtures is utilized to monitor the kinetics of solvent reorientation. Reorientation times in the nanosecond to second range are obtained for (3:2 v/v) glycerol–water and (1:1 v/v) ethylene glycol–water at 140–240 °K. The results suggest that the process is one involving a cluster of solvent molecules and in which the chromophore plays a relatively passive role. Steady-state data and direct measurements of phosphorescence shifts as a function of time indicate that the solvent reorientation process is nonexponential in nature. The decay function derived from the temperature dependence of the steady state data is consistent with the decays observed directly as a function of time. Interpretation of this nonexponential decay in terms of a summation of rate processes leads to a distribution dominated by two reorientation rate constants. The relative contributions of the slow and faster reorientation rate constants in addition to their activation parameters differ for the glycerol–water and ethylene glycol–water mixtures

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

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

A nonlinear scalar model of extreme mass ratio inspirals in effective field theory II. Scalar perturbations and a master source

The motion of a small compact object (SCO) in a background spacetime is investigated further in a class of model nonlinear scalar field theories having a perturbative structure analogous to the General Relativistic description of extreme mass ratio inspirals (EMRIs). We derive regular expressions for the scalar perturbations generated by the SCO's motion valid through third order in $\epsilon$, the size of the SCO to the background curvature length scale. Our expressions are compared to those calculated through second order in $\epsilon$ by Rosenthal in [E. Rosenthal, CQG 22, S859 (2005)] and found to agree but our procedure for regularizing the scalar perturbations is considerably simpler. Following the Detweiler-Whiting (DW) scheme, we use our regular expressions for the field and derive the regular self-force corrections through third order. We find agreement with our previous derivation based on a variational principle of an effective action for the worldline associated with the SCO thus demonstrating the internal consistency of our formalism. This also explicitly demonstrates that the DW decomposition of Green's functions is a valid and practical method of self force computation at higher orders in perturbation theory and, as we show in an appendix, at all orders in perturbation theory. Finally, we identify a master source from which all other physically relevant quantities are derivable. Knowing the master source perturbatively allows one to construct the waveform measured by an observer, the regular part of the field on the worldline, the regular part of the self force, and orbital quantities such as shifts of the innermost stable circular orbit, etc. The existence of a master source together with the regularization methods implemented in this series should be indispensable for derivations of higher-order gravitational self force corrections.Comment: For Part 1 of this series, see arXiv:1012.4488. 20 pages, 7 figure

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

A nonlinear scalar model of extreme mass ratio inspirals in effective field theory I. Self force through third order

The motion of a small compact object in a background spacetime is investigated in the context of a model nonlinear scalar field theory. This model is constructed to have a perturbative structure analogous to the General Relativistic description of extreme mass ratio inspirals (EMRIs). We apply the effective field theory approach to this model and calculate the finite part of the self force on the small compact object through third order in the ratio of the size of the compact object to the curvature scale of the background (e.g., black hole) spacetime. We use well-known renormalization methods and demonstrate the consistency of the formalism in rendering the self force finite at higher orders within a point particle prescription for the small compact object. This nonlinear scalar model should be useful for studying various aspects of higher-order self force effects in EMRIs but within a comparatively simpler context than the full gravitational case. These aspects include developing practical schemes for higher order self force numerical computations, quantifying the effects of transient resonances on EMRI waveforms and accurately modeling the small compact object's motion for precise determinations of the parameters of detected EMRI sources.Comment: 30 pages, 8 figure

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

Properties of the ferrimagnetic double-perovskite A_{2}FeReO_{6} (A=Ba and Ca)

Ceramics of A_{2}FeReO_{6} double-perovskite have been prepared and studied for A=Ba and Ca. Ba_{2}FeReO_{6} has a cubic structure (Fm3m) with $a\approx$8.0854(1) \AA whereas Ca_{2}FeReO_{6} has a distorted monoclinic symmetry with $a\approx 5.396(1) \AA, b\approx 5.522(1) \AA, c\approx 7.688(2) \AA$ and $\beta =90.4^{\circ} (P21/n)$. The barium compound is metallic from 5 K to 385 K, i.e. no metal-insulator transition has been seen up to 385 K, and the calcium compound is semiconducting from 5 K to 385 K. Magnetization measurements show a ferrimagnetic behavior for both materials, with T_{c}=315 K for Ba_{2}FeReO_{6} and above 385 K for Ca_{2}FeReO_{6}. A specific heat measurement on the barium compound gave an electron density of states at the Fermi level, N(E_{F}) equal to 6.1$\times 10^{24} eV^{-1}mole^{-1}$. At 5 K, we observed a negative magnetoresistance of 10 % in a magnetic field of 5 T, but only for Ba_{2}FeReO_{6}. Electrical, thermal and magnetic properties are discussed and compared to the analogous compounds Sr_{2}Fe(Mo,Re)O_{6}.Comment: 5 pages REVTeX, 7 figures included, submitted to PR