Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

A family of simple benzene 1,3,5-tricarboxamide (BTA) aromatic carboxylic acid hydrogels.

We present the characterisation of a hydrogel forming family of benzene 1,3,5-tricarboxamide (BTA) aromatic carboxylic acid derivatives. The simple, easy to synthesise compounds presented here exhibit consistent gel formation at low concentrations through the use of a pH trigger.

A single-Stream jet noise prediction model for a family of chevron nozzles

This study develops a single-stream jet noise prediction model for a family of chevron nozzles. An original equation is proposed for the fourth-order space-time cross-correlations. They are expressed in flow parameters such as streamwise circulation and turbulent kinetic energy. The cross-correlations based on a Reynolds Averaged Navier-Stokes (RANS) flowfield showed a good agreement with those based on a Large Eddy Simulation (LES) flowfield. This proves that the proposed equation describes the cross-correlations accurately. With this novel source description, there is an excellent agreement between our model's far-field noise predictions and measurements1 for a wide range of frequencies and radiation angles. Our model captures the spectral shape, amplitude and peak frequency very well. This establishes that our model holds good for a family of chevron nozzles. As our model provides quick and accurate predictions, a parametric study was performed to understand the effects of a chevron nozzle geometry on jet noise and thrust loss. Chevron penetration is the underpinning factor for jet noise reduction. The reduction of jet noise per unit thrust loss decreases linearly with chevron penetration. The number of chevrons also has a considerable effect on jet noise.