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British Journal of Anaesthesia - current issue

British Journal of Anaesthesia - RSS feed of current issue
  1. Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn interneurones
    Background

    Surgical interventions like skin incisions trigger withdrawal reflexes which require motor neurones and local circuit interneurones in the spinal ventral horn. This region plays a key role in mediating immobilizing properties of the GABAergic anaesthetic propofol. However, it is unclear how propofol modulates GABA(A) receptors in the spinal ventral horn and whether tonic or phasic inhibition is involved.

    Methods

    Organotypic spinal cord tissue slices were prepared from mice. Whole-cell recordings were performed for quantifying effects of propofol on GABA(A) receptor-mediated phasic transmission and tonic conductance.

    Results

    Propofol increased GABAergic phasic transmission by a prolongation of the decay time constant in a concentration-dependent manner. The amount of the charge transferred per inhibitory post-synaptic current, described by the area under the curve, was significantly augmented by 1 µM propofol (P<0.01). A GABA(A) receptor-mediated tonic current was not induced by 1 µM propofol but at a concentration of 5 µM (P<0.05).

    Conclusions

    Propofol depresses ventral horn interneurones predominantly by phasic rather than by tonic GABA(A) receptor-mediated inhibition. However, the present results suggest that the involvement of a tonic inhibition might contribute to the efficacy of propofol to depress nociceptive reflexes at high concentrations of the anaesthetic.

  2. Macrophage-sensory neuronal interaction in HIV-1 gp120-induced neurotoxicity
    Background

    Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most frequent neurological complication of HIV disease. Among the probable mechanisms underlying HIV-SN are neurotoxicity induced by the HIV glycoprotein gp120 and antiretroviral therapies (ART). Since HIV-SN prevalence remains high in patients who have not been exposed to toxic ART drugs, here we focused on gp120-mediated mechanisms underlying HIV-SN.

    Methods

    We hypothesized that a direct gp120–sensory neurone interaction is not the cause of neurite degeneration; rather, an indirect interaction of gp120 with sensory neurones involving macrophages underlies axonal degeneration. Rat dorsal root ganglion (DRG) cultures were used to assess gp120 neurotoxicity. Rat bone marrow-derived macrophage (BMDM) cultures and qPCR array were used to assess gp120-associated gene expression changes.

    Results

    gp120 induced significant, but latent onset, neurite degeneration until 24 h after application. gp120–neurone interaction occurred within 1 h of application in <10% of DRG neurones, despite neurite degeneration having a global effect. Application of culture media from gp120-exposed BMDMs induced a significant reduction in DRG neurite outgrowth. Furthermore, gp120 significantly increased the expression of 25 cytokine-related genes in primary BMDMs, some of which have been implicated in other painful polyneuropathies. The C–C chemokine receptor type 5 (CCR5) antagonist, maraviroc, concentration-dependently inhibited gp120-induced tumour necrosis factor-α gene expression, indicating that these effects occurred via gp120 activation of CCR5.

    Conclusions

    Our findings highlight macrophages in the pathogenesis of HIV-SN and upstream modulation of macrophage response as a promising therapeutic strategy.

  3. Textbook of Post-ICU Medicine, The Legacy of Critical Care
  4. Pharmacology for Anaesthesia and Intensive Care
  5. Challenging Concepts in Anaesthesia. Cases with Expert Commentary
  6. Does fasting time alter fluid responsiveness after induction of anaesthesia?
  7. The IFT (isolated forearm technique) and consciousness
  8. Anesthesiologist's Manual of Surgical Procedures
  9. Avoiding awareness in Caesarean sections under general anaesthesia
  10. Reliability of bispectral index analysis in patients undergoing Caesarean section
  11. Isolated forearm movement does not equate to awareness
  12. Reply from the authors
  13. Simulation-based training in anaesthesia: have we been training non-technical skills?
  14. Pre-ictal bispectral index values; are they accurate?
  15. Reply from the authors