Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.

BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

A prospective randomised controlled trial of ultrasound guided versus nerve stimulation guided distal sciatic nerve block at the popliteal fossa.

The direct visualisation of nerves and adjacent anatomical structures may make ultrasonography the preferred method for nerve localisation. In this prospective randomised study, we investigated whether, for distal sciatic nerve block in the popliteal fossa, an ultrasound guided technique would result in the use of less local anaesthetic without changing block characteristics and quality. Using electrical nerve stimulation or ultrasound guidance, the nerve was identified in two groups of 20 patients scheduled for lower limb surgery. Hereafter lignocaine 1.5% with adrenaline 5 microg/ml was injected. The attending anaesthesiologist assessed the injected volume. Significantly less local anaesthetic was injected in the ultrasound group compared to the nerve stimulation group (17 vs. 37 ml, P < 0.001), while the overall success rate was increased (100% vs. 75%; P = 0.017). We conclude that the use of ultrasound localisation for distal sciatic nerve block in the popliteal fossa reduces the required dose of local anaesthetic significantly, and is associated with a higher success rate compared to nerve stimulation without changing block characteristics.

Pharmacokinetics of the infusion of alfentanil in man.

The pharmacokinetics of alfentanil under the conditions of an empirically derived 1-h continuous infusion of 3 micrograms kg-1 min-1, with a bolus of 80 micrograms kg-1, both i.v., were determined in five patients. The distribution half-life (mean +/- SD) (7.4 +/- 3.1 min), elimination half-life (86.7 +/- 15.8 min), apparent volume of distribution, Varea (0.44 +/- 0.15 litre kg-1) and elimination clearance (3.33 +/- 0.75 ml kg-1 min-1) were similar to those previously reported for a single bolus of alfentanil. These values for apparent volume of distribution and clearance can be used to calculate correct bolus and infusion doses to maintain any desired steady state plasma concentration using standard formulae: for example, to maintain a steady state plasma concentration of 400 ng ml-1, a bolus dose of 176 micrograms kg-1 and an infusion of 1.3 micrograms kg-1 min1 would be required.