Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8+ T-cell-dependent manner.

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8+ T cells, and CD8+ T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8+ T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design.

[The time-course of action of rapacuronium and mivacurium after early reversal following equally lasting relaxation]. / Spontane und induzierte neuromuskuläre Erholung nach gleich langer Relaxierung mit Rapacuronium und Mivacurium.

This study was designed to compare the time course of action and the safety profile of Rapacuronium and Mivacurium in day case dental surgery. After Ethics Committee approval 61 healthy adult patients, scheduled for dental day case surgery, were randomised in an assessor-blinded manner to receive either 1.5 mg/kg Rapacuronium with and without 0.05 neostigmine 5 min later (19 patients each) or a total of 0.25 mg/kg Mivacurium (n = 16). Anaesthesia was induced using Propofol 2 - 5.1 mg/kg and Remifentanil 24 - 73 mcg/kg/h and maintained with Desflurane in N2O/O2 (2/1). Endotracheal intubation was performed when maximum blockade was achieved and scored by a blinded intubator. Neuromuscular block was monitored using the train-of-four response to supramaximal stimuli at the ulnar nerve every 15 seconds using acceleromyography (TOF Watch SX). Onset time, clinical duration (reappearance of the third twitch of a TOF-stimulation) and recovery to T4/T1 > 0.9 were recorded. Speed of recovery was evaluated by the time difference between reappearance of the third twitch and T4/T1 > 0.9. The intubating conditions at the time of maximum block revealed no statistically significant differences between the three groups. Changes in blood pressure, heart rate and airway pressure were not significant. Onset time in subjects who received Rapacuronium (99 +/- 29 s) was faster compared to the onset time in those who received Mivacurium (157 +/- 36 s). Also clinical duration was significantly shorter following Rapacuronium without reversal (12 +/- 4 min) as well as with reversal (9 +/- 1 min) compared with Mivacurium (21 +/- 5 min)). Patients treated with Rapacuronium and reversal recovered faster (14 +/- 8 min)) compared to the other two groups (Mivacurium: 20 +/- 6 min, Rapacuronium without reversal: 31 +/- 9 min). The fraction of clinical duration of the total duration was highest following Mivacurium (51 %) when compared with Rapacuronium/Neostigmine (43 %) and Rapacuronium (28 %).