Mycobacterial heparin-binding haemagglutinin antigen (HBHA) is a virulence factor that induces apoptosis of macrophages. Endoplasmic reticulum (ER) stress-mediated apoptosis is an important regulatory response that can be utilised to study the pathogenesis of tuberculosis. In the present study, HBHA stimulation induced ER stress sensor molecules in a caspase-dependent manner. Pre-treatment of RAW 264.7 cells with an IκB kinase 2 inhibitor reduced not only C/EBP homology protein expression but also IL-6 and monocyte chemotactic protein-1 (MCP-1) production. BAPTA-AM reduced both ER stress responses and caspase activation and strongly suppressed HBHA-induced IL-6 and MCP-1 production in RAW 264.7 cells. Enhanced reactive oxygen species (ROS) production and elevated cytosolic [Ca2+]i levels were essential for HBHA-induced ER stress responses. Collectively, our data suggest that HBHA induces cytosolic [Ca2+]i, which influences the generation of ROS associated with the production of proinflammatory cytokines. These concerted and complex cellular responses induce ER stress-associated apoptosis during HBHA stimulation in macrophages. These results indicate that the ER stress pathway has an important role in the HBHA-induced apoptosis during mycobacterial infection.

The purpose of this study was to examine possible peripheral mechanisms for the reduction of propofol injection pain by the addition of ketamine. We hypothesised that pH changes associated with the addition of ketamine to propofol decrease propofol-induced pain on injection. We compared the efficacy of intravenous ketamine pretreatment under tourniquet with ketamine added to the propofol. In the pre-treatment group, patients received ketamine 10 mg in a total volume of 1.0 ml with 0.9% saline (n=94; Group P) under tourniquet for 30 seconds before administration of propofol after release of the tourniquet. In the mixture group, propofol 9 ml was mixed with ketamine 10 mg in 0.9% NaCl 1.0 ml (n=94, Group M). Pain was assessed with a four-point scale: 0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain at the time of propofol injection. The pH of propofol, ketamine and a range of propofol-ketamine mixtures were also measured. Forty-eight patients (51%) in Group P complained of pain on injection compared with 28 patients (30%) in Group M (P=0.005). The pH of the 1% propofol-ketamine mixture was 5.84 while 1% propofol had a pH of 7.86. Our results support pH changes as a more important cause for the decrease in propofol injection pain with the addition of ketamine to propofol than a peripheral effect of ketamine.

Patients with acute or acute-on-chronic SCFE can be safely managed with straight-leg traction for up to 6 days, followed by in situ screw fixation without manipulation. Manipulation is not recommended in such slips, due to a higher avascular necrosis risk.

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