Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation.

Neutrophilic inflammation with prolonged neutrophil survival is common to many inflammatory conditions, including chronic obstructive pulmonary disease (COPD). There are few specific therapies that reverse neutrophilic inflammation, but uncovering mechanisms regulating neutrophil survival is likely to identify novel therapeutic targets. Screening of 367 kinase inhibitors in human neutrophils and a zebrafish tail fin injury model identified ErbBs as common targets of compounds that accelerated inflammation resolution.

A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia.

Background: Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility.

Methods: Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a.

Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis.

Background: The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF).

Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice.

The regulation of neutrophil lifespan by induction of apoptosis is critical for maintaining an effective host response and preventing excessive inflammation. The hypoxia-inducible factor (HIF) oxygen-sensing pathway has a major effect on the susceptibility of neutrophils to apoptosis, with a marked delay in cell death observed under hypoxic conditions. HIF expression and transcriptional activity are regulated by the oxygen-sensitive prolyl hydroxylases (PHD1-3), but the role of PHDs in neutrophil survival is unclear.

Manual assessment of the initial fall in blood pressure after orthostatic challenge at high altitude.

Objective: Dizziness is a symptom of acute mountain sickness (AMS). This study tested whether immediate fall in systolic blood pressure (BP) on standing was more severe at altitude and whether this was associated with symptoms of dizziness.

Methods: Eighty-five lowlanders flew into La Paz, Bolivia (3650 m), and after 4 to 5 days of acclimatization ascended in 90 minutes to the Chacaltaya Laboratory (5200 m) by road.

Catastrophe for a campanologist.

A campanologist was involved in a nonfatal hanging incident. On presentation she had no midline bony tenderness and only subtle abnormalities on plain X-ray films of her cervical spine; however, a CT scan showed a type III odontoid peg fracture. We believe this is the first reported cervical spine fracture sustained while bell-ringing.