A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

Background: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α.

Objective: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy.

Design: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study.

Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O) to the tissues and subsequent O utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body.

Biological effects of p38 MAPK inhibitor losmapimod does not translate to clinical benefits in COPD.

Rationale: p38 mitogen-activated protein kinase (MAPK) expression is increased in chronic inflammatory disease. Losmapimod, a p38 MAPK inhibitor, has been developed as a potential anti-inflammatory therapy in COPD.

Objectives: To evaluate the effect of losmapimod in reducing exacerbations in subjects with moderate-to-severe COPD.

A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus.

Objective: Evidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM.

A post-hoc subgroup analysis of data from a six month clinical trial comparing the efficacy and safety of losmapimod in moderate-severe COPD patients with ≤2% and >2% blood eosinophils.

Background: A six month study of the p38 MAPK inhibitor, losmapimod, suggested a trend in reducing COPD exacerbations with the 15 mg twice daily dose.

Objective And Methods: Using data from this study which evaluated the efficacy of twice daily losmapimod, 2.5 mg, 7.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single-dose antiinterleukin- 18 mAb GSK1070806 in healthy and obese subjects.

Objective: To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK1070806, a novel IgG1 mAb that neutralizes human interleukin (IL)-18.

Methods: In this first-timein-human (FTIH) study, cohorts of healthy and obese subjects were randomly allocated to receive single doses of GSK1070806 (0.008 - 10 mg/kg) or placebo.

Impact of intrinsic DNA structure on processing of plasmids for gene therapy and DNA vaccines.

Several non-Watson Crick DNA structures have been discovered to date, which may be incorporated into future plasmid constructs for gene therapy and DNA vaccine products. In this study, intrinsic DNA structures were included at a defined point in a 2.9 kb plasmid, and their effects on cell growth rate, total plasmid yield, and topology (i.