A diagnostic that can be used on a large scale has not yet been identified.”
“Background and objective Acute lung injury (ALI) is characterized by disruption of lung epithelial and endothelial cells, leading to increased membrane permeability and loss of barrier function. Claudins are key components of tight junctions (TJ) that regulate paracellular 3-MA nmr permeability, and play an important role in alveolar epithelial barrier function and fluid clearance. However, whether claudin-3, -4, -18 or -5 expression changes in Pseudomonas aeruginosa (PA)-induced ALI and the clinical
significance of such change is unknown. Methods Rats underwent intratracheal instillation of PA, and samples were collected prior to and 3, 9 and 24h after instillation. Lung injury was evaluated by bronchoalveolar lavage fluid (BALF) total protein, arterial blood gas selleck inhibitor analysis, lung injury score, and expression of surfactant protein and von Willebrand factor. Claudin expression in lung was measured with quantitative real-time polymerase chain reaction and western blotting, and in BALF by enzyme-linked immunosorbent assay. The relationship between
claudins in BALF and lung injury grade were analysed with Spearman’s rank correlation. Alveolar epithelium, endothelium and TJ ultrastructure were observed with electron microscopy. Results Claudin-4, -18 and -5mRNA levels increased significantly 24h after PA instillation in the most severe lung injury cases, whereas there was no significant change in protein levels. Claudin-3, -4 and -18 levels in BALF increased most 24h after PA instillation; this paralleled alveolar epithelial disruption and lung injury severity. Conclusions Claudin-3, -4 and -18 released into the alveolar compartment is highly associated with barrier function loss caused by alveolar epithelial injury.”
“Speaking for the in Thought Expert Discussion
Series in February, Dr George Tsokos mirrored the opinion of many PND-1186 lupus thought leaders: Human Genome Sciences (HGS) and GlaxoSmithKline’s (GSK) belimumab (Benlysta (R)) was likely to be approved by the US FDA and, despite modest efficacy, will be used by a large proportion of lupus patients.
Dr Tsokos praised HGS and GSK’s clinical trial program for belimumab, noting that huge trials and unique trial endpoints were needed to demonstrate the drug’s efficacy, allowing it to succeed where so many other lupus drugs have failed.
Still, belimumab’s trial design may not become standard in future lupus trials questions about identification of appropriate lupus patients with active disease, trial endpoints, and subgrouping lupus patients remain.