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Simvastatin up-regulates adenosine deaminase and suppresses osteopontin expression in COPD patients through an IL-13-dependent mechanism

Background Adenosine deaminase (ADA) and osteopontin (OPN) may play opposing roles in the pathogenesis of COPD. Deficiency of ADA results in enhanced adenosine signaling which up-regulates OPN expression. Although statins suppress OPN in cancer cells, little is known about their effects on ADA and OPN in COPD patients. Methods We extended a previous randomized double-blind...

The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given ‘as needed’ in mild asthma: study protocols for two randomised controlled trials

payment for delivering lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Takeda, as well as from Novartis for the development of education presentations. Peter ... Barnes has served on Scientific Advisory Boards for AstraZeneca, Boehringer Ingelheim, Chiesi, Daiichi-Sankyo, GlaxoSmithKline, Novartis, Nycomed, Pfizer, Teva, and UCB; has received research funding from

Protein tyrosine phosphatase PTP-RR regulates corticosteroid sensitivity

Background We have recently reported that protein phosphate 2A (PP2A) inactivation resulted in increased phosphorylation of the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase 1 (JNK1) and glucocorticoid receptors (GR) at Ser 226 , thereby reducing GR nuclear translocation and causing corticosteroid insensitivity in severe asthmatics. Protein tyrosine phosphatases...

Nasal inflammation and its response to local glucocorticoid regular treatment in patients with persistent non-allergic rhinitis: a pilot study

Background The pathogenesis of non-allergic rhinitis (NAR) is still largely unknown. Furthermore, it is unclear whether there is a correlation between the effect of nasal glucocorticoids on nasal inflammation and on nasal symptoms and quality of life. Methods In this pilot study we recruited 12 healthy subjects and 24 patients with recently diagnosed persistent NAR [12 untreated...

Deletion of FoxN1 in the Thymic Medullary Epithelium Reduces Peripheral T Cell Responses to Infection and Mimics Changes of Aging

Aging increases susceptibility to infection, in part because thymic involution culminates in reduced naïve T-lymphocyte output. Thymic epithelial cells (TECs) are critical to ensure normal maturation of thymocytes and production of peripheral T cells. The forkhead-class transcription factor, encoded by FoxN1, regulates development, differentiation, and function of TECs, both in...

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial

controlled trial Graham Devereux 0 Seonaidh Cotton 2 Peter Barnes 1 Andrew Briggs 7 Graham Burns 6 Rekha Chaudhuri 5 Henry Chrystyn 4 Lisa Davies 9 Anthony De Soyza 8 Shona Fielding 3 Simon Gompertz 12 John

Do Children Who Move Home and School Frequently Have Poorer Educational Outcomes in Their Early Years at School? An Anonymised Cohort Study

Frequent mobility has been linked to poorer educational attainment. We investigated the association between moving home and moving school frequently and the early childhood formal educational achievement. We carried out a cohort analysis of 121,422 children with anonymised linked records. Our exposure measures were: 1) the number of residential moves registered with a health care...