Radiographic airway abnormalities in untreated early rheumatoid arthritis are associated with peripheral neutrophil activation.

Background: The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear. Up to 10% of RA patients develop interstitial lung disease which remains a clinical challenge. Understanding early disease mechanisms is of great importance.

Targets of Neutrophil Influx and Weaponry: Therapeutic Opportunities for Chronic Obstructive Airway Disease.

Neutrophils are important effector cells of antimicrobial immunity in an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), there is excessive infiltration and activation of neutrophils, subsequent production of reactive oxygen species, and release of serine proteases, matrix metalloproteinases, and myeloperoxidase-resulting in collateral damage as the cells infiltrate into the tissue. Increased neutrophil survival through dysregulated apoptosis facilitates continued release of neutrophil-derived mediators to perpetuate airway inflammation and tissue injury.

Pharmacological characterization of AZD5069, a slowly reversible CXC chemokine receptor 2 antagonist.

In normal physiologic responses to injury and infection, inflammatory cells enter tissue and sites of inflammation through a chemotactic process regulated by several families of proteins, including inflammatory chemokines, a family of small inducible cytokines. In neutrophils, chemokines chemokine (CXC motif) ligand 1 (CXCL1) and CXCL8 are potent chemoattractants and activate G protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXCR2. Several small-molecule antagonists of CXCR2 have been developed to inhibit the inflammatory responses mediated by this receptor.

A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses.

Rationale: Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids.

Objectives: We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses.

Methods: Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 μg) once daily, budesonide 200 μg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study.

A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2).

Amelogenesis imperfecta (AI) is an inherited tooth disorder affecting tooth enamel formation only. A gene for autosomal dominant AI, the local hypoplastic form, has been localized to a 4 Mb region on chromosome 4q (AIH2). The enamelin gene (ENAM ), has been mapped to chromosome 4q21, to the same region as AIH2, and was recently shown to be mutated in patients with smooth and thin hypoplastic autosomal dominant AI (ADAI).