Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol.

Trial Design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.

Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment.

Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells.

Important differences exist in the responses to photodynamic agents of normal and tumour-derived pancreatic acinar cells. In the present study amylase release has been used to assess the mechanisms by which the photodynamic drugs tetra- and disulphonated aluminium phthalocyanine (A1PcS4, A1PcS2) act on pancreatic cells via energy and calcium-dependent activation and transduction pathways. The photodynamic release of amylase was found to be energy dependent and inhibited by the chelation of free cytoplasmic calcium but not by the removal of extracellular calcium.

Immunoglobulin-G-dependent stimulation of guinea pig lung mast cells and macrophages.

Alveolar macrophages and mast cells isolated from guinea pig lung were passively sensitized with IgG1, IgG2, or serum obtained from guinea pigs actively sensitized with ovalbumin. The release of histamine by mast cells and of thromboxane A2 by alveolar macrophages upon ovalbumin challenge indicated that both antibodies and serum were capable of sensitizing these cells with similar effectiveness. Heating the serum at 56 degrees C for 4 h to inactivate IgE did not modify the antigen-dependent response of lung cells.

Photodynamic drug action on isolated rat pancreatic acini. Mobilization of arachidonic acid and prostaglandin production.

Chloro-aluminium phthalocyanine sulphonate (SALPC) when photon-activated generates singlet oxygen, elicits amylase release and causes plasma membrane permeabilization of pancreatic acinar cells (Matthews and Cui, Biochem Pharmacol 39: 1444-1457, 1990). Amylase release precedes membrane permeabilization suggesting that the initial release of amylase may be due to direct stimulation by singlet oxygen of secretagogue receptors or their coupled guanine nucleotide binding proteins (G-proteins) and effector systems including phospholipase A2 (PLA2). The aim of the experiments reported here was to establish the extent to which PLA2 activation, arachidonic acid mobilization, and prostaglandin production are involved in the photon-induced action of SALPC on dispersed, perifused acini isolated from the rat pancreas.

On the mechanism of action of sodium orthovanadate in inducing histamine release from rat peritoneal mast cells.

Sodium orthovanadate produced a dose-dependent release of histamine and prostaglandin D2 from rat peritoneal mast cells. The release of histamine was selectively inhibited by the anion channel blockers SITS and DIDS, and by theophylline and dibutyryl cyclic-AMP, but was unaffected by disodium cromoglycate and lanthanum ions. Unlike IgE-directed ligands, vanadate did not produce any change in the intracellular concentration of cyclic-AMP but did promote a substantial uptake of calcium-45 from the incubation medium.