In vitro effects of Uriage spring water on the apoptosis of human eosinophils.

The influx of eosinophils in tissues plays a central role in the pathophysiology of allergic diseases such as allergic rhinitis, allergic asthma or atopic dermatitis. The death of eosinophils by apoptosis is an important factor for the resolution of hypereosinophilia. In the present study, we have shown that Uriage spring water induced in vitro the apoptosis of IL-5-primed eosinophils. This effect was dose-dependent and was statistically significant at Uriage water concentrations above 20%. The induction of apoptosis was related to the Ca2+ content of Uriage water. Indeed, Ca2+ at the same concentration as in Uriage water mimicked the apoptotic effect of the spring water. Furthermore, EGTA reversed the apoptotic effect of Uriage water. These results suggest that topically applied, Uriage water could contribute to the resolution of eosinophilic inflammation.

A population pharmacokinetic study of alminoprofen penetration into synovial fluid.

The pharmacokinetics of alminoprofen in plasma and synovial fluid (SF) at steady state (300 mg t.i.d.) was studied in 45 patients with knee effusion. Plasma and SF samples, one each per patient, were obtained. Six groups were made according to the time of sampling after ingestion of the 13th dose: 1 h (n = 7), 2 h (n = 7), 4 h (n = 7), 6 h (n = 10), 8 h (n = 6), 12 h (n = 8). A three-compartment model was used to describe alminoprofen kinetics in plasma and SF, with two parameterizations, a 'classical' and a 'physiological' one. The non-linear mixed effect model approach was used to estimate the mean and variance of the pharmacokinetic parameters. The mean +/- SE of the estimates (coefficient of variation of interindividual variability as a percentage) were volume of distribution, 11.0 +/- 1.711 (12%); elimination rate constant, 0.236 +/- 0.025 h-1 (18%); absorption rate constant 2.80 +/- 0.31 h-1 (464%), clearance of influx into SF, 0.29 +/- 0.14 mL min-1; clearance of efflux into plasma, 0.56 +/- 0.25 mL min-1. These two clearances were not significantly different, which indicates that passive diffusion occurs in both directions. The mean +/- SD alminoprofen concentration versus time curve in plasma and SF at steady state was simulated and showed that the mean +/- SD maximal concentration in SF was 8.1 +/- 6.3 mg L-1 and was obtained 4 h after dose administration.