Significant receptor affinities of metabolites and a degradation product of mometasone furoate

Mometasone furoate (MF) is a highly potent glucocorticoid used topically to treat inflammation in the lung, nose and on the skin. However, so far no information has been published on the human glucocorticoid receptor activity of the metabolites or degradation products of MF. We have now determined the relative receptor binding affinities of the known metabolite 6β-OH MF and the degradation product 9,11-epoxy MF to understand their possible contribution to undesirable systemic side effects. In competition experiments with human lung glucocorticoid receptors we have determined the relative receptor affinities (RRA) of these substances with reference to dexamethasone (RRA = 100). We have discovered that 6β-OH MF and 9,11-epoxy MF display RRAs of 206 ± 15 and 220 ± 22, respectively. This level of activity is similar to that of the clinically used inhaled corticosteroid flunisolide (RRA 180 ± 11). Furthermore we observed that 9,11-epoxy MF is a chemically reactive metabolite. In recovery experiments with human plasma and lung tissue we found a time dependent decrease in extractability of the compound. Hence, we provide data that might contribute to the understanding of the pharmacokinetics as well as the clinical effects of MF

3D Gasdynamic Modelling of the Changes in the Flow Structure During Transition From Quiescent to Active State in Symbiotic Stars

The results of 3D modelling of the flow structure in the classical symbiotic system Z~Andromedae are presented. Outbursts in systems of this type occur when the accretion rate exceeds the upper limit of the steady burning range. Therefore, in order to realize the transition from a quiescent to an active state it is necessary to find a mechanism able to sufficiently increase the accretion rate on a time scale typical to the duration of outburst development. Our calculations have confirmed the transition mechanism from quiescence to outburst in classic symbiotic systems suggested earlier on the basis of 2D calculations (Bisikalo et al, 2002). The analysis of our results have shown that for wind velocity of 20 km/s an accretion disc forms in the system. The accretion rate for the solution with the disc is ~22.5-25% of the mass loss rate of the donor, that is, ~4.5-5*10^(-8)Msun/yr for Z And. This value is in agreement with the steady burning range for white dwarf masses typically accepted for this system. When the wind velocity increases from 20 to 30 km/s the accretion disc is destroyed and the matter of the disc falls onto the accretor's surface. This process is followed by an approximately twofold accretion rate jump. The resulting accretion rate growth is sufficient for passing the upper limit of the steady burning range, thereby bringing the system into an active state. The time during which the accretion rate is above the steady burning value is in a very good agreement with observations. The analysis of the results presented here allows us to conclude that small variations in the donor's wind velocity can lead to the transition from the disc accretion to the wind accretion and, as a consequence, to the transition from quiescent to active state in classic symbiotic stars.Comment: 21 pages, 7 figure

Development and validation of models for optimisation and control of batch and continuous crystallisation processes

The work presented in this paper constitute the main results from the SINC-PRO project (IMS project focussing on crystalliser design and control) as regards off-line model use. A generic modelling framework applicable to a wide range of solution crystallisation processes is briefly presented. This framework enables the rapid development of consistent process models, which predict process behaviour and product performance (mainly in terms of CSD and purity) as a function of design and operational parameters