CFD as an Enginer's Tool for Investigation of Large-Scale-Flow-Phenomena "at Land, Sea and Air"

Along with prospective fashion of solving the engineering-tasks (if development would allow us a such approach while answering the technology-questions of some project in future), goes alternatively corrective performance of those engineering tools, used to compensate for needed changes in some already existing technical solution. A unique chance to compare the needs of traffic-intentions (while setting the modern road communications through the southern of Bosnia and Herzegovina) verses natural occurrences in the atmosphere (such is a strong north-wind in this geographic region) offers the high-way-section Pocitelj-Zvirovici. Exactly in such cases (and before the actual construction of an engineering-construction is realized) "for the sake" of prospective-and certainly self-sustainable engineering-the tool of CFD (the tool for performing the Computational Fluid Dynamics) was applied to engaged the problem. Again, in the same moment while solving prospectively (through application of the CFD-based research prospectively in) several technical issues on submarine tidal-turbines in bay-area of Swansea in Wales (UK) for electricity production, a corrective way of engineering is requested to research on both imagined fire-scenarion in road-tunnel of Vranduk, close to Zenica (Bosnia) as as well as in case of investigative observing the (large-scale) combustion of the flare-stack in the refinery in town of Lendava (Slovenia). Coming from the both steady-state (k-epsilon turbulence-treatment) and time-dependent applied CFD-based explorations (Large-Eddy Simulation in Smagorinsky-Lilly mode), the unexpected and unwanted strong gaseous flows were detected and the results coming out of this are explained and discussed

Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure

The efficacy of aripiprazole therapy and the risk of adverse reactions are influenced by substantial inter-individual variability in aripiprazole metabolizing capacity. In vitro studies assigned the potential role in aripiprazole metabolism to CYP2D6 and CYP3A enzymes; therefore, the association between the steady-state aripiprazole plasma concentrations and patients' CYP2D6 and CYP3A statuses (CYP2D6, CYP3A4, and CYP3A5 genotypes, and CYP3A4 expression) and/or co-medication with CYP function modifying medications has been investigated in 93 psychiatric patients on stable aripiprazole therapy. The patients' CYP2D6 genotype had a major effect on aripiprazole plasma concentrations, whereas contribution of CYP3A genotypes and CYP3A4 expression to aripiprazole clearance were considered to be minor or negligible. The role of CYP3A4 expression in aripiprazole metabolism did not predominate even in the patients with nonfunctional CYP2D6 alleles. Furthermore, dehydroaripiprazole exposure was also CYP2D6 genotype-dependent. Dehydroaripiprazole concentrations were comparable with aripiprazole levels in patients with functional CYP2D6 alleles, and 35% or 22% of aripiprazole concentrations in patients with one or two non-functional CYP2D6 alleles, respectively. The concomitant intake of CYP2D6 inhibitors, risperidone, metoprolol, or propranolol was found to increase aripiprazole concentrations in patients with at least one wild-type CYP2D6*1 allele. Risperidone and 9-hydroxy-risperidone inhibited both dehydrogenation and hydroxylation of aripiprazole, whereas metoprolol and propranolol blocked merely the formation of the active dehydroaripiprazole metabolite, switching towards the inactivation pathways. Patients' CYP2D6 genotype and co-medication with CYP2D6 inhibitors can be considered to be the major determinants of aripiprazole pharmacokinetics. Taking into account CYP2D6 genotype and co-medication with CYP2D6 inhibitors may improve the outcomes of aripiprazole therapy