Search results for "in silico model"
showing 5 items of 5 documents
Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles.
2009
BACKGROUND: PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors. OBJECTIVE AND METHODS: In this study we investigated the effects of two common polymorphism of the PCSK9 gene (E670G and I474V) on the intima media thickness of the common carotid artery and the possible relation with polymorphisms of apolipoprotein E in 1541 middle aged subjects selected from the general population enrolled in the PLIC study and confirmed the major findings in a second free-living population enrolled in the Ventimiglia study. RESULTS: 670G carriers showed significantly increased plasma total cholesterol, LDL-cholesterol, and Apo levels B while no significant d…
Nuovi derivati della Dopamina nell’Addiction da sostanze d’abuso: studi preclinici su modelli sperimentali murini
Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes
2015
The adverse effects to humans and environment of only few chemicals are well known. Absorption, distribution, metabolism, and excretion (ADME) are the steps of pharmaco/toxicokinetics that determine the internal dose of chemicals to which the organism is exposed. Of all the xenobiotic-metabolizing enzymes, the cytochrome P450 (CYP) enzymes are the most important due to their abundance and versatility. Reactions catalyzed by CYPs usually turn xenobiotics to harmless and excretable metabolites, but sometimes an innocuous xenobiotic is transformed into a toxic metabolite. Data on ADME and toxicity properties of compounds are increasingly generated using in vitro and modeling (in silico) tools.…
Molecular docking and oxidation kinetics of 3-phenyl coumarin derivatives by human CYP2A13
2021
CYP2A13 enzyme is expressed in human extrahepatic tissues, while CYP2A6 is a hepatic enzyme. Reactions catalysed by CYP2A13 activate tobacco-specific nitrosamines and some other toxic xenobiotics in lungs.To compare oxidation characteristics and substrate-enzyme active site interactions in CYP2A13 vs CYP2A6, we evaluated CYP2A13 mediated oxidation characteristics of 23 coumarin derivatives and modelled their interactions at the enzyme active site.CYP2A13 did not oxidise six coumarin derivatives to corresponding fluorescent 7-hydroxycoumarins. The Km-values of the other coumarins varied 0.85���97 ��M, Vmax-values of the oxidation reaction varied 0.25���60 min���1, and intrinsic clearance var…
On the Modeling of Transcatheter Therapies for the Aortic and Mitral Valves: A Review
2022
Transcatheter aortic valve replacement (TAVR) has become a milestone for the management of aortic stenosis in a growing number of patients who are unfavorable candidates for surgery. With the new generation of transcatheter heart valves (THV), the feasibility of transcatheter mitral valve replacement (TMVR) for degenerated mitral bioprostheses and failed annuloplasty rings has been demonstrated. In this setting, computational simulations are modernizing the preoperative planning of transcatheter heart valve interventions by predicting the outcome of the bioprosthesis interaction with the human host in a patient-specific fashion. However, computational modeling needs to carry out increasingl…