Search results for "3a"

Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport

2006

The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate …

Droplet-to-droplet microarray for drug screening in picoliter scale

2012

The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.

2015

Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…

CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7.

2008

CYP3A metabolizes 50% of currently prescribed drugs and is frequently involved in clinically relevant drug interactions. The understanding of roles and regulations of the individual CYP3A genes in pharmacology and physiology is incomplete.Using genomic sequences from 16 species we investigated the evolution of CYP3 genomic loci over a period of 450 million years.CYP3A genes in amniota evolved from two ancestral CYP3A genes. Upon the emergence of eutherian mammals, one of them was lost, whereas, the other acquired a novel genomic environment owing to translocation. In primates, CYP3A underwent rapid evolutionary changes involving multiple gene duplications, deletions, pseudogenizations, and …

CCDC 707421: Experimental Crystal Structure Determination

2009

Related Article: L.Kiss, M.Nonn, E.Forro, R.Sillanpaa, F.Fulop|2009|Tetrahedron Lett.|50|2605|doi:10.1016/j.tetlet.2009.03.119

Creating stable Floquet–Weyl semimetals by laser-driving of 3D Dirac materials

2017

Nature Communications 8, 13940 (2017). doi:10.1038/ncomms13940

The role of red yeast rice (RYR) supplementation in plasma cholesterol control: A review and expert opinion.

2019

1. Preamble : Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) [1]. Increased levels of low density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease (CHD) and many clinical trials have shown that reducing LDL-C levels significantly reduced the CHD and CVD risk [[2], [3], [4], [5]]. Thus LDL-C-lowering is the main approach for the management of cardiovascular disease. Current guidelines suggest LDL-C levels targets based on the individual CV risk; such targets can be achieved by several means, which include both lifestyle changes and pharmacological approaches [6], with statins being the cornerstone …

F-signature of pairs: Continuity, p-fractals and minimal log discrepancies

2011

This paper contains a number of observations on the {$F$-signature} of triples $(R,\Delta,\ba^t)$ introduced in our previous joint work. We first show that the $F$-signature $s(R,\Delta,\ba^t)$ is continuous as a function of $t$, and for principal ideals $\ba$ even convex. We then further deduce, for fixed $t$, that the $F$-signature is lower semi-continuous as a function on $\Spec R$ when $R$ is regular and $\ba$ is principal. We also point out the close relationship of the signature function in this setting to the works of Monsky and Teixeira on Hilbert-Kunz multiplicity and $p$-fractals. Finally, we conclude by showing that the minimal log discrepancy of an arbitrary triple $(R,\Delta,\b…

F-singularities via alterations

2011

For a normal F-finite variety $X$ and a boundary divisor $\Delta$ we give a uniform description of an ideal which in characteristic zero yields the multiplier ideal, and in positive characteristic the test ideal of the pair $(X,\Delta)$. Our description is in terms of regular alterations over $X$, and one consequence of it is a common characterization of rational singularities (in characteristic zero) and F-rational singularities (in characteristic $p$) by the surjectivity of the trace map $\pi_* \omega_Y \to \omega_X$ for every such alteration $\pi \: Y \to X$. Furthermore, building on work of B. Bhatt, we establish up-to-finite-map versions of Grauert-Riemenscheneider and Nadel/Kawamata-V…

Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes

2007

Objective: To find genetic markers of the individual cytochrome P450 (CYP)3A expression. Methods: A large collection of liver samples phenotyped for CYP3A expression and activity was genotyped for CYP3A variants. Data were analyzed for associations between CYP3A phenotypes and genotypes, and for evidence of recent selection. Results: We report associations between the hepatic CYP3A4 protein expression level, as well as its enzymatic activity, measured as verapamil N-dealkylation, and genetic polymorphisms from two regions within the CYP3A gene cluster. One region is defined by several variants, mostly located within CYP3A7, the other by a single nucleotide polymorphism in intron 7 of CYP3A…