Search results for "P3a"

The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and co…

2004

Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically relevant drug interactions. In contrast with other CYP3A family members, studies on the inducibility of CYP3A5 indicate conflicting results. We report the induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin. Furthermore, induction of CYP3A5 mRNA was observed in intestinal biopsies in three of eight probands following exposure to the antibiotic. The highest absolute levels of CYP3A5 transcripts were found following rifampin treatment in hepatocytes and intestines from carriers of CYP3A5*1 alleles. Elucidation of the mechanism involved in CYP3A5 induction revealed that constitutively act…

THE EFFECT OF CYP3A5 AND ABCB1 SINGLE NUCLEOTIDE POLYMORPHISMS ON TACROLIMUS DOSE REQUIREMENTS IN CAUCASIAN LIVER TRANSPLANT PATIENTS

2008

Transcriptional Regulation of Human CYP3A4 Basal Expression by CCAAT Enhancer-Binding Protein α and Hepatocyte Nuclear Factor-3γ

2003

Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more than 50% of currently used therapeutic drugs, yet the mechanisms that control CYP3A4 basal expression in liver are poorly understood. Several putative binding sites for CCAAT/enhancer-binding protein (C/EBP) and hepatic nuclear factor 3 (HNF-3) were found by computer analysis in CYP3A4 promoter. The use of reporter gene assays, electrophoretic mobility shift assays, and site-directed mutagenesis revealed that one proximal and two distal C/EBP alpha binding sites are essential sites for the trans-activation of CYP3A4 promoter. No trans-activation was found in similar reporter gene experiments with a HNF-3 gamma expression vec…

Auditory P3a response to native and foreign speech in children with or without attentional deficit

2023

The aim of this study was to investigate the attentional mechanism in speech processing of native and foreign language in children with and without attentional deficit. For this purpose, the P3a component, cognitive neuromarker of the attentional processes, was investigated in a two-sequence two-deviant oddball paradigm using Finnish and English speech items via event-related potentials (ERP) technique. The difference waves reflected the temporal brain dynamics of the P3a response in native and foreign language contexts. Cluster-based permutation tests evaluated the group differences over the P3a time window. A correlation analysis was conducted between the P3a response and the attention sc…

An in vitro tool to assess cytochrome P450 drug biotransformation-dependent cytotoxicity in engineered HepG2 cells generated by using adenoviral vect…

2011

Many adverse drug reactions leading to hepatotoxicity are caused by the cytochrome P450-dependent activation of non-toxic drugs or chemicals into reactive metabolites. To this end, adenoviruses were used as a tool to efficiently deliver specific CYP genes into cultured cells (i.e., human hepatoma cell line HepG2). Recombinant-defective adenoviral vectors encoding for genes CYP3A4 (Adv-CYP3A4), CYP2E1 (Adv-CYP2E1), CYP2A6 (Adv-CYP2A6) and CYP1A2 (Adv-CYP1A2) were used to confer specific CYP drug metabolic capabilities to HepG2 cells. Upgraded cells transiently expressed single specific cytochrome P450 enzymatic activities in terms of the number of the infecting virus particles used in their …

Non-negative matrix factorization Vs. FastICA on mismatch negativity of children

2009

In this presentation two event-related potentials, mismatch negativity (MMN) and P3a, are extracted from EEG by non-negative matrix factorization (NMF) simultaneously. Typically MMN recordings show a mixture of MMN, P3a, and responses to repeated standard stimuli. NMF may release the source independence assumption and data length limitations required by Fast independent component analysis (FastICA). Thus, in theory NMF could reach better separation of the responses. In the current experiment MMN was elicited by auditory duration deviations in 102 children. NMF was performed on the time-frequency representation of the raw data to estimate sources. Support to Absence Ratio (SAR) of the MMN co…

Luminometric sub-nanoliter droplet-to-droplet array (LUMDA) and its application to drug screening by phase I metabolism enzymes.

2012

Here we show the fabrication of the Luminometric Sub-nanoliter Droplet-to-droplet Array (LUMDA chip) by inkjet printing. The chip is easy to be implemented and allows for a multiplexed multi-step biochemical assay in sub-nanoliter liquid spots. This concept is here applied to the integral membrane enzyme CYP3A4, i.e. the most relevant enzymatic target for phase I drug metabolism, and to some structurally-related inhibitors.

A newin vitroapproach for the simultaneous determination of phase I and phase II enzymatic activities of human hepatocyte preparations

2007

Primary hepatocytes are still the best qualified in vitro system to anticipate drug metabolism in man. Recent advances in hepatocytes cryopreservation have notably increased their use not only for drug metabolism studies, but also for other applications such as cell transplantation. Evaluation of the drug-metabolizing competence of each hepatocytes preparation is needed. To date, the metabolic characterization of hepatocytes preparations relies on the assessment of phase I activities and the role of phase II enzymes receives little attention. A novel approach for the rapid assessment of the metabolic functionality of hepatocytes has been developed. A five-probe cocktail was used to simultan…

Somatosensory Deviance Detection ERPs and Their Relationship to Analogous Auditory ERPs and Interoceptive Accuracy

2022

Abstract. Automatic deviance detection has been widely explored in terms of mismatch responses (mismatch negativity or mismatch response) and P3a components of event-related potentials (ERPs) under a predictive coding framework; however, the somatosensory mismatch response has been investigated less often regarding the different types of changes than its auditory counterpart. It is not known whether the deviance detection responses from different modalities correlate, reflecting a general prediction error mechanism of the central nervous system. Furthermore, interoceptive functions have been associated with predictive coding theory, but whether interoceptive accuracy correlates with devian…

Impacto de la farmacogenética en la inmunosupresión con Tacrólimus en el trasplante hepático y renal

2017

Los trasplantes de órganos sólidos, en especial el trasplante hepático y renal, han permitido aumentar la supervivencia de la población, lo que se ha potenciado con el desarrollo de las técnicas quirúrgicas y de la inmunosupresión farmacológica, dentro de los que destaca la aparición de los inhibidores de la calcineurina (InC), especialmente tacrólimus. A pesar de estos avances, persisten cifras importantes de rechazo agudo y de toxicidad aguda y crónica precisamente por el uso de los InC que pueden dificultar la mejoría de la supervivencia y la calidad de vida de los pacientes trasplantados. Para reducir estos riesgos se han implementado intervenciones para mejorar la dosificación de los I…