Search results for "P3a"
showing 10 items of 98 documents
Informal musical activities are linked to auditory discrimination and attention in 2-3-year-old children: an event-related potential study
2012
The relation between informal musical activities at home and electrophysiological indices of neural auditory change detection was investigated in 2-3-year-old children. Auditory event-related potentials were recorded in a multi-feature paradigm that included frequency, duration, intensity, direction, gap deviants and attention-catching novel sounds. Correlations were calculated between these responses and the amount of musical activity at home (i.e. musical play by the child and parental singing) reported by the parents. A higher overall amount of informal musical activity was associated with larger P3as elicited by the gap and duration deviants, and smaller late discriminative negativity r…
Modulation of biotransformation and elimination systems by BM-21, an aqueous ethanolic extract from Thalassia testudinum, and thalassiolin B on human…
2012
Abstract BM-21 is an extract obtained from Thalassia testudinum marine plant with pharmacological properties. The effects of BM-21 and thalassiolin B (TB), its main component, on enzyme and transport proteins involved in drug metabolism and excretion in human cultured hepatocytes were evaluated. Cells were exposed for 48 h to sub-cytotoxic concentrations of BM-21 or TB. Effects on P450 isoforms revealed significant reductions of CYP1A2, 3A4 and 2D6 activities (up to 56%, 66% and 44% inhibition, respectively) after exposition to BM-21, no changes on CYP2A6 and 2C9 activities. TB produced a concentration-dependent reduction of all P450 activities. In addition, a decrease in total UGT and UGT2…
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes
2017
Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. H…
Effects of EPHX1 and CYP3A4 polymorphisms on carbamazepine metabolism in epileptic patients
2014
Antonietta Caruso, Chiara Bellia, Alessia Pivetti, Luisa Agnello, Federica Bazza, Concetta Scazzone, Giulia Bivona, Bruna Lo Sasso, Marcello CiaccioDepartment of Biopathology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, ItalyBackground: The aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we reported the genotype frequencies of …
Genetics of the variable expression of CYP3A in humans.
2004
CYP3A isozymes participate in the metabolism of 45-60% of currently used drugs and of a variety of other compounds such as steroid hormones, toxins, and carcinogens. The CYP3A expression status is a major determinant of drug efficacy and safety, and it may also affect an individual's predisposition to certain cancers. The inter- and intraindividual expression of CYP3A is variable because of a complex interplay between genetic and environmental factors. Markers predictive of the individual CYP3A activity could improve therapies with CYP3A substrates by personalised dose adjustments, but their development has been slower than for other drug-metabolizing enzymes. Here we summarize the recent p…
CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy
2020
Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results: CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p < 0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR = 0.07; 95% CI = 0.03–0.18 and OR = 0.45; 95% C…
Transcriptional regulation and expression of CYP3A4 in hepatocytes.
2007
CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected. The functional examination of up to 13 kb of the CYP3A4 5'-flanking region has revealed that the regulation of this gene is a complex issue, with…
Mangifera indica L. Extract and Mangiferin Modulate Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes in Primary Cultures of Human Hepatocytes
2012
The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti-inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P-450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP-glucuronosyltransferases (UGTs) in human-cultured hepatocytes have been examined. After hepatocytes underwent a 48-h treatment with sub-cytotoxic concentrations of the products (50-250 µg/mL), a concentration-dependent decrease of the activity of the five P450 enzymes measured (CYP1A…
Investigation of the steps involved in the difference of susceptibility of Ephestia kuehniella and Spodoptera littoralis to the Bacillus thuringiensi…
2011
BUPM95 is a Bacillus thuringiensis subsp. kurstaki strain producing the Vip3Aa16 toxin with an interesting insecticidal activity against the Lepidopteran larvae Ephestia kuehniella. Study of different steps in the mode of action of this Vegetative Insecticidal Protein on the Mediterranean flour moth (E. kuehniella) was carried out in the aim to investigate the origin of the higher susceptibility of this insect to Vip3Aa16 toxin compared to that of the Egyptian cotton leaf worm Spodoptera littoralis. Using E. kuehniella gut juice, protoxin proteolysis generated a major band corresponding to the active toxin and another band of about 22kDa, whereas the activation of Vip3Aa16 by S. littoralis …
The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.
2010
The individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability.We investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobiotics sensors PXR and CAR.The combination of a proximal ER6 element with XREM and CLEM represents the original scheme of CYP3A regulation by nuclear receptors in placental mammals. Among human CYP3A genes, this scheme is retained only in CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during primate evolution. In parallel, the number of elements outside XREM and CLEM potentially responsi…