Relevant bibliographies by topics / CYP4F2

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Academic literature on the topic 'CYP4F2'

Author: Grafiati
Published: 4 June 2021
Last updated: 11 March 2023

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Journal articles on the topic "CYP4F2"

1

HENG, Yee M., C. W. Sharon KUO, Paul S. JONES, et al. "A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but not of CYP4F, genes in mouse and humans." Biochemical Journal 325, no. 3 (1997): 741–49. http://dx.doi.org/10.1042/bj3250741.

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Genomic clones for Cyp4a12 and a novel member of the murine Cyp4a gene family were isolated. The novel gene, designated Cyp4a14, has a GC rich sequence immediately 5′ of the transcription start site, and is similar to the rat CYP4A2 and CYP4A3 genes. The Cyp4a14 gene spans approximately 13 kb, and contains 12 exons; sequence similarity to the rat CYP4A2 gene sequence falls off 300 bp upstream from the start site. In view of the known sex-specific expression of the rat CYP4A2 gene, the expression and inducibility of Cyp4a14 was examined. The gene was highly inducible in the liver when mice were treated with the peroxisome proliferator, methylclofenapate; induction levels were low in control animals and no sex differences in expression were observed. By contrast, the Cyp4a12 RNA was highly expressed in liver and kidney of control male mice but was expressed at very low levels in liver and kidney of female mice. Testosterone treatment increased the level of this RNA in female liver slightly, and to a greater extent in the kidney of female mice. In agreement with studies on the cognate RNA, expression of Cyp4a12 protein was male-specific in the liver of control mice and extremely high inducibility of Cyp4a10 protein, with no sex differences, was also demonstrated. In view of the overlapping patterns of inducibility of the three Cyp4a genes, we investigated whether the three genes were co-localized in the genome. Two overlapping yeast artificial chromosome (YAC) clones were isolated, and the three Cyp4a genes were shown to be present on a single YAC of 220 kb. The Cyp4a genes are adjacent to the Cyp4b1 gene, with Cyp4a12 most distant from Cyp4b1. The clustering of these two gene subfamilies in the mouse was replicated in the human, where the CYPA411 and CYP4B1 genes were present in a single YAC clone of 440 kb. However, the human CYP4F2 gene was mapped to chromosome 19. Phylogenetic analysis of the CYP4 gene families demonstrated that CYP4A and CYP4B are more closely related than CYP4F.
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Grangeon, Alexia, Valérie Clermont, Azemi Barama, Fleur Gaudette, Jacques Turgeon, and Veronique Michaud. "Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics." International Journal of Molecular Sciences 22, no. 23 (2021): 12791. http://dx.doi.org/10.3390/ijms222312791.

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The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.
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Ciapiene, Ieva, Vacis Tatarunas, Agne Giedraitiene, et al. "The Effect of Rivaroxaban on CYP4F2 and Transcription Factors’ Activity in HUVECs." Applied Sciences 11, no. 22 (2021): 10851. http://dx.doi.org/10.3390/app112210851.

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Interindividual variabilities between patients taking the anticoagulant rivaroxaban are a result of hepatic metabolism by CYP 450 enzymes. The objective of this study was to evaluate the impact of rivaroxaban on CYP4F2 and transcription factors’ activity in HUVECs. Rivaroxaban and its metabolites were detected by UPLC-ESI-MS and UPLC-QTOF-MS. CYP4F2, HNF4α, PXR and CAR expressions were determined in HUVECs by qPCR; CYP4F2 protein concentration was determined by ELISA. Rivaroxaban metabolites (M-1, M-2, M-5, M-8, M-10, M-11 and M-18) were detected in endothelial cells’ culture medium. Increasing concentrations of rivaroxaban determined lower 13-docosenamide concentrations. Rivaroxaban and dexamethasone reduced the expression of CYP4F2 when hsa-miR-24-3p—both CYP4F2 expression and CYP4F2 protein levels in HUVECs. The expression of the transcription factors HNF4α, PXR and CAR was not detected in HUVECs.
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Mota-Zamorano, Sonia, Nicolás R. Robles, Luz M. González, et al. "Genetics Variants in the Epoxygenase Pathway of Arachidonic Metabolism Are Associated with Eicosanoids Levels and the Risk of Diabetic Nephropathy." Journal of Clinical Medicine 10, no. 17 (2021): 3980. http://dx.doi.org/10.3390/jcm10173980.

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Genes in the epoxygenase pathway of arachidonic acid metabolism leading to vasoactive eicosanoids, mainly 20-hydroxyeicosatetraenoic (20-HETE) and epoxyeicosatrienoic (EETs) acids, have been related to glucose-induced renal damage in preclinical reports. We genotyped 1088 diabetic kidney disease (DKD) patients and controls for seven polymorphisms in five genes (CYP2C8, CYP2J2, CYP4F2, CYP4A11, and EPHX2) along this metabolic route and evaluated their effect on DKD risk, clinical outcomes, and the plasma/urine levels of eicosanoids measured by LC/MS/MS and immunoenzymatic assays. The CYP4F2 433M variant allele was associated with lower incidence of DKD (OR = 0.65 (0.48–0.90), p = 0.008), whilst the CYP2C8*3/*3 genotype was related to increased risk (OR = 3.21 (1.05–9.87), p = 0.036). Patients carrying the 433M allele also showed lower eGFR [median and interquartile range vs. wildtype carriers: 30.8 (19.8) and 33.0 (23.2) mL/min/1.73 m2, p = 0.037). Finally, the 433VM/MM variant genotypes were associated with lower urinary levels of 20-HETE compared with 433VV (3.14 (0.86) vs. 8.45 (3.69) ng/mg Creatinine, p = 0.024). Our results indicate that the CYP4F2 V433M polymorphism, by decreasing 20-HETE levels, may play an important role in DKD.
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Nguyen, Xuandai, Mong-Heng Wang, Komandla M. Reddy, John R. Falck, and Michal Laniado Schwartzman. "Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and isoform-specific inhibitors." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, no. 6 (1999): R1691—R1700. http://dx.doi.org/10.1152/ajpregu.1999.276.6.r1691.

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20-Hydroxyeicosatetraenoic acid (HETE), the cytochrome P-450 (CYP) 4A ω-hydroxylation product of arachidonic acid, has potent biological effects on renal tubular and vascular functions and on the control of arterial pressure. We have expressed high levels of the rat CYP4A1, -4A2, -4A3, and -4A8 cDNAs, using baculovirus and Sf 9 insect cells. Arachidonic acid ω- and ω-1-hydroxylations were catalyzed by three of the CYP4A isoforms; the highest catalytic efficiency of 947 nM−1 ⋅ min−1for CYP4A1 was followed by 72 and 22 nM−1 ⋅ min−1for CYP4A2 and CYP4A3, respectively. CYP4A2 and CYP4A3 exhibited an additional arachidonate 11,12-epoxidation activity, whereas CYP4A1 operated solely as an ω-hydroxylase. CYP4A8 did not catalyze arachidonic or linoleic acid but did have a detectable lauric acid ω-hydroxylation activity. The inhibitory activity of various acetylenic and olefinic fatty acid analogs revealed differences and indicated isoform-specific inhibition. These studies suggest that CYP4A1, despite its low expression in extrahepatic tissues, may constitute the major source of 20-HETE synthesis. Moreover, the ability of CYP4A2 and -4A3 to catalyze the formation of two opposing biologically active metabolites, 20-HETE and 11,12-epoxyeicosatrienoic acid, may be of great significance to the regulation of vascular tone.
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Kringen, Marianne K., Kari Bente Foss Haug, Runa M. Grimholt, et al. "Genetic Variation of VKORC1 and CYP4F2 Genes Related to Warfarin Maintenance Dose in Patients with Myocardial Infarction." Journal of Biomedicine and Biotechnology 2011 (2011): 1–5. http://dx.doi.org/10.1155/2011/739751.

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The aim of this study was to investigate whether the VKORC1*3 (rs7294/9041 G > A), VKORC1*4 (rs17708472/6009 C > T), and CYP4F2 (rs2108622/1347 C > T) polymorphisms were associated with elevated warfarin maintenance dose requirements in patients with myocardial infarction (n=105) from the Warfarin Aspirin Reinfarction Study (WARIS-II). We found significant associations between elevated warfarin dose requirements and VKORC1*3 and VKORC1*4 polymorphisms (P=.001andP=.004, resp.), whereas CYP4F2 (1347 C > T) showed a weak association on higher warfarin dose requirements (P=.09). However, analysing these variant alleles in a regression analysis together with our previously reported data on VKORC1*2, CYP2C9*2 and CYP2C9*3 polymorphisms, gave no significant associations for neither VKORC1*3, VKORC1*4 nor CYP4F2 (1347 C > T). In conclusion, in patients with myocardial infarction, the individual contribution to warfarin dose requirements from VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms was negligible. Our results indicate that pharmacogenetic testing for VKORC1*2, CYP2C9*2 and CYP2C9*3 is more informative regarding warfarin dose requirements than testing for VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms.
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Lin, Xianliang, Hao Chen, Le Ni, Yunqiang Yu, Zhurong Luo, and Lihong Liao. "Effects of EPHX1 rs2260863 polymorphisms on warfarin maintenance dose in very elderly, frail Han-Chinese population." Pharmacogenomics 21, no. 12 (2020): 863–70. http://dx.doi.org/10.2217/pgs-2020-0054.

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Aim: This study was conducted to investigate the effects of VKORC1, CYP2C9, CYP4F2 and EPHX1 and nongenetic factors on warfarin maintenance dose in a very elderly, frail Han-Chinese population. Materials & methods: 16 variants of VKORC1, CYP2C9, CYP4F2 and EPHX1 were genotyped. Univariate analysis and multivariable regression model were performed for the associations of gene variants and warfarin maintenance dose. Results & conclusion: EPHX1 rs2260863 nonvariant CC homozygotes required significantly lower daily warfarin dose than GC heterozygotes. In the multivariable model, VKORC1 rs9923231, CYP2C9 rs1057910, EPHX1 rs2260863, CYP4F2 rs2189784 and body surface area altogether explained 26.9% of dosing variability. This study revealed the main impact of genetic factors on warfarin response in this special population.
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Jarrar, Yazun, and Su-Jun Lee. "Effect of rosiglitazone on 20-hydroxyeicosatetraenoic acid levels and CYP4F2 expression in HepG2 cells." Tropical Journal of Pharmaceutical Research 20, no. 4 (2022): 703–8. http://dx.doi.org/10.4314/tjpr.v20i4.6.

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 Purpose: To determine the effect of rosiglitazone on the levels of the cardiotoxic arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), in the human liver hepatocellular carcinoma cell line, HepG2.
 Methods: HepG2 cells were treated with thiazolidinedione rosiglitazone and the mRNA and protein expressions of cytochrome P450 4F2 (CYP4F2) responsible for synthesizing 20-HETE were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The levels of 20-HETE were evaluated using liquid chromatography/mass spectrometry (LC-MS).
 Results: Rosiglitazone significantly increased the levels of CYP4F2 mRNA and protein when compared with the control group (p < 0.05). This was correlated with significantly increased 20-HETE levels in the culture medium of rosiglitazone-treated cells in a dose-dependent manner (p < 0.05). The PPARγ antagonist, GW9662, significantly repressed the increased production of 20-HETE and CYP4F2 mRNA protein (p < 0.05).
 Conclusion: Rosiglitazone increases the synthesis of 20-HETE via activation of PPARγ receptor and upregulation of CYP4F2. These findings may provide an additional explanation, at least in part, for the unwanted side effects of rosiglitazone on the cardiovascular system.
 
 
 
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Ivashchenko, Dmitriy, Ilya Rusin, Dmitriy Sychev, and Andrey Grachev. "The Frequency of CYP2C9, VKORC1, and CYP4F2 Polymorphisms in Russian Patients With High Thrombotic Risk." Medicina 49, no. 12 (2013): 81. http://dx.doi.org/10.3390/medicina49120081.

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Background and Objective. VKORC1, CYP2C9, and CYP4F2 are known to be responsible for the metabolism of warfarin. The aim was to explore the frequencies of these genotypes in the Russian population and compare the results with those for other populations. Material and Methods. In total, 91 Caucasian subjects with a mean age of 66.17 years (SD, 10.9) were recruited into the study. Of them, 40 patients (48.2%) were men. In order to obtain necessary clinical data, the medical records of the patients were reviewed. Blood (5 mL) was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3, –1639G/A VKORC1, and CYP4F2 V433M rs2108622 C>T, using the real-time polymerase chain reaction-restriction fragment length polymorphism assay. Results. The CYP2C9*1/*1 genotype was detected in 67.0%, CYP2C9*1/*2 in 9.9%, CYP2C9* 1/*3 in 11.0%, CYP2C9*2/*2 in 2.2%, CYP2C9*2/*3 in 8.8%, and CYP2C9*3/*3 in 1.1% of the patients. The results for VKORC1 were as follows: 49.5% (GG), 28.6% (GA), and 22.0% (AA); meanwhile, those for the genotype CYP4F2 were 57.1% (CC), 34.1% (CT), and 7.7% (TT). No significant deviations from the Hardy-Weinberg equilibrium were observed. The frequency of the polymorphisms in the Russian population was found to differ from Asian and close to Caucasian. There were no significant interethnic variations in the frequency of CYP4F2 among Russian, Asian, and Caucasian populations. Conclusion. The frequency of CYP2C9, CYP4F2, and VKORC1 polymorphisms in Russian patients is comparable with other European ethnic groups.
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Bairova, T. A., E. A. Novikova, F. I. Belyalov, et al. "FREQUENCIES OF POLYMORPHISMS IN THE CYTOCHROME’S P450 GENES OF WARFARIN TRANSFORMATION IN A EUROPEAN POPULATION OF EASTERN SIBERIA." Acta Biomedica Scientifica 3, no. 5 (2018): 39–48. http://dx.doi.org/10.29413/abs.2018-3.5.6.

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Background.Genotypes of the cytochrome p450 isoform (CYP2C9 and CYP4F2) determine warfarin dose requirements. Frequencies of risk alleles and genotypes of CYP2C9 and CYP4F2 gene vary in different races and ethnic groups.Aim.This study analyzed the frequencies of *2, *3 alleles of CYP2C9 gene and the 1347 C>T allele of CYP4F2 gene in the Caucasians of Eastern Siberia, and compare with other populations.Materials and methods.Participants were 147 patients (Caucasians): 67 (45.58 %) man and 80 (54.42 %) women), taking warfarin for the prevention of thrombosis with a mean age of 64.74 ± 14.29 years. There were patients with atrial fibrillation – 77 (52.38 %) persons, coronary artery disease – 10 (6.80 %), pulmonary embolism – 5 (3.40 %), 15 (10.20 %) patients after implantation of an mechanical heart valve, etc. The subjects were genotyped for CYP2C9 (*1,*2,*3), and CYP4F2 (1347 C>T) by real-time polymerase chain reaction (RT-PCR) using “Pharmacogenetics Warfarin” reagent kits (DNA technology, Russia).Results.69.4 % of Caucasians of Eastern Siberia (Russians), have two functional alleles (*1/*1) of CYP2C9 (they’re extensive/normal metabolizers), the number of intermediate metabolizers (*1/*2, *1/*3) was 29.8 % and 0.68 % of slow metabolizers (*3/*3). Homozygous carriers of two non-functional alleles *2 and *3 (*2/*2, *2/*3) were absent. Carriers of one coumarin-resistant Т-allele of CYP4F2 were 57 (38.7 %) respondents, two coumarin-resistant alleles – 10 (6.8 %) respondents.Conclusions.Frequencies of polymorphisms in the Cytochrome’s p450 genes of warfarin transformation in a European population of Eastern Siberia have no differences with other European populations of the world
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Dissertations / Theses on the topic "CYP4F2"

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Majeed, Habeeb. "Supplementation to Improve Anticoagulation Control with Low Dose Vitamin K as an Adjuvant to Warfarin Therapy: A Double-blind, Placebo-controlled Randomized Controlled Trial." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23237.

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Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]
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Bylund, Johan. "Cytochrome P450 enzymes in oxygenation of prostaglandin endoperoxides and arachidonic acid : Cloning, expression and catalytic properties of CYP4F8 and CYP4F21." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1066.

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<p>Cytochrome P450 (P450 or CYP) is an enzyme system involved in the oxygenation of a wide range of endogenous compounds as well as foreign chemicals and drugs. This thesis describes investigations of P450-catalyzed oxygenation of prostaglandins, linoleic and arachidoniacids.</p><p>The formation of bisallylic hydroxy metabolites of linoleic and arachidonic acids was studied with human recombinant P450s and with human liver microsomes. Several P450 enzymes catalyzed the formation of bisallylic hydroxy metabolites. Inhibition studies and stereochemic analysis of metabolites suggest that the enzyme CYP1A2 may contribute to the biosynthesis of bisallylic hydroxy fatty acid metabolites in adult human liver microsomes.</p><p>19<i>R</i>-Hydroxy-PGE and 20-hydroxy-PGE are major components of human and ovine semen, respectively. They are formed in the seminal vesicles, but the mechanism of their biosynthesis is unknown. Reverse transcription-polymerase chain reaction using degenerate primers for mammalian <i>CYP4</i> family genes, revealed expression of two nov P450 genes in human and ovine seminal vesicles. The full coding regions of the genes were cloned and the enzymes were expressed in a yeast system. The human enzyme was designated CYP4F8 and the ovine enzyme was designated CYP4F21. Comparison of their deduced protein sequenceshowed that they had 74 % amino acid identity. Recombinant CYP4F8 oxygenated two prostaglandin endoperoxides (PGH<sub>1</sub> and PGH<sub>2</sub>) and three stable PGH<sub>2</sub> analogues int19-hydroxy metabolites. Oxygenation of these substrates was mirrored when incubated with microsomes isolated from human seminal vesicles. These results suggest that CYP4F8 is present in human seminal vesicles and that 19<i>R</i>-hydroxy-PGE is formed by CYP4F8-catalyze 19<i>R</i>-hydroxylation of PGH<sub>1</sub> and PGH<sub>2</sub>, followed by PGE synthase-catalyzed isomerization. Studies of catalytic properties of recombinant CYP4F21 suggest that 20-hydroxy-PGE may be formed by similar mechanisms in ovine seminal vesicles. CYP4F8 is the first enzyme shown to hydroxylate prostaglandin endoperoxides.</p>
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Rieger, Michael A. "CYP4Z1 und CYP4Z2P: Identifizierung neuer Mitglieder der humanen Cytochrom P450 Familie mit präferentieller Expression in Brustdrüsengewebe und Mammakarzinom." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2004. http://nbn-resolving.de/urn:nbn:de:swb:14-1093525824984-91466.

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Bei der adjuvanten Immuntherapie soll das Immunsystem von Tumorpatienten gezielt gegen Mikrometastasen aktiviert werden, die nach der operativen Entfernung des Primärtumors im Körper verbleiben. Tumor-assoziierte Antigene (TAA) spielen dabei die zentrale Rolle. Um der Heterogenität eines Tumors in der Expression einzelner TAAs Rechnung zu tragen, werden in modernen Vakzinierungsstrategien Pools von verschiedenen TAAs eingesetzt. Für das Mammakarzinom sind aber bislang nur wenige TAAs bekannt. Auf der Suche nach unbekannten Genen mit Mamma- bzw. Mammakarzinom-restringierter Expression in der Transkriptomdatenbank GeneExpress® wurde ein EST gefunden, das nur in 2 % der getesteten weibl. Normalgewebe ohne Mamma mit einer marginalen mittleren Expression von 16 FE (Fluoreszenzeinheit) detektiert wurde, aber in 63 % der Mammanormalgewebe (159 FE) und in 61 % der Mammakarzinome (339 FE) exprimiert wurde. Das korrespondierende UniGene-Cluster gab erste Hinweise auf die Zugehörigkeit dieses neuen Gens zu der Cytochrom P450 (CYP) Familie. Durch computergestützte Homologievergleiche mit verwandten Mitgliedern dieser Familie in Kombination mit RT-PCR konnte die cDNA-Sequenz dieses neuen CYP ermittelt werden: Durch Amplifikation der Gesamtlängen-cDNA wurden drei Transkripte in der Mammakarzinomzelllinie SK-BR-3 gefunden, die von zwei neuen CYP Genen stammen, CYP4Z1 und dem Pseudogen CYP4Z2P. Die cDNA von CYP4Z1 kodiert für ein 505 As großes Protein, das aufgrund von Homologien einer neuen Subfamilie innerhalb der CYP4 Familie zugeordnet werden kann. Sowohl die Sequenz als auch die vorhergesagte Sekundärstruktur zeigen alle charakteristischen Merkmale eines funktionellen Mitglieds dieser Familie. Aufgrund einer Nonsensemutation in Exon 8 kodiert die cDNA von CYP4Z2P (1436 bp) für ein verkürztes, nichtfunktionelles P450 von 340 As, das zu 96% identisch mit P450 4Z1 ist. Außerdem wurde in SK-BR-3 eine Spleißvariante von CYP4Z1 identifiziert. CYP4Z1 (50,8 kb) und CYP4Z2P (57,3 kb) liegen auf Chromosom 1p33-p34.1 und bestehen aus 12 Exons mit konservierten Exon-Intron-Grenzen. CYP4Z2P ist aus einer inversen Duplikation von CYP4Z1 hervorgegangen. Mittels Realtime RT-PCR mit cDNA von 17 Normalgeweben von gepoolten Spendern und von Mammakarzinomen konnte die auf Brustdrüsengewebe restringierte Expression beider Gene demonstriert werden: Die Expression von CYP4Z1 war in Mammakarzinomgewebe 3,6-mal höher als in Mammanormalgewebe, 60-mal höher als in Lunge und 84-mal höher als in Leber. Alle anderen getesteten weibl. Normalgewebe zeigten eine noch geringere Expression. Ein ähnlich stringentes Expressionsprofil ergab die Analyse von CYP4Z2P, allerdings mit einer deutlich niedrigeren Expressionsstärke. Das Mamma-restringierte Expressionsverhalten von CYP4Z1 wurde durch einen ?Cancer-Profiling-Array? (241 Tumor-/Normalgewebepaare von 13 Gewebetypen) bestätigt. Damit konnte gezeigt werden, dass CYP4Z1 bei 52 % der getesteten 50 Brustkrebspatientinnen im Tumor versus peritumoralem Normalgewebe überexprimiert war. Mit einem spezifischen Kaninchen-Antiserum konnte die Expression von P450 4Z1 Protein sowohl in CYP4Z1-transduzierten Zelllinien als auch in Mammagewebeproben mittels Western-Blot nachgewiesen werden. Konfokale Laser-Scanning Mikroskopie von MCF-7 Zellen, die das Fusionsprotein CYP4Z1-EGFP exprimierten, und die subzelluläre Fraktionierung der CYP4Z1-Transduktanten zeigten P450 4Z1 als integrales Membranprotein des endoplasmatischen Retikulums (ER). Für die Lokalisation und die Zurückhaltung im ER ohne Recycling aus dem Prä-Golgiapparat sind die ersten 32 As erforderlich, was Studien mit unterschiedlichen Deletionsmutanten aus der N-terminalen Sequenz von 4Z1 zeigten. Die Entdeckung eines neuen Mamma-spezifisch exprimierten P450 Enzyms eröffnet neue Möglichkeiten sowohl in Hinsicht auf eine Immuntherapie von Brustkrebs als auch für die Entwicklung neuer Chemotherapeutika, die spezifisch durch P450 4Z1 am Tumorort umgesetzt werden können.
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Horley, Neill. "Molecular basis of CYP2B2 induction." Thesis, University of Nottingham, 1999. http://eprints.nottingham.ac.uk/10397/.

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Many structurally unrelated chemicals can induce members of the cytochrome P450 superfamily with phenobarbital (PB) being a typical example. PB induces CYP2B1/2, which are most highly expressed in the liver. Their mechanism of activation has not yet been elucidated, with advances hampered by the absence of a suitable cell culture system to mimic the in vivo PB-mediated induction. During this thesis a primary rat hepatocyte culture system has been developed which is highly responsive to PB at both RNA and protein levels. A sensitive and specific RNAse protection assay (RPA) has been used to demonstrate that CYP2B2 mRNA is highly inducible in vitro by PB. This response occurs in a time and dose-dependent manner. The use of RPA and Western blotting has demonstrated that this primary rat hepatocyte culture system supports the induction of CYP2B2 mRNA and protein levels by PB. Sequencing -1.4kb of the 5' flanking region of the CYP2B2 gene identified genomic regulatory elements and highlighted the location of the phenobarbital response element (PBRE). The PBRE was sub-cloned into various reporter constructs and transfection technology was used to determine its PB-mediated induction. A comparative study of the constructs generated in this thesis to that of a construct provided by Anderson's group (Trottier et al., 1995) was undertaken and no differences were found in their PB-responsiveness. The Anderson construct containing the PBRE was shown here to confer a 3.3-fold PB-mediated induction of the CYP2B2 gene by CAT reporter assays. This induction was shown to be both dose and time dependent. The induction is lower than that obtained by other workers due primarily to assay conditions which were not yet optimal. However, the effects of androstane on the constitutively active receptor (CAR) may also play a role in the small inductive response of the phenobarbital response element to PB.
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Peterson, Sabrina. "Effects of apiaceous vegetable constituents on CYP1A2 activity in humans and a yeast expression system : implications for CYP1A2-activated procarcinogens /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/6612.

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Hirashima, Takako. "Choroidal Vasculature in Bietti Crystalline Dystrophy With CYP4V2 Mutations and in Retinitis Pigmentosa With EYS Mutations." Kyoto University, 2020. http://hdl.handle.net/2433/253205.

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Dunning, Rebecca. "Insecticide detoxication in drosophila melanogaster : The role of Cyp6a2." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531811.

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Markov, Gabriel. "Evolution de la signalisation stéroïdienne chez les Métazoaires." Thesis, Lyon, École normale supérieure, 2011. http://www.theses.fr/2011ENSL0634/document.

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La signalisation stéroïdienne médiée par des récepteurs nucléaires est impliquée dans de nombreux processus ayant trait au développement des animaux. La compréhension de ces phénomènes est importante pour répondre à des questions de santé publique, d’agronomie ou de biologie de la conservation. Ceci nécessite de connaître et de mettre en relation l’évolution des récepteurs qui fixent ces stéroïdes et des voies de synthèse qui produisent les stéroïdes. Mon travail s’est articulé autour de trois grands axes. 1. La mise à jour des relations de parenté entre les récepteurs nucléaires impliqués dans la fixation des stéroïdes, mais aussi de ceux qui sont impliqués dans la régulation de la stéroïdogenèse, pour comprendre quand et dans quel contexte cette machinerie est apparue. 2. La démonstration que les enzymes impliquées dans la stéroïdogenèse étaient apparues indépendamment par recrutement d’enzymes à spécificité de substrat plus large impliquées dans la détoxification des xénobiotiques. 3. L'élucidation des relations de parenté entre des voies métaboliques, montrant que les voies de la stéroïdogenèse avaient évolué comme des voies de dégradation du cholestérol. Ces résultats aboutissent à un modèle dans lequel la signalisation hormonale des animaux à symétrie bilatérale serait l’héritière de voies de détoxification de molécules stéroïdiennes contenues dans leur alimentation. Ce modèle expliquerait le couplage entre l’accumulation de nutriments et la maturation sexuelle, ainsi que les nombreux dérèglements touchant à la fois le métabolisme et la reproduction dus aux perturbateurs endocriniens ou à certaines molécules thérapeutiques<br>Nuclear receptor mediated steroid signaling is involved in many processes in metazoandevelopment, such as puberty in vertebrates, molting in insects and entry into infective stage in some parasitic nematodes. Understanding those phenomena is important regarding public health, agronomical and conservation biology issues. This necessitates to know and to explore the interactions between the evolution of steroid-binding receptors and steroid-synthesizing pathways. My work was articulated around three major parts. First, using the historical expertise of the laboratory, I updated the relationships between nuclear receptors that are involved in steroid binding, but also from all those that are involved in steroidogenesis regulation, in order to elucidate when and in which context this machinery has arisen. Second, using a classical comparative genomic approach, I showed that the steroidogenetic enzymes have appeared independently by duplication from xenobiotic-metabolizing enzyme with a wider range of substrate specificity.Third, I explored the relationships between metabolic pathways using tools from comparative anatomy. This has confirmed and completed the previous results, showing that steroidogenetic pathways have evolved with the pattern of cholesterol degradation pathways.The synthesis of all these results has led to an evolutionary model where hormonal signaling in bilaterian animals has been inherited from the detoxification of dietary sterols. This model may explain the coupling between nutrient accumulation and sexual maturation, and also the link between metabolic disorders and endocrine disruption due to environmental chemicals or drugs
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Alavi, Hajar Karimi. "Development of mechanistic mathematical models for gene-mediated drug-drug interactions." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/development-of-mechanistic-mathematical-models-for-genemediated-drugdrug-interactions(b38da88a-bb2a-4667-9809-21a09c8feeeb).html.

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The glucocorticoid receptor (GR) is a member of the nuclear hormone receptors family and has been shown to exert significant effects on the induction of cytochrome P450 (CYP) enzymes responsible for the metabolism of many xenobiotics. CYP3A4/5 and CYP2C9 are important CYP enzymes which metabolise more that 60% of drugs. Induction or inhibition of the enzymatic activity and the levels of these enzymes can have significant effects on drug metabolism. Understanding the role of GR and other nuclear receptors, pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), in the mechanisms effecting CYP3A4/5 and CYP2C9 levels and activity can aid in the development of in vitro and in vivo models which have become a target for scientists in the clinic and the industry. The commonly prescribed synthetic glucocorticoid (GC) drug, dexamethasone (Dex), can induce GR, PXR and CAR and was used in this study to analyse its effects on the CYP enzymes studied. The hypothesis of this project was that changes in CYP3A4/5 and CYP2C9 gene expression affect drug metabolism and changes in gene expression of these CYP enzymes was under GR, PXR and CAR control, thus affecting the concentration and therapeutic activity of drugs metabolized by these enzymes during chronic use of GCs in conditions such as rheumatoid arthritis and asthma. This study aimed to measure mRNA, protein, ROS and enzymatic activity levels in human HepG2 hepatocytes treated with Dex for 120 h and analyze the results for various time points to produce a mathematical model. Our study has shown that changes in mRNA, protein and enzymatic activity levels of CYP3A4/5 and CYP2C9 in HepG2 cells were induced by Dex at sub-micromolar (0.1 µM) and supra-micromolar (1.5 mM) concentrations. The induction of CYP3A4/5 and CYP2C9 enzymes during 120 h treatment with Dex may be affected by the NRs studied; GR, phosphorylated GR, PXR and CAR protein levels were also shown to be induced by Dex. The efflux transporter, P-gp’s protein levels were also induced by 0.1 µM Dex, highlighting the importance of considering bioavailability of other drugs co-administered with Dex. The results of some of these laboratory experiments have been used to produce mechanistic mathematical models by MATLAB software with reference to previous studies in rats concentrating on the effects of steroids on GR. The models developed were not effective at the lower Dex concentration of 0.1 µM but were better modelled at the higher Dex concentration of 1.5 mM. The basic mechanistic models developed using HepG2 cells in this study can be utilised to design and conduct drug-drug interaction (DDI) analyses of the induction of CYP3A4/5 and CYP2C9 in other human liver cells and starting pre-clinical studies in animals to aid in drug development.
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Norman, Albin. "Co-localization of CYP4F22 and CERS3 in HeLa and HEKn cells could point towards metabolic pathway interactions." Thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-300422.

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The skin is the largest organ in the body. Its function is to protect the body from potential harm and to maintain homeostasis. The epidermis is the outermost layer of the skin. Stratum corneum is the outermost layer of the epidermis, composed of corneocytes and surrounding lipids. The lipids are produced by different enzymes that all play a role in the formation and function of the skin permeability barrier. Mutations in genes coding for these enzymes can lead to barrier dysfunction and could cause autosomal recessive congenital ichthyosis (ARCI). Nine genes have been identified as ARCI-causative and two of them are CYP4F22 and CERS3.   The purpose of this project was to study co-localization of CYP4F22 with CERS3 and also mutated CYP4F22 enzymes, by transfecting plasmids into HeLa and HaCaT cells and performing PLA on HEKn cells. Co-localization could indicate potential interactions and by studying these more in the future, novel treatment strategies can be developed for ARCI patients.   Transfection attempts showed a low transfection grade of wild type genes in both HeLa and HaCaT cells. Tendencies towards co-localization was seen in both cell types and some HeLa cells showed strong correlation after image analysis. Transfection of mutated genes failed, unfortunately. PLA showed co-localization in normal keratinocytes. The obtained results indicated a co-localization, but results need to be confirmed by immunoprecipitation and immunoblotting in the future.
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Books on the topic "CYP4F2"

1

Zhou, Yang Thomas. Assessment of caffeine as a probe for CYP1A2 activity. National Library of Canada, 1995.

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Pastrakuljic, Aleksandra. In vitro activities associated with CYP1A1 and CYP1A2 in normal human liver specimens. National Library of Canada, 1996.

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Bylund, Johan. Cytochrome P450 Enzymes in Oxygenation of Prostaglandin Endoperoxides & Arachidonic Acid: Cloning, Expression & Catalytic Properties of Cyp4F8 & Cyp4F21 ... from the Faculty of Pharmacy, 231). Uppsala Universitet, 2000.

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Constitutive embryonic and fetal expression of xenobiotic-metabolizing cytochromes: CYP1A1, CYP1A2, and CYP1B1. National Library of Canada, 1996.

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Geracioti, Thomas D., Jeffrey R. Strawn, and Matthew D. Wortman. Mechanisms of Action in the Pharmacology of PTSD. Edited by Israel Liberzon and Kerry J. Ressler. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190215422.003.0020.

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This chapter reviews medications currently available for PTSD in the context of their mechanisms of action, pathophysiological relevance, and clinical efficacy data. It systematically reviews aminergic mechanisms in PTSD pharmacology, including commonly used serotonin and norepinephrine agents, selective reuptake inhibitors and receptors drugs, as well as dopaminergic agents and psychostimulants. It also discusses the use of anticonvusants and antianxiety agents that modulate GABAergic and glutamatergic signaling, such as carbamazepine, VPA, benzodiazepines, gabapentine, and others. It also reviews other clinically available agents as well as HPA axis-modulating compounds, both for treatment and secondary prevention of PTSD. It concludes with the suggestion that clinical selection of one or more of these medications for PTSD should be based on individual patient considerations, including target symptoms, PTSD subtype, post-traumatic interval, comorbidities, genotypes for CYP450 enzymes, and genetic polymorphisms of clinical relevance.
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Book chapters on the topic "CYP4F2"

1

Zahid, Sarwar, Kari Branham, Dana Schlegel, et al. "CYP4V2." In Retinal Dystrophy Gene Atlas. Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-10867-4_26.

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Hoyer, Daniel, Eric P. Zorrilla, Pietro Cottone, et al. "CYP450." In Encyclopedia of Psychopharmacology. Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_4172.

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Bidlingmaier, M. "CYP450 11B1-Mutation." In Springer Reference Medizin. Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_809.

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Bidlingmaier, M. "CYP450 21A2-Mutation." In Springer Reference Medizin. Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_810.

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Bidlingmaier, M. "CYP450 11B1-Mutation." In Lexikon der Medizinischen Laboratoriumsdiagnostik. Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_809-1.

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Bidlingmaier, M. "CYP450 21A2-Mutation." In Lexikon der Medizinischen Laboratoriumsdiagnostik. Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_810-1.

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Roussel, Danielle, Emily Hagn, and Randal O. Dull. "CYP1A2: The Switch-hitter." In A Case Approach to Perioperative Drug-Drug Interactions. Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4614-7495-1_8.

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Dossetter, Alexander G., Marcel J. de Groot, and Sarah E. Skerratt. "CHAPTER 11. Strategies to Mitigate CYP450 Inhibition." In Drug Discovery. Royal Society of Chemistry, 2021. http://dx.doi.org/10.1039/9781788016414-00220.

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Spriet, I., and W. Meersseman. "Relevant CYP450-mediated Drug Interactions in the ICU." In Yearbook of Intensive Care and Emergency Medicine. Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-92276-6_79.

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Spriet, I., and W. Meersseman. "Relevant CYP450-mediated Drug Interactions in the ICU." In Intensive Care Medicine. Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-92278-2_79.

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Conference papers on the topic "CYP4F2"

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Li, Yuhong, Hong Wang, Jing Hu, Zhongling Zhu, Zhiwei Zhao, and Yongyi Bi. "Induction of Cytochrome CYP4F3 in Hydroquinone-Treated HL-60 Cells." In 2010 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE). IEEE, 2010. http://dx.doi.org/10.1109/icbbe.2010.5518232.

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Dehghani, Mehdi, Anneliese O. Gonzalez, Neda Hashemi-Sadraei, Songlin Zhang, and Kevin P. Rosenblatt. "Abstract P5-10-09: Correlation between germline and tumor CYP450 2D6 gene polymorphisms." In Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.sabcs14-p5-10-09.

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Du, Juan, Yaran Zhang, Lan Li, Xiaodan Qin, Yujie Ke, and Shumao Ding. "Notice of Retraction: Effect of Formaldehyde Exposure on CYP450 of Liver Cells of Mice." In 2011 5th International Conference on Bioinformatics and Biomedical Engineering. IEEE, 2011. http://dx.doi.org/10.1109/icbbe.2011.5781407.

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Belic, Ale, Damjana Rozman, Manna Temesvari, et al. "Modelling of DHEA Effect on CYP1A2 Expression in LNCaP and MCF-7 Cell Lines." In 2013 8th EUROSIM Congress on Modelling and Simulation (EUROSIM). IEEE, 2013. http://dx.doi.org/10.1109/eurosim.2013.114.

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Li, Yinsheng, Xiuhong Wang, and Jiangping Qiu. "Notice of Retraction: Effect of Oxytetracycline on Two Enzymes in CYP450 2B Subfamily in Earthworm." In 2011 5th International Conference on Bioinformatics and Biomedical Engineering. IEEE, 2011. http://dx.doi.org/10.1109/icbbe.2011.5781401.

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Wu, Cheng-Chia, Yunmeng Liu, Jonathan Chen, et al. "Abstract LB-160: CYP4F isoform expression and 20-HETE synthesis in prostate cancer cells are regulated by androgen and contribute to growth." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-lb-160.

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Vasilevich, Natalya, Anna Aksenova, Elena Aksenova, and Ilya Afanasyev. "Design and Synthesis of Macrocyclic Scaffolds for Compounds with Potential Antituberculosis/Antibacterial Activity and Improved CYP450 Properties." In 2nd International Electronic Conference on Medicinal Chemistry. MDPI, 2016. http://dx.doi.org/10.3390/ecmc-2-a013.

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Shabaldin, A. V., L. N. Igisheva, and A. A. Rumyanceva. "CONTRIBUTION OF GENETIC PREDICTORS TO FORMATION OF HEALTH DEFICIENCY IN THE SEPARATE PERIOD AFTER CARDIAC SURGERY TREATMENT OF CONGENITAL HEART DEFECTS." In I International Congress “The Latest Achievements of Medicine, Healthcare, and Health-Saving Technologies”. Kemerovo State University, 2023. http://dx.doi.org/10.21603/-i-ic-151.

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Objective: To study the contribution of xenobiotic biotransformation enzyme genes,&#x0D; transcription factors, inflammatory and immune response receptors in determining health deficiency&#x0D; in the separated period after cardiac surgery for congenital heart disease.&#x0D; Materials and methods. 116 children who underwent radical correction of CHD were&#x0D; examined. An assessment of the catamnesis of these children and genetic typing of genes encoding&#x0D; enzymes for the biotransformation of xeno- and endobiotics (GSTP, CYP1A2, CYP1A1), involved&#x0D; in the determination of cardiogenesis and processes in cardiomyocytes (CRELD-1, GATA-6,&#x0D; NOTCH-1), innate ( TREM-1) and adaptive (HLA-DR) immunity. The search for predictors of&#x0D; functioning deficit by physical, psycho-emotional, social, mental types was carried out using&#x0D; multiple logistic regression.&#x0D; Results. The level of functioning of various components of health one year after surgical&#x0D; treatment was associated with the same factors. These factors negatively affecting the health of&#x0D; children one year after heart surgery were: unfavorable living conditions, as well as genetic&#x0D; predictor markers HLA-DRB1*07 and Creld1 T/C (rs9878047)*T.
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Watson, J., D. Picking, A. Lamm та R. Delgoda. "CYP450 activity inhibition by Guazuma ulmifolia and major phytochemical constituent, procyanidin β2 in vitro: assessing the potential for drug interactions". У 67th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) in cooperation with the French Society of Pharmacognosy AFERP. © Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-3400137.

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Frias, D. P., K. Yoshizaki, K. Maier, et al. "Expression of CYP450 Genes and Cytokine Secretion Following Exposure to Cinnamyl Alcohol of BEAS-2B and Dendritic Cells Co-Culture." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7683.

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Reports on the topic "CYP4F2"

1

Merino, Diane, Arnaud Fernandez, Alexandre Gérard, et al. Protocol: Adverse Drug Reactions of Olanzapine, Clozapine and Loxapine in Children and Youth: A Systematic Pharmacogenetic Review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, 2022. http://dx.doi.org/10.37766/inplasy2022.5.0025.

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Review question / Objective: In children and youth treated with olanzapine, clozapine, or loxapine and having undergone genotyping, which are the pharmacogenetic variants underlying the antipsychotics' adverse drug reactions and efficacy? What are the most frequently investigated adverse drug reactions and variants ? What is described about the specific effect of CYP1A2 variants ? Therefore, we aimed to review the pharmacogenetic variants underlying olanzapine, clozapine and loxapine ADRs and/or efficacy, in children and youth having undergone genotyping. Then, assessed the most frequently investigated ADRs and genetic polymorphisms in this population. Finally, we investigated the specific effect of CYP1A2 variants in the occurrence of ADRs and/or lack of therapeutic effect. Condition being studied: This review focuses on children, adolescents and youth treated with antipsychotics (olanzapine, clozapine, loxapine) and experienced adverse drug reactions.
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Draeger, E., B. Bennion, F. Gygi, and F. Lightstone. Understanding the Mechanism of Human P450 CYP1A2 Using Coupled Quantum-Classical Simulations in a Dynamical Environment. Office of Scientific and Technical Information (OSTI), 2006. http://dx.doi.org/10.2172/899113.

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