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Breast Cancer Research | Full text | Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a ... CYP1A2 activity was found in both menopausal groups, through stepwise and maximum R regression, to be independently associated with a number of covariates, including smoking status, serum levels of SHBG, circulating levels of blood cholesterol, and triglycerides. In a twin study of Caucasians conducted in Denmark [28], CYP1A2 activity was determined for 49 monozygotic twin pairs and 34 same-sex dizygotic twin pairs concordant for nonsmoking and nonuse of oral contraceptives. CYP1A2 activity is lower in women [6], reduced by 35–50% during pregnancy [7], inhibited by oral contraceptives [6] and hormone replacement therapy [43], and may be lower during the late luteal phase of the menstrual cycle, when estradiol concentrations peak [44]. breast-cancer-research.com /content/6/4/R352   (7359 words)

Breast Cancer Research | Full text | Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: ...   (Site not responding. Last check: 2007-10-13) CYP1A2 activity in postmenopausal women, but not in premenopausal women, was positively associated with mammographic density, suggesting that increased CYP1A2 activity after the menopause is a risk factor for breast cancer. Because examination of CYP1A2 activity in relation to mammographic density was not a goal of the original study, patients were subsequently mailed a letter describing the goals of the phenotypic component of this study, and written consent was obtained to phenotype CYP1A2 activity. CYP1A2 is known to activate several heterocyclic and aromatic amine promutagens [15,45,46] as well as tobacco smoke-specific nitrosamines [47]. breast-cancer-research.com /content/6/4/R338   (6744 words)

4-Aminobiphenyl-Induced Liver and Urinary Bladder DNA Adduct Formation in Cyp1a2(-/-) and Cyp1a2(+/+) Mice -- Tsuneoka ... Polymorphisms in the CYP1A2 (10) and NAT2 (11) genes CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice. Decrease in 4-aminobiphenyl-induced methemoglobinemia in Cyp1a2(–/–) knockout mice. jnci.oxfordjournals.org /cgi/content/full/95/16/1227   (7206 words)

WHO EMRO - NON COMMUNICABLE DISEASES The present study is the first to describe the frequency of four known allelic variants of CYP1A2 among the Egyptian population. CYP1A2* 1C and * 1E occurred at frequencies significantly lower than that in Japanese, while similar frequencies were observed for CYP1A2* 1D and * 1F. The CYP1A2* 1F frequency appeared to be identical to that of Caucasians. www.emro.who.int /ncd/Genetics-egy-03-3.htm   (198 words)

details CYP1A2 activity was measured by plasma paraxanthine/caffeine (1,7X/1,3,7X) ratio 6 h after administration of 300 mg caffeine. The CYP1A2 activity of men was higher than that of women (median: 0.33 vs 0.23, P<0.001). A probit plot of CYP1A2 activity in men was shifted to the left compared with that in women. cmbi.bjmu.edu.cn /ChinaPaper/details.asp?PubMedID=10671909   (277 words)

Health and DNA: 1A2 CYP1A2 is also involved in the metabolic activation of carcinogens from chemical toxins such as those found in cigarette smoke. Genetic polymorphisms in the CYP1A2 gene influence the magnitude of CYP1A2 induction. Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1. www.healthanddna.com /professional/1A2testmenu.htm   (1336 words)

Bioline International Official Site (site up-dated regularly) CYP1A2 is the second most abundant CYP isozyme and contributes to approximately 15% of hepatic CYP content in humans. Since theophylline is metabolised mainly by CYP1A2, it is plausible that induction of CYP1A2 by SJW may explain the reduced theophylline concentrations and loss of therapeutic efficacy. To examine the effect of SJW on the expression of CYP1A2, cells were treated with increasing concentrations of the extract (1x, 10x, and 100x) for 48 hours. www.bioline.org.br /request?jp02032   (2077 words)

Intrinsic hepatic phenotype associated with the Cyp1a2 gene as shown by cDNA expression microarray analysis of the ... CYP1A2 expression is constitutively high in mouse liver and is well known for metabolizing several drugs and many procarcinogens to reactive intermediates that can cause toxicity or cancel. CYP1A2 is also known to carry out several endogenous functions such as uroporphyrinogen and melatonin oxidation and the 2- and 4-hydroxylations of estradiol. Besides Cyp1a2, the gene exhibiting the greatest downregulation was Igfbp1 (insulin-like growth factor binding protein-l), showing only 12% expression of that in the Cyp1a2(+/+) wild-type liver. www.findarticles.com /p/articles/mi_m0CYP/is_6_111/ai_105367014?lstpn=article_results&lstpc=search&lstpr=external&lstprs=other&lstwid=1&lstwn=search_results&lstwp=body_middle   (685 words)

details   (Site not responding. Last check: 2007-10-13) Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2. CYP1A2 activity was determined on three occasions, namely on day 1, day 9 and day 16 using the caffeine plasma index (the ratio of the concentrations of paraxanthine to caffeine), 6 h after oral administration of 200 mg caffeine. CONCLUSION: The CYP1A2*1C and CYP1A2*1F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole. cmbi.bjmu.edu.cn /ChinaPaper/details.asp?PubMedID=12445035   (228 words)

PCB exposure and in vivo CYP1A2 activity among native Americans Environmental Health Perspectives - Find Articles To address this issue, a study was conducted of CYP1A2 activity among Native Americans exposed to polychlorinated biphenyls (PCBs) from the consumption of fish from the St. Lawrence River. The results support the notion that CYP1A2 activity may be a marker of an early biological effect of exposure to PCBs in humans and that the CBT may be a useful tool to monitor such effects. In humans, CYP1A2 has been detected primarily in the liver, in contrast to the closely related CYP1A1, which is expressed in extrahepatic tissues such as lung, placenta, and lymphocytes (Kawajiri 1999). www.findarticles.com /p/articles/mi_m0CYP/is_3_113/ai_n13559696   (930 words)

Coffee, CYP1A2 genotype, and risk of myocardial infarction. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction. Association of caffeine intake and CYP1A2 genotype with ovarian cancer. www.tripdatabase.com /spider.html?itemid=284212   (467 words)

Directory of open access journals Our objective was to characterise the effect of SJW on the expression of CYP1A2 in the LS180 intestinal cell model. CYP1A2 protein content was measured by Western blot analysis using monoclonal antibody. Time-dependent expression of CYP1A2 was assessed during exposure to SJW extract for 24 hours and following its removal for another 24 hours. www.doaj.org /abstract?id=85890&toc=y   (200 words)

Infotrieve Online CYP1A2 is essential in murine uroporphyria caused by hexachlorobenzene and iron. Using Cyp1a2(-/-) mice we previously showed that CYP1A2 is absolutely required for hepatic uroporphyrin accumulation caused by iron and 5-aminolevulinate (ALA) treatment, both in the presence and absence of an inducer of CYP1A2. A similar requirement for CYP1A2 was found in uroporphyria produced in HCBZ and iron-treated mice in the absence of ALA. www4.infotrieve.com /newmedline/detail.asp?NameID=10631128&Session=&searchQuery=Uroporphyrinogens&count=155   (303 words)

Dissertations from Karolinska Institutet - Published by Karolinska Institutet Karolinska Institutet - ki.se The overall aim of this thesis was to evaluate probe drugs to be used in phenotyping studies of the main drug metabolising CYP enzymes. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. CYP1A2 activity in Caucasians-relationship to smoking habits, use of oral contraceptives and 3 SNPs in the CYP1A2 promoter region. diss.kib.ki.se /2003/91-7349-522-0   (808 words)

Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes ... Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1 -- Aklillu et al. Rasmussen BB, Brix TH, Kyvik KO, and Brosen K (2002) The interindividual differences in the 3-demethylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Shimoda K, Someya T, Morita S, Hirokane G, Yokono A, Takahashi S, and Okawa M (2002) Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position –2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia. molpharm.aspetjournals.org /cgi/content/full/64/3/659   (7584 words)

Allergy & Asthma Disease Management Center: Ask the Expert Our objective was to determine the time course of CYP1A2 activity changes after smoking cessation in heavy smokers as the basis for dosing adaptation schemes. Subjects were phenotyped for CYP1A2 activity at 6, 4, and 1 day before smoking cessation and at 0, 1, 2, 3, 6, 8, 10, and 13 days thereafter by use of the paraxanthine-to-caffeine ratio in plasma 6 hours after a 148-mg caffeine test dose. A monoexponential decay of CYP1A2 activity to a residual value was fitted to the data by nonlinear regression analysis. www.aaaai.org /aadmc/ate/category.asp?cat=1151   (902 words)

Article 37   (Site not responding. Last check: 2007-10-13) Their plasma levels to dose ratios of CLO (median; range, 0.34; 0.22 to 0.40 ng x day/mL x mg) were significantly lower than ratios calculated from another study with 29 patients (0.75; 0.22 to 2.83 ng x day/mL x mg; P < 0.01). These patients were confirmed as being CYP1A2 ultrarapid metabolizers by the caffeine phenotyping test (median systemic caffeine plasma clearance; range, 3.85; 3.33 to 4.17 mL/min/kg) when compared with previous studies (0.3 to 3.33 mL/min/kg). The sequencing of the entire CYP1A2 gene from genomic DNA of these patients suggests that the -164C > A mutation (CYP1A2*1F) in intron 1, which confers a high inducibility of CYP1A2 in smokers, is the most likely explanation for their ultrarapid CYP1A2 activity. www.uni-essen.de /~tjp030/schizophrenia/html/article_37.html   (222 words)

BioVentures :: Product Catalog :: DMG Diversity Navigator - Navigating the Universe of Genetic Diversity The human cytochrome P450 1A2 (CYP1A2) gene produces an aryl hydrocarbon hydroxylase involved in the metabolism of endogenous compounds and xenobiotics. The CYP1A2 gene is located on the complementary strand of chromosome 15q22 and is transcribed into a wild type mRNA (GenBank accession number NM000761) containing seven exons. The DMG Diversity Navigator™ for CYP1A2 enables the detection of virtually all relevant genetic variants by providing bidirectional sequence coverage for the exons and flanking intronic regions. www.bioventures.com /products/dmg/cyp1a2   (579 words)

vgn-ext-hidden_PubMed   (Site not responding. Last check: 2007-10-13) Suppression of hepatocyte CYP1A2 expression by Kupffer cells via AhR pathway: The central role of proinflammatory cytokines. Although we have recently shown that CYP1A2, one of the major isoforms of CYP in rats, is downregulated in sepsis, the underlying mechanism and possible therapeutic approaches warrant further investigation. This reduction was associated with increased expression of AhR and CYP1A2. www.plwc.org /portal/site/ASCO/menuitem.a3fb42726842a82627c4c291ee37a01d/?vgnextoid=d70b3608f9958010VgnVCM100000f2730ad1RCRD&index=n&pmid=16820944   (332 words)

Coffee-Gene Interaction Raises Heart Attack Risk - CME Teaching Brief® - MedPage Today Specifically, a substitution - dubbed CYP1A2*1F -- in the CYP1A2 gene decreases its activity, and carriers of the allele, whether homo- or heterozygous, are called "slow" metabolizers of caffeine. They were genotyped to see which CYP1A2 allele they carried and a food frequency questionnaire was used to assess how much caffeinated coffee they drank. The effect of CYP1A2 genotype on the risk of MI was similar among smokers and nonsmokers. www.medpagetoday.com /Cardiology/AcuteCoronarySyndrome/tb/2808   (1080 words)

ROFECOXIB IS A POTENT, METABOLISM-DEPENDENT INHIBITOR OF CYP1A2 - IMPLICATIONS FOR IN VITRO PREDICTION OF DRUG ... Karjalainen MJ, Neuvonen PJ, Backman JT Rofecoxib was recently found to greatly increase plasma concentrations of the cytochrome P450 1A2 (CYP1A2) substrate drug tizanidine in humans, but there are no published in vitro studies on the CYP1A2 inhibiting effects of rofecoxib. Inactivation of CYP1A2 by rofecoxib required NADPH, and was characterized by a KI of 4.8 microM and a kinact of 0.07 min(-1). In conclusion, rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2, a CYP-form contributing to rofecoxib metabolism. counsellingresource.com /medications-research/2006/09/22/rofecoxib-is-a-potent-metabolism-dependent-inhibitor-of-cyp1a2-implications-for-in-vitro-prediction-of-drug-interactions   (449 words)

Cymbalta, Duloxetine Hydrochloride Pharmacology - HealthyPlace.com Inhibitors of CYP1A2 — When duloxetine was co-administered with fluvoxamine, a potent CYP1A2 inhibitor, to male subjects (n=14) the AUC was increased approximately 6-fold, the Cmax was increased about 2.5-fold, and duloxetine t1/2 was increased approximately 3-fold. Although duloxetine is an inhibitor of the CYP1A2 isoform in in vitro studies, the pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg BID). Drugs Metabolized by CYP1A2 — In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity, and it is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates (see CLINICAL PHARMACOLOGY, Drug Interactions). concernedcounseling.com /Medications/cymbalta.asp   (9127 words)

Effect of St. John's Wort extract on intestinal expression of cytochrome P4501A2: studies in LS180 cells. Karyekar CS, ... [12] Since theophylline is metabolised mainly by CYP1A2, it is plausible that induction of CYP1A2 by SJW may explain the reduced theophylline concentrations and loss of therapeutic efficacy. Cells treated in plain medium and BNF (50 ?M), a known inducer of CYP1A2, were used as negative and positive controls, respectively. Exposure of LS180 cells to SJW extract resulted in a concentration dependent increase in the expression of CYP1A2 [Figure - 1]. www.jpgmonline.com /article.asp?issn=0022-3859;year=2002;volume=48;issue=2;spage=97;epage=100;aulast=Karyekar   (2151 words)

Breast Cancer Research | Abstract | Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a ...   (Site not responding. Last check: 2007-10-13) Cytochrome P450 1A2 (CYP1A2) is responsible for the metabolism of estrogens and many exogenous compounds, including caffeine. In a cross-sectional study of 146 premenopausal and 149 postmenopausal women, we examined the relationships between CYP1A2 activity and known or suspected risk factors for breast cancer. In postmenopausal women CYP1A2 activity was positively associated with insulin-like growth factor-1, and negatively associated with plasma triglyceride, high-density lipoprotein cholesterol, and age at menarche. www.breast-cancer-research.com /content/6/4/R352/abstract   (332 words)

Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2-mediated theophylline metabolism by ... CYP1A2-mediated formations of 3-methylxanthine and 1-methyluric acid were almost totally inhibited in control subjects, whereas they were only reduced by one third in patients with Child class C cirrhosis. Inhibition of 1,3-dimethyluric acid formation, which is catalyzed by CYP1A2 and CYP2E1, progressively decreased from 58% in healthy subjects to 43% and 7% in patients with mild cirrhosis and those with severe cirrhosis, respectively. Therefore, for any drug metabolized by CYP1A2, the clinical consequences of enzyme inhibition are expected to become less and less important as liver function worsens. counsellingresource.com /medications-research/2006/05/15/liver-dysfunction-markedly-decreases-the-inhibition-of-cytochrome-p450-1a2-mediated-theophylline-metabolism-by-fluvoxamine   (580 words)

Dissertations from Karolinska Institutet - Published by Karolinska Institutet Karolinska Institutet - ki.se The aim of this thesis was to investigate the molecular genetics of drug metabolising enzymes, in particular CYP2D6, CYP2C19, CYP2C9, CYP1B1, CYP1A2 and XO, with special emphasis on the Ethiopian population. CYP1A2 gene from 12 subjects revealed the presence of a novel intron 1 SNP, -730C>T. Genotyping and molecular haplotyping methods for the intron 1 SNPs were developed and 4 different haplotypes were identified: Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression. diss.kib.ki.se /2003/91-7349-460-7   (689 words)

British Journal of Pharmacology - Contribution of human cytochrome P-450 isoforms to the metabolism of the simplest ... Accordingly, the contribution of CYP3A4 and CYP1A2 to the 5-sulphoxidation and N-demethylation of promazine in the whole liver should be relatively greater than in the Supersomes. Therefore, we attempted to estimate roughly the contribution of the CYP isoforms studied to the 5-sulphoxidation and N-demethylation of promazine in liver microsomes on the basis of the rate of those reactions in the Supersomes (Tables 5 and 6). In summary, CYP1A2 and CYP3A4 are the main isoforms responsible for 5-sulphoxidation, while CYP1A2 and CYP2C19 mainly catalyse the N-demethylation of promazine in human liver. www.nature.com /bjp/journal/v138/n8/full/0705195a.html   (5329 words)

Oncostatin M Down-regulates Basal and Induced Cytochromes P450 in Human Hepatocytes -- Guillén et al. 285 (1): ... CYP1A2 activity were reached after 48 hr of treatment with cytokines. CYP1A2 activity (A) and de novo synthesis of CYP1A2 (B) were measured 48 hr later as described in the text. Muntané-Relat J, Ourlin JC, Domergue J and Maurel P (1995) Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. jpet.aspetjournals.org /cgi/content/full/285/1/127   (5545 words)

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