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Cytochrome 450

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https://www.readbyqxmd.com/read/29328413/prevalence-of-the-cyp2c19-2-681-g-a-3-636-g-a-and-17-%C3%A2-806-c-t-alleles-among-an-iranian-population-of-different-ethnicities
#1
Mahshid Dehbozorgi, Behnam Kamalidehghan, Iman Hosseini, Zahra Dehghanfard, Mohammad Hossein Sangtarash, Maryam Firoozi, Fatemeh Ahmadipour, Goh Yong Meng, Massoud Houshmand
Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles in an Iranian population cohort of different ethnicities were examined and then compared with previously published frequencies within other populations...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29324864/safety-of-single-low-dose-primaquine-in-glucose-6-phosphate-dehydrogenase-deficient-falciparum-infected-african-males-two-open-label-randomized-safety-trials
#2
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
https://www.readbyqxmd.com/read/29290096/protective-effect-of-fenofibrate-against-ischemia-reperfusion-induced-cardiac-arrhythmias-in-isolated-rat-hearts
#3
Ishfaq A Bukhari, Abdulrahman A Almotrefi, Osama Y Mohamed, Abeer A Al-Masri, Saeed Ahmed Sheikh
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating, cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase inducing properties that leads to increase in endogenous EETs production. In the current investigations fenofibrate (100 mg/kg, orally) for two weeks decreased ischemia/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT) and ventricular fibrillation (VF) in the isolated rat hearts...
December 31, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29286360/conditional-knockdown-of-gene-expression-in-cancer-cell-lines-to-study-the-recruitment-of-monocytes-macrophages-to-the-tumor-microenvironment
#4
Marta H Kubala, Yves A DeClerck
siRNA and shRNA-mediated knock down (KD) methods of regulating gene expression are invaluable tools for understanding gene and protein function. However, in the case that the KD of the protein of interest has a lethal effect on cells or the anticipated effect of the KD is time-dependent, unconditional KD methods are not appropriate. Conditional systems are more suitable in these cases and have been the subject of much interest. These include Ecdysone-inducible overexpression systems, Cytochrome P-450 induction system1, and the tetracycline regulated gene expression systems...
November 23, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29274758/efficacy-and-safety-outcomes-of-direct-oral-anticoagulants-and-amiodarone-in-patients-with-atrial-fibrillation
#5
Florentino Lupercio, Jorge Romero, Bradley Peltzer, Carola Maraboto, David Briceno, Pedro Villablanca, Kevin Ferrick, Jay N Gross, Soo Kim, John Fisher, Luigi Di Biase, Andrew Krumerman
BACKGROUND: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of non-valvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. DOAC levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone...
December 21, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/29162613/the-jak1-2-inhibitor-ruxolitinib-reverses-interleukin-6-mediated-suppression-of-drug-detoxifying-proteins-in-cultured-human-hepatocytes
#6
Marie Febvre-James, Arnaud Bruyere, Marc Le Vee, Olivier Fardel
The inflammatory cytokine interleukin (IL)-6, which basically activates the JAK/STAT signaling pathway, is well-known to repress expression of hepatic cytochromes P-450 (CYPs) and transporters. Therapeutic proteins, like mAbs targeting IL-6 or its receptor, have been consequently demonstrated to restore full hepatic detoxification capacity, which results in inflammatory disease-related drug-drug interactions (idDDIs). In the present study, we investigated whether ruxolitinib, a small drug acting as a JAK1/2 inhibitor and currently used in the treatment of myeloproliferative neoplasms, may also counteract IL-6 repressing effects towards hepatic detoxifying systems...
November 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29143479/encapsulation-of-rifampin-in-a-polymeric-layer-by-layer-structure-for-drug-delivery
#7
Akbar Esmaeili, Meissam Khodaei
Rifampin (RIF) is a bactericidal antibiotic drug and potent inducer of hepatic and intestinal cytochrome P-450 (CYP-450) enzyme systems. Given by mouth or intravenously, it can cause numerous clinical drug interactions; thus, alternative systems of drug delivery that bypass some or all of its toxic effects are well worth investigating. In this study, a controlled layer-by-layer (LBL) process of encapsulating RIF in biocompatible alginate and chitosan polymers loaded onto Fe3 O4 nanoparticles was developed. Fe3 O4 nanoparticles were synthesized from FeCl3 ·6H2 O using a hydrothermal procedure...
November 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29140411/effect-of-angiotensin-ii-and-acth-on-adrenal-blood-flow-in-the-male-rat-adrenal-gland-in-vivo
#8
Abdul J Shah, Tamas Kriska, Kathryn M Gauthier, John R Falck, William B Campbell
Angiotensin II (Ang II) and adrenocorticotropic hormone (ACTH) regulate adrenal vascular tone in vitro through endothelial and/or zona glomeulosa cell-derived mediators. The role of these mediators in regulating adrenal blood flow (ABF) and mean arterial pressure (MAP) was examined in anesthetized rats. Ang II (0.01-100 ng/kg) increased ABF (maximal increase of 97.2 ± 6.9 perfusion units (PU) at 100 ng/kg) and MAP (basal, 115 ± 7 mm Hg; Ang II, 163 ± 5 mm Hg). ACTH (0.1-1000 ng/kg) also increased ABF (maximum increase of 91...
November 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29092654/changes-in-cyp2d-enzyme-activity-following-induction-of-type-2-diabetes-and-administration-of-cinnamon-and-metformin-an-experimental-animal-study
#9
Ali Taheri, Hoda Lavasani, Sara Kasirzadeh, Behjat Sheikholeslami, Yalda H Ardakani, Mohammad-Reza Rouini
1. Alterations in the activity of hepatic cytochrome P-450 isoenzymes result in changes in the pharmacokinetic behavior of drugs. This study was designed to explore the impact of type II diabetes, metformin and cinnamon on the activity of CYP2D isoenzyme. 2. Streptozotocin-nicotinamide-induced diabetic and normal rats were gavaged by cinnamon and/or metformin for 14 days. Using isolated perfusion of rat livers, the metabolic activity of CYP2D in the study groups was evaluated based on the oxidative biotransformation of tramadol hydrochloride...
November 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29071994/-effect-of-jiaji-ex-b-2-electroacupuncture-preconditioning-on-expression-of-cytochrome-p-450-signaling-pathways-in-myocardial-ischemia-reperfusion-rats
#10
Yang Li, Ming-Lu Shao, Hui-Juan Yu, Qi-Wen Tan, Hua-Feng Cui
OBJECTIVE: To investigate the effect of "Jiaji"(EX-B 2)-electroacupuncture(EA) preconditioning on the myocardium and expression of cytochrome P 450 signaling pathways of myocardial cells in myocardial ischemia-reperfusion injury(MI/RI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, Jiaji, Neiguan(PC 6), Yanglingquan(GB 34) and Quchi(LI 11) groups (n=10 in each group). MI/RI model was established by occlusion of the descen-ding anterior branch of the left coronary artery...
February 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29042382/drugs-and-life-threatening-ventricular-arrhythmia-risk-results-from-the-dare-study-cohort
#11
Abigail L Coughtrie, Elijah R Behr, Deborah Layton, Vanessa Marshall, A John Camm, Saad A W Shakir
OBJECTIVES: To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases. SETTING: Suspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected. PARTICIPANTS: Two expert cardiologists reviewed data for 293 referred cases: 130 were included...
October 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29038839/hepatotoxic-combination-effects-of-three-azole-fungicides-in-a-broad-dose-range
#12
T Heise, F Schmidt, C Knebel, S Rieke, W Haider, I Geburek, L Niemann, P Marx-Stoelting
Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action...
October 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28992765/phenotyping-of-cyp-4501a2-activity-by-total-overnight-salivary-caffeine-assessment-tosca-in-patients-on-warfarin-treatment-a-cross-sectional-study
#13
Giovanni Tarantino, Domenico Capone, Paola Contaldi, Adriana Gianno, Mosca Teresa, Antonella Tufano
Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28986745/nutritional-and-metabolic-stressors-on-ovine-oocyte-development-and-granulosa-cell-functions-in-vitro
#14
S Nandi, S K Tripathi, P S P Gupta, S Mondal
The present study was undertaken to study the effect of ammonia, urea, non-esterified fatty acid (NEFA), and β-hydroxybutyric acid (β-OHB) on oocyte development and granulosa cell (GC) growth parameter of ovine (Ovis aries). Ovine oocytes were matured in vitro in the presence of different concentration of ammonia, urea, NEFA, and β-OHB for 24 h, in vitro inseminated and evaluated for cleavage and blastocyst yield. Same concentrations of ammonia, urea, NEFA, and β-OHB were examined on growth parameters and hormone secretion activity of granulosa cells in vitro...
October 6, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28962866/in-vitro-metabolism-of-4-5-dimethoxycanthin-6-one-by-human-liver-microsomes-and-its-inhibition-on-human-cyp1a2
#15
Xiaolei Miao, Jiaojiao You, Junjun Wang, Yong Chen
AIMS: P. quassioides is a traditional Chinese medicine used for the treatment of gastroenteritis, snakebite, infection and hypertension in China. 4, 5-dimethoxycanthin-6-one is one of the main active canthinone alkaloid isolated from P. quassioides. The aim of this work was to identify the cytochrome P (CYP) 450 enzymes responsible for the metabolism of 4, 5-dimethoxycanthin-6-one (DCO) and to evaluate the inhibitory effect of DCO on CYP activity in human liver microsomes (HLM) in vitro...
December 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28951593/microrna-regulation-of-cyp-1a2-cyp3a4-and-cyp2e1-expression-in-acetaminophen-toxicity
#16
Pritmohinder Gill, Sudeepa Bhattacharyya, Sandra McCullough, Lynda Letzig, Prasun J Mishra, Chunqiao Luo, Harsh Dweep, Laura James
MicroRNAs (miRNAs) that regulate the cytochrome P-450 isoforms involved in acetaminophen (APAP) toxicity were examined in HepaRG cells treated with APAP (20 mM). In-vitro studies found that APAP protein adducts were increased at 1 h, followed by ALT increases at 12 and 24 h. CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRNAs were increased for miR-122-5p, miR-378a-5p, miR-27b-3p at 6 h and miR-125b-5p at 12 h and miR-27b-3p at 24 h. Putative miRNA binding sites on the 3'UTRs of the CYPs were identified in-silico...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28945341/biocompatible-60-70-fullerenols-potent-defense-against-oxidative-injury-induced-by-reduplicative-chemotherapy
#17
Yue Zhou, Jie Li, Haijun Ma, Mingming Zhen, Jun Guo, Liping Wang, Li Jiang, Chunying Shu, Chunru Wang
Chemotherapy as a conventional cancer treatment suffers from critical systemic side effects, which is generally considered as the consequence of reactive oxygen species (ROS). Fullerenes have been widely studied for their excellent performance in radicals scavenging. In the present study, we report a solid-liquid reaction to synthesize fullerenols and their application as ROS scavengers in chemotherapy protection. The solid-liquid reaction is carried out without catalyst and suitable for mass production. The novel [60]/[70] fullerenols show a high stability in water, and the [70] fullerenols (C70-OH) exhibit radical scavenging capability superior to that of [60] fullerenols (C60-OH) in chemotherapy protection...
October 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28927781/function-of-38-variants-cyp2c9-polymorphism-on-ketamine-metabolism-in%C3%A2-vitro
#18
Xiang Zheng, Ping Fang, Su-Su Bao, Dan Lin, Jian-Ping Cai, Guo-Xin Hu
BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 μM-1000 μM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS)...
September 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28892923/atorvastatin-induced-adverse-drug-reactions-among-south-indian-tamils
#19
Chandrasekaran Indumathi, Natarajan Anusha, Kolar Vishwanath Vinod, Satheesh Santhosh, Steven Aibor Dkhar
INTRODUCTION: Atorvastatin is the most widely used statin world-over. Although atorvastatin is beneficial in reducing cardiovascular morbidity and mortality, they are associated with Adverse Drug Reactions (ADRs) which are under-recognized as well as under-reported. There is no data on safety of atorvastatin in ethnic populations like South Indian Tamils and hence the need for this study. AIM: To report the Adverse Events (AEs) associated with atorvastatin use, their causality and severity in dyslipidemic south Indian Tamils...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28780894/gene-therapy-for-hypertension
#20
Ludovit Paulis, Heinrich Franke, Fedor Simko
The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: We have searched for studies using gene therapy in hypertension reporting BP outcomes. We have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents...
August 17, 2017: Expert Opinion on Biological Therapy
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