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Drug metabolism

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https://www.readbyqxmd.com/read/28817575/mck1-is-a-novel-regulator-of-myo-inositol-phosphate-synthase-mips-that-is-required-for-inhibition-of-inositol-synthesis-by-the-mood-stabilizer-valproate
#1
Wenxi Yu, Joshua Daniel, Dhara Mehta, Krishna Rao Maddipati, Miriam L Greenberg
Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS), which catalyzes the rate-limiting step of inositol synthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28817486/overcoming-clopidogrel-resistance-three-promising-novel-antiplatelet-drugs-developed-in-china
#2
Hong-Guang Xie, Yu-Meng Jia, Ting Tai, Jin-Zi Ji
Clopidogrel is one of the most frequently prescribed drugs worldwide; however, the presence of clopidogrel resistance and high susceptibility to genetic variations and drug interactions are facilitating the development of other antiplatelet drugs. To overcome clopidogrel resistance, several promising clopidogrel analogues have been developed in China, such as vicagrel (and its deuterated analogues), PLD-301, and W1. These novel chemical analogues are all characterized by much faster and more efficient bioconversion to clopidogrel thiolactone (or 2-oxo-clopidogrel, the precursor of clopidogrel active metabolite) in the intestine than clopidogrel through bypassing the first-step P450-mediated oxidation of clopidogrel in the liver...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28816926/feasibility-and-relevance-of-antipsychotic-safety-monitoring-in-children-with-tourette-syndrome-a-prospective-longitudinal-study
#3
Tamara Pringsheim, Josephine Ho, Justyna R Sarna, Tracy Hammer, Scott Patten
PURPOSE/BACKGROUND: Antipsychotics are efficacious for tics and are increasingly prescribed to children with behavioral disorders. Antipsychotics have important adverse effects, and systematic monitoring of drug safety is infrequently performed. The objectives of this study were to determine the feasibility of antipsychotic safety monitoring in children with Tourette Syndrome using a defined protocol and to evaluate the risk of adverse effects with chronic use. METHODS/PROCEDURES: A prospective longitudinal study of children prescribed antipsychotics was performed...
August 14, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28816925/treatment-of-diabetic-ketoacidosis-associated-with-antipsychotic-medication-literature-review
#4
Antonia Vuk, Maja Baretic, Martina Matovinovic Osvatic, Igor Filipcic, Nikolina Jovanovic, Martina Rojnic Kuzman
BACKGROUND: The second-generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation, which may be associated with the use of SGAs. This study aims to review published reports of patients with schizophrenia and antipsychotic drug-associated DKA, focusing on the effective management of both conditions. METHODS: Using a predefined search strategy, we searched PubMed and EMBASE from their inception to July 2016...
August 15, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28816832/reversible-splenial-lesion-syndrome-after-intravenous-immunoglobulin-treatment-for-guillain-barre-syndrome
#5
Elif Uygur Kucukseymen, Burcu Yuksel, Fatma Genc, Eylem Ozaydin Goksu, Sevim Yildiz, Yasemin Bicer Gomceli
Reversible corpus callosum splenial (CCS) lesions have been described in patients with varied etiologies. The most common causes of previously reported reversible focal lesions of the CCS are viral encephalitis, antiepileptic drug toxicity/withdrawal, and metabolic disorders. Intravenous immunoglobulin (IVIG) therapy is used for different immune-mediated diseases. It is generally safe, and serious adverse reactions are uncommon. We presented a rare case of disturbed consciousness with reversible CCS lesions after IVIG therapy for Guillain-Barre syndrome in an adult woman...
August 14, 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28816773/synergistic-antitumor-effect-of-3-bromopyruvate-and-5-fluorouracil-against-human-colorectal-cancer-through-cell-cycle-arrest-and-induction-of-apoptosis
#6
Dianlong Chong, Linyan Ma, Fang Liu, Zhirui Zhang, Surong Zhao, Qiang Huo, Pei Zhang, Hailun Zheng, Hao Liu
3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28816644/cyp2b6-haplotype-predicts-efavirenz-plasma-concentration-in-black-south-african-hiv-1-infected-children-a-longitudinal-pediatric-pharmacogenomic-study
#7
Riaan Reay, Collet Dandara, Michelle Viljoen, Malie Rheeders
South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816105/thiazolidinedione-drugs-in-the-treatment-of-type-2-diabetes-mellitus-past-present-and-future
#8
Melissa A Davidson, Donald R Mattison, Laurent Azoulay, Daniel Krewski
Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes...
August 17, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28816066/stressing-the-epi-genome-dealing-with-ros-in-cancer
#9
Akshay V Bhat, Shainan Hora, Ananya Pal, Sudhakar Jha, Reshma Taneja
SIGNIFICANCE: Growing evidence indicates cross-talk between Reactive oxygen species (ROS) and several key epigenetic processes like DNA methylation, histone modifications and miRNAs in normal physiology and human pathologies including cancer. This review focuses on how ROS-induced oxidative stress, metabolic intermediates and epigenetic processes influence each other in various cancers. Recent Advances: ROS alters chromatin structure and metabolism which impact the epigenetic landscape in cancer cells...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28815282/correction-of-vitamin-d-status-by-calcidiol-pharmacokinetic-profile-safety-and-biochemical-effects-on-bone-and-mineral-metabolism-of-daily-and-weekly-dosage-regimens
#10
S Minisola, L Cianferotti, P Biondi, C Cipriani, C Fossi, F Franceschelli, F Giusti, G Leoncini, J Pepe, H A Bischoff-Ferrari, M L Brandi
RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis...
August 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28814986/2-deoxy-d-glucose-restore-glucocorticoid-sensitivity-in-acute-lymphoblastic-leukemia-via-modification-of-n-linked-glycosylation-in-an-oxygen-tension-independent-manner
#11
Zaira Leni, Paulina Ćwiek, Valeriya Dimitrova, Andrea S Dulcey, Nicola Zamboni, Cedric Simillion, Geetha Rossi, Kurt Leibundgut, Alexandre Arcaro
In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28814868/nano-sized-cytochrome-p450-3a4-inhibitors-to-block-hepatic-metabolism-of-docetaxel
#12
Marion Paolini, Laurence Poul, Céline Berjaud, Matthieu Germain, Audrey Darmon, Maxime Bergère, Agnès Pottier, Laurent Levy, Eric Vibert
Most drugs are metabolized by hepatic cytochrome P450 3A4 (CYP3A4), resulting in their reduced bioavailability. In this study, we present the design and evaluation of bio-compatible nanocarriers trapping a natural CYP3A4-inhibiting compound. Our aim in using nanocarriers was to target the natural CYP3A4-inhibiting agent to hepatic CYP3A4 and leave drug-metabolizing enzymes in other organs undisturbed. In the design of such nanocarriers, we took advantage of the nonspecific accumulation of small nanoparticles in the liver...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28814306/blood-acid-base-status-in-impala-aepyceros-melampus-immobilised-and-maintained-under-total-intravenous-anaesthesia-using-two-different-drug-protocols
#13
Gareth E Zeiler, Leith C R Meyer
BACKGROUND: In mammals, homeostasis and survival are dependent on effective trans-membrane movement of ions and enzyme function, which are labile to extreme acid-base changes, but operate efficiently within a narrow regulated pH range. Research in patients demonstrating a pH shifts outside the narrow regulated range decreased the cardiac output and systemic vascular resistance and altered the oxygen binding to haemoglobin. These cardiopulmonary observations may be applicable to the risks associated with anaesthesia and performance of wildlife ungulates on game farms...
August 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28814197/book-review-drug-metabolism-in-diseases-xie-wen-ed-drug-metabolism-in-diseases-san-diego-ca-academic-press-2017-283-pp-150-isbn-978-0-12-802949-7
#14
https://www.readbyqxmd.com/read/28813681/uncoupling-the-mitogenic-and-metabolic-functions-of-fgf1-by-tuning-fgf1-fgf-receptor-dimer-stability
#15
Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J Conklin, Thomas A Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(ΔHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(ΔHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#16
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28813442/a-parallel-metaheuristic-for-large-mixed-integer-dynamic-optimization-problems-with-applications-in-computational-biology
#17
David R Penas, David Henriques, Patricia González, Ramón Doallo, Julio Saez-Rodriguez, Julio R Banga
BACKGROUND: We consider a general class of global optimization problems dealing with nonlinear dynamic models. Although this class is relevant to many areas of science and engineering, here we are interested in applying this framework to the reverse engineering problem in computational systems biology, which yields very large mixed-integer dynamic optimization (MIDO) problems. In particular, we consider the framework of logic-based ordinary differential equations (ODEs). METHODS: We present saCeSS2, a parallel method for the solution of this class of problems...
2017: PloS One
https://www.readbyqxmd.com/read/28813419/vaccine-driven-pharmacodynamic-dissection-and-mitigation-of-fenethylline-psychoactivity
#18
Cody J Wenthur, Bin Zhou, Kim D Janda
Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813144/stimulated-raman-imaging-reveals-aberrant-lipogenesis-as-a-meta-bolic-marker-for-azole-resistant-candida-albicans
#19
Caroline W Karanja, Weili Hong, Waleed Younis, Hassan E Eldesouky, Mohamed N Seleem, Ji-Xin Cheng
Candida albicans (C. albicans) is the single most prevalent cause of fungal bloodstream infections worldwide causing significant mortality as high as fifty percent. This high mortality rate is, in part, due to the inability to initiate an effective antifungal therapy early in the disease process. Mortality rates significantly increase after twelve hours of delay in initiating the appropriate antifungal therapy following a positive blood culture. Early administration of appropriate antifungal therapy is hampered by the slow turnovers of the conventional antimicrobial testing techniques, which require days of incubation...
August 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28812950/expression-of-cytochrome-p450-regulators-in-cynomolgus-macaque
#20
Yasuhiro Uno, Hiroshi Yamazaki
1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed seventeen P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of seventeen P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered, with the human orthologs...
August 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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