keyword
MENU ▼
Read by QxMD icon Read
search

Oct1

keyword
https://www.readbyqxmd.com/read/29352482/influence-of-pharmacogenetic-polymorphisms-and-demographic-variables-on-metformin-pharmacokinetics-in-an-admixed-brazilian-cohort
#1
Ana Beatriz Santoro, Mariana Rodrigues Botton, Claudio José Struchiner, Guilherme Suarez-Kurtz
AIM: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry...
January 20, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29330289/brca1-through-its-e3-ligase-activity-regulates-the-transcription-factor-oct1-and-carbohydrate-metabolism
#2
Karina Vázquez-Arreguín, Jessica Maddox, Jinsuk Kang, Dongju Park, Reuben R Cano, Rachel E Factor, Thomas Ludwig, Dean Tantin
The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with pro-glycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells towards a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29246313/assessment-of-the-drug-interaction-potential-of-unconjugated-and-galnac3-conjugated-2-moe-asos
#3
Colby S Shemesh, Rosie Z Yu, Mark S Warren, Michael Liu, Mirza Jahic, Brandon Nichols, Noah Post, Song Lin, Daniel A Norris, Eunju Hurh, Jane Huang, Tanya Watanabe, Scott P Henry, Yanfeng Wang
Antisense oligonucleotides are metabolized by nucleases and drug interactions with small drug molecules at either the cytochrome P450 (CYP) enzyme or transporter levels have not been observed to date. Herein, a comprehensive in vitro assessment of the drug-drug interaction (DDI) potential was carried out with four 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides (2'-MOE-ASOs), including a single triantennary N-acetyl galactosamine (GalNAc3)-conjugated ASO. Several investigations to describe the DDI potential of a 2'-MOE-ASO conjugated to a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors are explored...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29236753/effects-of-genetic-polymorphisms-on-the-oct1-and-oct2-mediated-uptake-of-ranitidine
#4
Marleen Julia Meyer, Tina Seitz, Jürgen Brockmöller, Mladen Vassilev Tzvetkov
BACKGROUND: Ranitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. Ranitidine was reported to be a substrate of the organic cation transporters OCT1 and OCT2. The hepatic transporter OCT1 is highly genetically variable. Twelve major alleles confer partial or complete loss of OCT1 activity. The effects of these polymorphisms are highly substrate-specific and therefore difficult to predict. The renal transporter OCT2 has a common polymorphism, Ala270Ser, which was reported to affect OCT2 activity...
2017: PloS One
https://www.readbyqxmd.com/read/29212823/quantitative-expression-of-hepatobiliary-transporters-and-functional-uptake-of-substrates-in-hepatic-2d-sandwich-cultures-a-comparative-evaluation-of-upcyte-and-primary-human-hepatocytes
#5
Michelle Schaefer, Gaku Morinaga, Akiko Matsui, Gerhard Schanzle, Daniel Bischoff, Roderich D Sussmuth
Deficient functional expression of drug transporters incapacitates most hepatic cell lines as reliable tool for evaluating transporter-mediated drug-drug interactions. Recently, genetically-modified cells, referred to as upcyte hepatocytes, have emerged as an expandable, non‑cancerous source of human hepatic cells. Herein, we quantified mRNA and protein levels of key hepatobiliary transporters and assessed associated uptake activity in short- and long-term cultures of upcyte human hepatocytes (UHH), in comparison to cryopreserved primary human hepatocytes (cPHH)...
December 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29193038/emerging-clinical-importance-of-hepatic-organic-cation-transporter-1-oct1-in-drug-pharmacokinetics-dynamics-pharmacogenetic-variability-and-drug-interactions
#6
Maciej J Zamek-Gliszczynski, Kathleen M Giacomini, Lei Zhang
Hepatic organic cation transporter 1 (OCT1) can be a determinant of drug clearance and distribution, which can impact drug exposure and response. OCT1 was shown recently to be the rate-determining step in the clearance of several drugs in humans, and thereby a mechanism of pharmacogenetic variability and drug-drug interactions (DDIs). OCT1 mediates metformin distribution to the liver (key biophase). As OCT1 modulation impacts metformin response, but not pharmacokinetics (PK), metformin DDI studies require pharmacodynamic endpoint(s) to inform rational metformin dose adjustment...
November 28, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29191019/affinity-of-ketamine-to-clinically-relevant-transporters
#7
Markus Keiser, Mahmoud Hasan, Stefan Oswald
Ketamine is a widely used intravenous anaesthetic drug that has also a pronounced analgesic effect. Moreover, one of its metabolites was very recently shown to possess antidepressant activity. Consequently, oral administration of ketamine may become of interest in the future. There is evidence from in vitro data, drug-drug interactions and from the physicochemical properties of the drug that ketamine may be a substrate of drug transporters. Thus, it was the aim of this study to investigate the affinity of ketamine to clinically relevant transporter proteins that are expected to affect its intestinal absorption, distribution and excretion...
November 30, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29162613/the-jak1-2-inhibitor-ruxolitinib-reverses-interleukin-6-mediated-suppression-of-drug-detoxifying-proteins-in-cultured-human-hepatocytes
#8
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/29138286/transporter-expression-in-non-cancerous-and-cancerous-liver-tissue-from-donors-with-hepatocellular-carcinoma-and-chronic-hepatitis-c-infection-quantified-by-lc-ms-ms-proteomics
#9
Sarah Billington, Adrian S Ray, Laurent Salphati, Guangqing Xiao, Xiaoyan Chu, W Griffith Humphreys, Mingxiang Liao, Caroline A Lee, Anita A Mathias, Cornelis E C A Hop, Christopher Rowbottom, Raymond Evers, Yurong Lai, Edward J Kelly, Bhagwat Prasad, Jashvant D Unadkat
Protein expression of major hepatobiliary drug transporters (NTCP, OATPs, OCT1, BSEP, BCRP, MATE1, MRPs and P-gp) in cancerous (C, n=8) and adjacent non-cancerous (NC, n=33) liver tissues obtained from chronic hepatitis C patients with hepatocellular carcinoma (HCV-HCC) were quantified by LC-MS/MS proteomics. Herein, we compare our results with our previous data from non-infected non-cirrhotic (control, n=36) and HCV-cirrhotic (n=30) livers. The amount of membrane protein yielded from NC and C HCV-HCC tissues decreased (31%, 67%) relative to control livers...
November 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29089306/organic-cation-transporter-1-is-responsible-for-hepatocellular-uptake-of-the-tyrosine-kinase-inhibitor-pazopanib
#10
Waleed Elsayed Ahmed Ellawatty, Yusuke Masuo, Ken-Ichi Fujita, Erina Yamazaki, Hiroo Ishida, Hiroshi Arakawa, Noritaka Nakamichi, Ramadan Abdelwahed, Yasutsuna Sasaki, Yukio Kato
Pazopanib is an orally active tyrosine kinase inhibitor that exhibits hepatotoxicity in some patients. Despite the clinical importance of its hepatic distribution, the transporter(s) responsible for hepatic uptake of pazopanib in humans remain undetermined. In order to characterize its hepatic uptake mechanism, we screened the effects of several transporter inhibitors, including tetrapentylammonium (TPeA) for organic cation transporters (OCTs) and cyclosporin A (CsA) for organic anion-transporting polypeptides (OATPs), on both plasma disappearance and hepatic distribution of pazopanib in mice after its intravenous administration...
October 31, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29080172/quantitative-trait-loci-for-root-growth-response-to-cadaverine-in-arabidopsis
#11
Nicole M Gibbs, Laura Vaughn Rouhana, Patrick H Masson
Root growth architecture is a major determinant of agricultural productivity and plant fitness in natural ecosystems. Here we describe the methods used in a Quantitative Trait Loci (QTL) study that allowed the identification of ORGANIC CATION TRANSPORTER 1 (OCT1) as a determinant of root growth response to cadaverine treatment in Arabidopsis thaliana. This protocol screens natural accessions to characterize the variation in root growth response to the naturally occurring polyamine cadaverine, then uses recombination mapping to identify loci that are responsible for the variation existing between two accessions with contrasting phenotypes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29061131/proguanil-and-cycloguanil-are-organic-cation-transporter-and-multidrug-and-toxin-extrusion-substrates
#12
Maarten van der Velden, Albert Bilos, Jeroen J M W van den Heuvel, Sanna R Rijpma, Evelien G E Hurkmans, Robert W Sauerwein, Frans G M Russel, Jan B Koenderink
BACKGROUND: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at physiological pH, they are likely to interact with human organic cation transporters 1 and 2 (OCT1 and OCT2). These transporters are involved in the uptake of drugs into hepatocytes and proximal tubule cells for subsequent metabolic conversion or elimination...
October 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29061087/oct1-pharmacogenetics-in-pain-management-is-a-clinical-application-within-reach
#13
Mladen V Tzvetkov
Beside drug metabolizing enzymes alsogenetically variable membrane transporters may substantially contribute to the interindividual variability in pharmacokinetics and efficacy of opioids and other analgesics. The organic cation transporter OCT1 is strongly expressed in the sinusoidal membrane of the human liver. It may affect hepatic uptake and thus limit metabolic rates. OCT1 is highly genetically variable. Genetic polymorphisms lead to substantially reduced OCT1 activity in up to 9% of the Europeans and the white Americans...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29032766/the-effects-of-drug-metabolizing-enzyme-inhibitors-on-hepatic-efflux-and-uptake-transporters
#14
Jonathan Cheong, Jason S Halladay, Jasleen K Sodhi, Emile Plise, Laurent Salphati
BACKGROUND: Non-selective chemical inhibitors of phase I and phase II enzymes are commonly used in in vitro metabolic studies to elucidate the biotransformation pathways of drugs. However, the inhibition of the inhibitors on efflux and uptake transporters is not well investigated, potentially leading to unexpected and ambiguous results in these studies. OBJECTIVE: The commonly used metabolizing enzyme inhibitors, 1-aminobenzotriazole (ABT), SKF-525A, pargyline, allopurinol, menadione, methimazole, piperine and raloxifene, were examined for their potential inhibition of the major hepatic ABC (ATP binding cassette) and SLC (solute carrier) transporters...
October 10, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29019117/physiologically-based-pharmacokinetic-modeling-of-transporter-mediated-hepatic-clearance-and-liver-partitioning-of-oatp-and-oct-substrates-in-cynomolgus-monkeys
#15
Bridget L Morse, Jamus G MacGuire, Anthony M Marino, Yue Zhao, Maxine Fox, Yueping Zhang, Hong Shen, W Griffith Humphreys, Punit Marathe, Yurong Lai
In the present investigations, we evaluate in vitro hepatocyte uptake and partitioning for the prediction of in vivo clearance and liver partitioning. Monkeys were intravenously co-dosed with rosuvastatin and bosentan, substrates of the organic anion transporting polypeptides (OATPs), and metformin, a substrate of organic cation transporter 1 (OCT1). Serial plasma and liver samples were collected over time. Liver and plasma unbound fraction was determined using equilibrium dialysis. In vivo unbound partitioning (Kpu,u) for rosuvastatin, bosentan, and metformin, calculated from total concentrations in the liver and plasma, were 243, 553, and 15, respectively...
November 2017: AAPS Journal
https://www.readbyqxmd.com/read/28986476/colistin-is-substrate-of-the-carnitine-organic-cation-transporter-2-octn2-slc22a5
#16
Michele Visentin, Zhibo Gai, Angelo Torozi, Christian Hiller, Gerd A Kullak-Ublick
Colistin is a polycation antibiotic used for the treatment of multidrug-resistance (MDR) gram-negative infections; nevertheless, its use is often limited by the high incidence of renal damage. The mechanism underlying colistin-induced nephrotoxicity is not known, but perhaps related to its accumulation in the renal cortex upon extensive reabsorption from the nascent urine. Because little is known about the membrane transport of colistin, the purpose of the present study was to characterize better the transport system involved in colistin renal handling by using HEK293 cells stably transfected with the main organic cation transporters expressed at the apical membrane of the proximal tubule...
October 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28971610/mechanistic-in%C3%A2-vitro-studies-confirm-that-inhibition-of-the-renal-apical-efflux-transporter-multidrug-and-toxin-extrusion-mate-1-and-not-altered-absorption-underlies-the-increased-metformin-exposure-observed-in-clinical-interactions-with-cimetidine-trimethoprim
#17
Robert Elsby, Stephen Chidlaw, Samuel Outteridge, Sarah Pickering, Amy Radcliffe, Rebecca Sullivan, Hayley Jones, Philip Butler
Metformin is a common co-medication for many diseases and the victim of clinical drug-drug interactions (DDIs) perpetrated by cimetidine, trimethoprim and pyrimethamine, resulting in decreased active renal clearance due to inhibition of organic cation transport proteins and increased plasma exposure of metformin. To understand whether area under the plasma concentration-time curve (AUC) increases relate to absorption, in vitro inhibitory potencies of these drugs against metformin transport by human organic cation transporter (OCT) 1, and the apical to basolateral absorptive permeability of metformin across Caco-2 cells in the presence of therapeutic intestinal concentrations of cimetidine, trimethoprim or pyrimethamine, were determined...
October 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28955749/structure-organization-and-tissue-expression-of-the-pig-slc13a1-and-slc13a4-sulfate-transporter-genes
#18
Samuel K Barnes, Yvonne A Eiby, Soohyun Lee, Barbara E Lingwood, Paul A Dawson
Sulfate is an obligate nutrient for fetal growth and development. In mice, the renal Slc13a1 sulfate transporter maintains high maternal circulating levels of sulfate in pregnancy, and the placental Slc13a4 sulfate transporter mediates sulfate supply to the fetus. Both of these genes have been linked to severe embryonal defects and fetal loss in mice. However, the clinical significance of SLC13A1 and SLC13A4 in human gestation is unknown. One approach towards understanding the potential involvement of these genes in human fetal pathologies is to use an animal model, such as the pig, which mimics the developmental trajectory of the human fetus more closely than the previously studied mouse models...
July 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28947922/diabetes-medication-associates-with-dna-methylation-of-metformin-transporter-genes-in-the-human-liver
#19
Sonia García-Calzón, Alexander Perfilyev, Ville Männistö, Vanessa D de Mello, Emma Nilsson, Jussi Pihlajamäki, Charlotte Ling
BACKGROUND: Given that metformin is the most common pharmacological therapy for type 2 diabetes, understanding the function of this drug is of great importance. Hepatic metformin transporters are responsible for the pharmacologic action of metformin. However, epigenetics in genes encoding metformin transporters has not been fully elucidated. We examined the DNA methylation of these genes in the liver of subjects with type 2 diabetes and tested whether epigenetic alterations associate with diabetes medication, i...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28936218/atoma1-affects-the-oxphos-system-and-plant-growth-in-contrast-to-other-newly-identified-atp-independent-proteases-in-arabidopsis-mitochondria
#20
Iwona Migdal, Renata Skibior-Blaszczyk, Malgorzata Heidorn-Czarna, Marta Kolodziejczak, Arnold Garbiec, Hanna Janska
Compared with yeast, our knowledge on members of the ATP-independent plant mitochondrial proteolytic machinery is rather poor. In the present study, using confocal microscopy and immunoblotting, we proved that homologs of yeast Oma1, Atp23, Imp1, Imp2, and Oct1 proteases are localized in Arabidopsis mitochondria. We characterized these components of the ATP-independent proteolytic system as well as the earlier identified protease, AtICP55, with an emphasis on their significance in plant growth and functionality in the OXPHOS system...
2017: Frontiers in Plant Science
keyword
keyword
68437
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"