14 results on '"Oleschuk C"'
Search Results
2. Anti-Inflammatory Lipid Mediator Lipoxin A4 Production Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
- Author
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Cuvelier, G.D.E., primary, Oleschuk, C., additional, Ellison, C.A., additional, Swajczer, D., additional, and Wall, D.A., additional
- Published
- 2011
- Full Text
- View/download PDF
3. Prediction of fetal macrosomia using sonographically measured abdominal subcutaneous tissue thickness.
- Author
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Petrikovsky, Boris M., Oleschuk, Catherine, Lesser, Martin, Gelertner, Natalie, Gross, Beth, Petrikovsky, B M, Oleschuk, C, Lesser, M, Gelertner, N, and Gross, B
- Published
- 1997
- Full Text
- View/download PDF
4. Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids.
- Author
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M, Leslie E, Q, Mao, J, Oleschuk C, G, Deeley R, and P, Cole S
- Abstract
The 190-kDa phosphoglycoprotein multidrug resistance protein 1 (MRP1) (ABCC1) confers resistance to a broad spectrum of anticancer drugs and also actively transports certain xenobiotics with reduced glutathione (GSH) (cotransport) as well as conjugated organic anions such as leukotriene C(4) (LTC(4)). In the present study, we have investigated a series of bioflavonoids for their ability to influence different aspects of MRP1 function. Most flavonoids inhibited MRP1-mediated LTC(4) transport in membrane vesicles and inhibition by several flavonoids was enhanced by GSH. Five of the flavonoids were competitive inhibitors of LTC(4) transport (K(i), 2.4-21 microM) in the following rank order of potency: kaempferol > apigenin (+ GSH) > quercetin > myricetin > naringenin (+ GSH). These flavonoids were less effective inhibitors of 17beta-estradiol 17beta-(D-glucuronide) transport. Moreover, their rank order of inhibitory potency for this substrate differed from that for LTC(4) transport inhibition but correlated with their relative lipophilicity. Several flavonoids, especially naringenin and apigenin, markedly stimulated GSH transport by MRP1, suggesting they may be cotransported with this tripeptide. Quercetin inhibited the ATPase activity of purified reconstituted MRP1 but stimulated vanadate-induced trapping of 8-azido-alpha-[(32)P]ADP by MRP1. In contrast, kaempferol and naringenin stimulated both MRP1 ATPase activity and trapping of ADP. In intact MRP1-overexpressing cells, quercetin reduced vincristine resistance from 8.9- to 2.2-fold, whereas kaempferol and naringenin had no effect. We conclude that dietary flavonoids may modulate the organic anion and GSH transport, ATPase, and/or drug resistance-conferring properties of MRP1. However, the activity profile of the flavonoids tested differed from one another, suggesting that at least some of these compounds may interact with different sites on the MRP1 molecule.
- Published
- 2001
5. Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.
- Author
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Callum J, Putowski Z, Alhazzani W, Belley-Cote E, Møller MH, Curry N, Al Duhailib Z, Fung M, Giocobbo L, Granholm A, Louw V, Maybohm P, Muller M, Nielsen N, Oleschuk C, Raza S, Scruth E, Siegal D, Stanworth SJ, Vlaar APJ, White M, and Oczkowski S
- Subjects
- Adult, Humans, Critical Care methods, Critical Care standards, Blood Specimen Collection instrumentation, Blood Specimen Collection methods, Blood Specimen Collection standards, Intensive Care Units standards
- Abstract
Background: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes?, Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework., Results: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation., Conclusion: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)
- Published
- 2024
- Full Text
- View/download PDF
6. The Pharmacokinetics and Pharmacodynamics of Carfentanil After Recreational Exposure: A Case Report.
- Author
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Uddayasankar U, Lee C, Oleschuk C, Eschun G, and Ariano RE
- Subjects
- Adult, Fentanyl pharmacokinetics, Fentanyl pharmacology, Fentanyl poisoning, Humans, Male, Substance Abuse Detection, Fentanyl analogs & derivatives, Illicit Drugs poisoning
- Abstract
Carfentanil and related fentanyl analogs have been linked to a number of overdose deaths from drug users in several cities across North America. Diagnosis of carfentanil exposure requires a very high index of clinical suspicion, especially because available laboratory narcotic screens do not detect this agent. We describe a 34-year-old man admitted with depressed level of consciousness and in respiratory failure after recreational exposure to a white powder later inferred to contain carfentanil. Urine and whole blood samples were obtained for conventional preliminary drug screen immunoassays for unknown exposures, in addition to utilizing a high-pressure liquid chromatography-tandem mass spectrometry assay for quantification of carfentanil and its metabolite. The patient was intubated and required mechanically assisted ventilation for 31 hours until he was able to breathe safely on his own. Pharmacokinetic modeling of three timed blood samples identified the elimination half-life as 5.7 hours for carfentanil and 11.8 hours for the norcarfentanil metabolite. Awakening and breathing spontaneously corresponded to an interpolated blood carfentanil concentration of 0.52 ng/ml. This is the first pharmacokinetic and pharmacodynamic case report on the recreational use of carfentanil. Critical care clinicians should anticipate long periods of ventilatory support in the care of patients exposed to carfentanil., (© 2018 Pharmacotherapy Publications, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
7. Effect of high dose vitamin D3 therapy on serum vitamin D3 levels in vitamin D insufficient adults with cystic fibrosis.
- Author
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Regalado Lam Chew Tun R, Porhownik N, Taback S, and Oleschuk C
- Subjects
- Adolescent, Adult, Body Mass Index, Diet, Dietary Supplements, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Retrospective Studies, Seasons, Young Adult, Cholecalciferol administration & dosage, Cholecalciferol blood, Cystic Fibrosis blood, Vitamin D Deficiency blood, Vitamin D Deficiency drug therapy
- Abstract
Background: The effect of a high dose oral cholecalciferol repletion strategy in Vitamin D insufficient adults with CF is still unknown. Therefore, we assessed the effectiveness of our current approach, giving oral vitamin D3 supplementation at a dose of 10,000 IU from Monday to Friday for a total of 50,000 IU D3 weekly in vitamin D insufficient adult with CF., Methods: We performed a retrospective chart review of all 59 adult CF patients between the ages of 17 and 64 years routinely followed at the CF Adult Program of Winnipeg Health Sciences Centre. Through consultation with the endocrinologist, our clinic vitamin D repletion protocol for treating CF adult patients who have serum 25-hydroxyvitamin D (25-OHD) < 30 ng/ml (<75 nmol/L) was to prescribe vitamin D3 10,000 IU orally from Monday to Friday (or the weekly equivalent of 50,000 IU) for 12 weeks in addition to their regular CF vitamin that supplied from 800 to 2000 IU vitamin D3 daily. Cholecalciferol was conveniently administered orally as either one capsule (oil-based) 10,000 IU or one tablet (powder-based) 10,000 IU. All patients were instructed to obtain follow-up serum 25-OHD levels post completion of treatment., Results: Of the 59 adult patients at our CF Clinic, 35 patients (59%) had below optimal serum 25-OHD levels. Of the 35 patients identified, 10 patients with insufficient serum 25-OHD levels between 10 and 30 ng/ml (25-75 nmol/L) fulfilled the inclusion criteria. A significant increase in serum 25-OHD levels was observed (P < 0.01) from mean value of 21.6 ± 5.9 ng/ml (54.1 ± 14.8 nmol/L) at baseline to 31.7 ± 9.1 ng/ml (79.3 ± 22.8 nmol/L) ≥ 2 months post intervention. The current treatment approach was successful in treating Vitamin D insufficiency in 70% of the patients with low 25-OHD levels., Conclusion: The results of this study demonstrate that a large number of adults attending Winnipeg Health Sciences Centre CF Clinic have serum 25-OHD levels below 30 ng/ml (75 nmol/L). This supports the need for dedicated and individualized approach to manage this condition. High dose therapy of vitamin D3, although a more aggressive treatment approach, may result in achieving optimal levels of serum 25-OHD in adults with CF., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
8. Suicidal Fatality from Azide Ingestion.
- Author
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Meatherall R and Oleschuk C
- Subjects
- Adult, Chromatography, Gas, Chromatography, Liquid, Enzyme Inhibitors analysis, Humans, Male, Sodium Azide analysis, Tandem Mass Spectrometry, Vitreous Body chemistry, Enzyme Inhibitors poisoning, Sodium Azide poisoning, Suicide
- Abstract
A 35-year-old man ingested an unknown amount of sodium azide and died within 2 h. The postmortem interval was 3 days. No alcohol or drugs were found in the blood and urine. Azide was derivatized in the peripheral blood, urine, and vitreous fluid with propionic anhydride. A portion of the headspace was injected onto a gas chromatograph with a nitrogen-phosphorus detector. Azide was quantitated in the peripheral blood (1.1 μg/mL), urine (7.5 μg/mL), and vitreous (43 μg/mL). The vitreous appears to be a better fluid for azide screening because of slower degradation., (© 2015 American Academy of Forensic Sciences.)
- Published
- 2015
- Full Text
- View/download PDF
9. The utility of thiopurine methyltransferase enzyme testing in inflammatory bowel disease.
- Author
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Chisick L, Oleschuk C, and Bernstein CN
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Azathioprine administration & dosage, Azathioprine adverse effects, Azathioprine therapeutic use, Dose-Response Relationship, Drug, Female, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Leukopenia epidemiology, Leukopenia etiology, Male, Manitoba, Mercaptopurine administration & dosage, Mercaptopurine adverse effects, Mercaptopurine therapeutic use, Middle Aged, Retrospective Studies, Young Adult, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Immunosuppressive Agents therapeutic use, Methyltransferases metabolism
- Abstract
Objective: To assess the levels of red blood cell thiopurine methyltransferase (TPMT) in subjects with inflammatory bowel disease (IBD) and to determine how these levels impacted thiopurine dosing and leukopenia over the first six months of therapy., Methods: A retrospective chart review was performed on all adult IBD patients (n=423, 88.2% Caucasian) who had TPMT levels measured by 11 participating gastroenterologists in Manitoba between 2008 and 2010. In addition to descriptive data, white blood cell count, dose and reason for discontinuation were analyzed for the first six months of therapy. Patients receiving ≥2.0 mg/kg of azathioprine (AZA) or ≥1.0 mg/kg of 6-mercapatopurine were considered to be 'substantially' dosed., Results: Of the 423 patients, 8.3% had intermediate levels and 93.4% had normal levels of TPMT. Only one subject had a low level. A total of 216 patients had sufficient data to be included for full analysis. Patients with intermediate TPMT levels were generally started at lower doses of thiopurine than patients with normal TPMT levels (mean [± SD] 1.0±0.6 mg/kg versus 1.8±0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with ≥2.0 mg/kg of AZA. Each month, approximately 5% of subjects were leukopenic. These subjects received a mean overall AZA dose of 1.9±0.3 mg/kg and had a mean white blood cell count of 3.8±0.4×10(9)/L., Conclusions: Normal TPMT levels did not prevent the development of leukopenia, although life-threatening leukopenia was rare. Physicians are not using TPMT levels to substantially dose thiopurines at the outset, which may limit the speed at which adequate doses are reached to facilitate remission.
- Published
- 2013
- Full Text
- View/download PDF
10. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening.
- Author
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Rabeneck L, Rumble RB, Thompson F, Mills M, Oleschuk C, Whibley A, Messersmith H, and Lewis N
- Subjects
- Canada, Globins immunology, Guaiac, Humans, Immunochemistry, Practice Guidelines as Topic, Adenoma diagnosis, Colorectal Neoplasms diagnosis, Globins analysis, Mass Screening methods, Occult Blood
- Abstract
Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women - accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario's Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials, and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.
- Published
- 2012
- Full Text
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11. Cardiac troponin testing in the acute care setting: ordering, reporting, and high sensitivity assays--an update from the Canadian society of clinical chemists (CSCC).
- Author
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Kavsak PA, Allen LC, Apple FS, Booth RA, Chan PC, Delvin E, Fraser A, Fu L, Gornall D, Collier C, Hill S, Hoffman B, Huang Y, Lavoie J, Lou A, Mattman A, McQueen M, Meng QH, Oleschuk C, Pudek M, Randell E, Sohn KY, Thorlacius L, Yip PM, Dahdah N, Devereaux PJ, Dhesy-Thind S, Hotte SJ, and Worster A
- Subjects
- Acute Coronary Syndrome diagnosis, Adult, Aged, Canada, Emergency Medical Services methods, Female, Guidelines as Topic, Humans, Male, Medical Laboratory Personnel, Middle Aged, Myocardial Infarction diagnosis, Sensitivity and Specificity, Young Adult, Clinical Chemistry Tests methods, Troponin analysis
- Published
- 2011
- Full Text
- View/download PDF
12. Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity.
- Author
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Ito K, Oleschuk CJ, Westlake C, Vasa MZ, Deeley RG, and Cole SP
- Subjects
- Amino Acid Sequence, Base Sequence, Biological Transport drug effects, Cell Line, DNA Primers, Estradiol metabolism, Glucuronides metabolism, Humans, Leukotriene C4 metabolism, Molecular Sequence Data, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins chemistry, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Substrate Specificity, Sulfinpyrazone pharmacology, Membrane Transport Proteins, Methotrexate metabolism, Multidrug Resistance-Associated Proteins genetics, Multidrug Resistance-Associated Proteins metabolism, Tryptophan genetics
- Abstract
The ATP-binding cassette (ABC) proteins comprise a large superfamily of transmembrane transporters that utilize the energy of ATP hydrolysis to translocate their substrates across biological membranes. Multidrug resistance protein (MRP) 2 (ABCC2) belongs to subfamily C of the ABC superfamily and, when overexpressed in tumor cells, confers resistance to a wide variety of anticancer chemotherapeutic agents. MRP2 is also an active transporter of organic anions such as methotrexate (MTX), estradiol glucuronide (E217betaG), and leukotriene C4 and is located on the apical membrane of polarized cells including hepatocytes where it acts as a biliary transporter. We recently identified a highly conserved tryptophan residue in the related MRP1 that is critical for the substrate specificity of this protein. In the present study, we have examined the effect of replacing the analogous tryptophan residue at position 1254 of MRP2. We found that only nonconservative substitutions (Ala and Cys) of Trp1254 eliminated [3H]E217betaG transport by MRP2, whereas more conservative substitutions (Phe and Tyr) had no effect. In addition, only the most conservatively substituted mutant (W1254Y) transported [3H]leukotriene C4, whereas all other substitutions eliminated transport of this substrate. On the other hand, all substitutions of Trp1254 eliminated transport of [3H]MTX. Finally, we found that sulfinpyrazone stimulated [3H]E217betaG transport by wild-type MRP2 4-fold, whereas transport by the Trp1254 substituted mutants was enhanced 6-10-fold. In contrast, sulfinpyrazone failed to stimulate [3H]MTX transport by either wild-type MRP2 or the MRP2-Trp1254 mutants. Taken together, our results demonstrate that Trp1254 plays an important role in the ability of MRP2 to transport conjugated organic anions and identify this amino acid in the putative last transmembrane segment (TM17) of this ABC protein as being critical for transport of MTX.
- Published
- 2001
- Full Text
- View/download PDF
13. Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids.
- Author
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Leslie EM, Mao Q, Oleschuk CJ, Deeley RG, and Cole SP
- Subjects
- Adenosine Diphosphate metabolism, Adenosine Triphosphatases drug effects, Antineoplastic Agents, Phytogenic pharmacology, Azides metabolism, Binding, Competitive, Biological Transport drug effects, Cell Division drug effects, Chromatography, High Pressure Liquid, Drug Interactions, Estradiol chemistry, Estradiol metabolism, Estrogen Antagonists pharmacology, Flavonoids chemistry, Glutathione metabolism, HeLa Cells, Humans, Kinetics, Leukotriene C4 metabolism, Multidrug Resistance-Associated Proteins, Phosphorus Radioisotopes, Quercetin analogs & derivatives, Quercetin pharmacology, Transfection, Tritium, Vanadates pharmacology, Vincristine pharmacology, ATP-Binding Cassette Transporters metabolism, Adenosine Diphosphate analogs & derivatives, Adenosine Triphosphatases metabolism, Flavanones, Flavonoids pharmacology, Kaempferols
- Abstract
The 190-kDa phosphoglycoprotein multidrug resistance protein 1 (MRP1) (ABCC1) confers resistance to a broad spectrum of anticancer drugs and also actively transports certain xenobiotics with reduced glutathione (GSH) (cotransport) as well as conjugated organic anions such as leukotriene C(4) (LTC(4)). In the present study, we have investigated a series of bioflavonoids for their ability to influence different aspects of MRP1 function. Most flavonoids inhibited MRP1-mediated LTC(4) transport in membrane vesicles and inhibition by several flavonoids was enhanced by GSH. Five of the flavonoids were competitive inhibitors of LTC(4) transport (K(i), 2.4-21 microM) in the following rank order of potency: kaempferol > apigenin (+ GSH) > quercetin > myricetin > naringenin (+ GSH). These flavonoids were less effective inhibitors of 17beta-estradiol 17beta-(D-glucuronide) transport. Moreover, their rank order of inhibitory potency for this substrate differed from that for LTC(4) transport inhibition but correlated with their relative lipophilicity. Several flavonoids, especially naringenin and apigenin, markedly stimulated GSH transport by MRP1, suggesting they may be cotransported with this tripeptide. Quercetin inhibited the ATPase activity of purified reconstituted MRP1 but stimulated vanadate-induced trapping of 8-azido-alpha-[(32)P]ADP by MRP1. In contrast, kaempferol and naringenin stimulated both MRP1 ATPase activity and trapping of ADP. In intact MRP1-overexpressing cells, quercetin reduced vincristine resistance from 8.9- to 2.2-fold, whereas kaempferol and naringenin had no effect. We conclude that dietary flavonoids may modulate the organic anion and GSH transport, ATPase, and/or drug resistance-conferring properties of MRP1. However, the activity profile of the flavonoids tested differed from one another, suggesting that at least some of these compounds may interact with different sites on the MRP1 molecule.
- Published
- 2001
- Full Text
- View/download PDF
14. Structure-activity studies of verapamil analogs that modulate transport of leukotriene C(4) and reduced glutathione by multidrug resistance protein MRP1.
- Author
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Loe DW, Oleschuk CJ, Deeley RG, and Cole SP
- Subjects
- ATP-Binding Cassette Transporters genetics, Biological Transport drug effects, Cell Membrane metabolism, Chromatography, High Pressure Liquid, HeLa Cells, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology, Humans, Multidrug Resistance-Associated Proteins, Oxidation-Reduction, Stereoisomerism, Structure-Activity Relationship, Sulfur Compounds chemistry, Sulfur Compounds pharmacology, Transfection, Tumor Cells, Cultured, Verapamil chemistry, ATP-Binding Cassette Transporters metabolism, Glutathione metabolism, Leukotriene C4 metabolism, Verapamil analogs & derivatives, Verapamil pharmacology
- Abstract
The 190-kDa multidrug resistance protein MRP1 is an ATP-binding cassette protein that confers resistance to multiple antineoplastic agents and actively transports conjugated organic anions. We have previously shown that MRP1-mediated GSH transport is stimulated by verapamil but transport of verapamil in the presence or absence of GSH is not observed. We have now examined 20 sulfur-containing verapamil analogs for their ability to inhibit MRP1-mediated leukotriene C(4) (LTC(4)) transport and stimulate GSH uptake into inside-out membrane vesicles. All of the derivatives were poor inhibitors of LTC(4) uptake. However, the inhibitory potency of the more lipophilic dithiane compounds could be enhanced by coincubation with GSH whereas this was not the case for the more hydrophilic dithiane tetraoxides. The dithiane derivatives stimulated GSH transport whereas, with one exception, the dithiane tetraoxides did not. One pair of dithiane stereoisomers differed significantly in their ability to stimulate GSH transport although their ability to inhibit LTC(4) uptake in the presence of GSH was comparable. Our findings indicate that the GSH transport activity of MRP1 can be dissociated from its conjugated organic anion transport activity., (Copyright 2000 Academic Press.)
- Published
- 2000
- Full Text
- View/download PDF
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