scholarly journals Intracellular Metabolism of Uranium and the Effects of Bisphosphonates on Its Toxicity

10.5772/29245 ◽  
2012 ◽  
Author(s):  
Debora R. ◽  
Nadia S. ◽  
Carola Bozal ◽  
Angela M. ◽  
Rmulo L.
Keyword(s):  
Intracellular Metabolism

scholarly journals Comparison of the intracellular metabolism and trafficking of 25-hydroxycholesterol and cholesterol in macrophages

1996 ◽  
Vol 37 (9) ◽  
pp. 2041-2051
Author(s):  
D W Morel ◽  
M E Edgerton ◽  
G E Warner ◽  
W J Johnson ◽  
M C Phillips ◽  
...  
Keyword(s):  
Intracellular Metabolism

scholarly journals POLYMORPHONUCLEAR LEUCOCYTES (PML) AS A MODEL TO ASSESS INTRACELLULAR METABOLISM IN DIALYSED PATIENTS

1987 ◽  
Vol 22 (2) ◽  
pp. 236-236
Author(s):  
G Distler ◽  
K E Bonzel ◽  
R Weber ◽  
T Graser ◽  
J Metcoff ◽  
...  
Keyword(s):  
Polymorphonuclear Leucocytes ◽  
Intracellular Metabolism

Decreased Nitroblue Tetrazolium Dye Reduction in the Phagocytes of Patients Receiving Prednisone

PEDIATRICS ◽  
1970 ◽  
Vol 45 (5) ◽  
pp. 861-865
Author(s):  
Denis R. Miller ◽  
Henry G. Kaplan
Keyword(s):  
Chronic Granulomatous Disease ◽  
Nitroblue Tetrazolium ◽  
Quantitative Assay ◽  
Granulomatous Disease ◽  
Host Defenses ◽  
Dye Reduction ◽  
Slide Test ◽  
Intracellular Metabolism

Nitroblue tetrazolium (NBT) dye reduction by leukocytes of 21 patients receiving prednisone was significantly decreased. Nineteen percent of the patients had values similar to those found in children with chronic granulomatous disease, and 57% had heterozygous-range NBT dye reduction. A qualitative NBT dye reduction "slide test" correlated well with the quantitative assay. The uptake of particles by the phagocytes of steroid-treated patients appeared normal. The exact mechanism of corticosteroid action remains unknown. The decreased dye reduction observed in vitro suggests an induced defect of intracellular metabolism which may be related to known alterations of host defenses which occur in patients receiving these hormones.

scholarly journals Intracellular Metabolism and Persistence of the Anti-Human Immunodeficiency Virus Activity of 2′,3′-Didehydro-3′-Deoxy-4′-Ethynylthymidine, a Novel Thymidine Analog

2007 ◽  
Vol 51 (11) ◽  
pp. 3870-3879 ◽  
Author(s):  
Elijah Paintsil ◽  
Ginger E. Dutschman ◽  
Rong Hu ◽  
Susan P. Grill ◽  
Wing Lam ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Phosphoglycerate Kinase ◽  
Drug Resistant ◽  
Therapeutic Benefits ◽  
Thymidine Analog ◽  
Immunodeficiency Virus ◽  
Drug Removal ◽  
Intracellular Metabolism ◽  
Anti Hiv ◽  
In Cells

ABSTRACT The therapeutic benefits of current antiretroviral therapy are limited by the evolution of drug-resistant virus and long-term toxicity. Novel antiretroviral compounds with activity against drug-resistant viruses are needed. 2′,3′-Didehydro-3′-deoxy-4′-ethynylthymidine (4′-Ed4T), a novel thymidine analog, has potent anti-human immunodeficiency virus (HIV) activity, maintains considerable activity against multidrug-resistant HIV strains, and is less inhibitory to mitochondrial DNA synthesis in cell culture than its progenitor stavudine (D4T). We investigated the intracellular metabolism and anti-HIV activity of 4′-Ed4T. The profile of 4′-Ed4T metabolites was qualitatively similar to that for zidovudine (AZT), with the monophosphate metabolite as the major metabolite, in contrast to that for D4T, with relatively poor formation of total metabolites. The first phosphorylation step for 4′-Ed4T in cells was more efficient than that for D4T but less than that for AZT. The amount of 4′-Ed4T triphosphate (4′-Ed4TTP) was higher than that of AZTTP at 24 h in culture. There was a dose-dependent accumulation of 4′-Ed4T diphosphate and 4′-Ed4TTP on up-regulation of thymidylate kinase and 3-phosphoglycerate kinase expression in Tet-On RKO cells, respectively. The anti-HIV activity of 4′-Ed4T in cells persisted even after 48 h of drug removal from culture in comparison with AZT, D4T, and nevirapine (NVP). The order of increasing persistence of anti-HIV activity of these compounds after drug removal was 4′-Ed4T > D4T > AZT > NVP. In conclusion, with the persistence of 4′-Ed4TTP and persistent anti-HIV activity in cells, we anticipate less frequent dosing and fewer patient compliance issues than for D4T. 4′-Ed4T is a promising antiviral candidate for HIV type 1 chemotherapy.

scholarly journals Anti-Human Immunodeficiency Virus Type 1 Activity, Intracellular Metabolism, and Pharmacokinetic Evaluation of 2′-Deoxy-3′-Oxa-4′-Thiocytidine

1999 ◽  
Vol 43 (8) ◽  
pp. 1835-1844 ◽  
Author(s):  
Jean-Marc de Muys ◽  
Henriette Gourdeau ◽  
Nghe Nguyen-Ba ◽  
Debra L. Taylor ◽  
Parvin S. Ahmed ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Phase Cell ◽  
Logarithmic Phase ◽  
Thymidine Uptake ◽  
Immunodeficiency Virus ◽  
Drug Naïve ◽  
Intracellular Metabolism ◽  
Hiv 1

ABSTRACT The racemic nucleoside analogue 2′-deoxy-3′-oxa-4′-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism studies showed that dOTC is phosphorylated within cells via the deoxycytidine kinase pathway and that approximately 2 to 5% of dOTC is converted into the racemic triphosphate derivatives, which had measurable half-lives (2 to 3 hours) within cells. Both 5′-triphosphate (TP) derivatives of dOTC were more potent than 3TC-TP at inhibiting HIV-1 reverse transcriptase (RT) in vitro. The Ki values for dOTC-TP obtained against human DNA polymerases α, β, and γ were 5,000-, 78-, and 571-fold greater, respectively, than those for HIV RT (28 nM), indicating a good selectivity for the viral enzyme. In culture experiments, dOTC is a potent inhibitor of primary isolates of HIV-1, which were obtained from antiretroviral drug-naive patients as well as from nucleoside therapy-experienced (3TC- and/or zidovudine [AZT]-treated) patients. The mean 50% inhibitory concentration of dOTC for drug-naive isolates was 1.76 μM, rising to only 2.53 and 2.5 μM for viruses resistant to 3TC and viruses resistant to 3TC and AZT, respectively. This minimal change in activity is in contrast to the more dramatic changes observed when 3TC or AZT was evaluated against these same viral isolates. In tissue culture studies, the 50% toxicity levels for dOTC, which were determined by using [3H]thymidine uptake as a measure of logarithmic-phase cell proliferation, was greater than 100 μM for all cell lines tested. In addition, after 14 days of continuous culture, at concentrations up to 10 μM, no measurable toxic effect on HepG2 cells or mitochondrial DNA replication within these cells was observed. When administered orally to rats, dOTC was well absorbed, with a bioavailability of approximately 77%, with a high proportion (approximately 16.5% of the levels in serum) found in the cerebrospinal fluid.

scholarly journals Application of luminescence spectral assay for monitoring of intracellular metabolism in hepatocytes

2020 ◽  
Vol 1679 ◽  
pp. 022004
Author(s):  
S V Akchurin ◽  
S V Larionov ◽  
E S Krasnikova ◽  
I V Akchurina ◽  
A V Krasnikov
Keyword(s):  
Intracellular Metabolism
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