Faculty Opinions recommendation of Determination of the EC50 amnesic concentration of etomidate and its diffusion profile in brain tissue: implications for in vitro studies.

2007 ◽  
Author(s):  
Bernd Antkowiak
Keyword(s):  
Brain Tissue ◽  
Diffusion Profile ◽  
In Vitro Studies

Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies

1990 ◽  
Vol 36 (9) ◽  
pp. 1638-1641 ◽  
Author(s):  
S C Kazmierczak ◽  
W J Castellani ◽  
F Van Lente ◽  
E D Hodges ◽  
B Udis
Keyword(s):  
Flow Cytometry ◽  
Lactate Dehydrogenase ◽  
Cell Types ◽  
In Vitro Studies ◽  
Hemolytic Disease ◽  
Dehydrogenase Isoenzyme ◽  
Disease Analysis

Abstract We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 1.1.1.27) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes.

Intracerebral microdialysis for determination of the neuropharmacokinetics and neuropharmacodynamics of temozolomide in patients with primary or metastatic brain tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2074-2074 ◽  
Author(s):  
J. Portnow ◽  
B. Badie ◽  
B. Xi ◽  
A. Liu ◽  
D. Hovda ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Brain Tissue ◽  
Extracellular Fluid ◽  
Published Data ◽  
Intracerebral Microdialysis ◽  
Mri Scans ◽  
Lactate And Pyruvate ◽  
Grade 3

2074 Background: Microdialysis (MD) is a technique for continuously analyzing concentrations of endogenous chemicals and drugs in the extracellular fluid (ECF) of a body tissue. The purpose of this study is to apply MD to the determination of the neuropharmacokinetics (nPK) and neuropharmacodynamics (nPD) of temozolomide (TMZ) following systemic administration. Methods: After surgical debulking, a MD catheter is placed in peritumoral brain tissue. Artificial cerebrospinal fluid (CSF) is continuously perfused at a rate of 1 μl/min. Fused CT/MRI scans confirm correct placement of the catheter in non-enhancing brain. Starting 24 hrs after surgery, patients are given a dose of TMZ (150 mg/m2), and serial ECF and plasma samples are collected over 24 hrs. TMZ concentrations are determined by LC/MS/MS. In vitro recovery of TMZ via the MD catheter has been determined to be 87±5.5% at a flow rate of 1 μl/min. Prior to and 24 hrs post TMZ, additional ECF samples are collected for analysis of glucose, glutamate, lactate, and pyruvate, which are measured using a CMA 600 Analyzer®. Results: Four patients have been enrolled. There have been no grade 3 or 4 catheter-related adverse events. Mean peak TMZ concentrations in brain ECF and plasma are 0.4±0.2 and 5.5±1.4 μg/ml, respectively. Mean TMZ AUC in brain ECF and plasma are 3.2±1.6 and 18.2±4.6 μg/mLxhr, with an average ECF/plasma AUC ratio of 18±4%. Mean basal levels of glucose, glutamate, lactate, and pyruvate in ECF are 0.4±0.3, 34±66, 3±4, 69±62 mM, respectively. No consistent changes were seen in these nPD markers 24 hrs after TMZ. Conclusions: Concentrations of TMZ in brain ECF obtained by MD are similar to published data of TMZ concentrations in the CSF (Clin Cancer Res 2004;10:3728–36). Baseline values of markers of brain tissue metabolism are consistent with previous data in patients with brain tumors (J Neuro-Oncol 2003; 61:151–60). Intracerebral MD is an important tool that can be applied to nPK/nPD studies of new and targeted agents for the treatment of brain tumors. (Supported by CA01727) No significant financial relationships to disclose.

scholarly journals 452 DIRECT DETERMINATION OF 17α-HYDROXYLASE (170Hase) DEFICIENCY IN A MALE PSEUDOHERMAPHRODITE BY IN VITRO STUDIES OF TESTICULAR STEROID BIOSYNTHESIS

1981 ◽  
Vol 15 ◽  
pp. 515-515 ◽  
Author(s):  
A Vargas ◽  
E O Reiter ◽  
K Kula ◽  
L J Rodriguez-Rigau ◽  
E Steinberger ◽  
...  
Keyword(s):  
Direct Determination ◽  
In Vitro Studies ◽  
Steroid Biosynthesis

Molecular Docking Supplements an In vitro Determination of the Leading CYP Isoform for Arylpiperazine Derivatives

2019 ◽  
Vol 22 (6) ◽  
pp. 370-378 ◽  
Author(s):  
Szymon Ulenberg ◽  
Tomasz Bączek ◽  
Joanna Zieliñska ◽  
Mariusz Belka ◽  
Marek Król ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Three Dimensional ◽  
In Vitro Studies ◽  
Three Dimensional Model ◽  
Promising Tool ◽  
Three Dimensional Models ◽  
Early Drug

Background: Molecular docking has often been used before to calculate in silico affinity of drugs towards their molecular target, but not to estimate leading CYP isoform responsible for metabolism of studied compounds. Objective: The aim of this study is to present molecular docking as a valid alternative for costly in vitro studies resulting in estimation of leading CYP isoform. Method: In vitro part was based on incubations of studied compounds with isolated CYP3A4 isoform followed by LC-MS analysis. The in silico stage consisted of docking three-dimensional models of the studied compounds with a three-dimensional model of the leading metabolizing isoform (CYP3A4), which was designated during the in vitro part of the study. XenoSite P450 metabolism prediction was also used to predict sites of metabolism and calculate probability values. Results: The calculated affinities showed a clear similarity when the in vitro results were compared with the calculated in silico affinity values. XenoSite CYP3A4 metabolism probability values also confirm significant participation of CYP3A4 in metabolism of studied compounds. Conclusion: Both molecular docking and XenoSite P450 metabolism prediction provide data that stands in agreement with in vitro studies, granting a more detailed spectrum on predicting CYP3A4 metabolism, and presenting molecular docking as a promising tool to cut costs and increase effectiveness in early drug development stages.

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