scholarly journals Influence of pre-analytical sample preparation on drug concentration measurements in peritoneal tissue: an ex-vivo study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Arianna Castagna ◽  
Iaroslav Sautkin ◽  
Frank-Jürgen Weinreich ◽  
Hannah Heejung Lee ◽  
Alfred Königsrainer ◽  
...  
Keyword(s):  
Sample Preparation ◽  
Drug Concentration ◽  
High Performance ◽  
Tissue Concentration ◽  
Ex Vivo ◽  
Peritoneal Surface ◽  
Depth Ratio ◽  
Peritoneal Tissue ◽  
Different Diameters ◽  
Ex Vivo Study

Abstract Objectives Biopsy morphology (surface/depth ratio) and sample processing might affect pharmacological measurements in peritoneal tissue. Methods This is an ex-vivo study on inverted bovine urinary bladders (IBUB). We compared cisplatin (CIS) and doxorubicin (DOX) concentration in 81 standardized transmural punch biopsies of different diameters (6 and 12 mm). Then, we assessed the effect of dabbing the peritoneal surface before analysis. After automatized tissue homogenization with ceramic beads followed by lyophilisation, DOX concentration was quantified by high-performance liquid chromatography (HPLC), CIS concentration by atomic absorption spectroscopy. Experiments were performed in triplicate; the analysis was blinded to the sample origin. Comparisons were performed using non-parametric tests. Results Concentrations are given in mean (CI 5–95%). Results were reproducible between experiments (for CIS p=0.783, for DOX p=0.235) and between different localizations within the IBUB (for CIS p=0.032, for DOX p=0.663). Biopsy diameter had an influence on CIS tissue concentration (6 mm biopsies: 23.2 (20.3–26.1), vs. 12 mm biopsies: 8.1 (7.2–9.2) ng/mg, p<0.001) but not on DOX: (0.46, 0.29–0.62) vs. 0.43 (0.33–0.54) ng/mg respectively, p=0.248). Dabbing the peritoneal surface reduced DOX tissue concentration (dry biopsies: 0.28 (0.12–0.43) vs. wet biopsies: 0.64 (0.35–0.93) ng/mg, p=0.025) but not CIS (23.5 (19.0–28.0) vs. 22.9 (18.9–26.9) ng/mg, respectively, p=0.735). Conclusions Measurements of drug concentration in peritoneal tissue can be influenced by the biopsy’s surface/depth ratio and after drying the biopsy’s surface. This influence can reach a factor three, depending on the drug tested. The biopsy technique and the pre-analytical sample preparation should be standardized to ensure reliable pharmacological measurements in peritoneal tissue.

scholarly journals Corneal Penetration of Low-Dose Atropine Eye Drops

2021 ◽  
Vol 10 (4) ◽  
pp. 588
Author(s):  
Henning Austermann ◽  
Frank Schaeffel ◽  
Ute Mathis ◽  
Verena Hund ◽  
Frank Mußhoff ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
High Performance ◽  
Low Dose ◽  
Ex Vivo ◽  
Therapeutic Window ◽  
Eye Drops ◽  
Liquid Liquid Extraction ◽  
Liquid Chromatography Tandem Mass ◽  
Ex Vivo Study ◽  
Corneal Penetration

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

scholarly journals Influence of Prior Exposure to Zidovudine on Stavudine Phosphorylation In Vivo and Ex Vivo

2001 ◽  
Vol 45 (2) ◽  
pp. 577-582 ◽  
Author(s):  
P. G. Hoggard ◽  
S. D. Sales ◽  
D. Phiboonbanakit ◽  
J. Lloyd ◽  
B. A. Maher ◽  
...  
Keyword(s):  
High Performance ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Hiv Positive ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Ex Vivo Study ◽  
Level 2

ABSTRACT Intracellular phosphorylation of stavudine (d4T) and zidovudine (ZDV) was investigated in peripheral blood mononuclear cells (PBMCs) isolated from ZDV-naive and ZDV-experienced human immunodeficiency virus (HIV)-positive patients. An in vivo study measured the amount of d4T triphosphate (d4TTP), while an ex vivo study assessed the capacity of cells to phosphorylate added d4T. Endogenous dTTP was also measured. d4TTP and dTTP were determined in vivo using a reverse transcriptase chain termination assay. In ex vivo studies, d4T (1 μM) was incubated in resting and phytohemagglutinin-stimulated (10 μg ml−1; 72 h) PBMCs for 24 h. After washing and methanol extraction, radiolabeled anabolites were detected by high-performance liquid chromatography. d4TTP reached its highest level 2 to 4 h after dosing (0.21 ± 0.14 pmol/106cells; n = 27 [mean ± standard deviation]). Comparison of ZDV-naive and ZDV-experienced individuals showed no significant difference in levels of d4TTP (ZDV naive, 0.23 ± 0.17 pmol/106 cells [n = 7] versus ZDV experienced, 0.20 ± 0.14 pmol/106 cells [n = 20]; P = 0.473) or the d4TTP/dTTP ratio (0.14 ± 0.12 [n = 7] and 0.10 ± 0.08 [n = 20], respectively;p = 0.391). Ex vivo data demonstrated no significant difference in the formation of d4TTP or total d4T phosphates in naive and experienced patients (0.086 ± 0.055 pmol/106cells in ZDV-naive patients [n = 17] versus 0.081 ± 0.038 pmol/106 cells in ZDV-experienced patients [n = 22]; P = 0.767). The ability of HIV-infected patients to phosphorylate d4T in vivo and ex vivo was unchanged with increasing exposure to ZDV.

Direct Visualization of A2, A3, and A4 Finger Flexor Pulley Injuries at 3-T and 7-T MRI: An Ex Vivo Study

2020 ◽  
Author(s):  
Rafael Heiss ◽  
Frank W. Roemer ◽  
Christoph Lutter ◽  
Rolf Janka ◽  
Volker Schöffl ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Direct Visualization ◽  
Ex Vivo Study

Impact of metal artefacts in QCT of the hip caused by a contralateral Gamma type nail: an ex vivo study

2014 ◽  
Author(s):  
Klaus Engelke ◽  
Nicolas Bouler ◽  
Oleg Museyko Fuerst ◽  
Sebastien Parratte ◽  
Thomas Fuerst ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Metal Artefacts ◽  
Ex Vivo Study

Interactions between programmable shunt valves and magnetically controlled growing rods for scoliosis

2020 ◽  
Vol 26 (6) ◽  
pp. 667-670
Author(s):  
Thomas Larrew ◽  
Mohammed Alshareef ◽  
Robert F. Murphy ◽  
Ramin Eskandari ◽  
Libby Kosnik Infinger
Keyword(s):  
Remote Control ◽  
Ex Vivo ◽  
Shunt Valve ◽  
Growing Rods ◽  
Growing Rod ◽  
Before And After ◽  
Magnetically Controlled Growing Rods ◽  
Ex Vivo Study

OBJECTIVEAlthough the advent of magnetic growing rod technology for scoliosis has provided a means to bypass multiple hardware lengthening operations, it is important to be aware that many of these same patients have a codiagnosis of hydrocephalus with magnet-sensitive programmable ventricular shunts. As the magnetic distraction of scoliosis rods has not previously been described to affect the shunt valve setting, the authors conducted an investigation to characterize the interaction between the two devices.METHODSIn this ex vivo study, the authors carried out 360 encounters between four different shunt valve types at varying distances from the magnetic external remote control (ERC) used to distract the growing rods. Valve settings were examined before and after every interaction with the remote control to determine if there was a change in the setting.RESULTSThe Medtronic Strata and Codman Hakim valves were found to have setting changes at distances of 3 and 6 inches but not at 12 inches. The Aesculap proGAV and Codman Certas valves, typically described as MRI-resistant, did not have any setting changes due to the magnetic ERC regardless of distance.CONCLUSIONSAlthough it is not necessary to check a shunt valve after every magnetic distraction of scoliosis growing rods, if there is concern that the magnetic ERC may have been within 12 inches (30 cm) of a programmable ventricular shunt valve, the valve should be checked at the bedside with a programmer or with a skull radiograph along with postdistraction scoliosis radiographs.

Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)

2016 ◽  
Vol 16 (12) ◽  
pp. 1615-1621 ◽  
Author(s):  
Erik Andrade-Jorge ◽  
Marycarmen Godínez-Victoria ◽  
Luvia Enid Sánchez-Torres ◽  
Luis Humberto Fabila-Castillo ◽  
José G. Trujillo-Ferrara
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Leukemia Cells ◽  
Ex Vivo Study ◽  
Murine Leukemia
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