Application of Experimental Polystyrene Partition Constants and Diffusion Coefficients to Predict the Sorption of Neutral Organic Chemicals to Multiwell Plates in in Vivo and in Vitro Bioassays

2018 ◽  
Vol 52 (22) ◽  
pp. 13511-13522 ◽  
Author(s):  
Fabian C. Fischer ◽  
Olaf A. Cirpka ◽  
Kai-Uwe Goss ◽  
Luise Henneberger ◽  
Beate I. Escher
Keyword(s):  
Diffusion Coefficients ◽  
Organic Chemicals ◽  
Partition Constants ◽  
In Vitro Bioassays ◽  
And Diffusion ◽  
Multiwell Plates

In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals

2017 ◽  
Vol 36 (7) ◽  
pp. 1934-1946 ◽  
Author(s):  
Yung-Shan Lee ◽  
Justin C. Lo ◽  
S.Victoria Otton ◽  
Margo M. Moore ◽  
Chris J. Kennedy ◽  
...  
Keyword(s):  
Organic Chemicals ◽  
Hydrophobic Organic Chemicals ◽  
In Vivo Extrapolation

Affinity to lectin, biological and immunological characteristics of human chorionic gonadotropins from pregnant women and trophoblastic tumour patients

1986 ◽  
Vol 112 (4) ◽  
pp. 579-585 ◽  
Author(s):  
Koji Koyama ◽  
Kazushi Toda ◽  
Daisaku Kuriyama ◽  
Shinzo Isojima
Keyword(s):  
Affinity Chromatography ◽  
Pregnant Women ◽  
Hydatidiform Mole ◽  
Affinity Column ◽  
Unbound Fraction ◽  
Lentil Lectin ◽  
In Vitro Bioassays ◽  
Trophoblastic Tumours

Abstract. To compare the affinity to lectin of human chorionic gonadotropins (hCG) from pregnant women and trophoblastic tumour patients, a small amount of urine was fractionated by a lentil lectin (LcH) affinity chromatography. The LcH-bound fractions were eluted with 2% mannoside solution, and each fraction was assayed for hCG activities by radioimmunoassay. In pregnant women, more than 90% of hCG immunoactivity in urine was bound to the LcH column and eluted from it, whereas 8 to 26% and 37 to 51% of the activity were not adsorbed to the affinity column and were recovered in the LcH-unbound fraction in the patients with hydatidiform mole and choriocarcinoma, respectively. These results suggest that LcH affinity chromatography of urinary hCG contributes to differential diagnosis between pregnancy and trophoblastic tumours. To characterize the properties of hCG from the urine of choriocarcinoma patients, with or without the LcH affinity, hCG activities in both LcH-unbound and LcH-bound fractions were measured by in vivo and in vitro bioassays and each of the activities was compared with the activities measured by radioimmunoassay. The results showed that the LcH-unbound fraction contained hCG molecules defecting to induce the biological activity of hCG in vivo.

Use of an Enhanced Gradient System for Diffusion MR Imaging with Motion-Artifact Reduction

1995 ◽  
Vol 36 (4-6) ◽  
pp. 662-670 ◽  
Author(s):  
S. Brockstedt ◽  
C. Thomsen ◽  
R. Wirestam ◽  
J. De Poorter ◽  
C. De Wagter ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Diffusion Coefficients ◽  
Pulse Sequence ◽  
Phase Correction ◽  
Gradient System ◽  
Mean Values ◽  
Diffusion Mr ◽  
Diffusion Mr Imaging

Purpose: A spin-echo diffusion-sensitized pulse sequence using high gradients (23 mT/m) is introduced. Material and Methods: In order to minimize motion artefacts, velocity-compensating gradients, ECG-triggering and post-processing with phase correction and raw data averaging using navigator echoes was performed. The in vitro ratio of diffusion coefficients for water and acetone was determined and the water self-diffusion coefficient at different temperatures was evaluated. The pulse sequence was tested in 7 healthy volunteers and in 2 tumour patients with astrocytomas of grades I—II and III—IV. Both single-slice and multi-slice techniques were used. Results: The incorporation of phase correction clearly improved the quality of both diffusion-encoded images and the calculated diffusion maps. Mean values of the diffusion coefficients in vivo were for CSF 2.66×10−9 m2/s and for white and grey matter 0.69×10−9 m2/s and 0.87×10−9 m2/s, respectively. Conclusion: Velocity-compensating gradients in combination with a high gradient strength were shown to be useful for in vivo diffusion MR imaging.

THIOCYANATE ION IN SERUM AS AN INTERFERING FACTOR IN THE IN-VITRO BIOASSAY OF THYROTROPHIN

1973 ◽  
Vol 57 (1) ◽  
pp. 1-6 ◽  
Author(s):  
J. R. BOURKE ◽  
S. W. MANLEY ◽  
R. W. HAWKER
Keyword(s):  
Specific Activity ◽  
Cobalt Nitrate ◽  
Ferric Nitrate ◽  
In Vitro Bioassay ◽  
Rat Serum ◽  
Thiocyanate Ion ◽  
Serum Thiocyanate ◽  
In Vitro Bioassays

SUMMARY The presence of thiocyanate ion in human and rat serum has been shown to account entirely for the non-specific activity of sera in an in-vitro bioassay for thyrotrophin. Thiocyanate was identified by its chromatographic behaviour on Sephadex G-10, G-15 and G-25, and by the ferric nitrate and cobalt nitrate tests. Cigarette smoking increased mean serum thiocyanate levels (as NaSCN) from 0·2 to 0·56 mg/100 ml. It is suggested that serum thiocyanate levels are sufficient to inhibit significantly iodide trapping in vivo and that these findings may be relevant to the non-specific responses observed with other in-vitro bioassays based on radioiodine dynamics.

scholarly journals Activity and Diffusion of Tigecycline (GAR-936) in Experimental Enterococcal Endocarditis

2003 ◽  
Vol 47 (1) ◽  
pp. 216-222 ◽  
Author(s):  
Agnès Lefort ◽  
Matthieu Lafaurie ◽  
Laurent Massias ◽  
Yolande Petegnief ◽  
Azzam Saleh-Mghir ◽  
...  
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Type Strain ◽  
Postantibiotic Effect ◽  
Bacteriostatic Effect ◽  
Elimination Half ◽  
Resistant Mutants ◽  
And Diffusion

ABSTRACT The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 μg/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 μg/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [14C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.

scholarly journals Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Allegra Conti ◽  
Rémi Magnin ◽  
Matthieu Gerstenmayer ◽  
Nicolas Tsapis ◽  
Erik Dumont ◽  
...  
Keyword(s):  
Diffusion Process ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Diffusion Coefficients ◽  
Brain Barrier ◽  
Apparent Diffusion Coefficients ◽  
Blood Brain ◽  
The Brain ◽  
And Diffusion

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their diffusion through in vivo experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from in vitro studies and of apparent diffusion coefficients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and diffusion processes occurring in the brain tissue. This model takes into account acoustic pressure, particle size, blood pharmacokinetics, and diffusion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.

In Vivo and In Vitro Bioassays for Porcine Ovarian Inhibin and Its Partial Purification

2010 ◽  
Vol 8 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Chiaki Yazaki ◽  
Yoshihisa Hasegawa ◽  
Kaoru Miyamoto ◽  
Takashi Minegishi ◽  
Katsumi Yazaki ◽  
...  
Keyword(s):  
Partial Purification ◽  
In Vitro Bioassays ◽  
Ovarian Inhibin

scholarly journals Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists

2019 ◽  
Author(s):  
Maria Lucey ◽  
Philip Pickford ◽  
James Minnion ◽  
Jan Ungewiss ◽  
Katja Schoeneberg ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Receptor Trafficking ◽  
Appetite Suppression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Diffusion

AbstractObjectiveTo determine how pharmacokinetically advantageous acylation impacts on glucagon-like peptide-1 receptor (GLP-1R) signal bias, trafficking, anti-hyperglycaemic efficacy and appetite suppression.MethodsIn vitro signalling responses were measured using biochemical and biosensor assays. GLP-1 receptor trafficking was determined by confocal microscopy and diffusion-enhanced resonance energy transfer. Pharmacokinetics, glucoregulatory effects and appetite suppression were measured in acute, sub-chronic and chronic settings in mice.ResultsA C-terminally acylated ligand, exendin-phe1-C16, was identified with undetectable β-arrestin recruitment and GLP-1R internalisation. Depending on the cellular system used, this molecule was up to 1000-fold less potent than the comparator exendin-asp-3-C16 for cyclic AMP signalling, yet was considerably more effective in vivo, particularly for glucose regulation.ConclusionsC-terminal acylation of biased GLP-1R agonists increases their degree of signal bias in favour of cAMP production and improves their therapeutic potential.

Clot Lysis in a Perfusion System

1966 ◽  
Vol 15 (01/02) ◽  
pp. 205-219
Author(s):  
C. A Bouvier ◽  
J Gruendlinger ◽  
S Berthoud
Keyword(s):  
Aminocaproic Acid ◽  
Clot Lysis ◽  
Fibrin Gel ◽  
Standard Size ◽  
Lysis Time ◽  
Therapeutic Thrombolysis ◽  
And Diffusion ◽  
Diffusion Problems

SummaryMost information on clot lysis is derived from in vitro methods whereby various components of the clotting and fibrinolytic systems are mixed before an actual clot is formed. This situation bears little relationship to thrombolysis in vivo. Therefore several techniques have been recently proposed, in which pre-formed clots are exposed to the effects of active agents by contact and diffusion rather than by intimate mixing prior to clotting. We describe an apparatus whereby a perfusion is delivered at controlled rates to clots of standard size and volume formed in calibrated tubes. The composition of the clots can be varied as well as the rate of perfusion and the content of perfusate. The surface of contact between the fluid and the fibrin gel is kept constant throughout and the clot-perfusate relationship is as close as possible to the in vivo situation during thrombolytic therapy. Under these conditions clot lysis by Streptokinase appears as a linear function of time, and the rate of lysis is directly related to kinase concentration. Since the clot intrinsic plasminogen-proactivator content is sufficient to ensure lysis, the lysis time finally depends upon the rate of diffusion of the kinase into the gel. Inhibition obtained with various amounts of E-aminocaproic acid incorporated to the clots or added to the perfusion fluid also suggests that diffusion problems are of major importance in physiological and therapeutic thrombolysis.

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