Kinetic modelling for distribution and removal of plasma proteins with altered biological behaviour in vivo

1984 ◽  
pp. 71-86
Author(s):  
F. Vitek ◽  
G. Mariani ◽  
R. Bianchi
Keyword(s):  
Plasma Proteins ◽  
Kinetic Modelling ◽  
Biological Behaviour

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

scholarly journals Unraveling the In Vivo Protein Corona

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Johanna Simon ◽  
Gabor Kuhn ◽  
Michael Fichter ◽  
Stephan Gehring ◽  
Katharina Landfester ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Ex Vivo ◽  
Protein Corona ◽  
Blood Proteins ◽  
Therapeutic Application ◽  
Complex Situation ◽  
Ex Vivo Approach ◽  
In Vivo Administration

Understanding the behavior of nanoparticles upon contact with a physiological environment is of urgent need in order to improve their properties for a successful therapeutic application. Most commonly, the interaction of nanoparticles with plasma proteins are studied under in vitro conditions. However, this has been shown to not reflect the complex situation after in vivo administration. Therefore, here we focused on the investigation of magnetic nanoparticles with blood proteins under in vivo conditions. Importantly, we observed a radically different proteome in vivo in comparison to the in vitro situation underlining the significance of in vivo protein corona studies. Next to this, we found that the in vivo corona profile does not significantly change over time. To mimic the in vivo situation, we established an approach, which we termed “ex vivo” as it uses whole blood freshly prepared from an animal. Overall, we present a comprehensive analysis focusing on the interaction between nanoparticles and blood proteins under in vivo conditions and how to mimic this situation with our ex vivo approach. This knowledge is needed to characterize the true biological identity of nanoparticles.

Apoptosis, cell proliferation and in vivo biological behaviour of primary and metastatic tumour cells of an AKR lymphoma variant

APOPTOSIS ◽  
1997 ◽  
Vol 2 (2) ◽  
pp. 214-220 ◽  
Author(s):  
N. Donin ◽  
D. Katzenelson ◽  
J. Ravia ◽  
J. Hiss ◽  
G. Schiby ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumour Cells ◽  
Metastatic Tumour ◽  
Biological Behaviour

scholarly journals Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon

2021 ◽  
Author(s):  
Shensheng Zhao ◽  
Sebastiaan Wesseling ◽  
Bert Spenkelink ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
Kinetic Modelling ◽  
Ache Inhibition ◽  
Response Curves ◽  
Alternative Testing ◽  
Dose Response Curves ◽  
Physiologically Based Kinetic Modelling ◽  
Point Of Departure

AbstractThe present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration–response curves for AChE inhibition obtained in the current study to predicted in vivo dose–response curves. The predicted dose–response curves for rat matched available in vivo data on AChE inhibition, and the benchmark dose lower confidence limits for 10% inhibition (BMDL10 values) were in line with the reported BMDL10 values. Humans were predicted to be 6-fold more sensitive than rats in terms of AChE inhibition, mainly because of inter-species differences in toxicokinetics. It is concluded that the TEF-coded DZN PBK model combined with quantitative in vitro to in vivo extrapolation (QIVIVE) provides an adequate approach to predict RBC AChE inhibition upon acute oral DZN exposure, and can provide an alternative testing strategy for derivation of a point of departure (POD) in risk assessment.

scholarly journals Analysis of free and protein-bound nitrotyrosine in human plasma by a gas chromatography/mass spectrometry method that avoids nitration artifacts

2000 ◽  
Vol 345 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Matthew T. FROST ◽  
Barry HALLIWELL ◽  
Kevin P. MOORE
Keyword(s):  
Reactive Nitrogen Species ◽  
Plasma Proteins ◽  
Biological Fluids ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Gas Chromatography Mass Spectrometry ◽  
Highly Sensitive ◽  
Acidic Conditions ◽  
First Time

Measurement of nitrotyrosine in biological fluids and tissues is increasingly being used to monitor the production of reactive nitrogen species in vivo. The detection of nitrotyrosine in vivo has been reported with the use of a variety of methods including immunoassay, HPLC and GLC/MS. The validity of HPLC and immunoassays have been questioned with regard to their selectivity and sensitivity limits. In principle, the measurement of nitrotyrosine by GLC/MS permits a highly specific, highly sensitive and fully quantitative assay. The nitration of tyrosine under acidic conditions in the presence of nitrite is well documented. Derivatization for the full quantification of nitrotyrosine by using GLC/MS can lead to the artifactual nitration of tyrosine if performed under acidic conditions in the presence of nitrite. We describe a novel alkaline method for the hydrolysis and derivatization of nitrotyrosine and tyrosine, and demonstrate its applicability to the measurement of plasma concentrations of both free and protein-bound nitrotyrosine and tyrosine. A detection limit of 1 pg for nitrotyrosine and 100 pg for tyrosine has been achieved. Our method allows, for the first time, the analysis of free and protein-bound nitrotyrosine and tyrosine in biological samples. The plasma concentrations (means±S.E.M.) of free tyrosine and nitrotyrosine in eight normal subjects were 12±0.6 μg/ml and 14±0.7 ng/ml respectively. Plasma proteins contained tyrosine and nitrotyrosine at 60.7±1.7 μg/mg and 2.7±0.4 ng/mg respectively.

scholarly journals In vitro and In vivo Assessment of Suitable Reference Region and Kinetic Modelling for the mGluR1 Radioligand [11C]ITDM in Mice

2019 ◽  
Vol 22 (4) ◽  
pp. 854-863 ◽  
Author(s):  
Daniele Bertoglio ◽  
Jeroen Verhaeghe ◽  
Špela Korat ◽  
Alan Miranda ◽  
Leonie wyffels ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Pet Imaging ◽  
Metabotropic Glutamate Receptor ◽  
Kinetic Modelling ◽  
Input Function ◽  
Dependent Manner ◽  
Reference Region ◽  
Suitable Reference

Abstract Purpose This study aimed at investigating binding specificity, suitability of reference region-based kinetic modelling, and pharmacokinetics of the metabotropic glutamate receptor 1 (mGluR1) radioligand [11C]ITDM in mice. Procedures We performed in vivo blocking as well as displacement of [11C]ITDM during positron emission tomography (PET) imaging using the specific mGluR1 antagonist YM-202074. Additionally, we assessed in vitro blocking of [3H]ITDM at two different doses of YM-202074. As an alternative to reference region models, we validated the use of a noninvasive image-derived input function (IDIF) compared to an arterial input function measured with an invasive arteriovenous (AV) shunt using a population-based curve for radiometabolite correction and characterized the pharmacokinetic modelling of [11C]ITDM in the mouse brain. Finally, we also assessed semi-quantitative approaches. Results In vivo blocking with YM-202074 resulted in a decreased [11C]ITDM binding, ranging from − 35.8 ± 8.0 % in pons to − 65.8 ± 3.0 % in thalamus. Displacement was also markedly observed in all tested regions. In addition, in vitro [3H]ITDM binding could be blocked in a dose-dependent manner. The volume of distribution (VT) based on the noninvasive IDIF (VT (IDIF)) showed excellent agreement with the VT values based on the metabolite-corrected plasma input function regardless of the metabolite correction (r2 > 0.943, p < 0.0001). Two-tissue compartmental model (2TCM) was found to be the preferred model and showed optimal agreement with Logan plot (r2 > 0.960, p < 0.0001). A minimum scan duration of 80 min was required for proper parameter estimation. SUV was not reliable (r2 = 0.379, p = 0.0011), unlike the SUV ratio to the SUV of the input function, which showed to be a valid approach. Conclusions No suitable reference region could be identified for [11C]ITDM as strongly supported by in vivo and in vitro evidence of specific binding in all brain regions. However, by applying appropriate kinetic models, [11C]ITDM PET imaging represents a promising tool to visualize mGluR1 in the mouse brain.

Isolation and Characterization of Human Platelet β-Thromboglobulin

1975 ◽  
Author(s):  
D. S. Pepper ◽  
S. Moore ◽  
J. D. Cash
Keyword(s):  
Molecular Weight ◽  
Plasma Proteins ◽  
Human Platelet ◽  
Weight Fraction ◽  
Human Platelets ◽  
Low Molecular Weight ◽  
Purification Procedure ◽  
Isolation And Characterization

The thrombin released products from washed human platelets were separated by filtration on 4% agarose in 0.15 M NaCl. The high molecular weight PF4 complex was dissociated and re-chromatographed in 0.75 M NaCl. The low molecular weight fraction, including β thromboglobulin and a low MW anti-heparin was freed of plasminogen anti-activator by dissociation and chromatography in pH 3.5 pyridine acetic acid. The anti-activator was irreversibly denatured and albumin was removed in the void volume of the column. A more suitable purification procedure for recovery of all activities was affinity chromatography on heparin-agarose. The anti-activator was excluded and could be obtained free of plasma proteins by Sephadex G-200 chromatography. The βTG eluted at 0.3 M NaCl and the low MW anti-heparin at 1.5 M NaCl. The pure βTG (MW 36,000) was injected into rabbits and the resulting antiserum used to produce a radioimmunoassay for the release reaction in vivo.

TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo

1988 ◽  
Vol 254 (1) ◽  
pp. E79-E83
Author(s):  
G. Chaudhuri ◽  
K. A. Steingold ◽  
W. M. Pardridge ◽  
H. L. Judd
Keyword(s):  
Steroid Hormones ◽  
Plasma Proteins ◽  
Steroid Hormone ◽  
Rabbit Serum ◽  
Injection Technique ◽  
Metabolic Clearance ◽  
Adrenal Steroid ◽  
Corticosteroid Binding Globulin

The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of 3H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E2) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction greater than 80%). The extractions of dihydrotestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of [3H]corticosteroid-binding globulin or bovine [3H]albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se.

Sign in / Sign up

Export Citation Format

Share Document