scholarly journals In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor

2020 ◽  
Author(s):  
Shuqi Zhang ◽  
Anita Penkova ◽  
Mark Humayun ◽  
Juan Carlos Martinez-Camarillo ◽  
Abegail C. Tadle ◽  
...  

Abstract In order to measure the effective diffusion coefficient of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the 'contour method' and in vivo OCT measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result. By floating the diffusion coefficient, different theoretical contours were constructed and the least-squares best fit to the experimental contours was performed at each time point to get the best fit solution. The approach generated consistent diffusion coefficient values based on the experiments on four rabbit eyes over a period of 3 hours each, which gave , D=1.2±0.6×(?10?^(-6) ?cm?^2)/s and the corresponding theoretical contours matched well with the experimental contours. The quantitative measurement of concentration using OCT and fluorescein labeling gives a new approach for the "non-contact" in vivo drug distribution measurement within vitreous and other ocular tissues.

2006 ◽  
Vol 188 (17) ◽  
pp. 6115-6123 ◽  
Author(s):  
Michael C. Konopka ◽  
Irina A. Shkel ◽  
Scott Cayley ◽  
M. Thomas Record ◽  
James C. Weisshaar

ABSTRACT The first in vivo measurements of a protein diffusion coefficient versus cytoplasmic biopolymer volume fraction are presented. Fluorescence recovery after photobleaching yields the effective diffusion coefficient on a 1-μm-length scale of green fluorescent protein within the cytoplasm of Escherichia coli grown in rich medium. Resuspension into hyperosmotic buffer lacking K+ and nutrients extracts cytoplasmic water, systematically increasing mean biopolymer volume fraction, <φ>, and thus the severity of possible crowding, binding, and confinement effects. For resuspension in isosmotic buffer (osmotic upshift, or Δ, of 0), the mean diffusion coefficient, <D>, in cytoplasm (6.1 ± 2.4 μm2 s−1) is only 0.07 of the in vitro value (87 μm2 s−1); the relative dispersion among cells, σ D /<D> (standard deviation, σ D , relative to the mean), is 0.39. Both <D> and σ D /<D> remain remarkably constant over the range of Δ values of 0 to 0.28 osmolal. For a Δ value of ≥0.28 osmolal, formation of visible plasmolysis spaces (VPSs) coincides with the onset of a rapid decrease in <D> by a factor of 380 over the range of Δ values of 0.28 to 0.70 osmolal and a substantial increase in σ D /<D>. Individual values of D vary by a factor of 9 × 104 but correlate well with f VPS, the fractional change in cytoplasmic volume on VPS formation. The analysis reveals two levels of dispersion in D among cells: moderate dispersion at low Δ values for cells lacking a VPS, perhaps related to variation in φ or biopolymer organization during the cell cycle, and stronger dispersion at high Δ values related to variation in f VPS. Crowding effects alone cannot explain the data, nor do these data alone distinguish crowding from possible binding or confinement effects within a cytoplasmic meshwork.


1998 ◽  
Vol 35 (5) ◽  
pp. 811-827 ◽  
Author(s):  
P C Lim ◽  
S L Barbour ◽  
D G Fredlund

The role of degree of saturation on the coefficient of diffusion of contaminants in the aqueous phase is presented and theoretical models for predicting the coefficient of diffusion at any degree of saturation are described. Three predictive models were developed based on three different diffusion modes: diffusion in parallel and series arrangements and combination of both. Diffusion tests were conducted on a sand at various water contents ranging from saturation to the residual degree of saturation using potassium and chloride ions as tracers to verify the applicability of the models. Results from the diffusion tests showed a decrease in effective diffusion coefficient of potassium with a decrease in degree of saturation. The functional relationship between the normalized diffusion coefficient for potassium and the degree of saturation is slightly nonlinear. The results for chloride also showed a decreasing trend, although the data were quite scattered and further verification is needed. Model verification based on the results for potassium showed that among the three models proposed, the model which combines the diffusion pathways in parallel and series arrangements provides the best fit to the experimental data.Key words: unsaturated, contaminant transport, aqueous diffusion, degree of saturation.


Author(s):  
Thaís A. de S. Smaniotto ◽  
Osvaldo Resende ◽  
Kelly A. de Sousa ◽  
Daniel E. C. de Oliveira ◽  
Rafael C. Campos

ABSTRACT The objectives of this study were to fit different mathematical models to experimental data of drying of sunflower grains, determine and evaluate the effective diffusion coefficient and obtain the activation energy for the process during the drying under various conditions of air. The sunflower grains were collected with an initial moisture content of 0.5267 dry basis (d.b.) and dried in an oven with forced air ventilation under five temperature conditions: 35, 50, 65, 80 and 95 °C, until reaching the moisture content of 0.0934 ± 0.0061 (d.b.). Among the analyzed models, Wang and Singh showed the best fit to describe the drying phenomenon. The effective diffusion coefficient of sunflower grains increased with the increment in air temperature and has activation energy for liquid diffusion in the sunflower drying of 29.55 kJ mol-1.


2012 ◽  
Vol 550-553 ◽  
pp. 158-163 ◽  
Author(s):  
Zi Yuan Liu ◽  
Sheng Li Chen ◽  
Peng Dong ◽  
Xiu Jun Ge

Through the measured effective diffusion coefficients of Dagang vacuum residue supercritical fluid extraction and fractionation (SFEF) fractions in FCC catalysts and SiO2model catalysts, the relation between pore size of catalyst and effective diffusion coefficient was researched and the restricted diffusion factor was calculated. The restricted diffusion factor in FCC catalysts is less than 1 and it is 1~2 times larger in catalyst with polystyrene (PS) template than in conventional FCC catalyst without template, indicating that the diffusion of SFEF fractions in the two FCC catalysts is restricted by the pore. When the average molecular diameter is less than 1.8 nm, the diffusion of SFEF fractions in SiO2model catalyst which average pore diameter larger than 5.6 nm is unrestricted. The diffusion is restricted in the catalyst pores of less than 8 nm for SFEF fractions which diameter more than 1.8 nm. The tortuosity factor of SiO2model catalyst is obtained to be 2.87, within the range of empirical value. The effective diffusion coefficient of the SFEF fractions in SiO2model catalyst is two orders of magnitude larger than that in FCC catalyst with the same average pore diameter. This indicate that besides the ratio of molecular diameter to the pore diameter λ, the effective diffusion coefficient is also closely related to the pore structure of catalyst. Because SiO2model catalyst has uniform pore size, the diffusion coefficient can be precisely correlated with pore size of catalyst, so it is a good model material for catalyst internal diffusion investigation.


2016 ◽  
Vol 138 (11) ◽  
Author(s):  
Hua Wang ◽  
Xiaoyan Zhang ◽  
Shauna M. Dorsey ◽  
Jeremy R. McGarvey ◽  
Kenneth S. Campbell ◽  
...  

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.


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