Miller, Richard H.
(2012)
Albumin in Artificial Liver Support Systems.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
While liver transplantation is the only accepted therapy for liver failure, bound solute dialysis (BSD) may provide an alternative. Current BSD methods, MARS and SPAD, are unfortunately poorly characterized. The studies presented here address basic questions involved in making BSD effective. First, Biacore surface plasmon resonance (SPR) was used to measure binding and reaction rate constants of albumin-solute pairs relevant to designing and testing BSD systems. Much is known about albumin equilibrium binding properties, but little is known regarding albumin-solute binding kinetics. Additionally, testing and clinical application of BSD systems are often done at different temperatures (i.e. room temperature (22°C) and body temperature (37°C)), and changes in reaction rates and binding constants with temperature need to be considered. Human and bovine serum albumin were immobilized on Biacore sensor chip surfaces, and reacting solutes (bilirubin, FK506, cyclosporine A, cholate, deoxycholate, and glycocholate) flowed across the surfaces. The SPR response was tracked during the association and dissociation of the albumin-solute complex. Reactions were performed at 22°C and 37°C. Equilibrium constants consistent with previously reported values and reaction rates were determined for all reactions tested except cyclosporine A. Second, I developed a mathematical model describing the removal of albumin bound solutes using BSD that incorporates albumin-solute reaction kinetics. Previous BSD models focused on the amount of binder in the dialysate, ultrafiltration, and the use of solid adsorbents. The new model relaxes the assumption of reaction equilibrium built into previous BSD models. For a given equilibrium binding constant and set of mass transport parameters, the model was solved for several reaction rates. In all cases tested, the equilibrium BSD model overestimated removal compared to the kinetic model, but the kinetic model displayed greater numerical instability. A third project explored methods to direct visualize protein deposition in and on commercial dialysis membranes during use. A novel slide dialyzer design incorporating commercial renal dialyzer membranes was developed and tested.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
26 September 2012 |
| Date Type: |
Publication |
| Defense Date: |
3 July 2012 |
| Approval Date: |
26 September 2012 |
| Submission Date: |
6 July 2012 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
163 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Chemical Engineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
ALSS, ALF, ACLF, tacrolimus, OLTx, Matlab |
| Date Deposited: |
26 Sep 2012 15:09 |
| Last Modified: |
19 Dec 2016 14:38 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/12733 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}