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Osmotic dehydration of replacement lung surfactant: Implications for ARDS therapy.

Ngo, An Thien (2005) Osmotic dehydration of replacement lung surfactant: Implications for ARDS therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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The potentially fatal condition of Acute Respiratory Distress Syndrome (ARDS) begins with damage to the lung, which then becomes flooded with fluid rich in serum protein. These serum proteins inactivate the lung surfactant (LS) that lines the alveoli, raising alveolar surface tension and resulting in lung collapse. Previous studies have shown that the addition of nonionic polymers to therapeutic replacement lung surfactant (RLS) restores the surface activity of RLS in the presence of inactivating substances, a possible explanation being the dehydration of RLS vesicles by polymer-induced depletion forces. This study tested the hypothesis that RLS whose surface activity responds to the addition of polymer will also experience dehydration upon application of known osmotic stress. The interlamellar spacing (d) of the porcine extract RLS Curosurf and the synthetic RLS Exosurf was measured using small-angle X-ray scattering in the presence of polymer and/or bovine serum albumin (BSA) at various concentrations. Polymers used were polyethylene glycol (PEG, 10 or 20 kDa) and 150 kDa Dextran. The applied osmotic pressures were 10^0 - 10^8 dynes/cm^2. Over this range of pressures, Curosurf experiences a 50Å change in d that fits an exponential curve with decay constant of 7.22 ± 0.23 Å, similar to the Debye length in 150 mM solution. This may indicate the presence of electrostatic interactions. The Exosurf d lie within a range of 59-72 Å but exhibit no definite trend. These results suggest that added polymer in the concentrations utilized would not improve the surface activity of Exosurf, but that osmotic stress may indeed be a mechanism by which polymers restore the function of inactivated Curosurf. To investigate the effect of PEG on the surface activity of Exosurf, pressure-area isotherms of Exosurf spread from chloroform on 150 mM NaCl, 5 mM CaCl2, 1.5 mM tris-HCl, pH 7.2-7.4, were recorded at 24.5ºC in the presence and absence of 5% PEG (m.w. 10 kDa) and 2 mg/mL BSA. Upon repeated compressions of Exosurf on 5% PEG solution, a decrease in the length of the fluid-condensed phase coexistence region in the isotherm suggested the dissolution of Tyloxapol into the subphase.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Ngo, An
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWaldeck, David H.dave@pitt.eduDAVE
Committee MemberWalker, Gilbert
Committee MemberWeber, Stephen G.sweber@pitt.eduSWEBER
Date: 7 June 2005
Date Type: Completion
Defense Date: 16 December 2004
Approval Date: 7 June 2005
Submission Date: 16 January 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: air-water interface; Langmuir trough; lipid membrane; multilamellar vesicle; phase transition; polymer brush configuration; tyloxapol
Other ID:, etd-01162005-163022
Date Deposited: 10 Nov 2011 19:31
Last Modified: 15 Nov 2016 13:36


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