Results with Artificial Surfactant: Aspects of Morphological Appearance, Surface Activity, and in vivo Activity of Artificial Surfactant1

2015 ◽  
pp. 247-252
Author(s):  
M. Obladen ◽  
H. Schwarz ◽  
E. Kattner ◽  
P. Stevens
Keyword(s):  
Surface Activity ◽  
Morphological Appearance ◽  
Artificial Surfactant

Synthetic surfactant scavenges oxidants and protects against hyperoxic lung injury

1994 ◽  
Vol 77 (3) ◽  
pp. 1217-1223 ◽  
Author(s):  
A. J. Ghio ◽  
P. J. Fracica ◽  
S. L. Young ◽  
C. A. Piantadosi
Keyword(s):  
Thiobarbituric Acid ◽  
Cetyl Alcohol ◽  
Synthetic Surfactant ◽  
Active Components ◽  
Lung Weight ◽  
Hyperoxic Lung Injury ◽  
Surface Active ◽  
Artificial Surfactant

Injury and mortality after exposure to 100% oxygen can be diminished by surfactants that may operate by mechanisms other than those responsible for surface tension effects. We tested the hypotheses that 1) synthetic surfactant and its components function as antioxidants in vitro and 2) decrements in hyperoxic injury after treatment with a surfactant and its components are associated with decreases in oxidative stress to the lung. A synthetic surfactant (Exosurf) and its non-surface-active components tyloxapol and cetyl alcohol were incubated in an iron-containing hydroxyl radical-generating system to determine their abilities to prevent oxidation of deoxyribose. Doses of tyloxapol, cetyl alcohol, and artificial surfactant diminished the absorbance of thiobarbituric acid-reactive products of deoxyribose. Similarly, tyloxapol, cetyl alcohol, and the surfactant decreased hydroxylated products of salicylate in the same system. Rats were instilled intratracheally with saline, tyloxapol, tyloxapol plus cetyl alcohol, or artificial surfactant and immediately exposed to air or 100% oxygen. After 61 h of oxygen exposure, pleural fluid volume and wet-to-dry lung weight ratios were decreased in animals treated with surfactant and/or its components. There were also decrements in thiobarbituric acid-reactive products of lung tissue. In separate experiments, mean survival of saline-treated rats exposed to 100% oxygen was 67.3 +/- 8.1 h and > 96 h for rats given the surfactant or its components. We conclude that tyloxapol, cetyl alcohol, and Exosurf can function as antioxidants in vitro and their in vivo instillation is associated with reduction in measures of hyperoxic injury, oxidized tissue products, and mortality.

Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata

1998 ◽  
Vol 84 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Olga V. Lopatko ◽  
Sandra Orgeig ◽  
Christopher B. Daniels ◽  
David Palmer
Keyword(s):  
Surface Tension ◽  
Surface Properties ◽  
Surface Activity ◽  
Pulmonary Surfactant ◽  
Lung Surfactant ◽  
Lung Compliance ◽  
Equilibrium Surface Tension ◽  
Sminthopsis Crassicaudata

Lopatko, Olga V., Sandra Orgeig, Christopher B. Daniels, and David Palmer. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84(1): 146–156, 1998.—Torpor changes the composition of pulmonary surfactant (PS) in the dunnart Sminthopsis crassicaudata [C. Langman, S. Orgeig, and C. B. Daniels. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol. 40): R437–R445, 1996]. Here we investigated the surface activity of PS in vitro. Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the subphase of a Wilhelmy-Langmuir balance at 20°C and stabilized for 20 min. After 4 h of torpor, the adsorption rate increased, and equilibrium surface tension (STeq), minimal surface tension (STmin), and the %area compression required to achieve STmin decreased, compared with the warm-active group. After 8 h of torpor, STmin decreased [from 5.2 ± 0.3 to 4.1 ± 0.3 (SE) mN/m]; %area compression required to achieve STmindecreased (from 43.4 ± 1.0 to 27.4 ± 0.8); the rate of adsorption decreased; and STeqincreased (from 26.3 ± 0.5 to 38.6 ± 1.3 mN/m). ST-area isotherms of warm-active dunnarts and mice at 20°C had a shoulder on compression and a plateau on expansion. These disappeared on the isotherms of torpid dunnarts. Samples of whole lavage (from warm-active and 8-h torpor groups) containing 100 μg phospholipid/ml were studied by using a captive-bubble surfactometer at 37°C. After 8 h of torpor, STmin increased (from 6.4 ± 0.3 to 9.1 ± 0.3 mN/m) and %area compression decreased in the 2nd (from 88.6 ± 1.7 to 82.1 ± 2.0) and 3rd (from 89.1 ± 0.8 to 84.9 ± 1.8) compression-expansion cycles, compared with warm-active dunnarts. ST-area isotherms of warm-active dunnarts at 37°C did not have a shoulder on compression. This shoulder appeared on the isotherms of torpid dunnarts. In conclusion, there is a strong correlation between in vitro changes in surface activity and in vivo changes in lipid composition of PS during torpor, although static lung compliance remained unchanged (see Langman et al. cited above). Surfactant from torpid animals is more active at 20°C and less active at 37°C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts.

scholarly journals A sulfur-free peptide mimic of surfactant protein B (B-YL) exhibits high in vitro and in vivo surface activities

2018 ◽  
Vol 2 ◽  
pp. 13 ◽  
Author(s):  
Frans J. Walther ◽  
Monik Gupta ◽  
Larry M. Gordon ◽  
Alan J. Waring
Keyword(s):  
Ftir Spectroscopy ◽  
Preterm Infants ◽  
Surface Activity ◽  
High Surface ◽  
Lung Surfactant ◽  
Scale Up ◽  
Free Oxygen Radical ◽  
Α Helix

Background: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B covalently joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B. Here, we studied ‘B-YL’, a 41-residue SMB variant that has its four cysteine and two methionine residues replaced by tyrosine and leucine, respectively, to test whether these hydrophobic substitutions produce a surface-active, α-helix hairpin. Methods: Structure and function of B-YL and SMB in surfactant lipids were compared with CD and FTIR spectroscopy, and surface activity with captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits. Results: CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to SMB in lipids. B-YL in surfactant lipids demonstrated excellent in vitro surface activity and good oxygenation and dynamic compliance in lavaged, surfactant-deficient adult rabbits, suggesting that the four tyrosine substitutions are an effective replacement for the disulfide-reinforced helix-turn of SMB. Here, the B-YL fold may be stabilized by a core of clustered tyrosines linking the N- and C-helices through non-covalent interactions involving aromatic rings. Conclusions: ‘Sulfur-free’ B-YL forms an amphipathic helix-hairpin in surfactant liposomes with high surface activity and is functionally similar to SMB and native SP-B. The removal of the cysteines makes B-YL more feasible to scale up production for clinical application. B-YL’s possible resistance against free oxygen radical damage to methionines by substitutions with leucine provides an extra edge over SMB in the treatment of respiratory failure in preterm infants with RDS.

scholarly journals Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from macromolecular crowding to inhibition

2018 ◽  
Vol 475 (21) ◽  
pp. 3417-3436 ◽  
Author(s):  
Richard Berwick ◽  
David J. Vaux ◽  
Létitia Jean
Keyword(s):  
Molecular Mass ◽  
Surface Activity ◽  
Type Ii Diabetes ◽  
Volume Fraction ◽  
Macromolecular Crowding ◽  
Monomer Concentration ◽  
Vinyl Pyrrolidone ◽  
Bulk Solution ◽  
Type Ii

Deposition of misfolded amyloid polypeptides, associated with cell death, is the hallmark of many degenerative diseases (e.g. type II diabetes mellitus and Alzheimer's disease). In vivo, cellular and extracellular spaces are occupied by a high volume fraction of macromolecules. The resulting macromolecular crowding energetically affects reactions. Amyloidogenesis can either be promoted by macromolecular crowding through the excluded volume effect or inhibited due to a viscosity increase reducing kinetics. Macromolecular crowding can be mimicked in vitro by the addition of non-specific polymers, e.g. Ficoll, dextran and polyvinyl pyrrolidone (PVP), the latter being rarely used to study amyloid systems. We investigated the effect of PVP on amyloidogenesis of full-length human islet amyloid polypeptide (involved in type II diabetes) using fibrillisation and surface activity assays, ELISA, immunoblot and microscale thermophoresis. We demonstrate that high molecular mass PVP360 promotes amyloidogenesis due to volume exclusion and increase in effective amyloidogenic monomer concentration, like other crowders, but without the confounding effects of viscosity and surface activity. Interestingly, we also show that low molecular mass PVP10 has unique inhibitory properties as inhibition of fibril elongation occurs mainly in the bulk solution and is due to PVP10 directly and strongly interacting with amyloid species rather than the increase in viscosity typically associated with macromolecular crowding. In vivo, amyloidogenesis might be affected by the properties and proximity of endogenous macromolecular crowders, which could contribute to changes in associated pathogenesis. More generally, the PVP10 molecular backbone could be used to design small compounds as potential inhibitors of toxic species formation.

A Synthetic Segment of Surfactant Protein A: Structure, in Vitro Surface Activity, and in Vivo Efficacy

1996 ◽  
Vol 39 (6) ◽  
pp. 938-946 ◽  
Author(s):  
Frans J Walther ◽  
Remedios David-Cu ◽  
Carol Leung ◽  
Roberta Bruni ◽  
José Hernández-Juviel ◽  
...  
Keyword(s):  
Surface Activity ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
In Vivo Efficacy

Immunomodulatory Drugs (Thalidomide and Lenalidomide) Up-Regulate Endothelial Tissue Factor in Vitro Resulting in An Acquired Hypercoagulable State.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1893-1893
Author(s):  
Serena Valsami ◽  
Maria Sybille Leikauf ◽  
Jerzy Madon ◽  
Wolfram Ruf ◽  
Lars M Asmis
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Surface Activity ◽  
Hypercoagulable State ◽  
Immunomodulatory Drugs ◽  
Whole Cell ◽  
Cell Lysates ◽  
Micro Particles ◽  
Inflammatory Conditions

Abstract Background: The immunomodulatory drugs (IMIDs), thalidomide and lenalidomide, are considered first line treatments for multiple myeloma and are being investigated for an expanding range of indications including myelodysplastic syndrome, chronic lymphocytic leukaemia, and other B-Cell malignancies. One of the adverse effects of IMIDs are venous thromboembolic events (VTE). Tissue factor (TF) is the cellular receptor for clotting factor VII/VIIa and plays a central role in the initiation of coagulation in vivo. Presently there is no consensus regarding the optimal thromboprophylaxis strategy in IMID treated patients. We hypothesize that in the presence of an inflammatory stimulus IMIDs induce a hypercoagulable state through increased endothelial TF expression and activity. Materials and Methods: Commercially available endothelial cells (HUVEC) were cultured to subconfluent conditions and incubated with thalidomide, lenalidomide or vector control (DMSO) under inflammatory conditions induced by TNFα (10ng/ml). Drug concentrations used were similar to therapeutic human plasma levels. The following parameters were evaluated: TF procoagulant surface activity (colorimetric assay), TF antigen in whole cell lysates (ELISA), and TF mRNA (real time-PCR). Each experiment was repeated at least 3 times. Neutralizing anti TF antibodies were used as a quality control for the functional TF assay. To investigate endothelial cell derived “micro”particles culture supernatants were first centrifuged for 10 minutes at 300g to remove detached whole cells. The resulting supernatant was centrifuged twice at 17000 g for 30min to precipitate potential “micro”particles. Size and surface markers of resuspended particles were investigated by flow cytometry. Results: In the presence of inflammatory conditions (TNFα 10 ng/ml) IMIDs, thalidomide and lenalidomide (both tested at 0.5μM), increase surface related TF activity by 31% and 16% respectively (p<0.01, Wilcoxon test) compared to inflammatory baseline levels. IMID induced increased TF activity could be specifically inhibited by a cocktail of two monoclonal anti TF antibodies. These findings suggest that TF protein accounts for >95% of the TF activity we observed. TF antigen estimated in whole cell lysates was upregulated by 26% by thalidomide and 24% by lenalidomide (vs TNFα treated cells). To evaluate whether the observed TF surface activity and antigen up-regulation was due to a possible effect of IMIDs on TF gene transcription, TF mRNA was measured by RT-PCR after one and six hours. Compared to TNFα treated cells thalidomide and lenalidomide increased TF mRNA by 53 and 33% at one hour while at six hours the corresponding values were 17 and 18% respectively. Cell culture media from TNF, thalidomide and lenalidomide treated cells contained precipitable particles that when resuspended showed TF activity while media from control cells lacked such activity. Conclusions: Under inflammatory conditions thalidomide and lenalidomide lead to increased endothelial cell TF synthesis, increased TF antigen and increased activity of surface bound TF. We furthermore detected increased endothelial derived “micro”particles with TF activity indicating an overall increased turnover and shedding of endothelial TF. Our findings need to be reproduced in vivo but may provide insights into the hypercoaglubale state observed in patients treated with IMIDs und thus may be utile in designing efficient thromboprophylaxis strategies.

Altered function of pulmonary surfactant in fatty acid lung injury

1990 ◽  
Vol 69 (3) ◽  
pp. 1143-1149 ◽  
Author(s):  
S. B. Hall ◽  
R. H. Notter ◽  
R. J. Smith ◽  
R. W. Hyde
Keyword(s):  
Fatty Acid ◽  
Lung Injury ◽  
Surface Activity ◽  
Pulmonary Surfactant ◽  
Free Fraction ◽  
Phospholipid Content ◽  
Pulmonary Mechanics ◽  
Polymorphonuclear Cells

To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids.

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