Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury

Background Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury Methods C57Bl/6 mice were exposed to aerosolized LPS (500 mu g/ml) for 30min and treated with Aspirin (100 mu g/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5 mu g/g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury

Chemical design of non-ionic polymer brushes as biointerfaces : poly(2-oxazine)s outperform both poly(2-oxazoline)s and PEG

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation

Mixing Poly(ethylene glycol) and Poly(2-alkyl-2-oxazoline)s Enhances Hydration and Viscoelasticity of Polymer Brushes and Determines Their Nanotribological and Antifouling Properties

ISSN:1944-8244ISSN:1944-825

The hierarchical bulk molecular structure of poly(acrylamide) hydrogels: beyond the fishing net

The polymeric structure of hydrogels is commonly presented in the literature as resembling a fishing net. However, this simple view cannot fully capture all the unique properties of these materials. Crucial for a detailed description of the bulk structure in free-radical polymerized vinylic hydrogels is a thorough understanding of the cross-linker distribution. This work focuses on the precise role of the tetra-functional cross-linker in the hydrogel system: acrylamide-N,N′-methylenebis(acrylamide). Clusters of crosslinker smaller than 4 nm and their agglomerates, as well as polymer domains with sizes from the 100 nm to the μm-range, have been identified by means of both X-ray and visible-light scattering. Placed in the context of the extensive literature on this system, these observations demonstrate the heterogeneous organisation of the polymer within the hydrogel network structure, and can be accounted for by the different polymerization behavior of the monomer and crosslinker. Together with polymer-network chain-length approximations based on swelling experiments and structural observations with scanning electron microscopy, these results indicate a hierarchical structure of the polymer network surrounding pockets of water.ISSN:1744-683XISSN:1744-684

Structuring Hydrogel Surfaces for Tribology

Hydrogels are often used as model systems for articular cartilage due to similarities in their tribological properties. However, neither the structures nor the friction mechanisms of either system are fully understood. A key aspect of hydrogel lubrication is the nature of the polymeric structure at the surface, and the lubricating water film. A combination of neutron reflectometry and infrared spectroscopy is used to probe polymer volume fraction from the interface into the bulk hydrogel and its dependence on the molding material. The depth dependence of the polymer‐network density influences the compressibility of the hydrogel surfaces, as demonstrated by both atomic force microscopy (AFM)‐ and micro indentation. By changing molding materials, substantial differences in the gradient of polymer‐network density are observed with depth. The lower the volume fraction of polymer at the hydrogel surface, the more water it can maintain at its interface as a substantial water film that is stable even under static conditions. Such films render the hydrogel highly lubricious, with a speed‐independent friction coefficient of μ = 0.01, measured in gemini contact. This result provides experimental evidence that the presence of these highly lubricious water films is strongly dependent on the polymer‐network structure at the surface.ISSN:2196-735

Expression of platelet-derived chemokines (CCL5 (RANTES) and CXCL4 (PF4)) and NET release.

<p>Mice were challenged with LPS via inhalation and sacrificed 4 hours later. Mice were treated with tirofiban ((0.5μg/ g bodyweight via tail vein injection) 30 min before or 1 hour after LPS exposure as indicated or with aspirin (100μg/g bodyweight via intraperitoneal injection) 30 min before or 1 hour after LPS exposure as indicated. <b>A:</b> Plasma concentration of PF4 (CXCL4) after treatment as indicated. <b>B:</b> Plasma concentration of CCL5 after treatment as indicated. <b>C and D:</b> NET formation in the plasma (<b>C</b>) and supernatant of the lyzed lung (<b>D</b>). Values are presented as percentage increase of absorbance in comparison to the control group. n = 6–8 for each bar. * indicates significant difference compared to LPS-treated animals.</p

Aspirin reduces LPS-induced acute lung injury by interference with neutrophil recruitment.

<p>Mice were challenged with LPS via inhalation and sacrificed 4 hours later. Mice were treated with aspirin (100μg/g bodyweight via intraperitoneal injection) 30 min before or 1 hour after LPS exposure as indicated. <b>A:</b> Quantification of alveolar (left), interstitial (middle), and intravascular neutrophils (right) in mice treated as indicated. <b>B:</b> protein concentration (left) and FITC-dextran clearance (right), in BAL fluids in mice treated as indicated. n = 6–8 for each bar. * indicates significant difference compared to LPS-treated animals.</p

Tirofiban displays no protective effect in LPS-induced acute lung injury.

<p>Mice were challenged with LPS via inhalation and sacrificed 4 hours later. Mice were treated with tirofiban ((0.5μg/ g bodyweight via tail vein injection) 30 min before or 1 hour after LPS exposure as indicated. <b>A:</b> Quantification of alveolar (left), interstitial (middle), and intravascular neutrophils (right) in mice treated as indicated. <b>B:</b> protein concentration (left) and FITC-dextran clearance (right), in BAL fluids in mice treated as indicated. n = 6–8 for each bar. * indicates significant difference compared to LPS-treated animals.</p