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BackgroundExposure to environmental tobacco smoke (ETS) leads to higher rates of pulmonary diseases and infections in children. To study the biochemical changes that may precede lung diseases, metabolomic effects on fetal and maternal lungs and plasma from rats exposed to ETS were compared to filtered air control animals. Genome- reconstructed metabolic pathways may be used to map and interpret dysregulation in metabolic networks. However, mass spectrometry-based non-targeted metabolomics datasets often comprise many metabolites for which links to enzymatic reactions have not yet been reported. Hence, network visualizations that rely on current biochemical databases are incomplete and also fail to visualize novel, structurally unidentified metabolites.ResultsWe present a novel approach to integrate biochemical pathway and chemical relationships to map all detected metabolites in network graphs (MetaMapp) using KEGG reactant pair database, Tanimoto chemical and NIST mass spectral similarity scores. In fetal and maternal lungs, and in maternal blood plasma from pregnant rats exposed to environmental tobacco smoke (ETS), 459 unique metabolites comprising 179 structurally identified compounds were detected by gas chromatography time of flight mass spectrometry (GC-TOF MS) and BinBase data processing. MetaMapp graphs in Cytoscape showed much clearer metabolic modularity and complete content visualization compared to conventional biochemical mapping approaches. Cytoscape visualization of differential statistics results using these graphs showed that overall, fetal lung metabolism was more impaired than lungs and blood metabolism in dams. Fetuses from ETS-exposed dams expressed lower lipid and nucleotide levels and higher amounts of energy metabolism intermediates than control animals, indicating lower biosynthetic rates of metabolites for cell division, structural proteins and lipids that are critical for in lung development.ConclusionsMetaMapp graphs efficiently visualizes mass spectrometry based metabolomics datasets as network graphs in Cytoscape, and highlights metabolic alterations that can be associated with higher rate of pulmonary diseases and infections in children prenatally exposed to ETS. The MetaMapp scripts can be accessed at http://metamapp.fiehnlab.ucdavis.edu.

We present broadband vibrational sum-frequency generation (VSFG) spectra of Langmuir-Blodgett monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and different mixtures of them as model systems of pulmonary surfactants. The systematic study explored the dependence of the vibrational spectra as a function of surface tension and mixture ratio in various polarization combinations. The extremely short acquisition time and the high spectral resolution of our recently developed spectrometer helped minimize sample degradation under ambient conditions throughout the duration of the measurement and allowed the detection of previously unseen vibrational bands with unprecedented signal-to-noise ratio. The dramatically improved capability to record reliable vibrational spectra together with the label-free nature of the VSFG method provides direct access to native lipid structure and dynamics directly in the monolayer. The resulting data deliver quantitative information for structural analysis of multi-component phospholipid monolayers and may aid in the development of new synthetic pulmonary surfactants. [ABSTRACT FROM AUTHOR]

Understanding interactions between inhaled nanoparticles and lung surfactants (LS) present at the air-water interface in the lung, is critical to assessing the toxicity of these nanoparticles. Specifically, in this work, we assess the impact of engineered carbon nanoparticles (ECN) on the ability of healthy LS to undergo reversible collapse, which is essential for proper functioning of LS. Using a Langmuir trough, multiple compression-expansion cycles are performed to assess changes in the surface pressure vs. area isotherms with time and continuous cyclic compression-expansion. Further, theoretical analysis of the isotherms is used to calculate the ability of these lipid systems to retain material during monolayer collapse, due to interactions with ECNs. These results are complemented with fluorescence images of alterations in collapse mechanisms in these monolayer films. Four different model phospholipid systems, that mimic the major compositions of LS, are used in this study. Together, our results show that the ECN does not impact the mechanism of collapse. However, the ability to retain material at the interface during monolayer collapse, as well as re-incorporation of material after a compression-expansion cycle is altered to varying extent by ECNs and depends on the composition of the lipid mixtures.

The effect of chitin nanoparticles on surface behavior of lipid systems containing dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) is studied by surface pressure (π)-area (A) isotherms, polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS), Brewster angle microscopy (BAM). The variation of surface behavior of DPPC/DPPG monolayers is induced mainly by electrostatic interactions between nanoparticles and head groups of phospholipids. At lower surface pressure, nanoparticles can penetrate into the monolayers and the positive charges carried by nanoparticles benefits the enrichment of phospholipid molecules at surface, which not only increases the mean molecular area but also hinders the formation of phospholipid liquid-condensed (LC) phase. However, when surface pressure is higher, the nanoparticles flee away from the surface and some of the phospholipid molecules are pulled out of the monolayers together to the subphase and decrease the order degree of the monolayers. Moreover, nanoparticles can destroy the hydrogen-bond between water molecules and phosphate head groups and thus lead to the dehydration of phosphate groups. This work confirms that chitin nanoparticles can affect the surface behavior of DPPC/DPPG monolayers. Furthermore, the results obtained using mixed monolayer containing two major lung surfactants DPPC/DPPG and nanoparticles will be helpful for deep understanding the harm of PM2.5 to lung health. [ABSTRACT FROM AUTHOR]

To the Editor, We have read, with great interest, the Letter to the Editor by Grotberg et al.(2017), which puts forward reduced alveolar delivery as the major cause of the unexpectedly disappointing results of phase III, multi-center, controlled clinical trials of surfactant therapy in adults with acute respiratory distress syndrome (ARDS). We do hope that this will fuel a long-anticipated discussion on the causes of the failure of surfactant therapy for ARDS, despite abundant evidence from animal models with ARDS and some clinical trials that surfactant therapy is efficacious.

• A mixed mode DSPE approach was developed using organic polymers. • The method was used to lung surfactants determination in EBC samples. • Density functional theory calculations were used to show the nature of the chemical interactions. • Simplex centroid experimental design was used for optimization of the sorbent composition. A mixed mode dispersive solid phase extraction method was introduced for the extraction of three lung surfactants from exhaled breath condensate samples. Considering the trends to green analytical chemistry, organic polymers including polystyrene (PS), polymethylmethacrylate (PMMA-15 K), and polymethylmethacrylate (PMMA-45 K) were utilized as the sorbent for extraction of the analytes. The extraction capability for each polymer toward the studied analytes was evaluated using simplex centroid design. Based on the results, a mixture of sorbents consisting of PS, PMMA-15 K, and PMMA-45 K mixture with the mass ratio of 1:2:1: w/w/w was selected as the suitable sorbent. The effective parameters influencing the method's efficiency were investigated and optimized. Based on the figure of merit for the developed method, the calibration curves were linear in the concentration range of 0.76–1000 ng mL–1 and limits of detection were from 0.09 to 0.19 ng mL–1. The method repeatability was investigated at three concentrations as inter- and intra-day precisions and the obtained data showed that they were in the ranges of 5.2–9.1 and 4.2–8.9%, respectively. The enrichment factors were in the range of 88–100. The developed method was successfully employed in the analysis of the surfactants in the exhaled breath samples of three premature infants collected from the expiratory circuits of the mechanical ventilators. The nature of the chemical interactions with PMMA-PS complex system of the surfactants was investigated through Density Functional Theory calculations. Calculated binding energies showed that PMMA-PS complex system exhibit high performance in the extraction of lung surfactants. The most powerful interaction is between PMMA-PS complex system and 1-palmitoyl-2-oleoylsn‑glycero-3-phosphocholine. [ABSTRACT FROM AUTHOR]

The overall goal of this work is to study the combined effects of Mini-B, a 34 residue synthetic analog of the lung surfactant protein SP-B, and cholesterol, a neutral lipid, on a model binary lipid mixture containing dipalmitolphosphatidylcholine (DPPC) and palmitoyl-oleoyl-phosphatidylglycerol (POPG), that is often used to mimic the primary phospholipid composition of lung surfactants. Using surface pressure vs. mean molecular area isotherms, fluorescence imaging and analysis of lipid domain size distributions; we report on changes in the structure, function and stability of the model lipid-protein films in the presence and absence of varying composition of cholesterol. Our results indicate that at low cholesterol concentrations, Mini-B can prevent cholesterol's tendency to lower the line tension between lipid domain boundaries, while maintaining Mini-B's ability to cause reversible collapse resulting in the formation of surface associated reservoirs. Our results also show that lowering the line tension between domains can adversely impact monolayer folding mechanisms. We propose that small amounts of cholesterol and synthetic protein Mini-B can together achieve the seemingly opposing requirements of efficient LS: fluid enough to flow at the air–water interface, while being rigid enough to oppose irreversible collapse at ultra-low surface tensions. [ABSTRACT FROM AUTHOR]

The number of potential applications of nanosized molecular assemblies such as vesicles, nanocapsules, biodegradable polyester matrix and more complex structures in drug research and nanomedicine is rapidly increasing with the developed technologies to tune and control their bulk and mainly surface properties. For a better understanding of nanoparticle behavior at the membrane interfaces an in vitro study of the mechanisms of loss of mechanical stability and their reorganization on various membrane systems seems indispensable. By using the simplest convenient monolayer models the mechanisms of destabilization and reorganization of various classical or modifi ed nanosized molecular assemblies spread or adsorbed on pure air/water interface or at the preformed model membrane were studied. [ABSTRACT FROM AUTHOR]

Contrast in confocal microscopy of phase-separated monolayers at the air-water interface can be generated by the selective adsorption of water-soluble fluorescent dyes to disordered monolayer phases. Optical sectioning minimizes the fluorescence signal from the subphase, whereas convolution of the measured point spread function with a simple box model of the interface provides quantitative assessment of the excess dye concentration associated with the monolayer. Coexisting liquid-expanded, liquid-condensed, and gas phases could be visualized due to differential dye adsorption in the liquid-expanded and gas phases. Dye preferentially adsorbed to the liquid-disordered phase during immiscible liquid-liquid phase coexistence, and the contrast persisted through the critical point as shown by characteristic circle-to-stripe shape transitions. The measured dye concentration in the disordered phase depended on the phase composition and surface pressure, and the dye was expelled from the film at the end of coexistence. The excess concentration of a cationic dye within the double layer adjacent to an anionic phospholipid monolayer was quantified as a function of subphase ionic strength, and the changes in measured excess agreed with those predicted by the mean-field Gouy-Chapman equations. This provided a rapid and noninvasive optical method of measuring the fractional dissociation of lipid headgroups and the monolayer surface potential. [ABSTRACT FROM AUTHOR]

Abstract: Two novel C16:0 sulfur-linked phosphonolipids (S-lipid and SO2-lipid) and two ether-linked phosphonolipids (C16:0 DEPN-8 and C16:1 UnDEPN-8) were studied for surface behavior alone and in mixtures with purified bovine lung surfactant proteins (SP)-B and/or SP-C. Synthetic C16:0 phosphonolipids all had improved adsorption and film respreading compared to dipalmitoyl phosphatidylcholine, and SO2-lipid and DEPN-8 reached maximum surface pressures of 72mN/m (minimum surface tensions of <1mN/m) in compressed films on the Wilhelmy balance (23°C). Dispersions of DEPN-8 (0.5mg/ml) and SO2-lipid (2.5mg/ml) also reached minimum surface tensions of <1mN/m on a pulsating bubble surfactometer (37°C, 20cycles/min, 50% area compression). Synthetic lung surfactants containing DEPN-8 or SO2-lipid+0.75% SP-B+0.75% SP-C had dynamic surface activity on the bubble equal to that of calf lung surfactant extract (CLSE). Surfactants containing DEPN-8 or SO2-lipid plus 1.5% SP-B also had very high surface activity, but less than when both apoproteins were present together. Adding 10wt.% of UnDEPN-8 to synthetic lung surfactants did not improve dynamic surface activity. Surfactants containing DEPN-8 or SO2-lipid plus 0.75% SP-B/0.75% SP-C were chemically and biophysically resistant to phospholipase A2 (PLA2), while CLSE was severely inhibited by PLA2. The high activity and inhibition resistance of synthetic surfactants containing DEPN-8 or SO2-lipid plus SP-B/SP-C are promising for future applications in treating surfactant dysfunction in inflammatory lung injury. [Copyright &y& Elsevier]

Abstract: Pulmonary surfactants little affected the release ratio of rifampicin from rifampicin-loaded poly(lactide-co-glycolide) PLGA microspheres. The release ratio of rifampicin was depending on pH of pulmonary surfactant solution, showing that rifampicin-loaded PLGA microspheres have an ideal property to deliver rifampicin into alveolar macrophages inside of which Mycobacterium tuberculosis bacilli reside and to kill them. That is, little amount of rifampicin is released in alveolar lining liquid before the microspheres are phagocytosed by alveolar macrophages, then rifampicin is released in phagosome or cytoplasm, but little amount of rifampicin is released in lysosome of alveolar macrophages after the microspheres are internalized. Pulmonary surfactants also little affected the changes in molecular weight of residual PLGA during its hydrolytic degradation process. From the electrophoretic mobility measurements of PLGA microspheres, it was shown that pulmonary surfactants changed the surface charge density of PLGA microspheres by adsorbing on their surfaces. [Copyright &y& Elsevier]

rSP-C surfactant monolayers spread on a native physiological model substrate show two plateau regions in the π/A-isotherm. The first corresponds to the main phase transition in the monolayer from a LE to a LC phase. Its course is non-horizontal because of the complex composition of the lung surfactant. The second plateau, which is much more pronounced, cannot be attributed to a change of the phase state. Brewster angle microscopy images taken in this region show a sharp apparent decrease of the aggregation degree from the LE to the LC state. This process can be considered as a change in the monolayer orientation relative to the direction of the propagated light. Such a change can be the result of monolayer folding and formation of a thicker layer, which is supported by results of rheological measurements. The dilatation elasticity obtained from oscillating barrier and longitudinal wave measurements reveals a pure elastic behaviour with a steep increase in the second plateau region. Because of the insolubility of the pure lipid components, a possible explanation is squeezing protein components of rSP-C or its complexes with lipids out of the monolayer into the bulk. [Copyright &y& Elsevier]

Understanding interactions between inhaled nanoparticles and lung surfactants (LS) present at the air-water interface in the lung, is critical to assessing the toxicity of these nanoparticles. Specifically, in this work, we assess the impact of engineered carbon nanoparticles (ECN) on the ability of healthy LS to undergo reversible collapse, which is essential for proper functioning of LS. Using a Langmuir trough, multiple compression-expansion cycles are performed to assess changes in the surface pressure vs. area isotherms with time and continuous cyclic compression-expansion. Further, theoretical analysis of the isotherms is used to calculate the ability of these lipid systems to retain material during monolayer collapse, due to interactions with ECNs. These results are complemented with fluorescence images of alterations in collapse mechanisms in these monolayer films. Four different model phospholipid systems, that mimic the major compositions of LS, are used in this study. Together, our results show that the ECN does not impact the mechanism of collapse. However, the ability to retain material at the interface during monolayer collapse, as well as re-incorporation of material after a compression-expansion cycle is altered to varying extent by ECNs and depends on the composition of the lipid mixtures. [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation., Methods: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4  °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. The severity of ALI was evaluated by lung weight/body weight ratio, lung histopathological score, serum nitric oxide (NO) and endothelin (ET)-1 levels, lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography., Results: With extended donor liver cold preservation time (CPT), lung histopathological scores, serum ET-1 levels, lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21, P < 0.001; 343.59 ± 53.97 vs 141.53 ± 48.48, P < 0.001; 0.00687 ± 0.00037 vs 0.00557 ± 0.00056, P < 0.001; 17.5 ± 3.0 vs 1.3 ± 0.3, P < 0.001; 10.8 ± 2.3 vs 1.8 ± 0.4, P < 0.001), but serum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18, P < 0.001). The expression of lung phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was < 120 min, and decreased when CPT was > 180 min (PC: 1318.89 ± 54.79 vs 1011.18 ± 59.99, P < 0.001; PE: 1504.45 ± 119.96 vs 1340.80 ± 76.39, P = 0.0019; PI: 201.23 ± 34.82 vs 185.88 ± 17.04, P = 0.2265; PS: 300.43 ± 32.95 vs 286.55 ± 55.55, P = 0.5054). All these ALI-associated indexes could be partially reversed by PDTC treatment., Conclusion: Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decompensation stage, and some antioxidants (e.g., PDTC) may reverse the pathological process partially.