Effective stabilization of per- and polyfluoroalkyl substances (PFAS) precursors in wastewater treatment sludge by surfactant-modified clay.

The application of biosolids or treated sewage sludge containing per- and polyfluoroalkyl substances (PFAS) in agricultural lands and the disposal of sludge in landfills pose high risks to humans and the environment. Although PFAS precursors have not been regulated yet, their potential transformation to highly regulated perfluoroalkyl acids (PFAAs) may enable them to serve as a long-term source and make remediation of PFAAs a continuing task. Therefore, treating precursors in sewage sludge is even more, certainly not less, critical than treating or removing PFAAs. In this study, a green surfactant-modified clay sorbent was evaluated for its efficacy in stabilizing two representative PFAA precursors in sludge, e.g., N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA), in comparison with unmodified clay and powdered activated carbon (PAC). Results showed N-EtFOSAA and 6:2 FTSA exhibited distinct adsorption behaviors in the sludge without sorbents due to their different physicochemical properties, such as hydrophobicity and functional groups. Among the three sorbents, the modified clay reduced the water leachability of N-EtFOSAA and 6:2 FTSA by 91.5% and 95.4%, respectively, compared to controls without amendments at the end of the experiment (47 days). Within the same duration, PAC decreased the water leachability of N-EtFOSAA and 6:2 FTSA by 60.6% and 37.3%, respectively. At the same time, the unmodified clay demonstrated a poor stabilization effect and even promoted the leaching of precursors. These findings suggested that the modified clay had the potential for stabilization of precursors, while negatively charged and/or hydrophilic sorbents, such as the unmodified clay, should be avoided in the stabilization process. These results could provide valuable information for developing effective amendments for stabilizing PFAS in sludge or biosolids. Future research should evaluate the long-term effect of the stabilization approach using actual sludge from wastewater treatment facilities.

Corn Oil-Water Separation: Interfacial Behavior of Extended Surfactant and Glutelin.

The purification and collection of various products from oil/water mixtures are routine procedures. However, the presence of emulsifiers that can displace other surface active components in the mixtures can significantly influence the efficiency of such procedures. Previously, we investigated interfacial mechanisms of zein protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement. In this paper, we further investigated a different class of protein, glutelin, inside corn and proved that glutelin acts as an oil/water emulsifier in an acidic water environment. Furthermore, an extended surfactant's protein disordering and removal ability was tested and compared with a conventional surfactant. An extended surfactant contains a poly(propylene oxide) or poly(propylene oxide)-poly(ethylene oxide) chain inserted between the hydrophilic head and the hydrophobic tail. In this study, a nonlinear optical spectroscopic technique, sum frequency generation (SFG) vibration spectroscopy, was used to study the behavior of glutelin and extended as well as regular surfactants at the corn oil/water or aqueous solution interface. In most cases, the conventional surfactant shows better protein disordering or removal ability than the extended surfactant. However, with the addition of heat and salt to an extended surfactant solution, the experiment resulted in a substantial increase in the extended surfactant's protein disorder or removal ability.

Engine performance and emissions evaluation of surfactant-free B30 biodiesel-diesel/water emulsion as alternative fuel.

Malaysia is one of the top exporters of palm oil, and although currently facing fierce resistance towards palm oil imports in some parts of the globe, one of the ways to utilize this commodity is by increasing palm biodiesel content in local commercial diesel. However, due to the oxygen-rich nature of biodiesel, its utilization suffers from increased nitrogen oxides (NOx) emission compared to conventional diesel. To mitigate this issue and improve diesel engine performance and emissions using biodiesel-diesel blends, this study attempted to investigate implementation of a real-time non-surfactant emulsion fuel supply system (RTES) which produces water-in-diesel emulsion as fuel without surfactants. NOx reducing capability of water-in-diesel produced by RTES has been well documented. Therefore, in this study, 30% biodiesel-diesel (B30) was used as the base fuel while B30-derived emulsions consisting of 10 wt%, 15 wt% and 20 wt% water content were supplied into a 100 kVA, 5.9-L common rail turbocharged diesel engine electric generator. Fuel consumption and exhaust emissions were measured and compared with commercially available Malaysian low grade diesel fuel (D2M). Evidence suggested that emulsified B30 biodiesel-diesel produced by RTES was able to increase brake thermal efficiency (BTE) up to a maximum of 36% and reduce brake specific fuel consumption (BSFC) up to 8.70%. Furthermore, B30 biodiesel-diesel emulsions produced significantly less NOx, carbon monoxide and smoke at high engine load. In conclusion, B30 biodiesel-diesel emulsions can be readily utilized in current diesel engines without compromising on performance and emissions.

Surfactant-enhanced bioremediation of petroleum-contaminated soil and microbial community response: A field study.

Surfactant-enhanced bioremediation (SEBR) is frequently employed to clean up soil polluted with petroleum hydrocarbons, but few studies have focused on how surfactants affect microbial communities and different fractions of petroleum hydrocarbons, particularly in the field. Here, the surfactants sodium dodecyl benzene sulfonate (SDBS), alpha olefin sulfonate (AOS), Triton X-100 (TX-100), Tween80, and rhamnolipid were combined with the oil-degrading bacterium Pseudomonas sp. SB to remediate oil-contaminated soil in the laboratory. AOS gave the highest removal efficiency (65.1%) of total petroleum hydrocarbons (TPHs). Therefore, AOS was used in a field experiment with Pseudomonas sp. SB and the removal efficiency of TPHs and long-chain hydrocarbons C21-C40 reached 57.4 and 53.0%, respectively, significantly higher than the other treatments. During bioremediation the addition of Pseudomonas sp. SB significantly stimulated the growth of bacterial genera such as Alcanivorax, Luteimonas, Parvibaculum, Stenotrophomonas, and Pseudomonas and AOS further stimulated the growth of Sphingobacterium, Pseudomonas and Alcanivorax. This study validates the feasibility of surfactant-enhanced bioremediation in the field and partly reveals the mechanism of surfactant-enhanced bioremediation from the perspective of changes in different fractions of petroleum and microbial community dynamics.

How to Regulate the Migration Ability of Emulsions in Micro-Scale Pores: Droplet Size or Membrane Strength?

Micro visualization has become an important means of solving colloid and interface scientific problems in enhanced oil recovery. It can establish a relationship between a series of performance evaluations of an oil-water interface under macroscopic dimensions and the actual application effect in confined space, and more truly and reliably reflect the starting and migration behavior of crude oil or emulsion in rock pores. In this article, zwitterionic surfactant alkyl sulfobetaine (ASB) and anionic extended surfactant alkyl polyoxypropylene sulfate (A145) were employed as flooding surfactants. The macroscopic properties of the surfactant solutions, such as the oil-water interfacial tension (IFT), the interfacial dilational rheology and the viscosity of crude oil emulsions, have been measured. At the same time, we link these parameters with the oil displacement effect in several visual glass models and confirm the main factors affecting the migration ability of emulsions in micro-scale pores. The experimental results show that ASB reduces the IFT through mixed adsorption with crude oil fractions. The flat arrangement of the large hydrophilic group of ASB molecules enhances the interactions between the surfactant molecules on the oil-water interface. Compared with sulfate, betaine has higher interfacial membrane strength and emulsion viscosity. A145 has a strong ability to reduce the IFT against crude oil because of the larger size effect of the PO chains at the oil side of the interface. However, the membrane strength of A145 is moderate and the emulsion does not show a viscosity-increasing effect. During the displacement process, the deformation ability of the front emulsions or oil banks is the main controlling factor of the displacement efficiency, which is determined by the membrane strength and emulsion viscosity. The strong interfacial membrane strength and the high emulsion viscosity are not conducive to the migration of droplets in pore throats and may result in low displacement efficiency.

An Overview on the Treatment of Oil Pollutants in Soil Using Synthetic and Biological Surfactant Foam and Nanoparticles.

Oil-contaminated soil is one of the most concerning problems due to its potential damage to human, animals, and the environment. Nanoparticles have effectively been used to degrade oil pollution in soil in the lab and in the field for a long time. In recent years, surfactant foam and nanoparticles have shown high removal of oil pollutants from contaminated soil. This review provides an overview on the remediation of oil pollutants in soil using nanoparticles, surfactant foams, and nanoparticle-stabilized surfactant foams. In particular, the fate and transport of oil compounds in the soil, the interaction of nanoparticles and surfactant foam, the removal mechanisms of nanoparticles and various surfactant foams, the effect of some factors (e.g., soil characteristics and amount, nanoparticle properties, surfactant concentration) on remediation efficiency, and some advantages and disadvantages of these methods are evaluated. Different nanoparticles and surfactant foam can be effectively utilized for treating oil compounds in contaminated soil. The treatment efficiency is dependent on many factors. Thus, optimizing these factors in each scenario is required to achieve a high remediation rate while not causing negative effects on humans, animals, and the environment. In the future, more research on the soil types, operating cost, posttreatment process, and recycling and reuse of surfactants and nanoparticles need to be conducted.

Applications of functional nanoparticle-stabilized surfactant foam in petroleum-contaminated soil remediation.

Surfactant foam (SF) can be used to remediate petroleum-contaminated soil because of its easy transfer to inhomogeneous and low-permeability formations. Nanoparticles (NPs) not only stabilize SF under extreme conditions but also impart various functions, aiding the removal of petroleum contaminants. This review discusses the stabilization mechanisms of nanoparticle-stabilized SF (NP-SF) as well as the effects of NP size, chargeability, wettability, and NP-to-surfactant ratio on foam stability. SF stabilized by inert SiO2 NPs is most commonly used to remediate soil contaminated with crude oil and diesel. Low dose of SF stabilized by nano zero-valent iron is cost-effective for treating soil contaminated with chlorinated organics and heavy metal ions. The efficiency and recyclability of Al2O3/Fe3O4 NPs in the remediation of diesel and crude oil contamination could be enhanced by applying a magnetic field. This review provides a theoretical basis and practical guidelines for developing functional NP-SF to improve the remediation of petroleum-contaminated soils. Future research should focus on the structural design of photocatalytic NPs and the application of catalytic NP-SF in soil remediation.

Study on Oil Recovery Mechanism of Polymer-Surfactant Flooding Using X-ray Microtomography and Integral Geometry.

Understanding pore-scale morphology and distribution of remaining oil in pore space are of great importance to carry out in-depth tapping of oil potential. Taking two water-wet cores from a typical clastic reservoir in China as an example, X-ray CT imaging is conducted at different experimental stages of water flooding and polymer-surfactant (P-S) flooding by using a high-resolution X-ray microtomography. Based on X-ray micro-CT image processing, 3D visualization of rock microstructure and fluid distribution at the pore scale is achieved. The integral geometry newly developed is further introduced to characterize pore-scale morphology and distribution of remaining oil in pore space. The underlying mechanism of oil recovery by P-S flooding is further explored. The results show that the average diameter of oil droplets gradually decreases, and the topological connectivity becomes worse after water flooding and P-S flooding. Due to the synergistic effect of "1 + 1 > 2" between the strong sweep efficiency of surfactant and the enlarged swept volume of the polymer, oil droplets with a diameter larger than 124.58 µm can be gradually stripped out by the polymer-surfactant system, causing a more scattered distribution of oil droplets in pore spaces of the cores. The network-like oil clusters are still dominant when water flooding is continued to 98% of water cut, but the dominant pore-scale oil morphology has evolved from network-like to porous-type and isolated-type after P-S flooding, which can provide strong support for further oil recovery in the later stage of chemical flooding.

Study on the thermal washing of oily sludge used by rhamnolipid/sophorolipid binary mixed bio-surfactant systems.

Demulsification and crude oil desorption are usually a necessary step for the treatment of oily sludge in the petroleum industry. In this study a binary mixed bio-surfactant (rhamnolipid / sophorolipid, RL/SL) was used to strengthen the removing oil efficiency for oily sludge by thermal washing method. Surface tension values of the single and the mixed surfactants were carried out to investigate the effect of mixing systems on reducing critical micelle concentrations (CMC) value. The models proposed by Clint, Rubingh and Gibbs et al. had been employed to interpret the formation of mixed micelles and synergism and found out in case of the mass ratios of 4:6 the synergism was the strongest in RL and SL mixed surfactant systems, which was selected as the washing agents to treat the oily sludge produced from Huabei oilfield. Through the optimization of oil washing process parameters, the oil removal rate reached the maximum value (95.66%, residual oil rate 1.98%) at the condition of heating temperature of 45 °C, detergents concentration of 500 mg/L, washing time of 3 h, liquid/solid mass ratio of 1:4, stirring speed of 300 r/min, and washing 4 times. The factors affecting the oil washing effect were analyzed from the composition and performance characteristics of oily sludge samples, washing oil system and washing process parameters. The results showed that low oil content of oily sludge, small specific surface area, strong wetting and solubilization of the oil-washing system all can increase the oil-washing effect and the washing time and temperature had a great influence on the oil-washing effect. Compared with the results of other researchers, the oil washing temperature and the concentration of oil washing agent were significantly lower and high oil removal rate and low residual oil rate were obtained in this study. It was confirmed that thermal oil washing method using RT/SL binary bio-surfactant mixing system was proved to a high-efficiency, low-consumption and wide range of applications technology.

Optimization of conditions for a surfactant-producing strain and application to petroleum hydrocarbon-contaminated soil bioremediation.

Petroleum hydrocarbon-contaminated sites have been mainly remediated through the surfactant-enhanced soil leaching method. However, the commonly used chemical surfactants have poor biocompatibility and are prone to form residues in fields. Therefore, the purpose of this research is to establish an effective system of biosurfactant remediation in the field and provide instructions for common bioremediation challenges. First, wild-type Bacillus amyloliquefaciens A3, which produced lipopeptide biosurfactant, was used to improve the production of biosurfactant by atmosphere and room temperature plasma (ARTP) mutagenesis. Second, the mutant 1-24 was selected from a total of 174 mutants due to the outstanding yield. Subsequently, 1-24 was applied in the soil column leaching experiments and removed 45.44% of petroleum hydrocarbons by changing the relevant enzyme activities. Biosurfactant addition and 1-24 inoculation effectively activated a portion of the petroleum hydrocarbons in the soil columns, and 1-24 presented potential as a desired candidate for bioremediation. This is the first report of using ARTP mutagenesis to improve the production of biosurfactants. Simultaneously, we first propose a theoretical system in which the yield of biosurfactant was increased using ARTP mutagenesis for strains and applied the mutants in situ soil bioremediation. This research indicated that the theoretical system was useful in soil columns to simulate field remediation conditions, providing practical references for the bioremediation of contaminated soil.

Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-analyses.

IMPORTANCE: Bronchopulmonary dysplasia (BPD) has multifactorial etiology and long-term adverse consequences. An umbrella review enables the evaluation of multiple proposed interventions for the prevention of BPD. OBJECTIVE: To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020. STUDY SELECTION: Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed in duplicate. Quality of systematic reviews was evaluated using Assessment of Multiple Systematic Reviews version 2, and certainty of evidence was assessed using Grading of Recommendation, Assessment, Development, and Evaluation. MAIN OUTCOMES AND MEASURES: (1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA. RESULTS: A total of 154 systematic reviews evaluating 251 comparisons were included, of which 110 (71.4%) were high-quality systematic reviews. High certainty of evidence from high-quality systematic reviews indicated that delivery room continuous positive airway pressure compared with intubation with or without routine surfactant (relative risk [RR], 0.80 [95% CI, 0.68-0.94]), early selective surfactant compared with delayed selective surfactant (RR, 0.83 [95% CI, 0.75-0.91]), early inhaled corticosteroids (RR, 0.86 [95% CI, 0.75-0.99]), early systemic hydrocortisone (RR, 0.90 [95% CI, 0.82-0.99]), avoiding endotracheal tube placement with delivery room continuous positive airway pressure and use of less invasive surfactant administration (RR, 0.90 [95% CI, 0.82-0.99]), and volume-targeted compared with pressure-limited ventilation (RR, 0.73 [95% CI, 0.59-0.89]) were associated with decreased risk of BPD or mortality at 36 weeks' PMA. Moderate to high certainty of evidence showed that inhaled nitric oxide, lower saturation targets (85%-89%), and vitamin A supplementation are associated with decreased risk of BPD at 36 weeks' PMA but not the competing outcome of BPD or mortality, indicating they may be associated with increased mortality. CONCLUSIONS AND RELEVANCE: A multipronged approach of delivery room continuous positive airway pressure, early selective surfactant administration with less invasive surfactant administration, early hydrocortisone prophylaxis in high-risk neonates, inhaled corticosteroids, and volume-targeted ventilation for preterm neonates requiring invasive ventilation may decrease the combined risk of BPD or mortality at 36 weeks' PMA.

Does antenatal corticosteroid therapy improve neonatal outcomes in late preterm birth?

BACKGROUND: Infants who are born at 340/7 to 366/7 weeks of gestation (late preterm) are at greater risk for respiratory and other neonatal morbidities. The objective of this study was to examine the effects of administration of antenatal corticosteroids (ACSs) to women at risk for late preterm delivery on the incidence of neonatal outcomes. METHODS: This was a prospective cohort study of singleton gestations at risk of imminent delivery between 340/7 and 366/7 weeks. Neonatal outcomes were compared between mothers who received ACS and those who did not. Primary outcome was the rate of composite respiratory morbidity defined as the need for treatment within 72 h of life (continuous positive airway pressure or high flow nasal cannula for least 2 h or supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least four continuous hours or mechanical ventilation). RESULTS: During the 3-year study period, 595 subjects were included in this study, comprising 234 subjects that received ACS and 361 that did not. Administration of ACS significantly reduced the rates of composite respiratory morbidity (adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.40-0.99), the use of CPAP or HFNC for at least 2 h (aOR 0.57, 95% CI 0.35-0.94) and transient tachypnea of newborn (aOR 0.48, 95% CI 0.28-0.82). Neonatal hypoglycemia was more significantly increased in the ACS group compared with controls (aOR 1.64, 95% CI 1.04-2.59). We found no significant between-group differences in the rate of respiratory distress syndrome, surfactant use, need for resuscitation, jaundice requiring phototherapy, admission to neonatal intensive care or special care nursery and duration of hospitalization. CONCLUSION: Administration of ACS during the late preterm period decreased neonatal respiratory complications, however, increased the rate of hypoglycemia.

Interaction in vitro of pulmonary surfactant with antifungal agents used for treatment and prevention of invasive aspergillosis.

BACKGROUND: Optimizing antifungal therapy is important to improve outcomes in severely immunocompromised patients. OBJECTIVES: We analysed the in vitro interaction between pulmonary surfactant and antifungal agents used for management of invasive pulmonary aspergillosis. METHODS: Amphotericin B formulations, mould-active triazoles and echinocandins were tested in vitro against 24 clinical isolates of different Aspergillus spp. with and without the addition of a commercial porcine surfactant (Curosurf®; Poractant alfa, Nycomed, Austria). The data are presented as MIC or minimum effective concentration (MEC) ranges, as MIC or MEC values that inhibited 90% of the isolates (MIC90 or MEC90) and as geometric mean (GM) MIC or MEC values. RESULTS: For amphotericin B products, addition of surfactant to a final concentration of 10% led to a statistically significant reduction of the GM MIC for all Aspergillus isolates tested after 24 h (0.765 versus 0.552 mg/L; P < 0.05). For the mould-active triazoles, addition of 10% surfactant resulted in a significantly higher GM MIC at 48 h (0.625 versus 0.898 mg/L; P < 0.05). For the echinocandins, the addition of 10% surfactant led to a significantly higher GM MEC after both 24 h (0.409 versus 0.6532 mg/L; P < 0.01) and 48 h (0.527 versus 0.9378 mg/L; P < 0.01). There were no meaningful differences between individual members of the three existing classes of antifungal agents or between the different Aspergillus spp. tested. CONCLUSIONS: Using EUCAST methodology, addition of porcine surfactant up to a concentration of 10% had a minor, and presumably non-relevant, impact on the in vitro activity of antifungal agents used in prophylaxis and treatment of invasive pulmonary aspergillosis.

Novel Adjuvant Therapy with Zinc Supplementation in Neonatal Respiratory Distress Syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is a common dangerous chest problem that is caused by a lack of surfactant. AIM: The aim of this study was to show the role of zinc as an adjuvant anti-inflammatory therapy in neonatal RDS. OBJECTIVE: To study the effect of zinc supplementation in cases of neonatal RDS. METHODS: A prospective randomized controlled trial (RCT) study was done on 90 neonates suffering from respiratory distress (RD) who had been diagnosed as RDS. The included neonates were classified into two groups: group 1, which received Zinc (Zn) supplementation, and group 2, which received a placebo. Down score, grades of RDS Malondialdehyde (MDA), Superoxide Dismutase (SOD) andInterleukin-8 (IL-8) were estimated on the 1st and 5th day in the presence of incubators. RESULTS: There were statistically significant differences (SSD) in grades of RDS, Down score, MDA, SOD and IL-8 on the 5th day between group 1 and 2(p = 0.001), and between 1st and 5th day in group 1 (p = 0.001) in the presence of an incubator. There was an SSD between groups 1 and 2 in the duration of hospitalization (p = 0.001) and the number of cases that needed mechanical ventilation (MV) (p = 0.049). CONCLUSION: Zn supplementation is associated with clinical and laboratory improvement in cases of neonatal RDS. RECOMMENDATION: Zn supplementation for RDS neonates.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.

Effect of Nanoparticles on the Bulk Shear Viscosity of a Lung Surfactant Fluid.

Inhaled nanoparticles (<100 nm) reaching the deep lung region first interact with the pulmonary surfactant, a thin lipid film lining the alveolar epithelium. To date, most biophysical studies have focused on particle-induced modifications of the film interfacial properties. In comparison, there is less work on the surfactant bulk properties and on their changes upon particle exposure. Here we study the viscoelastic properties of a biomimetic pulmonary surfactant in the presence of various engineered nanoparticles. The microrheology technique used is based on the remote actuation of micron-sized wires via the application of a rotating magnetic field and on time-lapse optical microscopy. It is found that particles strongly interacting with lipid vesicles, such as cationic silica (SiO2, 42 nm) and alumina (Al2O3, 40 nm) induce profound modifications of the surfactant flow properties, even at low concentrations. In particular, we find that silica causes fluidification, while alumina induces a liquid-to-soft solid transition. Both phenomena are described quantitatively and accounted for in the context of colloidal physics models. It is finally suggested that the structure and viscosity changes could impair the fluid reorganization and recirculation occurring during breathing.

Vitamin A Supplementation by Endotracheal Application of a Nano-encapsulated Preparation Is Feasible in Ventilated Preterm Lambs.

BACKGROUND: Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due to concerns about feasibility and pain. We studied VA kinetics, distribution, and the induction of early genetic expression of retinoid homeostatic genes in the lung after endotracheal and intravenous application in a preterm lamb model. METHODS: Lambs were delivered prematurely after 85% of gestation, intubated, and ventilated for 3 hours. The animals were randomized to receive no VA ("control"), a bolus of VA intravenously ("i.v."), or VA endotracheally directly after administration of surfactant ("e.t."). RESULTS: Animals treated with VA endotracheally directly after administration of surfactant showed significant increases of VA in serum and lung compared to controls. Animals treated with a bolus of VA intravenously showed significant increases of VA in serum, lung, and liver; however, peak serum concentrations and mRNA levels of homeostatic genes raised concerns about toxicity in this group. CONCLUSIONS: Endotracheal VA supplementation in preterm lambs is feasible and might offer advantages in comparison to i.v. Further studies are warranted to explore biological effects in the context of BPD.

Pulmonary toxicity following inhalation exposure to VX in anesthetized rats: Possible roles for compromised immunity and oxidative stress-induced lung injury.

The nerve agent VX is one of the most deadly threat agents available in weapons stockpiles for intentional release. While mostly considered a percutaneous toxicant, it can be fatal when aerosolized. The objective of this study was to investigate toxic responses in the lung up to two weeks following a single 10-minute exposure to inhaled VX. Anesthetized rats were exposed singly and only once to VX. The nebulization rate in this system was 0.2-0.3 ml per minute with the delivery of a consistent particle size of 2.1 µm. Following exposure, all rats were removed from the ventilator and allowed to recover in the glovebox for 10-15 minutes. Results showed that inhaled VX altered several respiratory parameters and caused increased lung resistance up to 6 h post-exposure (PE). There was a trending increase in SOD and xanthine oxidoreductase (XOR) activities, both of which are indicative of oxidative stress. Based on increased lung tissue p38 signaling, MAP kinase expression was activated after VX exposure. IL-6 expression was also increased at 6 h post-inhalation for the 31.6 mg/m3 exposed group. Innate survival response mechanisms in rats may be present due to increased lung tissue mRNA AChE expression 6 h after exposure. Immunohistochemistry showed reduced staining for surfactant D and increased expression of iNOS, indicating that the activation of •NO precursor pathways. Bronchoalveloar lavage fluid (BALF) results from 1 h to 2 weeks PE show that inflammatory cells are highly active as evidenced by the increased production of cytokines and chemokines. This is the first study linking VX-induced lung injury to a possible innate survival amplification of AChE and possibly compromised immune function. These results could supplement medical treatment strategies with regard to therapeutic approaches against VX inhalational challenge.

Novel therapeutic roles for surfactant-inositols and -phosphatidylglycerols in a neonatal piglet ARDS model: a translational study.

The biological and immune-protective properties of surfactant-derived phospholipids and phospholipid subfractions in the context of neonatal inflammatory lung disease are widely unknown. Using a porcine neonatal triple-hit acute respiratory distress syndrome (ARDS) model (repeated airway lavage, overventilation, and LPS instillation into airways), we assessed whether the supplementation of surfactant (S; poractant alfa) with inositol derivatives [inositol 1,2,6-trisphosphate (IP3) or phosphatidylinositol 3,5-bisphosphate (PIP2)] or phosphatidylglycerol subfractions [16:0/18:1-palmitoyloleoyl-phosphatidylglycerol (POPG) or 18:1/18:1-dioleoyl-phosphatidylglycerol (DOPG)] would result in improved clinical parameters and sought to characterize changes in key inflammatory pathways behind these improvements. Within 72 h of mechanical ventilation, the oxygenation index (S+IP3, S+PIP2, and S+POPG), the ventilation efficiency index (S+IP3 and S+POPG), the compliance (S+IP3 and S+POPG) and resistance (S+POPG) of the respiratory system, and the extravascular lung water index (S+IP3 and S+POPG) significantly improved compared with S treatment alone. The inositol derivatives (mainly S+IP3) exerted their actions by suppressing acid sphingomyelinase activity and dependent ceramide production, linked with the suppression of the inflammasome nucleotide-binding domain, leucine-rich repeat-containing protein-3 (NLRP3)-apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-caspase-1 complex, and the profibrotic response represented by the cytokines transforming growth factor-ß1 and IFN-γ, matrix metalloproteinase (MMP)-1/8, and elastin. In addition, IκB kinase activity was significantly reduced. S+POPG and S+DOPG treatment inhibited polymorphonuclear leukocyte activity (MMP-8 and myeloperoxidase) and the production of interleukin-6, maintained alveolar-capillary barrier functions, and reduced alveolar epithelial cell apoptosis, all of which resulted in reduced pulmonary edema. S+DOPG also limited the profibrotic response. We conclude that highly concentrated inositol derivatives and phosphatidylglycerol subfractions in surfactant preparations mitigate key inflammatory pathways in inflammatory lung disease and that their clinical application may be of interest for future treatment of the acute exudative phase of neonatal ARDS.

Intravenous anti-MRSA phosphatiosomes mediate enhanced affinity to pulmonary surfactants for effective treatment of infectious pneumonia.

The aim of this study was to develop PEGylated phosphatidylcholine (PC)-rich nanovesicles (phosphatiosomes) carrying ciprofloxacin (CIPX) for lung targeting to eradicate extracellular and intracellular methicillin-resistant Staphylococcus aureus (MRSA). Soyaethyl morphonium ethosulfate (SME) was intercalated in the nanovesicle surface with the dual goals of achieving strengthened bactericidal activity of CIPX-loaded phosphatiosomes and delivery to the lungs. The isothermal titration calorimetry (ITC) results proved the strong association of SME phosphatiosomes with pulmonary surfactant. We demonstrated a superior anti-MRSA activity of SME phosphatiosomes compared to plain phosphatiosomes and to free CIPX. A synergistic effect of CIPX and SME nanocarriers was found in the biofilm eradication. SME phosphatiosomes were readily engulfed by the macrophages, restricting the intracellular MRSA count by 1-2 log units. SME phosphatiosomes efficiently accumulated in the lungs after intravenous injection. In a rat model of lung infection, the MRSA burden in the lungs could be decreased by 8-fold after SME nanosystem application.