New Synthetic Surfactants – Basic Science

Curstedt, Tore; Johansson, Jan

doi:10.1159/000084881

Cited by 27 publications

(19 citation statements)

References 78 publications

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“…RDS represents the most frequent form of respiratory insufficiency in the preterm newborn, and is still a major cause of morbidity and mortality in this group of patients (26,27). However, significant variations in pulmonary outcomes of similar infants with comparable exposures to oxygen, mechanical ventilation and nutritional deficiencies suggest that genetic factors also contribute to different pulmonary outcomes (28).…”

Section: Discussionmentioning

confidence: 99%

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Lyra

Vaz

Moreira

et al. 2007

Braz J Med Biol Res

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Polymorphisms and mutations in the surfactant protein B (SP-B) gene have been associated with the pathogenesis of respiratory distress syndrome (RDS). The objective of the present study was to compare the frequencies of SP-B gene polymorphisms between preterm babies with RDS and healthy term newborns. We studied 50 preterm babies with RDS (inclusion criteria -newborns with RDS and gestational age between 28 and 33 weeks and 6 days), and 100 healthy term newborns. Four SP-B gene polymorphisms were analyzed: A/C at nucleotide -18, C/T at nucleotide 1580, A/G at nucleotide 9306, and G/C at nucleotide 8714, by PCR amplification of genomic DNA and genotyping by cRFLP. The healthy newborns comprised 42 female and 58 male neonates; 39 were white and 61 non-white. The RDS group comprised 21 female and 29 male preterm neonates; 28 were white and 22 non-white. Weight ranged from 640 to 2080 g (mean: 1273 g); mean gestational age was 31 weeks and 2 days (range: 28-33 weeks and 6 days). When white children were analyzed separately, a statistically significant difference in the G/C polymorphism at 8714 was observed between groups (P = 0.028). All other genotype frequencies were similar for both groups when sex and race were analyzed together. Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. These data demonstrate an association of GG genotype with RDS.

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Section: Discussionmentioning

confidence: 99%

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Lyra

Vaz

Moreira

et al. 2007

Braz J Med Biol Res

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“…The presence of positive charges around the helical circumference avoided self-oligomerisation while maintaining helical conformation [141]. Surfactant preparations containing the latter peptide displayed optimal properties in vitro [141], although in vivo performance was probably compromised by complex peptide/membrane interactions involving the leucine-rich region [142]. In order to overcome the low in vivo performance of the SP-C(SLK) peptide, a derivative form bearing a single lysine residue in the N-terminal region of the "-helical segment was more recently designed (SP-C33, Fig.…”

Section: Sp-c-related Synthetic Surfactantsmentioning

confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

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“…The more important trend clinically, is the fact that minimum surface tensions are increased with an increase in minimum bubble volume as well. The importance of the surface tension lowering abilities of surfactant are most relevant at maximum expiration where lower surface tensions allow greater compression of the alveolus and prevent alveolar collapse as well as increase pulmonary compliance [45]. The results of this study indicate a significant deficit in this surface tension lowering ability following exposure to S. chartarum spore products.…”

Section: Discussionmentioning

confidence: 70%

<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

Pollard¹,

Shaw²,

Sowa³

et al. 2013

OJPed

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Moulds, notably Stachybotrys chartarum (atra), are constant contributors to air pollution particularly to air quality in buildings. The spores themselves or their volatile organic products are present in variable amounts in almost all environments, particularly in buildings affected by flooding. These moulds and products can account for the sick building syndrome and have been tied to such occurrences as the outbreak of pulmonary hemosiderosis and hemorrhage in infants in Cleveland, Ohio. The present study was designed to investigate the effects of S. chartarum extracts on surfactant protein expression, surfactant quality and cell survival in the developing lung. S. chartarum extracts were incubated with cultures of several cell types; isolated fetal lung type II cells and fetal lung fibroblasts, and human lung A549 cells, a continuously growing cell line derived from surfactant producing type II alveolar cells. MTT formazan assays were employed to test cell viability. The synthesis and release of the predominant surfactant protein A (SP-A), which is involved in the regulation of surfactant turnover and metabolism, and surfactant protein B (SP-B) involved in shuttling phospholipids between surfactant subcompartments was also assessed. Antibodies to these proteins and western blotting results were used to assess the quantity of protein produced by the various cell types. A novel approach utilizing captive bubble surfactometry was employed to investigate the quality of surfactant in terms of surface tension and bubble volume measurements. Electron microscopy was used to examine changes in cellular structure of control and S. chartarum-treated cells. Results of the study showed that exposure to the S. chartarum extracts had deleterious effects on fetal lung epithelial cell viability and their ability to produce pulmonary surfactant. S. chartarum extracts also induced deleterious changes to the developing fetal lung cells in terms of expression of SP-A and SP-B as well as to the surface tension reducing abilities of the pulmonary surfactant. Ultrastructurally, spore toxin associated changes were apparent in the isolated lung cells most notably in the lamellar bodies of fetal rat lung alveolar type II and human A549 cells. This study has demonstrated the potential damage to surfactant production and function which may be induced by inhaling S. chartarum toxins.

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New Synthetic Surfactants – Basic Science

Cited by 27 publications

References 78 publications

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

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New Synthetic Surfactants – Basic Science

Cited by 27 publications

References 78 publications

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Comparison of surfactant protein B polymorphisms of healthy term newborns with preterm newborns having respiratory distress syndrome

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

&lt;i&gt;Stachybotrys chartarum&lt;/i&gt; (&lt;i&gt;atra&lt;/i&gt;) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

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<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells