| 1. |
- Grossmann, G, et al.
(författare)
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Experimental neonatal respiratory failure induced by lysophosphatidylcholine: effect of surfactant treatment
- 1999
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 86:2, s. 633-640
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to characterize the toxic effects of lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various doses of lyso-PC (from 0 to 40 mg/kg) were administered to near-term newborn rabbits. Lung-thorax compliance during mechanical ventilation was significantly decreased by doses ≥10 mg/kg, and static lung volumes during deflation were decreased by doses ≥20 mg/kg. Using the same experimental model, we investigated the effects of modified porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC at birth and treated simultaneously with surfactant showed a satisfactory therapeutic response, whereas those treated after 30 min failed to respond. These animals also had a much larger leak of albumin into the air spaces and an elevated minimum surface tension of the lavage fluid in a pulsating bubble surfactometer, suggesting inactivation of the exogenous surfactant. Timing of surfactant administration may thus be essential for the therapeutic effect in this experimental model of acute lung injury.
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| 2. |
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| 3. |
- ROBERTSON, B, et al.
(författare)
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Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits
- 1995
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 68:3, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.
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| 4. |
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| 5. |
- Tashiro, K, et al.
(författare)
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Modified protocols for surfactant therapy in experimental meconium aspiration syndrome
- 2003
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 83:1, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50–75 mg kg<sup>–1</sup>) through the airways. When the PaO<sub>2</sub> had decreased to <20 kPa (mean ± SD 12 ± 3.9 kPa), the rats were randomly allocated to ten groups (G). G 6–10 underwent lung lavage with diluted Curosurf (5 mg ml<sup>–1</sup>, 20 ml kg<sup>–1</sup>), whereas G 1–5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg<sup>–1</sup>), and G 3 and 8 received Curosurf (100 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>); G 4 and 9 received Curosurf (200 mg kg<sup>–1</sup>), and G 5 and G 10 received Curosurf (200 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO<sub>2</sub> transiently increased to 30–40 kPa. In G 4, 5, 9, and 10, the PaO<sub>2</sub> remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg<sup>–1</sup>) was nevertheless required to optimize gas exchange.
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| 6. |
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| 7. |
- Ahlström, J. Zebialowicz, et al.
(författare)
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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
- 2019
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.
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| 8. |
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| 9. |
- Almlen, A, et al.
(författare)
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Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity
- 2007
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 92:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. <i>Objectives:</i> To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol (68:31, w/w). <i>Methods:</i> Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. <i>Results:</i> Preparations containing ≧1% SP-C33 achieve minimum surface tension <5 mN/m indicating good biophysical activity, and increase tidal volumes in premature rabbit fetuses to the same level as a modified natural surfactant preparation does. Alveolar patency at end expiration, as evaluated by measurement of lung gas volumes, histological assessment of alveolar expansion and determination of alveolar volume density, was lower in the animals treated with synthetic surfactant than in those receiving modified natural surfactant. <i>Conclusions:</i> These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
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| 10. |
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| 11. |
- Almlen, A, et al.
(författare)
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Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome
- 2008
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 104:4, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of ∼5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.
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| 12. |
- Almlen, A, et al.
(författare)
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Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits
- 2010
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. <i>Objectives:</i> To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. <i>Methods:</i> Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. <i>Results:</i> Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. <i>Conclusions:</i> The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Basabe-Burgos, O, et al.
(författare)
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Disulphide Bridges in Surfactant Protein B Analogues Affect Their Activity in Synthetic Surfactant Preparations
- 2019
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 115:2, s. 134-141
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Limited supply and complicated manufacturing procedure of animal-derived surfactants make the development of synthetic surfactants warranted. The synthesis of surfactant protein (SP)-B and SP-C is complicated and several analogues have been developed. Mini-BLeu is an analogue that corresponds to the first and last helix of SP-B joined by a loop and linked by 2 disulphide bridges. SP-C33Leu is an SP-C analogue that can be cost-efficiently produced, but no such analogue has yet been described for SP-B. <b><i>Objective:</i></b> To design short SP-B analogues which lack disulphide bridges, are easy to produce and are efficacious in a preterm rabbit fetus model of neonatal RDS. <b><i>Methods:</i></b> Synthetic surfactants were prepared by adding 2 or 8% (w/w) of synthetic variants of Mini-B27, similar to Mini-BLeu but with a short loop, or different peptides covering helix 1 of SP-B to 2% (w/w) of SP-C33Leu in 80 mg/mL of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/egg yolk phosphatidylcholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 50: 40: 10 (by weight). Premature newborn rabbit fetuses were treated with 200 mg/kg of the surfactant preparations and ventilated with defined pressures for 30 min without positive end-expiratory pressure. Tidal volumes were registered during the experiments and lung gas volumes were measured at the end of the ventilation period. <b><i>Results:</i></b> Synthetic surfactant containing the Mini-B27 analogue with 2 disulphides gives similar lung gas volumes as treatment with an animal-derived surfactant preparation, but all other SP-B analogues gave lower lung gas volumes. All synthetic surfactants studied gave no significant differences in compliances except the surfactant containing the Mini-B27 analogue without cysteines that performed somewhat better at 30 min. <b><i>Conclusion:</i></b> The helix-loop-helix SP-B analogues tested in this study require the presence of 2 disulphide bridges for optimal activity in a rabbit RDS model.
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| 17. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Calkovska, A, et al.
(författare)
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Biophysical and physiological properties of porcine surfactant enriched with polymyxin B
- 2005
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 88:2, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objective:</i> We examined whether the biophysical and physiological properties of Curosurf<sup>®</sup> were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). <i>Methods:</i> Curosurf was diluted to 1–5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (γ<sub>min</sub>) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. <i>Results:</i> At surfactant concentration 2 mg/ml, γ<sub>min</sub> was high (17 ± 8.9 mN/m) but remained low (2.7 ± 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. <i>Conclusion:</i> Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Calkovska, A, et al.
(författare)
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Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits
- 2016
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 109:3, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. <b><i>Objectives:</i></b> To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. <b><i>Methods:</i></b> Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. <b><i>Results:</i></b> Treatment with Curosurf® or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (V<sub>T</sub>) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small V<sub>T</sub>, but after addition of both analogues V<sub>T</sub> was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-<i>sn</i>-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on V<sub>T</sub> and LGV as Curosurf. <b><i>Conclusions:</i></b> Phospholipid composition is important for V<sub>T</sub> while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding V<sub>T</sub> and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.
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| 36. |
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| 37. |
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| 38. |
- Calkovska, A, et al.
(författare)
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Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1–3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Curstedt, T, et al.
(författare)
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A unique story in neonatal research: the development of a porcine surfactant
- 2015
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 107:4, s. 321-329
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Tidskriftsartikel (refereegranskat)abstract
- Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf® (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by Christian Speer, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. Curosurf has also been compared with several synthetic and natural surfactants, and at a dose of 200 mg/kg Curosurf has been shown to be superior to either Survanta® or Curosurf used at a dose of 100 mg/kg. Recently, new-generation synthetic surfactants containing both phospholipids and proteins have been developed. After preclinical testing, CHF5633 (developed by Tore Curstedt and Jan Johansson in collaboration with Chiesi Farmaceutici) has undergone a preliminary first study in humans under the guidance of Christian Speer. If effective, this new surfactant preparation could revolutionize the treatment of preterm infants worldwide as it could be made consistently and safely in almost unlimited quantities. This story of a porcine surfactant preparation has been truly remarkable, and many thousands of preterm babies worldwide are now alive and well because of it.
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| 43. |
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| 44. |
- Curstedt, T, et al.
(författare)
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New generation synthetic surfactants
- 2013
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 103:4, s. 327-330
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Tidskriftsartikel (refereegranskat)abstract
- The treatment of preterm newborn rabbits with synthetic surfactants containing simple phospholipid mixtures and peptides gives similar tidal volumes to treatment with poractant alfa (Curosurf®). The addition of both surfactant protein B and C analogs to the phospholipid mixture will stabilize the alveoli, measured as lung gas volumes at end expiration, even if no positive end-expiratory pressure is applied. The effect on lung gas volumes seems to depend on the structure of the peptides as well as the phospholipid composition. It seems that synthetic surfactants containing two peptides and a more complex phospholipid composition will be able to replace natural surfactants within the near future, but more experiments need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants.
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| 45. |
- Curstedt, T, et al.
(författare)
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New synthetic surfactant - how and when?
- 2006
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 89:4, s. 336-339
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Tidskriftsartikel (refereegranskat)abstract
- Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.
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| 46. |
- Curstedt, T, et al.
(författare)
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New synthetic surfactants--basic science
- 2005
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 87:4, s. 332-7
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Tidskriftsartikel (refereegranskat)abstract
- The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface-active lipids to the air-liquid interface of the alveoli and are essential for alveolar stability and gas exchange. Synthetic surfactant preparations must contain at least one of these hydrophobic proteins, or analogs thereof, to have optimal effects when administered into the airways of patients with lung diseases. However, development of clinically active artificial surfactants has turned out to be more complicated than initially anticipated since the native hydrophobic proteins are structurally complex or unstable in pure form. The proteins have been replaced by different analogs which have the right conformation without forming oligomers. Increased understanding of the surfactant proteins will hopefully lead to development of effective synthetic surfactants which can be produced in large quantities for treatment of a wide range of respiratory disorders. Furthermore, the lipid composition seems to be important, as well as a high lipid concentration in the suspension. For successful treatment of many respiratory diseases, it is also desirable that the synthetic surfactant resists inactivation by plasma components leaking into the alveoli.
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| 47. |
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| 48. |
- Curstedt, T
(författare)
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Surfactant protein C: basics to bedside
- 2005
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Ingår i: Journal of perinatology : official journal of the California Perinatal Association. - : Springer Science and Business Media LLC. - 0743-8346. ; 25 Suppl 2, s. S36-8
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Tidskriftsartikel (refereegranskat)
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| 49. |
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| 50. |
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