scholarly journals In vitro activity of the clinical pulmonary surfactant Surfacen® against Leishmania amazonensis

2011 ◽  
Vol 53 (4) ◽  
pp. 235-238 ◽  
Author(s):  
Odalys Blanco ◽  
Yuliannis Lugones ◽  
Elaine Díaz ◽  
Lianet Monzote

Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.

Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.


2019 ◽  
Vol 121 ◽  
pp. 267-273 ◽  
Author(s):  
Ana Cláudia Nogueira da Silva ◽  
Renato Malveira Carreiro do Nascimento ◽  
Débora Caroline do Nascimento Rodrigues ◽  
Paulo Michel Pinheiro Ferreira ◽  
Cláudia Pessoa ◽  
...  

2014 ◽  
Vol 109 (8) ◽  
pp. 1050-1056 ◽  
Author(s):  
Yasmin Silva Rizk ◽  
Alice Fischer ◽  
Marillin de Castro Cunha ◽  
Patrik Oening Rodrigues ◽  
Maria Carolina Silva Marques ◽  
...  

2018 ◽  
Vol 90 (1) ◽  
pp. 64-66 ◽  
Author(s):  
David B. Huang ◽  
Leonard R. Duncan ◽  
Robert K. Flamm ◽  
Matthew Dryden ◽  
G. Ralph Corey ◽  
...  

1997 ◽  
Vol 272 (2) ◽  
pp. L335-L343 ◽  
Author(s):  
S. B. Hall ◽  
R. W. Hyde ◽  
M. C. Kahn

The large active particles of pulmonary surfactant are depleted in patients with acute respiratory distress syndrome and in animal models of this disorder. We studied in vitro conversion of large to small particles, separated by differential sedimentation, to determine how factors lavaged from rabbits injured by intravenous oleic acid would affect conversion. In half-filled test tubes rotated end over end, samples from injured animals increased the recovery of large particles from 40 +/- 6% of uncycled samples for controls to 62 +/- 21%. We hypothesized that proteins in the injured samples, and perhaps also the proteinase inhibitors used previously to block conversion (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222-230, 1990), stabilized surfactant particles by limiting access to the cycling interface. Hemoglobin, neutrophil elastase, and alpha1-antiproteinase (alpha1-PI) oxidized to eliminate its antiproteinase activity all stabilized large particles against conversion. Hemoglobin was most effective, increasing recovery from 18 +/- 5% for controls to 86 +/- 5% with 0.4 mg/ml hemoglobin. Native alpha1-PI had no effect on conversion. Our results suggest that acceleration of normal conversion is unlikely to explain the depletion of large particles in injured lungs. They also suggest that conversion of surfactant particles separated by differential sedimentation requires no proteinase susceptible to inhibition by alpha1-PI. They provide an alternate hypothesis related to interfacial effects rather than proteinase inhibition for the previously reported effect of alpha1-PI on conversion of particles separated according to density.


2018 ◽  
Vol 73 ◽  
pp. 299
Author(s):  
L.D.S. Braga ◽  
D.S.S.L. Lera ◽  
Á. C. F.H.R. Milaré ◽  
W. Caetano ◽  
S.M.A. Aristides ◽  
...  

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