In vivo effect of pneumonia on surfactant disaturated-phosphatidylcholine kinetics in newborn infants

Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs

Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes. METHODS: We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of (13)C-dipalmitoyl-phosphatidylcholine, we measured the (13)C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds. RESULTS: In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p < 0.05). Fluxes between tissue and alveoli and de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08). CONCLUSION: In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered

Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes. METHODS: We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of (13)C-dipalmitoyl-phosphatidylcholine, we measured the (13)C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds. RESULTS: In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p < 0.05). Fluxes between tissue and alveoli and de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08). CONCLUSION: In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered

Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-(13)C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Palmitic acid in surfactant PC became enriched 27 +/- 2 h after the start of the isotope infusion and was maximally enriched at 100 +/- 4 h. The fractional synthesis rate of PC palmitate in the beta group (1.5 +/- 0.2%/d) was increased by 129% above control (0.7 +/- 0.1%/d) (p < 0.02, Mann- Whitney U test). The absolute synthesis rate of PC in the beta group [1.6 +/- 0.3 micromol/kg/d] was increased by 128% above controls [0.7 +/- 0.2 micromol/kg/d] (p < 0.02). These data show that the synthesis of endogenous surfactant from plasma glucose as precursor is a slow process. It is shown, for the first time in vivo, that prenatal glucocorticosteroids stimulate the synthesis of surfactant PC in the very premature baboon

Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia

Peer reviewe

Philosophy of the world and philosophy of Karl Löwith as a precursor and incentive to the idea of integrative bioethics

Traditional cosmology, once used to explain the world, was suppressed by the domination of science over philosophy which happened after their separation. Nowadays, scientific (in terms of natural sciences) cosmology is given the advantage in answering the question what is the world, while the "non-empirical" catholicity (the basic characteristic of traditional cosmology) became useless. Encouragement of one’s effort to re-establish the category of catholicity can be found in the idea of integrative bioethics on one side and in the philosophy of the world on the other. In this paper the relation between the idea of integrative bioethics and the philosophy of the world will be established through philosophical discussions which were held in Augsburg and in Zagreb (1988, 1990, 1993) and also with reliance on understanding the world in philosophy of Karl Löwith