The regulation of CTP:Phosphocholine cytidylyltransferase in fetal type 2 cells

Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is an important cause of neonatal and infant mortality. Together with congenital malformations, it is the leading cause of death in preterm infants and is responsible for serious morbidity in survivors, associated with high costs to society. Since 1959 it is known that RDS is caused by lung immaturity with concomitant surfactant deficiency. Numerous small studies and large multicenter trials have demonstrated decreased death rates and complications from RDS as a result of treatment with surfactant. Despite its success however, surfactant therapy is not a panacea. Recent meta-analyses from the available data do not show a consistent decrease in long term pulmonary complications such as bronchopulmonary dysplasia, nor in the major nonpulmonary complications such as intraventricular haemorrhage

Risk of adverse pregnancy outcomes in women with periodontal disease and the effectiveness of interventions in decreasing this risk: Protocol for systematic overview of systematic reviews

Background: Periodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes. Methods: We will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before (<6 months) or during pregnancy and/or (ii) according to preventive or therapeutic interventions for periodontal disease. Eligible interventions include (combinations of) the following: oral hygiene education, use of antibiotics, subgingival scaling, and root planing. For preventive and/or therapeutic reviews, the following comparisons will be considered: no intervention, a placebo intervention, or an alternative intervent

Adequate feeding and the usefulness of the respiratory quotient in critically ill children

Objective: We determined incidences of underfeeding and overfeeding in children who were admitted to a multidisciplinary tertiary pediatric intensive care and evaluated the usefulness of the respiratory quotient (RQ) obtained from indirect calorimetry to assess feeding adequacy. Methods: Children 18 y and younger who fulfilled the criteria for indirect calorimetry entered our prospective, observational study and were studied until day 14. Actual energy intake was recorded, compared with required energy intake (measured energy expenditure plus 10%), and classified as underfeeding (<90% of required), adequate feeding (90% to 110% of required), o

Effect of SP-B peptides on the uptake of liposomes by alveolar cells

Background: Exogenous surfactant has been accepted worldwide as a therapy of RDS in premature and term infants. Exogenous surfactant is usually derived from lung extracts containing phospholipids and the surfactant proteins SP-B and SP-C. Synthetic peptides of SP-B and SP-C are being tested with the aim to develop a completely synthetic surfactant preparation. Nevertheless, the effects of these peptides on the endogenous surfactant metabolism remain unknown. Objectives: The effect of synthetic SP-B peptides on uptake of surfactant-like liposomes was investigated in alveolar cells. Native SP-B and seven SP-B peptides were included: monomeric and dimeric SP-B1-25(Cys-11 → Ala-11), SP-B63-78and Ala-SP-B63-78(Cys-71 → Ala-71;Cys-77 → Ala-77)and their serine mutants. Methods: In vitro, alveolar macrophages (AM) and alveolar type II cells (ATII) were incubated with liposomes containing SP-B or one of its peptides. In vivo, rats received intratracheally various SP-B peptides (SP-B/lipid ratio 1:33 w/w) incorporated in fluorescent surfactant-like liposomes. One hour after instillation, AM and ATII were isolated and cell-associated fluorescence was determined using flow cytometry. Confocal laser microscopy was performed to ensure internalization of the liposomes. Results: In vitro uptake by AM or ATII was not influenced by the SP-B peptides. In vivo, SP-B1-25and Ser-SP-B1-25increased the uptake by AM whereas dSP-B1-25decreased the uptake. Neither SP-B1-25nor dSP-B1-25affected total uptake by ATII. The overall uptake by SP-B63-78variants was not changed. Conclusions: Surface-active synthetic SP-B peptides do not interfere with the normaluptake of surfactant by ATII. Copyrigh

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

Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: Study protocol for a randomised controlled trial in the Netherlands

Introduction Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change. Methods and analysis This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m 2) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place. Ethics and dissemination Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed. Trial registration number ClinicalTrials.gov NCT02703753

Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure

We have assessed the effects of overinflation on surfactant function and composition in rats undergoing ventilation for 20 min with 100% oxygen at a peak inspiratory pressure of 45 cm H2O, with or without PEEP 10 cm H2O (groups 45/10 and 45/0, respectively). Mean tidal volumes were 48.4 (SEM 0.3) ml kg-1 in group 45/0 and 18.3 (0.1) ml kg-1 in group 45/10. Arterial oxygenation in group 45/0 was reduced after 20 min compared with group 45/10 (305 (71) vs 564 (10) mm Hg); maximal compliance of the P-V curve was decreased (2.09 (0.13) vs 4.16 (0.35) ml cm H2O-1 kg-1); total lung volume at a transpulmonary pressure of 5 cm H2O was reduced (6.5 (1.0) vs 18.8 (1.4) ml kg-1) and the Gruenwald index was less (0.22 (0.02) vs 0.40 (0.05)). Bronchoalveolar lavage fluid from the group of animals who underwent ventilation without PEEP had a greater protein concentration (2.18 (0.11) vs 0.76 (0.22) mg ml-1) and a greater minimal surface tension (37.2 (6.3) vs 24.5 (2.8) mN m-1) than in those who underwent ventilation with PEEP. Group 45/0 had an increase in non-active to active total phosphorus compared with nonventilated controls (0.90 (0.16) vs 0.30 (0.07)). We conclude that ventilation in healthy rats with peak inspiratory pressures of 45 cm H2O without PEEP for 20 min caused severe impairment of pulmonary surfactant composition and function which can be prevented by the use of PEEP 10 cm H2O

Endogenous surfactant turnover in preterm infants measured with stable isotopes

We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults