Effect of early Ambroxol treatment on lung functions in mechanically ventilated preterm newborns who subsequently developed a bronchopulmonary dysplasia (BPD)

AbstractIn a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg−1over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD.Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPeswas determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer.In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P<0·05) lung mechanics (VT/maxPes) in Ambroxol group compared to controls (9·4±2·7 ml kPa−1vs. 8·1±2·6 ml kPa−1) and (iii) no statistically significant difference in lung function between infants with and without BPD. At day 28 we found (i) no effect of early Ambroxol treatment on lung functions, (ii) significantly (P<0·05) higher f (58·5±11·7 min−1vs. 49·7±10·1 min−1) and significantly (P<0·01) lower VT(9·6±1·9 ml vs. 12·3±2·7 ml) and VT/maxPes(8·9±2·6 ml kPa−1vs. 12·0±2·9 ml kPa−1) in infants with BPD compared to infants without and (iii) these differences are not influenced by early Ambroxol treatment.If the process of BPD development is induced, early Ambroxol treatment has no influence on impaired lung function at day 28

Severe bronchopulmonary dysplasia improved by noninvasive positive pressure ventilation: a case report

<p>Abstract</p> <p>Introduction</p> <p>This is the first report to describe the feasibility and effectiveness of noninvasive positive pressure ventilation in the secondary treatment of bronchopulmonary dysplasia.</p> <p>Case presentation</p> <p>A former male preterm of Caucasian ethnicity delivered at 29 weeks gestation developed severe bronchopulmonary dysplasia. At the age of six months he was in permanent tachypnea and dyspnea and in need of 100% oxygen with a flow of 2.0 L/minute via a nasal cannula. Intermittent nocturnal noninvasive positive pressure ventilation was then administered for seven hours daily. The ventilator was set at a positive end-expiratory pressure of 6 cmH₂O, with pressure support of 4 cmH₂O, trigger at 1.4 mL/second, and a maximum inspiratory time of 0.7 seconds. Over the course of seven weeks, the patient's maximum daytime fraction of inspired oxygen via nasal cannula decreased from 1.0 to 0.75, his respiratory rate from 64 breaths/minute to 50 breaths/minute and carbon dioxide from 58 mmHg to 44 mmHg.</p> <p>Conclusion</p> <p>Noninvasive positive pressure ventilation may be a novel therapeutic option for established severe bronchopulmonary dysplasia. In the case presented, noninvasive positive pressure ventilation achieved sustained improvement in ventilation and thus prepared our patient for safe home oxygen therapy.</p

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Differences in tidal breathing between infants with chronic lung diseases and healthy controls

BACKGROUND: The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters. METHODS: In the age of 36–42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d, 3100 g) and 48 infants with CLD (80d, 2465 g)) using the deadspace-free flow-through technique. Once the infants had adapted to the mask and were sleeping quietly and breathing regularly, 20–60 breathing cycles were evaluated. Beside the shape of the tidal breathing flow-volume loop (TBFVL) 18 TB parameters were analyzed using ANOVA with Bonferroni correction. Receiver-operator characteristic (ROC) curves were calculated to investigate the discriminative ability of TB parameters. RESULTS: The incidence of concave expiratory limbs in CLD infants was 31% and significantly higher compared to controls (2%) (p < 0.001). Significant differences between CLD infants and controls were found in 11/18 TB parameters. The largest differences were seen in the mean (SD) inspiratory time 0.45(0.11)s vs. 0.65(0.14)s (p < 0.0001) and respiratory rate (RR) 55.4(14.2)/min vs. 39.2(8.6)/min (p < 0.0001) without statistically significant difference in the discriminative power between both time parameters. Most flow parameters were strongly correlated with RR so that there is no additional diagnostic value. No significant differences were found in the tidal volume and commonly used TB parameters describing the expiratory flow profile. CONCLUSION: The breathing pattern of CLD infants differs significantly from that of healthy controls. Concave TBFVL and an increased RR measured during quiet sleep and under standardized conditions may indicate diminished respiratory functions in CLD infants whereas most of the commonly used TB parameters are poorly predictive

A survey of transcutaneous blood gas monitoring among European neonatal intensive care units

BACKGROUND: PCO(2 )and PO(2 )are important monitoring parameters in neonatal intensive care units (NICU). Compared to conventional blood gas measurements that cause significant blood loss in preterms, transcutaneous (tc) measurements allow continuous, non-invasive monitoring of blood gas levels. The aim of the study was to survey the usage and opinions among German speaking NICUs concerning tc blood gas monitoring. METHODS: A questionnaire was developed and sent to 56 head nurses of different NICUs in Germany, Switzerland and Austria. RESULTS: A completely answered questionnaire was obtained from 41 NICUs. In two of these units tc measurements are not performed. In most NICUs (77%), both P(tc)O(2 )and P(tc)CO(2 )are measured simultaneously. Most units change the sensors every 3 hours; however, the recommended temperature of 44°C is used in only 15% of units. In only 8% of units are arterial blood gases obtained to validate tc values. Large variations were found concerning the targeted level of oxygen saturation [median upper limit: 95% (range 80–100%); median lower limit: 86% (range 75–93%)] and PO(2 )[median upper limit: 70 mmHg (range 45–90 mmHg); median lower limit: 44 mmHg (range 30–60 mmHg)]. CONCLUSION: Our survey shows that the use of tc monitors remains widespread among German speaking NICUs, despite earlier data suggesting that their use had been abandoned in many NICUs worldwide. In addition, we suggest that the current method of monitoring oxygenation may not prevent hyperoxemia in preterm infants

Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Serine⁶⁵

We have previously reported that the Parkinson's disease-associated kinase PINK1 (PTEN-induced putative kinase 1) is activated by mitochondrial depolarization and stimulates the Parkin E3 ligase by phosphorylating Ser(65) within its Ubl (ubiquitin-like) domain. Using phosphoproteomic analysis, we identified a novel ubiquitin phosphopeptide phosphorylated at Ser(65) that was enriched 14-fold in HEK (human embryonic kidney)-293 cells overexpressing wild-type PINK1 stimulated with the mitochondrial uncoupling agent CCCP (carbonyl cyanide m-chlorophenylhydrazone), to activate PINK1, compared with cells expressing kinase-inactive PINK1. Ser(65) in ubiquitin lies in a similar motif to Ser(65) in the Ubl domain of Parkin. Remarkably, PlNK1 directly phosphorylates Ser(65) of ubiquitin in vitro. We undertook a series of experiments that provide striking evidence that Ser(65)-phosphorylated ubiquitin (ubiquitin(Phospho-Ser65)) functions as a critical activator of Parkin. First, we demonstrate that a fragment of Parkin lacking the Ubl domain encompassing Ser(65) (Delta Ubl-Parkin) is robustly activated by ubiquitin(Phospho-Ser65), but not by non-phosphorylated ubiquitin. Secondly, we find that the isolated Parkin Ubl domain phosphorylated at Ser(65) (Ubl(phospho-Ser65)) can also activate Delta Ubl-Parkin similarly to ubiquitin(PhosPh-Ser65). Thirdly, we establish that ubiquitin(PhosPh-Ser65), but not non-phosphorylated ubiquitin or Ubl(PhosPh-Ser65) activates full-length wild-type Parkin as well as the non-phosphorylatable S65A Parkin mutant. Fourthly, we provide evidence that optimal activation of full-length Parkin E3 ligase is dependent on PINK1-mediated phosphorylation of both Parkin at Ser(65) and ubiquitin at Ser(65), since only mutation of both proteins at Ser(65) completely abolishes Parkin activation. In conclusion, the findings of the present study reveal that PINK1 controls Parkin E3 ligase activity not only by phosphorylating Parkin at Ser(65), but also by phosphorylating ubiquitin at Ser(65). We propose that phosphorylation of Parkin at Ser(65) serves to prime the E3 ligase enzyme for activation by ubiquitin(PhosPh-Ser65), suggesting that small molecules that mimic ubiquitin(PhosPh-Ser65) could hold promise as novel therapies for Parkinson's disease

A Realistic Validation Study of a New Nitrogen Multiple-Breath Washout System

Background For reliable assessment of ventilation inhomogeneity, multiple-breath washout (MBW) systems should be realistically validated. We describe a new lung model for in vitro validation under physiological conditions and the assessment of a new nitrogen (N2)MBW system. Methods The N2MBW setup indirectly measures the N2 fraction (FN2) from main-stream carbon dioxide (CO2) and side-stream oxygen (O2) signals: FN2 = 1−FO2−FCO2−FArgon. For in vitro N2MBW, a double chamber plastic lung model was filled with water, heated to 37°C, and ventilated at various lung volumes, respiratory rates, and FCO2. In vivo N2MBW was undertaken in triplets on two occasions in 30 healthy adults. Primary N2MBW outcome was functional residual capacity (FRC). We assessed in vitro error (√[difference]2) between measured and model FRC (100–4174 mL), and error between tests of in vivo FRC, lung clearance index (LCI), and normalized phase III slope indices (Sacin and Scond). Results The model generated 145 FRCs under BTPS conditions and various breathing patterns. Mean (SD) error was 2.3 (1.7)%. In 500 to 4174 mL FRCs, 121 (98%) of FRCs were within 5%. In 100 to 400 mL FRCs, the error was better than 7%. In vivo FRC error between tests was 10.1 (8.2)%. LCI was the most reproducible ventilation inhomogeneity index. Conclusion The lung model generates lung volumes under the conditions encountered during clinical MBW testing and enables realistic validation of MBW systems. The new N2MBW system reliably measures lung volumes and delivers reproducible LCI values

Short-Term Hurricane Impacts on a Neotropical Community of Marked Birds and Implications for Early-Stage Community Resilience

Populations in fragmented ecosystems risk extirpation through natural disasters, which must be endured rather than avoided. Managing communities for resilience is thus critical, but details are sketchy about the capacity for resilience and its associated properties in vertebrate communities. We studied short-term resilience in a community of individually marked birds, following this community through the catastrophic destruction of its forest habitat by Hurricane Iris in Belize, Central America. We sampled for 58 d immediately before the storm, 28 d beginning 11 d after Hurricane Iris, and for 69 d approximately one year later. Our data showed that the initial capacity for resilience was strong. Many banded individuals remained after the storm, although lower post-hurricane recapture rates revealed increased turnover among individuals. Changes occurred in community dynamics and in abundances among species and guilds. Survivors and immigrants both were critical components of resilience, but in a heterogeneous, species-specific manner. Delayed effects, including higher fat storage and increased species losses, were evident one year later

Pollination and Predation Limit Fruit Set in a Shrub, Bourreria succulents (Boraginaceae), after Hurricanes on San Salvador Island, Bahamas 1

Hurricanes have been assumed to reduce the reproduction of plants, either directly by leaf stripping and stress or indirectly by reducing pollinators. I examined the pollination and fruit set of a common shrub, Bourreria succulenta , after hurricanes on San Salvador island, Bahamas. Contrary to the assumption of resource limitation, B. succulenta showed unusually prolific flowering after Hurricane Lili stripped leaves from most of the plants in October 1996. I predicted that the abundant flowering would saturate pollinators and that fruit set would be pollination-limited. Fruit set was strongly pollination-limited by 71 percent. Butterflies are probably the major pollinators and were present at the site, but they rarely visited B. succulenta flowers even though flowers were brimming with nectar. Nectarivorous birds (Bananaquits and Bahama Wbodstars) visit B. succulenta flowers, but their populations were decimated by Hurricane Lili and they rarely visited flowers during this time. Fruit set was also severely predation-limited; a moth caterpillar (Gelechiidae) was extremely abundant and ate buds, flowers, and fruits, causing a further 68 percent reduction in fruit set. Together, pollination limitation and predation limitation reduced fruit set to only 7 percent or less. Predation was also intense in 1999 after Hurricane Floyd and resulted in 11 percent fruit set or less. Whether or not hurricanes were the cause of limited pollinators or abundant predators, the resulting low fruit set could have population effects because hurricanes can provide opportunities for the recruitment of new plants. These results emphasize that understanding plant–animal interactions may be necessary for predicting the effects of hurricanes on plant reproductive success, which may affect subsequent recruitment. Species on small islands like San Salvador (150 km 2 ) with relatively few species may be especially vulnerable to environmental disturbances such as hurricanes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75721/1/j.1744-7429.2001.tb00184.x.pd