Effects of Phosphodiesterase 4 Inhibition on Alveolarization and Hyperoxia Toxicity in Newborn Rats

International audienceBACKGROUND: Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. METHODOLOGY/FINDINGS: Rat pups were placed under hyperoxia (FiO2>95%) or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. CONCLUSIONS: Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization

Preparation of alcohol-based handrub in COVID-19 Alsatian cluster

Alsace, in particular Haut-Rhin, is one of the main clusters of COVID-19 in France. There has been a shortage of essential supplies in the area, especially alcohol-based hand sanitizer. In this context, and in accordance with the decree dated March 6, 2020, our hospital management team asked us to start local production of alcohol-based handrub. This was a real challenge: In one week, we had to implement the production of handrub to meet the needs of a 1,400-bed hospital. The production had to comply with the French preparation guidelines and take place on specific premises, with qualified and calibrated equipment, by qualified staff, under the supervision of a pharmacist. The other big challenge we faced was the supply of pharmaceutical raw and packaging materials. During this particular critical period, all suppliers were out of stock. Here, we describe the organizational set-up and the decisions made, e. g., to use technical-grade ethanol before the publication of the decrees dated March 13 and March 23, 2020

Neodymium isotope composition of late Cretaceous fish teeth and debris

Circulation in the North Atlantic during the Late Cretaceous has implications for poleward heat transport and nutrient distribution during an extreme greenhouse interval with episodes of ocean anoxia. Nd isotopes of fossil fish teeth and debris represent one of the few water mass tracers that can be used to reconstruct deep ocean circulation. We present Nd isotopic data interpreted as bottom water values for 290 samples from three Ocean Drilling Program sites on Demerara Rise (Sites 1258, 1260, and 1261) along with 102 analyses from four other North Atlantic sites (Cape Verde, Goban Spur, Bermuda Rise and Blake Nose) that provide additional geographic and bathymetric control. Our results confirm the presence of a water mass with low e-Nd values (-14 to -17) that are believed to be influenced by continental material during local water mass formation at low latitudes. This Demerara Bottom Water (DBW) is the primary water mass in the region from the Cenomanian to Coniacian and from the late Campanian through early Maastrichtian following a hiatus of ~ 10 my. A positive 8 e-Nd unit excursion occurs during Ocean Anoxic Event 2 (OAE2) that cannot be explained by changes in weathering inputs, diagenesis or magmatic sources of Nd; instead, it appears to represent an influx of bottom waters sourced from the Tethys or North Atlantic. This replacement of DBW during OAE2 argues for decreased production of DBW or enhanced production of Tethys/North Atlantic waters during peak greenhouse conditions. From the late Campanian through early Maastrichtian, DBW becomes the only water mass recorded at Demerara Rise and it appears to expand to abyssal depths at Cape Verde in the Campanian. This water mass is ultimately replaced by waters that appear to be sourced from the North Atlantic starting in the late Maastrichtian. Observed variations in circulation in the tropical North Atlantic during the Late Cretaceous can account for extensive deposition of black shales in the region prior to the hiatus, as well as local warming during a global cooling event in the Maastrichtian

Neodymium isotope ratios of fish debris from late Cretaceous black shales

Neodymium isotopes of fish debris from two sites on Demerara Rise, spanning ~4.5 m.y. of deposition from the early Cenomanian to just before ocean anoxic event 2 (OAE2) (Cenomanian-Turonian transition), suggest a circulation-controlled nutrient trap in intermediate waters of the western tropical North Atlantic that could explain continuous deposition of organic-rich black shales for as many as ~15 m.y. (Cenomanian-early Santonian). Unusually low Nd isotopic data (epsilon-Nd(t) ~-11 to ~-16) on Demerara Rise during the Cenomanian are confirmed, but the shallower site generally exhibits higher and more variable values. A scenario in which southwest-flowing Tethyan and/or North Atlantic waters overrode warm, saline Demerara bottom water explains the isotopic differences between sites and could create a dynamic nutrient trap controlled by circulation patterns in the absence of topographic barriers. Nutrient trapping, in turn, would explain the ~15 m.y. deposition of black shales through positive feedbacks between low oxygen and nutrient-rich bottom waters, efficient phosphate recycling, transport of nutrients to the surface, high productivity, and organic carbon export to the seafloor. This nutrient trap and the correlation seen previously between high Nd and organic carbon isotopic values during OAE2 on Demerara Rise suggest that physical oceanographic changes could be components of OAE2, one of the largest perturbations to the global carbon cycle in the past 150 m.y