Hydrogen inhalation ameliorates ventilator-induced lung injury

Introduction\ud Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.\ud \ud Methods\ud VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.\ud \ud Results\ud Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.\ud \ud Conclusions\ud Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects

Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function.

BACKGROUND The long-term use of calcineurin inhibitors (CNI) after liver transplantation (LT) is associated with nephrotoxicity. METHODS 5-year follow-up data was retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mTOR-free immunosuppression (group A, n=264) was compared to a 50 % reduction of CNI and introduction of the mTOR inhibitor Sirolimus within 4 to 6 weeks after LT (group B, n=261). RESULTS Median MELD at LT was low with 10 (7 - 15) (group A) and 11 (8 - 15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months post transplantation. Renal function was preserved at 3 months after LT in the Sirolimus arm [eGFR 74 (57-95) versus 67 (55-85) ml/min/1.73m, p=0.004] but was similarly impaired thereafter compared to group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and Sirolimus treatment ≥ year 1 with significantly superior eGFR and lowest rate of chronic kidney disease (≥ stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder and hyperglycemia) were not associated with worse kidney function. CONCLUSIONS Prevention of CNI nephrotoxicity by Sirolimus-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and Sirolimus maintenance achieved better long-term renal outcomes compared to real-world practice

Pelagic key species and mechanisms driving energy flows in the northern Benguela upwelling ecosystem and their feedback into biogeochemical cycles

The northern Benguela Upwelling System (nBUS) has been facing increasing temperatures and decreasing dissolved oxygen (DO) levels over the last decades. This has implications for key processes and trophic interactions within the ecosystem including shifts in community composition, distribution ranges, and trophic levels, changes in energy flows and migration patterns with feedbacks to biogeochemical processes. Here we summarise the results gained from the GENUS project (Geochemistry and Ecology of the Namibian Upwelling System) focussing on the geochemical and ecological structures and processes dominating the pelagic component of the nBUS. Spatial and temporal distribution patterns of key species of zooplankton and fish larvae yielded biomass estimates (5 to 81 g Wet Mass m−2 (10 to 90% quantile) with a median of 19.5 g Wet Mass m−2 for the upper 200 m) and potential impacts on the vertical carbon flux. Vertical distribution ranges of key taxa were determined reflecting their specific abilities to tolerate hypoxia and, hence, their different adaptive mechanisms to cope with the Oxygen Minimum Zone (OMZ). The shoaling of the 2.5 mL O2 L−1-oxycline (0.24 m y−1) constrains sensitive species and hampers daily and seasonal vertical migrations. It may also affect the ability of organisms to maintain themselves within nearshore habitats by hindering vertical migration into deeper onshore currents. Respiration rates of key species were determined with one standard method (optode respirometry), showing an average respiration rate of 54.6 mL O2 d−1 (g Dry Mass)−1 for the bulk fraction of mesozooplankton, allowing also the estimate of DO consumption by mesozooplankton at different depth layers. Stable isotopic ratios (N, C) revealed trophic interactions and positions of zooplankton and fish. Our results reveal many players within a small range of trophic levels and a dominance of zooplankton taxa (copepods, euphausiids) in terms of biomass over small pelagic fish (sardine, anchovy), essential to consider for future higher-resolution ecosystem modelling