Hemoglobinuria is associated with kidney injury in various hemolytic pathologies. Currently, there is no treatment available and its pathophysiology is not completely understood. Here we studied the potential detrimental effects of hemoglobin (Hb) exposure to the distal nephron (DN). Involvement of the DN in Hb kidney injury was suggested by the induction of renal hepcidin synthesis (p < 0.001) in mice repeatedly injected with intravenous Hb. Moreover, the hepcidin induction was associated with a decline in urinary kidney injury markers 24p3/NGAL and KIM1, suggesting a role for hepcidin in protection against Hb kidney injury. We demonstrated that uptake of Hb in the mouse cortical collecting duct cells (mCCDcl1) is mediated by multi-protein ligand receptor 24p3R, as indicated by a significant 90% reduction in Hb uptake (p < 0.001) after 24p3R silencing. Moreover, incubation of mCCDcl1 cells with Hb or hemin for 4 or 24 h resulted in hepcidin synthesis and increased mRNA expression of markers for oxidative, inflammatory and ER stress, but no cell death as indicated by apoptosis staining. A protective role for cellular hepcidin against Hb-induced injury was demonstrated by aggravation of oxidative, inflammatory and ER stress after 4 h Hb or hemin incubation in hepcidin silenced mCCDcl1 cells. Hepcidin silencing potentiated hemin-mediated cell death that could be diminished by co-incubation of Nec-1, suggesting that endogenous hepcidin prevents necroptosis. Combined, these results demonstrate that renal hepcidin synthesis protects the DN against hemin and hemoglobin-mediated injury.

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The practice of farming implies a continuous process of re-moulding and re-balancing of resources.Normally, this process is slow and hardly noticeable, but in times of transition towards sustainability it is accelerated and becomes more visible. Re-moulding and re-balancing require a careful and multifaceted monitoring as well as a high degree of involvement of the farmers concerned. This article is an overview that documents several aspects of the changes realized by two farmer co-operatives in the northern Netherlands: Vereniging Eastermar's Lansdouwe (VEL) and Vereniging Agrarisch Natuur en Landschapsonderhoud Achtkarspelen (VANLA). It is shown that farmers process and manage manure, silages and diets. Emphasis is given to indications that the newly emerging balances are characterized by high levels of N efficiency. In a final combination of beta and gamma approaches it is shown that the goal-oriented practices of the VEL and VAN LA farmers clearly indicate new trajectories towards and prospects for sustainability. Furthermore it is shown that recognition of relevant heterogeneity is crucial and that inter-farm comparisons, careful integration of beta and gamma approaches and multivariate modes of analysis are needed.

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Op weg naar een integrale meetmethode kringlooplandbouw 2 De KPI-K-systematiek 3 Wat is nodig om tot een werkende KPI-K-systematiek te komen? Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal Ken getal

Dutch regulations for ammonia emission require farmers to inject slurry into the soil (shallow) or to apply it in narrow bands at the surface. For one commercial dairy farm in the Netherlands it was hypothesized that its alternative farming strategy, including low-protein feeding and surface spreading, could be an equally effective tool for ammonia emission abatement. The overall objective of the research was to investigate how management at this farm is related to nitrogen (N) losses to the environment, including groundwater and surface water. Gaseous emission of ammonia and greenhouse gasses from the naturally ventilated stables were 8.1 and 3.1 kg yr(-1) AU(-1) on average using the internal tracer (SF(6))-ratio method. Measurements on volatilization of ammonia from slurry application to the field using an integrated horizontal flux method and the micrometeorological mass balance method yielded relatively low values of ammonia emissions per ha (3.5-10.9 kg NH(3)-N ha(-1)). The mean nitrate concentration in the upper ground water was 6.7 mg L(-1) for 2004 and 3.0 mg L(-1) for 2005, and the half-year summer means of N in surface water were 2.3 mg N L(-1) and 3.4 mg N L(-1) for 2004 and 2005, respectively. Using a nutrient budget model for this farm, partly based on these findings, it was found that the calculated ammonia loss per ton milk (range 5.3-7.5 kg N Mg(-1)) is comparable with the estimated ammonia loss of a conventional farm that applies animal slurry using prescribed technologies.

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