Economic evaluation of water supply systems operated with solar-driven electro-chlorination in rural regions in Nepal, Egypt and Tanzania.

Reliable data on the economic feasibility of small-scale rural water supply systems are insufficient, which hampers the allocation of funds to construct them, even as the need for their construction increases. To address this gap, three newly constructed water supply systems with water points in Nepal, Egypt, and Tanzania were accompanied by the authors throughout the planning and implementation phases and up to several years of operation. This study presents an analysis of their economic feasibility and suggests important factors for successful water supply system implementation at other rural locations. The initial investment for construction of the new water supply systems ranged from 23,600 € to 44,000 €, and operation and maintenance costs ranged from 547 € to 1921 € per year. The water price and actual multi-year average quantity of tapped water at each site were 7.7 €/m³ & 0.67 m³/d in Nepal, 0.7 €/m³ & 0.88 m³/d in Egypt and 0.9 €/m³ & 8.65 m³/d in Tanzania. Although the new water supply systems enjoyed acceptance among the consumers, the actual average water quantity tapped ranged from just 17 to 30 % of the demand for which the new supply systems were designed. While two of three sites successfully yielded a cash surplus through the sale of water, sufficient for operation, maintenance and basic repairs, no site showed a realistic chance of recovering the initial investment (reaching the break-even point) within the projected lifetime of the technical infrastructure. Reaching the break-even point within 5 years, which would be necessary to attract private investors, would require an unrealistic increase of the water price or the water consumption by factors ranging from 5.2 to 9.0. The economic viability of such systems therefore depends strongly on the quantity of water consumed and the water price, as well as the availability of funding from governments, NGOs or other sponsors not primarily interested in a financial return on their investment.

Assessment of electrophile damage in a human brain endothelial cell line utilizing a clickable alkyne analog of 2-chlorohexadecanal.

Peripheral leukocytes aggravate brain damage by releasing cytotoxic mediators that compromise blood-brain barrier function. One of the oxidants released by activated leukocytes is hypochlorous acid (HOCl) that is formed via the myeloperoxidase-H2O2-chloride system. The reaction of HOCl with the endogenous plasmalogen pool of brain endothelial cells results in the generation of 2-chlorohexadecanal (2-ClHDA), a toxic, lipid-derived electrophile that induces blood-brain barrier dysfunction in vivo. Here, we synthesized an alkynyl-analog of 2-ClHDA, 2-chlorohexadec-15-yn-1-al (2-ClHDyA) to identify potential protein targets in the human brain endothelial cell line hCMEC/D3. Similar to 2-ClHDA, 2-ClHDyA administration reduced cell viability/metabolic activity, induced processing of pro-caspase-3 and PARP, and led to endothelial barrier dysfunction at low micromolar concentrations. Protein-2-ClHDyA adducts were fluorescently labeled with tetramethylrhodamine azide (N3-TAMRA) by 1,3-dipolar cycloaddition in situ, which unveiled a preferential accumulation of 2-ClHDyA adducts in mitochondria, the Golgi, endoplasmic reticulum, and endosomes. Thirty-three proteins that are subject to 2-ClHDyA-modification in hCMEC/D3 cells were identified by mass spectrometry. Identified proteins include cytoskeletal components that are central to tight junction patterning, metabolic enzymes, induction of the oxidative stress response, and electrophile damage to the caveolar/endosomal Rab machinery. A subset of the targets was validated by a combination of N3-TAMRA click chemistry and specific antibodies by fluorescence microscopy. This novel alkyne analog is a valuable chemical tool to identify cellular organelles and protein targets of 2-ClHDA-mediated damage in settings where myeloperoxidase-derived oxidants may play a disease-propagating role.

Assessment of blood-brain barrier function and the neuroinflammatory response in the rat brain by using cerebral open flow microperfusion (cOFM).

Blood-brain barrier (BBB) impairment in systemic inflammation leads to neuroinflammation. Several factors including cytokines, chemokines and signal transduction molecules are implicated in BBB dysfunction in response to systemic inflammation. Here, we have adopted a novel in vivo technique; namely, cerebral open flow microperfusion (cOFM), to perform time-dependent cytokine analysis (TNF-alpha, IL-6 and IL-10) in the frontal cortex of the rat brain in response to a single peripheral administration of lipopolysaccharide (LPS). In parallel, we monitored BBB function using sodium fluorescein as low molecular weight reporter in the cOFM sample. In response to the systemic LPS administration, we observed a rapid increase of TNF-alpha in the serum and brain, which coincides with the BBB disruption. Brain IL-6 and IL-10 synthesis was delayed by approximately 1 h. Our data demonstrate that cOFM can be used to monitor changes in brain cytokine levels and BBB disruption in a rat sepsis model.