Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects

Salt-losing tubulopathies with secondary hyperaldosteronism (SLT) comprise a set of well-defined inherited tubular disorders. Two segments along the distal nephron are primarily involved in the pathogenesis of SLTs: the thick ascending limb of Henle’s loop, and the distal convoluted tubule (DCT). The functions of these pre- and postmacula densa segments are quite distinct, and this has a major impact on the clinical presentation of loop and DCT disorders – the Bartter- and Gitelman-like syndromes. Defects in the water-impermeable thick ascending limb, with its greater salt reabsorption capacity, lead to major salt and water losses similar to the effect of loop diuretics. In contrast, defects in the DCT, with its minor capacity of salt reabsorption and its crucial role in fine-tuning of urinary calcium and magnesium excretion, provoke more chronic solute imbalances similar to the effects of chronic treatment with thiazides. The most severe disorder is a combination of a loop and DCT disorder similar to the enhanced diuretic effect of a co-medication of loop diuretics with thiazides. Besides salt and water supplementation, prostaglandin E2-synthase inhibition is the most effective therapeutic option in polyuric loop disorders (e.g., pure furosemide and mixed furosemide–amiloride type), especially in preterm infants with severe volume depletion. In DCT disorders (e.g., pure thiazide and mixed thiazide–furosemide type), renin–angiotensin–aldosterone system (RAAS) blockers might be indicated after salt, potassium, and magnesium supplementation are deemed insufficient. It appears that in most patients with SLT, a combination of solute supplementation with some drug treatment (e.g., indomethacin) is needed for a lifetime

Beam Characterization and Improvement with a Flux Mapping System for Dish Concentrators

ABSTRACT A flux mapping system able to measure the flux distribution of dish/Stirling systems in planes perpendicular to the optical axis was built and operated at the Plataforma Solar de Almería (PSA). It uses the indirect measuring method with a water-cooled Lambertian target placed in the beam path and a CCD-camera mounted on the concentrator taking images of the brightness distribution of the focal spot. The calibration is made by calculating the total power coming from the dish and relating it to the integrated gray value over the whole measurement area. The system was successfully operated in a DISTAL II stretched membrane dish and in the new EURODISH in order to characterize their beams and improve the flux distribution on their receivers

Verbesserte Isoliersysteme für solare Hochtemperaturanwendungen

Ziel des Projektes war die Verbesserung bestehender Dämmungen von Solarreceivern für Turmkraftwerke. In Vorgängerprojekten zeigte sich, dass Dämmsysteme einen Verbesserungsbedarf aufweisen, um Wärmeverluste zu reduzieren, Gesundheitsrisiken zu minimieren und besonders einen sicheren Betrieb und eine zuverlässige Funktion auch langfristig zu gewährleisten. Es wurden Isolierungmaterialien sowohl im Ofen als auch unter konzentrierter Solarstrahlung getestet und die Ergebnisse in einer Bewertungsmatrix zusammengefasst. Konzepte zum Aufbau von Cavitydämmungen wurden erstellt und die vielversprechendsten Lösungen im Labormaßstab getestet. Auf Basis der Ergebnisse wurde eine komplette Cavity gebaut und unter solaren Bedingungen bei über 100 h auf der Plataforma Solar de Almeria in Spanien getestet. Die Eignung der Cavity konnte in den Tests nachgewiesen werden. Im Versuch demonstrierte die entwickelte Cavityisolierung ihre Eignung für die Anwendung. Eine neuartige, rein metallische Effusionsdämmung für Rohrleitungen wurde entwickelt

Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation