Tolvaptan in ADPKD Patients With Very Low Kidney Function

Introduction: Tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in subjects with autosomal dominant polycystic kidney disease (ADPKD) in TEMPO 3:4 and REPRISE trials. Tolvaptan effects in subjects with eGFR 15 to 24 ml/min per 1.73 m2 were not investigated. This post hoc analysis retrospectively investigated eGFR decline in REPRISE versus an open-label, phase 3b extension trial (open-label extension [OLE] NCT02251275) in subjects who received placebo in REPRISE and tolvaptan in OLE with eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2, respectively. Methods: One data subset comprised subjects with OLE baseline eGFR 15 to 29 ml/min per 1.73 m2 who had received placebo in REPRISE and began tolvaptan in OLE. The second comprised subjects who had received tolvaptan in REPRISE and were matched to REPRISE placebo-treated subjects for REPRISE baseline characteristics. Annualized eGFR slopes in REPRISE versus OLE were compared within the REPRISE placebo (i.e., placebo vs. tolvaptan treatment) and tolvaptan (i.e., 2 periods of tolvaptan treatment) subsets. Results: Mean annualized eGFR slopes (ml/min per 1.73 m2) during tolvaptan treatment in OLE versus placebo treatment in REPRISE were -3.4 versus -5.2 for subjects with OLE baseline eGFR 15 to 29 (difference, 1.7; P < 0.001), -3.6 versus -5.4 with baseline eGFR 15 to 24 (difference, 1.8; P < 0.001), and -3.3 versus -4.9 with baseline eGFR 25 to 29 (difference, 1.6; P < 0.001). In REPRISE tolvaptan subjects who continued tolvaptan in OLE, treatment effect was maintained (no difference between mean annualized eGFR slopes). Conclusion: Initiating or maintaining tolvaptan therapy significantly delayed eGFR decline in subjects with baseline eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2

Mass spectral characterisation of a polar, esterified fraction of an organic extract of an oil sands process water.

RATIONALE: Characterising complex mixtures of organic compounds in polar fractions of heavy petroleum is challenging, but is important for pollution studies and for exploration and production geochemistry. Oil sands process-affected water (OSPW) stored in large tailings ponds by Canadian oil sands industries contains such mixtures. METHODS: A polar OSPW fraction was obtained by silver ion solid-phase extraction with methanol elution. This was examined by numerous methods, including electrospray ionisation (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) and ultra-high-pressure liquid chromatography (uHPLC)/Orbitrap MS, in multiple ionisation and MS/MS modes. Compounds were also synthesised for comparison. RESULTS: The major ESI ionisable compounds detected (+ion mode) were C15-28 SO3 species with 3-7 double bond equivalents (DBE) and C27-28 SO5 species with 5 DBE. ESI-MS/MS collision-induced losses were due to water, methanol, water plus methanol and water plus methyl formate, typical of methyl esters of hydroxy acids. Once the fraction was re-saponified, species originally detected by positive ion MS, could be detected only by negative ion MS, consistent with their assignment as sulphur-containing hydroxy carboxylic acids. The free acid of a keto dibenzothiophene alkanoic acid was added to an unesterified acid extract of OSPW in known concentrations as a putative internal standard, but attempted quantification in this way proved unreliable. CONCLUSIONS: The results suggest the more polar acidic organic SO3 constituents of OSPW include C15-28  S-containing, alicyclic and aromatic hydroxy carboxylic acids. SO5 species are possibly sulphone analogues of these. The origin of such compounds is probably via further biotransformation (hydroxylation) of the related S-containing carboxylic acids identified previously in a less polar OSPW fraction. The environmental risks, corrosivity and oil flow assurance effects should be easier to assess, given that partial structures are now known, although further identification is still needed

Untersuchungen schwer entschwefelbarer Verbindungen aus Erdöl und seinen Fraktionen

In der Arbeit wurde eine Trennmethode für schwefelhaltige Substanzen entwickelt, die im Gegensatz zu bisherigen Verfahren die Analyse bisher nicht untersuchbarer Schwefelverbindungen ermöglicht. Mit dieser Methode konnte eine neuartige Verbindungsklasse in tiefentschwefeltem Diesel entdeckt und untersucht werden. Diese Verbindungsklasse ist weitgehend resistent gegenüber den gängigen Entschwefelungsverfahren und erschwert so die Gewinnung schwefelfreier Treibstoffe, wie sie für neuartige Motoren oder Brennstoffzellen benötigt werden. Durch die Aufdeckung der neuen Verbindungen lassen sich die Entschwefelungsverfahren eventuell anpassen, um so saubere Treibstoffe zu gewinnen