Search

Objectives Prior research found the gut microbiota-dependent and pro-atherogenic molecule trimethylamine-N-oxide (TMAO) to be associated with cardiovascular events as well as all-cause mortality in different patient populations with cardiovascular disease. Our aim was to investigate the prognostic value of TMAO regarding clinical outcomes in patients after out-of-hospital cardiac arrest (OHCA). Methods We included consecutive OHCA patients upon intensive care unit admission into this prospective observational study between October 2012 and May 2016. We studied associations of admission serum TMAO with in-hospital mortality (primary endpoint), 90-day mortality and neurological outcome defined by the Cerebral Performance Category (CPC) scale. Results We included 258 OHCA patients of which 44.6% died during hospitalization. Hospital non-survivors showed significantly higher admission TMAO levels (μmol L−1) compared to hospital survivors (median interquartile range (IQR) 13.2 (6.6–34.9) vs. 6.4 (2.9–15.9), p Conclusions In patients after OHCA, TMAO levels were independently associated with in-hospital mortality and other adverse clinical outcomes and may help to improve prognostication for these patients in the future. Whether TMAO levels can be influenced by nutritional interventions should be addressed in future studies.

Meprin β is a dimeric type I transmembrane protein and acts as an ectodomain sheddase at the cell surface. It was shown that meprin β cleaves the amyloid precursor protein (APP), thereby releasing neurotoxic amyloid β peptides and implicating a role of meprin β in Alzheimer’s disease. In order to identify non-proteolytic regulators of meprin β, we performed a split ubiquitin yeast two-hybrid screen using a small intestinal cDNA library. In this screen we identified tetraspanin 8 (TSPAN8) as interaction partner for meprin β. Since several members of the tetraspanin family were described to interact with metalloproteases thereby affecting their localization and/or activity, we hypothesized similar functions of TSPAN8 in the regulation of meprin β. We employed cell biological methods to confirm direct binding of TSPAN8 to meprin β. Surprisingly, we did not observe an effect of TSPAN8 on the catalytic activity of meprin β nor on the specific cleavage of its substrate APP. However, both proteins were identified being present in tetraspanin-enriched microdomains. Therefore we hypothesize that TSPAN8 might be important for the orchestration of meprin β at the cell surface with impact on certain proteolytic processes that have to be further identified.

Urteil vom 16. 8. 2007 – IX ZR 63/06 1. Ein Teilurteil über eine Anfechtungsklage darf ergehen, wenn der Anfechtungsbeklagte Ansprüche sowohl zum Gegenstand einer Hilfsaufrechnung als auch einer Widerklage macht, die Hilfsaufrechnung jedoch verfahrensrechtlich präkludiert ist. 2. Kann der Anfechtungsgläubiger mit seiner Forderung, die der Anfechtung zugrunde liegt, gegen eine unstreitige oder titulierte Forderung des Schuldners aufrechnen, ist das Schuldnervermögen in diesem Umfang grundsätzlich nicht unzureichend. Dies gilt auch dann, wenn der Schuldner wegen eines nur ihn treffenden Aufrechnungsverbots nicht aufrechnen könnte. 3. Ist die Hauptforderung im Verhältnis zur Gegenforderung des Anfechtungsgläubigers nicht geringfügig, darf dieser von der Aufrechnung nicht deshalb absehen, weil er sich dadurch keine vollständige Befriedigung verschaffen kann. 4. Der Anfechtungsgegner kann den Anfechtungsgläubiger grundsätzlich nicht auf die Möglichkeit der Aufrechnung gegen eine Forderung des Schuldners verweisen, die bestritten ist. 5. Eine zunächst vorliegende Gläubigerbenachteiligung entfällt, wenn der Anfechtungsgegner dem Schuldner vor Schluss der letzten mündlichen Tatsachenverhandlung als (weitere) Gegenleistung der angefochtenen Leistung Vermögenswerte zuwendet, welche die angefochtene Leistung nunmehr vollständig ausgleichen und dem Zugriff des Gläubigers offen stehen. (Vorgehend: LG Kiel, 30. 6. 2004 – 17 O 201/03; OLG Schleswig, 24. 2. 2006 – 1 U 107/04)

Meprins are members of the astacin family of metalloproteases expressed in epithelial tissues, intestinal leukocytes and certain cancer cells. In mammals, there are two homologous subunits, which form complex glycosylated disulfide-bonded homo- and heterooligomers. Both human meprin α and meprin β cleave several basement membrane components, suggesting a role in epithelial differentiation and cell migration. There is also evidence that meprin β is involved in immune defence owing to its capability of activating interleukin-1β and the diminished mobility of intestinal leukocytes in meprin β-knockout mice. Here we show for the first time by reverse transcription PCR, immunoblotting and immunofluorescence analyses that meprins are expressed not only in mammals, but also in the zebrafish Danio rerio. In contrast to the human, mouse and rat enzymes, zebrafish meprins are encoded by three genes, corresponding to two homologous α subunits and one β subunit. Observations at both the mRNA and protein level indicate a broad distribution of meprins in zebrafish. However, there are strikingly different expression patterns of the three subunits, which is consistent with meprin expression in mammals. Hence, D. rerio appears to be a suitable model to gain insight into the basic physiological functions of meprin metalloproteases.