Capillary electrophoresis contributions to the hydromorphone metabolism in man

CE-ESI multistage IT-MS (CE-MS(n), n < or = 4) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of hydromorphone (HMOR) in human urine. Using the same CE conditions as previously developed for the analysis of urinary oxycodone and its metabolites, HMOR and its phase I metabolites produced by N-demethylation, 6-keto-reduction and N-oxidation and phase II conjugates of HMOR and its metabolites formed with glucuronic acid, glucose, and sulfuric acid could be detected in urine samples of a patient that were collected during a pharmacotherapy episode with daily ingestion of 48 mg of HMOR chloride. The CE-MS(n) data obtained with the HMOR standard, synthesized hydromorphol and hydromorphone-N-oxide, and CYP3A4 in vitro produced norhydromorphone were employed to identify the metabolites. This approach led to the identification of previously unknown HMOR metabolites, including HMOR-3O-glucide and various N-oxides, structures for which no standard compounds or mass spectra library data were available. Furthermore, the separation of alpha- and beta-hydromorphol, the stereoisomers of 6-keto-reduced HMOR, was achieved by CE in the presence of the single isomer heptakis(2,3-diacetyl-6-sulfato)-beta-CD. The obtained data indicate that the urinary excretion of alpha-hydromorphol is larger than that of beta-hydromorphol.

Plasma and urinary catecholamines as related to renal function in man

To assess the relationship between renal plasma flow (ERPF) or glomerular filtration rate (GFR) and the levels of norepinephrine (NE) or epinephrine (E) in plasma or urine in the presence of progressive degrees of non-oliguric renal functional impairment, these variables were assessed simultaneously in 18 normal subjects, 72 with parenchymal kidney disease and 14 with essential hypertension. ERPF and GFR were lower (P less than 0.01 to 0.001) in the groups with renal disease (mean +/- SD, 340 +/- 230 and 68 +/- 43 ml/min/1.73 m2, respectively) or essential hypertension (434 +/- 101 and 97 +/- 25 ml/min/1.73 m2) than normal subjects (597 +/- 133 and 118 +/- 14 ml/min/1.73 m2). Plasma and urinary NE and E did not differ significantly among groups and were unrelated with ERPF or GFR (range 4 to 160 ml/min/1.73 m2), except for reduced (P less than 0.001) urinary NE and E excretion in the presence of a GFR less than 20 ml/min. Subgroups with renal disease and a normal (N = 39) or high blood pressure (N = 33) also were comparable in their plasma and urinary NE and E, while ERPF and GFR tended to be lower in hypertensive patients. It is concluded that a chronic reduction in excretory kidney function may have no relevant impact on circulating levels of NE and E per se, although their urinary excretion falls distinctly at the stage of advanced renal failure. These aspects deserve consideration when pathogenetic or diagnostic studies of catecholamines are performed in normotensive or hypertensive patients with impaired kidney function.

Strobe-Statement: Wie berichtet man eine Beobachtungsstudie?

Eine internationale Gruppe schlägt eine Checkliste mit 22 Punkten vor, die von Studiendesign und Methoden bis zum Umgang mit quantitativen Variablen reicht.

Wie kann man vom 'Deutschen' leben? Zur Paxisrelevanz der interkulturellen Germanistik

In vielen Teilen der Welt ist die akademische Beschäftigung mit der deutschen Sprache, Literatur und Kultur in Bedrängnis geraten. Während mancherorts die Absolventen der (interkulturellen) Germanistik noch ohne Schwierigkeiten eine Anstellung finden, für die sie ausgebildet wurden, wird andernorts ein Studium der Germanistik mangels einschlägiger Berufsaussichten erst gar nicht mehr aufgenommen. Daher stellt sich die Frage, was im Fache und von seinen Repräsentanten getan werden kann, um die Praxisrelevanz der (interkulturellen) Germanistik zu begründen bzw. zu steigern und die Absolventen in die Lage zu versetzen, (wieder) ‘vom Deutschen’ leben zu können. Die internationale Germanistik mit ihren je eigenen, oft regional und gar lokal geprägten Fachidentitäten ist stark an der Ausbildung von komparativen, multiperspektivischen und interkulturellen Betrachtungs- und Zugangsweisen interessiert, die den methodologischen Unilateralismus überwinden. Gerade die ‘Auslandsgermanistiken’ könnten sich so als Schnittstellendisziplinen profilieren und zugleich konsolidieren.