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[nicht vorhanden / not available], Germania : Anzeiger der Römisch-Germanischen Kommission des Deutschen Archäologischen Instituts, Bd. 23, Nr. 4 (1939)

In vitro und in vivo Charakterisierung der zinkabhängigen Metalloprotease ADAM10. Charakterisierung der Proteasefunktion während der Entwicklung des murinen ZNS und der Funktion im sdulten, murinen ZNS. Charakterisierung eines neuen Interaktionspartners von ADAM10.

Dies ist Teil eines Berichts über ein Video-Experiment mit einem "Vorspiel" von C.Debussy (Bd.1, Nr.IX) . N =262 Probanden schätzten ein und dasselbe Musikstück unter fünf Bedingungen: eine Audio- und vier verschiedene Videoversionen. Unter allen Bedingungen bewerteten die Probanden ihre Höreindrücke mit Hilfe eines (unipolaren) semantischen Differentials. Nach den Ergebnissen früherer Experimente zu urteilen, waren erhebliche Effekte der Videos nicht zu erwarten ("Wahrnehmungskonstanz") . Die Ergebnisse zeigten u.a., dass sich nur bei einem sehr spektakulären Video der Höreindruck als Effekt des Videos veränderte. Die Probanden berichteten von sehr intensiven und divergierenden visuellen Phantasien im Audiozustand, wobei die Inhalte mit ihrer Bewertung der Musik zusammenhingen. Im Verlauf des 90-minütigen Experiments ergaben sich zwei wichtige Lernprozesse: Die "Irritation" gegenüber einer ungewöhnlichen Mediengattung wurde vermindert, junge Studenten und musikalisch unerfahrene Erwachsene neigten dazu, die Musik positiver zu bewerten, da sie die Musik mehr als einmal hörten und sahen. [Translated with www.DeepL.com], This is part of a report about a video-experiment with a »prelude« of C.Debussy (Vol.1, Nr.IX) . N =2 62 subjects appreciated the same piece of music under five conditions: one audio and four different video versions. Under all conditions subjects rated their listening impressions by the aid of a (unipolar) semantic differential. Judging from the results of previous experiments considerable effects of the videos were not to be expected (»perceptual constance«) . Results showed beside other things that only in the case of one very spectacular video, the listening impression changed as an effect of the video. Subjects reported very intense and diverging visual fantasies in the audio-condition, the contents being related to their evaluation of the music. In the course of the 90 minute-experiment two important learning processes emerged: »irritation« toward an unusual media genre was diminished, young students and musically inexpert adults tended to evaluate the music more positive as an effect of hearing and seeing the music more than one time.

The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively.

After intravenous, intramuscular and oral administration of 25 mg 14C-labelled 2-(3-[4-(m-chlorophenyl)-1-piperazinyl]-propyl)-s-triazolo[4,3-a]pyridin-3-(2H)-one-hydrochloride (trazodone), plasma levels, elimination and metabolite pattern in plasma and urine were investigated. The plasma levels after all routes of administration are almost identical. The absorption of the compound is fast and complete. The elimination of radioactivity occurs in a biphasic manner with a half-life of 1 h for the earlier and 13 h for the second phase, no matter what application route had been chosen. The comparison of the plasma levels of fasted and non-fasted subjects shows a shift of the plasma maximum from 1.5 to 2.5 h following administration and a decrease in the maximum level of 30%. The radioactivity is excreted predominantly by renal processes (70-75% within 72 h). The main product in plasma is unchanged trazodone, whereas in urine it is found only in minute amounts. The radioactivity in urine is represented by conjugates that had formed after hydroxylation on the chlorophenyl residue (20%), by a dihydrodiol-metabolite of trazodone (15%) and by a carboxylic acid originating from oxidative cleavage of the parent compound (35%).

Blood and plasma levels as well as urinary and fecal excretion were measured in humans after oral administration of radioactively labelled 4-[j-(2'-fluorobiphenylyl)]-4-hydroxycrotonic acid (S-H 766 MO). The radioactivity in the plasma reaches maximum values of about 10 mug eq./ml 1 to 2 h after application with either form. After repeated administration good agreement is found between the plasma levels measured and those simulated according to the pharmacokinetic parameters obtained after single application. The S-H 766 metabolites were investigated in blood and urine. The substance was found to undergo considerable metabolism, only approximately 2% being excreted in the urine unchanged. The conjugates, which constitute over 60% of the radioactivity of the urine, consist mainly of glucuronides and sulfates. The structure of the aglycones shows that the metabolism occurs along two pathways, by beta-oxidation of the aliphatic side chain into aryl acetic acids and by hydroxylation of the aromatic nucleus to phenolic compounds. It must be assumed that these biotransformations take place both simultaneously and successively.

The major pathway of biotransformation of beclobrate [(2-[4-[(4-chlorophenyl)methyl]phenoxy]-2-methylbutyric acid ethyl ester] is the ester cleavage to beclobrinic acid (M1), which is eliminated as glucuronide. Subsequent metabolic attack is occurring via oxidation of the methylene bridge to the carbinol (M2) as well as to the benzophenone (M3). The p-chloro substituted phenyl ring is oxidated via a postulated arene oxide to the 2'- and 3'-phenol metabolites (M5 and M6) and to the trans-2',3'-dihydrodiol (M4). Except M4, all metabolites are eliminated exclusively as glucuronides.

Following oral administration of 14C labelled 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) to the rat, rabbit, dog, rhesus monkey, baboon and man the metabolic pattern in plasma and urine was compared and human urinary metabolites were isolated. None of the animal species investigated shows a metabolic pattern identical to that of man. The plasma of rat, dog and rabbit shows wide variation of metabolites with high amounts of two unpolar metabolites of AR-L 115 BS (sulfoxide), namely M0/2 identical with AR-L 114 BS (sulfone with regard to AR-L 115 BS) and M0/1 identical with AR-L 113 BS (sulfide). In comparison to man the urines of the animals show higher amounts of the sulfone (AR-L 114 BS) and the sulfide (AR-L 113 BS). A main pathway of the metabolism of the pyrido-imidazole of the AR-L 115 BS-type is the oxidative pyridine-ring cleavage leading to N-acetylated 5-aminoimidazoles. Further metabolites are characterised by a hydroxyl group in the 6-position of the pyrido-imidazole moiety. Besides the oxidation of tthe sulfoxide function to the sulfone we could also observe the thioether (sulfide) not only of the parent compound itself but also of some of the metabolites in the series of the AR-L 115 BS-biotransformation. The identification of the human urinary metabolites, was carried out by means of TLC, HPLC, UV-, MS- and NMR-spectroscopy.