Determination of betaxolol, a new beta-blocker, by gas chromatography mass spectrometry: application to pharmacokinetic studies

Betaxolol, a beta selective adrenoceptor antagonist recently approved for the treatment of hypertension, was determined by monitoring in chemical ionization mode with ammonia the [MH]+ ions of the trimethylsilyl derivatives of the drug and of its internal standard [2H5)betaxolol). Its pharmacokinetic profile obtained following administration of a 20 mg oral dose was characterized by a half-life of 22 h and a bioavailability of 85%. The main acid metabolite formed by elimination of the isopropylamino group may also be determined as the methyl TMS derivative but methylation with BF3-methanol should be used with caution since it may induce the opening of the cyclopropyl group. The routine electron capture determination procedure was compared to this mass spectrometric method and an excellent correlation was found (r = 0.9974). Both procedures have the same sensitivity (1 ng ml-1). Finally it was observed that under electron impact mode betaxolol trimethylsilyl side chain rearranged to lose TMS-O-CH=CH2; this elimination was confirmed by deuterium labelling studies.     

Cytologic observations on the effects of metallocene dichlorides on human fibroblasts cultivated in vitro

The effects of the organometallic cytostatic agents titanocene dichloride (TDC) and vanadocene dichloride (VDC) and of the inorganic cytostatic drug cis-diamminedichloroplatinum(II) (DDP) on the morphologic appearance of human embryonal fibroblasts cultivated as monolayers in vitro were analyzed by light and electron microscopy. All three substances induced similar structural changes which consisted of nuclear as well as cytoplasmic alterations. Many fibroblasts enlarged but the nuclear volume increased more extensively than that of the cytoplasm. The nuclear envelopes underwent invagination so that segmented nuclei were formed and the nucleoli increased in size and density. Within the cytoplasm there was evidence of conspicuous protein synthesis, characterized morphologically by an increase in the size and number of mitochondria, Golgi apparatuses and of cisternae of the rER. The phenomena observed are interpreted as indicating unbalanced cell growth characterized by a selective inhibition of DNA synthesis, coupled with progressive RNA and protein syntheses.     

Transplantation of a time-signal in honeybees

Summary It has been possible — by transplantation of brain tissue (i.e. mushroom-bodies) — to perform an interindividual transfer of a learned time-signal in honeybees. The information of the donor bees becomes determinative for the temporal activity pattern of the recipients about 3 to 4 days following transplantation.As seen from histological investigations done in parallel, the donor tissue is treated as a xenograft by the recipient's organism including disintegration and encapsulation processes. These observations give evidence for a humoral transfer of information.The results are discussed from the point of view of the analysis of the mechanism of time reception.Dedicated to Prof. Dr. H. Autrum on the occasion of his 70th birthdaySupported by the Akademie der Wissenschaften und der Literatur zu Mainz, the Stiftung Volkswagenwerk and the Deutsche ForschungsgemeinschaftAll observations done were individual per hand registrations. We want to give thanks to all people in the department who helped us to do the experiments.     

Purification and characterization of a complex between cloacin and its immunity protein isolated from Enterobacter cloacae (Clo DF13). Dissociation and reconstitution of the complex.

Cell of Enterobacter cloacae (Clo DF13) produce a bacteriocin which is characterized by its very effective killing activity against sensitive bacteria. Purification and characterization of the excreted bacteriocin has revealed that this bacteriocin consists of an equimolar complex of two plasmid-specific gene products: the cloacin and its inhibitor the immunity protein. Dissociation of the complex by treatment with sodium dodecylsulfate induces the endonucleolytic activity of the cloacin but strongly reduces the killing activity. The purified complex possesses no activity in vitro. Both cloacin and immunity protein isolated from the complex were functionally identical to cloacin and immunity protein purified from the bacteriocinogenic cells by other methods. Reconstitution of the complex results in a partial restoration of killing activity.     

Verwertung von Trimethylammoniumverbindungen durch Acinetobacter calcoaceticus

Zusammenfassung Die Verwertung von Carnitin und Carnitinderivaten (O-Acylcarnitine, Carnitincarboxyl-derivate) und strukturverwandten Trimethylammoniumverbindungen (Betaine und Stickstoffbasen) durch Acinetobacter calcoaceticus wurde anhand des Wachstums und des quantitativen Nachweises der Metabolite untersucht. Der Stamm wuchs auf l-Carnitin, l-O-Acylcarnitinen und -Butyrobetain als jeweils einziger C-Quelle. Der Verbrauch dieser Verbindungen und das Wachstum korrelierten mit der Spaltung der C-N-Bindung und mit dem gebildeten Trimethylamin. d-Carnitin wurde metabolisiert, wenn als zusätzliche C-Quelle l-Carnitin im Nährmedium vorhanden war, oder wenn die Bakterien mit l-oder dl-Carnitin vorinkubiert worden waren. Mit d-Carnitin als einziger C-Quelle wuchsen die Bakterien jedoch nicht. Die Bakterien oxidierten Cholin zu Glycinbetain in Gegenwart einer zusätzlichen C-Quelle, Glycinbetain selbst wurde nicht assimiliert. In Hinsicht auf den Abbau quaternärer Stickstoffverbindungen besitzt Acinetobacter calcoaceticus im Vergleich zu anderen Carnitin-verwertenden Bakterienarten einen für ihn charakteristischen Stoffwechselweg.

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Utilization of trimethylammonium-compounds by Acinetobacter calcoaceticus

The utilization of carnitine and carnitine derivatives (O-acylcarnitines, carnitine carboxylderivatives) and structure-related trimethylammonium-compounds (betaines and nitrogen-bases) by Acinetobacter calcoaceticus was studied by means of the control of growth and the quantitative detection of metabolites. The strain grew only on l-carnitine, l-O-acylcarnitines, and -butyrobetaine as the sole carbon sources. The utilization of these compounds and the growth correlated with the cleavage of the C-N bond and thereby with the formation of trimethylamine. d-Carnitine was metabolized, if an additional carbon source, like l-carnitine, was present in the incubation mixture, or if the bacteria were preincubated with l-or dl-carnitine, but no growth was observed on d-carnitine as the sole carbon source. The bacteria oxidized choline to glycinebetaine in the presence of additional carbon sources, glycinebetaine itself was not assimilated. With regard to the catabolism of quaternary nitrogen compounds Acinetobacter calcoaceticus shows a different pathway in comparison with other bacterial species metabolizing carnitine.

     

The role of the AT pairs in the acid denaturation of DNA.

It has been determined previously that the protonation of the GC pairs induces a DNA conformation change which leads to a "metastable" structure. The role of the AT pairs, however, is no well known because the protonation does not modify their spectral properties. By means of an indirect method based on the binding of proflavine, it has been determined that the AT pairs are protonated before the acid-induced denaturation and that they seem to be unable to assume a conformation change when protonated. These results would indicate that the protonated AT pairs may be responsible for the induction of the acid denaturation and not the GC pairs as it was thought previously.     

A tumor-cell-agglutinating lectin in snail mucus from Arion lusitanicus (MAB) and Arion empiricorum (Fér.)

A lectin which agglutinates Zajdela hepatoma cells; rat red cells and lymphocytes, but no normal rat liver cells, was detected in the mucus, yielded by simple saline extraction, of the two snail species Arion empiricorum (Fér.) and Arion lusitanicus (MAB). The agglutination spectrum involves also human erythrocytes and red cells of several animal species.     

Characterization of ionomycin as a calcium ionophore.

The ionophorous properties of a new antibiotic, ionomycin, have been studied. It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase. The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier. The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant. The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible. Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry.     

Non-Linear Patterns of Complex Ramification Schemes in Higher Plants (Proposition for an Insight)

Die Seitenzweige von Cupressus sempervirens L. sind auf vier Orthostichen in scheinbar mehr oder weniger zufälligen, voneinander unabhängigen Mustern angeordnet. Eine auf L-Systeme sich berufende mathematische Konstruktion gestattet die Definition eines Morphismus. Acht Parameter, Periodizität der absoluten Wachstumsrate der zugrundeliegenden theoretischen Serien, die Väriation dieser Raten in komplementaren Unterserien und eine Schwellenreaktion sind die Hauptargumente.