A structure-function study of nucleic acid-fluorenone complexes.

Several 2.7-bis-[(dialkylamino)-acetylamino]-fluoren-9-one derivatives (fluoramides) were synthesized as analogues of the DNA binding compound tilorone (2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one). Previous studies showed the drugs to induce cytokines and inhibit reverse transcription. Here, their binding to DNA was evaluated using UV and circular dichroism studies. Like tilorone, the fluoramides derivatives also intercalate resulting in increased Tm values and new CD signatures. A preference to alternating A-T and G-C sequences was detected; only minor interaction to homologous sequences was observed. Moreover, no upper limit in the drug/DNA ratio was found, testing limit being the precipitation of the drug. However, surface plasmon resonance (SPR) studies of tilorone and 2,7-bis-[(dipropylamino)-acetyl-amino]-fluoren-9-one, indicate an astonishing drug/base pair ratio (r > 1), which point to a multitude of interactions under SPR conditions. Molecular modeling calculations, where the geometries of the complexes optimized under the assumption of intercalative and multitude of suprahelical arrangements, rationalize the observations. Based on the thermodynamic and biological studies, a structure-function model is proposed.

[The antipyrine test in occupational medicine research--evaluation of individual reproducibility and frequency distribution of half-life]. / Der Antipyrin-Test in der arbeitsmedizinischen Forschung--Bewertung der individuellen Reproduzierbarkeit und der Häufigkeitsverteilung der Halbwertszeit.

The antipyrine half-life is a reliable index of biotransformation capacity of the liver. The half-lives were estimated in 137 subjects; the result was a logarithmic normal distribution of these parameters. Therefore our patients were subdivided into groups of so-called fast, intermediate and slow metabolisers (fast: t50 less than 7.6 h and slow: t50 greater than 14.9 h). Under conditions given here the intraindividual coefficient of variation was about 11.5%. The antipyrine elimination curves were calculated by a computer programme and the values were analysed statistically.

[Cytochrome P-450 dependent drug metabolism--use of an in vitro test system in multiple chemical exposure]. / Cytochrom P-450-abhängige Fremdstoffmetabolisierung--Anwendung eines in-vitro-Testsystems bei chemischer Mehrfachexposition.

Investigations of the influence of an actual exposure on the in-vitro-activities and the inducibility of cytochrom P-450 dependent enzymes have not been described in the literature until now. First results gained from mitogen-stimulated lymphocytes of exposed and not-exposed individuals suggest such an influence of the given mixture of noxious agents on the basic deethylational ability of the examined cells acting in the sense of inhibition. Possible causes for this phenomenon are discussed.

[Analysis of serum zinc level in patients with atopic dermatitis, psoriasis vulgaris and in probands with healthy skin]. / Analyse des Serumzinkspiegels bei Patienten mit atopischer Dermatitis, Psoriasis vulgaris und bei Hautgesunden.

BACKGROUND AND OBJECTIVE: The significance of zinc in the pathogenesis of different dermatological conditions is controversial. Using our own patient collective, the present study aimed to determine variations in serum zinc levels in patients with atopic dermatitis and psoriasis as compared to levels in the normal population. PATIENTS/METHODS: The serum zinc levels of 97 patients with atopic dermatitis and 88 patients with psoriasis were compared to those in 22 healthy subjects and subjected to statistical analysis. RESULTS: In contrast to the data given in the literature, no statistically significant difference was found between the populations investigated. CONCLUSIONS: Zinc replacement therapy in patients with atopic dermatitis and psoriasis appears to be indicated only in those with a documented zinc deficiency.