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  • 1
    ISSN: 1432-1335
    Keywords: Multidrug resistance ; Reversibility ; Cyclosporin A ; Verapamil ; Dexniguldipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Multidrug-resistant tumor cells can be resensitized by combined application of the selecting cytostatic drug and a chemosensitizer, such as cyclosporin A (CsA) or a calcium channel blocker. Since clinical trials on the circumvention of multidrug resistance (MDR) with chemosensitizers report disparate results, we investigated whether tumor cells of the MDR phenotype can develop additional resistance to the cytostatic chemosensitizer combination. Thus, the Adriamycin(ADR)-selected, P-glycoprotein-positive MDR Friend leukemia cell line F4-6RADR was exposed to stepwise increased concentrations of CsA at a constant level of 0.05 μg/ml ADR. The initial CsA concentration (plus 0.05 μg/ml ADR) to inhibit cell growth of F4-6RADR cells by 50% (IC50) was 0.04 μg/ml. By continuous incubation for more than 6 months, the IC50 for CsA (at constant ADR) was elevated to 3.6 μg/ml (90-fold), thus generating the variant F4-6RADR-CsA. The F4-6RADR-CsA cells were cross-resistant for cyclosporin H (CsH), a non-immunosuppressive derivative of CsA. As shown by immunocytochemistry as well as by the polymerase chain reaction and by Western blotting including densitometry, P-glycoprotein was preserved in the F4-6RADR-CsA variant and was expressed at a 4-fold higher level than in F4-6RADR cells. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis analysis could detect no new proteins in F4-6RADR-CsA as compared to F4-6RADR. Interestingly, resistance of F4-6RADR-CsA cells remained reversible for the calcium antagonists verapamil and dihydropyridine B859-35 (dexniguldipine-HCl), indicating that CsA and these compounds interfere with the P glycoprotein function by different pharmacodynamic mechanisms. Transport studies with [14C]ADR, performed in the presence and absence of chemosensitizers, confirmed the good correlation of P-glycoprotein function with the pattern of resistance found in proliferation assays. Cellular accumulation of [3H]cyclosporin was reduced to 71% of that of the F4-6 controls in F4-6RADR-CsA cells, but remained at the level of controls in F4-6RADR cells. Results indicate that increased amounts of the P-glycoprotein — besides other, perhaps more important mechanisms that are as yet unknown — partially mediate CsA resistance in F4-6RADR-CsA cells. We have designated this new form of resistance “secondary combined resistance” (SCR). The results suggest that at least some clinical cases of insensitivity to chemosensitizers or of relapse after reversing therapy could be explained by SCR, and that resensitizing treatment of tumor patients should be based on the consideration of several chemosensitizers of different pharmacodynamics.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0878
    Keywords: Pineal gland ; Synaptic ribbons ; N-acetyl-transferase ; Melatonin ; Serotonin ; Protein synthesis ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To elucidate the role of protein synthesis in the nocturnal increase of synaptic ribbons in the rat pineal gland, actinomycin-D, which inhibits transcription, and cycloheximide, an inhibitor of translation, were used. To assure that the drugs were effective and to relate morphological changes to pineal biosynthetic phenomena, the activity of N-acetyltransferase and levels of pineal indoleamine were measured. Results of in-vivo, short-term and long-term treatment with either drug suggest that transcription of proteins related to synaptic ribbon formation occurs during the first half of the light phase, whereas translation takes place during the first few hours of the dark phase. In contrast, proteins involved in enhanced melatonin synthesis are transcribed and translated during the first few hours of the dark phase. In vitro, preincubation with inhibitors of protein synthesis abolished the increase in the numbers of synaptic ribbons after stimulation with dibutyryl-adenosinecyclic-monophosphate, indicating that the results of the in-vivo experiments are due to an interaction of the drugs with the pineal gland itself. The present study shows that, although in the rat pineal enhanced melatonin synthesis and increased numbers of synaptic ribbons occur at the same time, transcription of proteins involved in both rhythms is temporally separated.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Synaptic ribbons ; diestrous rats ; LHRH ; sex steroids ; dexamethasone ; NAT activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pineal glands of regularly cycling Sprague Dawley rats (180–220 g) killed on the diestrous morning (between 0900–1000 h) were incubated in appropriate media for six hours with LHRH (8.5 ΜM), progesterone (3.2 ΜM), estradiol-17 Β (370 nM) or dexamethasone (250 nM). Pineals incubated in hormone-free medium and unincubated glands served as controls. Six rats were used in each group. After incubation the glands were divided into two parts. One part was used to estimate serotonin N-acetyltransferase (NAT) activity. The other part was processed for electron microscopy to quantify synaptic ribbons (SR). The SR numbers were computed to 20,000 Μm2 area of pineal tissue. The number and distribution pattern of SR were identical in incubated as well as in the unincubated controls. In both these groups the SR located close to the cell membrane were more (23 ± 1) than those that lay away from it (9 ± 2). LHRH had no effect on the number of SR located close, to or distant from, the cell membrane. Incubation of pineals with progesterone significantly (p ⩽ 0.05) depressed the number of SR present close to membranes (23 ± 1 in controls vs 11 ± 2 in treated group), total SR (34 ± 3 in controls vs 21 ± 2 in treated group) and synaptic fields (26 ± 2 in controls vs 17 ± 2 in treated group). Likewise, in the estradiol-17 Β group also membrane-associated SR decreased significantly. The effect of progesterone was more severe than estrogen on the SR possibly due to the differences in the doses used. The SR situated distant from the membranes were unaffected in both progesterone and estrogen groups. In pineals incubated with dexamethasone there was a depressive trend in the number of SR but with no statistical significance. The NAT activity was undetectable in control and all experimental groups. The above findings demonstrate that ovarian sex steroids in vitro are capable of specifically depressing the number of SR located close to the cell membrane while those lying distant from it remain unaffected. Whether or not this differential response is also present in vivo remains to be elucidated.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0021-8383
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Investigation on Probe Properties of 7-Hydroxy-coumarines in Micellar Cetyl-triethyl-ammoniumbromide Solution - Means for Characterization of Micellar SystemsAnions of 3-substituted 7-hydroxy-coumarines (1a-c) as fluorescence probes have been studied in this work. Acid-base equilibria in water and micellar solution of cetyl-triethylammoniumbromide (cmc = 0,72 mmol l-1), fluorescence properties and fluorescence quenching by octacyano-molybdate-IV have been investigated. It has been confirmed that probe and quencher are completely micellized. Fluorescence life times and quenching constants per one quencher molecule in the micell of about 108 s-1 have been determined. The kinetics of saponification of the probe 3-acetyl-7-hydroxy-coumarine at pH = 12 in micellar solution has been followed by probe fluorescence.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The conjugation products of several reactive quinones with glutathione have been identified by fast atom bombardment mass spectrometry. Appropriate conditions have been developed which enabled the direct, dynamic mass spectral analysis of spontaneous, as well as glutathione transferase catalysed conjugation reactions. Applications to a series of quinones provided the direct detection and differentiation of the formation of mono- and bisglutathionyl adducts between regioisomeric quinone substrates in that only 1,4-quinones yielded bisglutathionyl adducts, which were not observed for the 1,2-isomers.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 608 (1992), S. 166-172 
    ISSN: 0044-2313
    Keywords: Spinel ; zinc, nickel manganite spinel ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Investigations on Electronically Conducting Oxide Systems. XXI [1] Stable Spinels ZnzNiMn2-zO4 and Comparison with Spinels MgzNiMn2-zO4Stable spinels are obtained in the result of substitution of ZnII for manganese in the series ZnzII NiIIMnzIVMn2-2zIIIO4 (O ≤ z ≤1). Different from spinels MgzII NiIIMnzIVMn2-2zIIIO4 (O ≤ z ≤1)they don't be submitted to decomposition in air during slow cooling at medium temperatures. ZnNiMnO4 (z=1) could not be prepared in a mono-phase state which is indicated by the composition of ZnNiMnO3.96 deduced from analysis by oxidimetric titration. The comparably small variation of the specific electrical conductivity and of the activation energy observed in the range O ≤ z ≤ 2/3 for ZnzNiMn2-z is discussed in relation to larger alterations in the series MgzNiMn2-zO4. Structural interpretation is proposed based on the comparison of the molar volume of spinels M Mn2O4 (M: Mn, Fe, Co, Ni, Cu, Zn, Mg).
    Notes: Die Substitution von ZnII anstelle von Mangan in der reihe ZnzII NiIIMnzIVMn2-2zIIIO4 (O ≤ z ≤1)ergibt stabile Spinelle, die im Unterschied zu Spinellen MgzIINiIIMnzIVMn2-2zIIIO4 (O ≤ z ≤1) beim langsamen Abkühlen im mittleren Temperaturbereich nicht dem Zerfall unter Sauerstoffaufnahme unterliegen. ZnNiMnO4 (z=1) konnte nach Bestimmung der mittleren Oxydationsstufe des Mangans nur in der Zusammensetzung ZnNiMnO3,96 und damit nicht völlig phasenrein erhalten werden. Die im Bereich O ≤ z ≤ 2/3 relativ geringe Änderung der spezifischen Leitfähigkeit und der Aktivierungsenergie wird im Vergleich mit einer stärkeren Variation der Eigenschaften in der Substitutionsreihe MgzNiMn2-zO4 diskutiert und im Zusammenhang mit einer Betrachtung der Molvolumina von M Mn2O4-Spinellen (M:Mn, fe, Co, Ni, Cu, Zn, Mg) strukturchemisch interpretiert.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0021-8383
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Effect of Cationic Detergents on the Spectral Properties of Pontachrome Azur blue and its Metal(III)-complexes - Micell Effect or Ternary Complex Formation?The results of studies of the metachromasy effect of pontachrome azur blue and its lakes, preferably with aluminium, and hexadecyl-, tetradecyl-, dodecyl- and decyltriethyl-ammonium-bromide, respectively can be explained on the basis of ternary complex formation. The surfactants can be applied at concentrations far below its critical micelle concentrations thus excluding micelle effects.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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