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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 399 (1999), S. 215-216 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Evolutionary psychology suggests that a woman's sexual attractiveness might be based on cues of reproductive potential. It has been proposed that a major determinant of physical attractiveness is the ratio between her waist and hip measurements (the waist-to-hip ratio, or WHR): for ...
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 237-241 
    ISSN: 1432-1041
    Keywords: Ambroxol ; Uricosuric effect ; uric acid clearance ; creatinine clearance ; hypoxanthine ; diurnal rhythm ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ambroxol is known to promote bronchial secretion and is used as an expectorant. Previous studies had suggested that high doses of ambroxol could reduce the plasma uric acid concentration. The present study was undertaken to confirm this finding, to determine its dose-response relationship and to identify the underlying mechanism of action. Using a placebo-controlled, double-blind parallel group design, 48 healthy male volunteers were randomly allocated to receive placebo b.d. and ambroxol 125 mg b.d., 250 mg b.d. or 500 mg b.d. (12 subjects per group). The subjects were hospitalised during a dietary run-in period of 3 days (Days -3 to -1) and a treatment period of 5 days (Days 1 to 5). On Day -1 (baseline) and Days 1 to 5, all urine was collected and blood samples were taken for the analysis of uric acid, creatinine, xanthine and ambroxol. The measurements were repeated four days after treatment had closed. Steady state plasma concentrations of ambroxol (trough levels) were reached after 2 or 3 days and were linearly related to dose. Ambroxol induced a significant, dose-dependent, reduction in plasma uric acid (250 mg b.d. about 20%; and at 500 mg b.d. about 30%). The diurnally fluctuating uric acid clearance was dose dependently increased and there was no notable effect on creatinine clearance. Plasma hypoxanthine levels were not affected by ambroxol. No severe adverse events were reported and no drug induced changes in the clinical laboratory values were observed. It is concluded that ambroxol has an uricosuric action following oral administration of higher doses (250 mg-500 mg b.d.) and it is well tolerated.
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  • 3
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
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  • 4
    ISSN: 1432-1041
    Keywords: oxitropium bromide ; pharmacokinetics ; radioreceptor assay ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competition between OXBR and3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg·ml−1 and 3 ng·ml−1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.4 l; t1/2α 5.3 min; t1/2β 142 min; AUC 8.9 h·ng·ml−1; renal excretion 50.2%, k10 3.5 l·h−1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug.
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  • 5
    ISSN: 1432-2242
    Keywords: Unstable alleles ; Flower variegation ; Gene regulation ; Petunia hybrida
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In a progeny of a selfed individual of the dark red-flowered cultivar ‘Roter Vogel’ some white-flowered plants appeared as the result of a mutation of the genetic factor Anl involved in anthocyanin synthesis. The white flowers of these plants had red spots owing to back-mutations in the dermal cells of the young corolla. Owing to a striking unstability of the new allele of Anl, a number of mutants originated which differ mutually in the frequency of reversion, which expressed itself in the very substantial differences in the spot density of the limb of the corolla. Between a mean number of less than one spot per cm2 of the limb and a mean number of over 10.000 spots/cm2, a series of transitions was found. The reversions did not remain restricted to the young epidermis but also occurred in sporogenous tissues. This resulted in the appearance of selfcoloured red descendants of plants with red-spotted white flowers. There is a positive correlation between the spot density of the parent plants and the percentage of plants with completely red corollas. The red spots on the corolla usually have the same colour as the wild type (‘Roter Vogel’), but occasionally mutants occur with paler spots, the colour varying from a very pale pink to a red nearly as deep as in the wild type. The selfcoloured descendants of such mutants also show this colour variation from pale pink to red. On the grounds of these observations a theory was formulated which postulates that the Anl locus consists of a structural gene responsible for an enzyme active during anthocyanin synthesis and a regulatory element built up from intermediate repetitive DNA. This regulatory element in turn is built up of two components, one of which, the ‘mutator’, decides the activation of the structural gene while the other, the ‘expressor’, modifies the rate of activation. The mutations must be considered representative of larger or smaller deletions within one or both of these components. Reversions are the result of the restoration of the deletions by means of an amplification of the repetitive DNA in dividing cells of the developing flower buds.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 1205-1211 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusie Het gebruikte micro-organisme blijkt bijzonder geschikt te zijn om de relatie structuur-fotobiologische activiteit te bestuderen. Bij het voorspellen van een eventueel risico bij therapeutisch gebruik, zal men zich bewust moeten zijn van het feit dat de experimentele resultaten verkregen zijn met een micro-organisme. Vanwege het grote verschil in celstructuur is een directe extrapolatie naar de mens dan ook niet mogelijk. Gelet op het feit dat chloordiazepoxide zowel bij de muis als bij therapeutisch gebruik bij de mens fototoxiciteit kan veroorzaken, zou een indicatie kunnen zijn dat zich hier een vergelijkbaar type van fotobiologische activiteit voordoet als in het bovengenoemde micro-organisme.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 2 (1980), S. 547-556 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract By labelling chlordiazepoxide and diazepam with14C it was possible to follow quantitatively the photochemical decomposition of these compounds. It was found for chlordiazepoxide that the wavelength of light does not determine the character, but only the concentrations of the products formed. On irradiation of chlordiazepoxide, dissolved in methanol or methanol-water (pH=7.4), an oxaziridine is formed, which is subsequently converted into a quinoxaline and a benzoxadiazocine derivative. However, by irradiation in the presence of glutathione, the rate of decomposition is increased and the scheme is completely changed. Instead of the quinoxaline and the benzoxadiazocine derivative, the reduced form of chlordiazepoxide and a conjugate are formed. It was established that the oxaziridine, the first photoproduct of chlordiazepoxide, reacts spontaneously with glutathione at room temperature without light. On irradiation of diazepam, dissolved in methanolwater (pH=7.4), with light of 300 nm a benzophenone derivative is the only decomposition product, while with light of 254 nm also a quinazoline derivative is formed as a minor product. With methanol as solvent (λ=254 nm) the concentration of the products formed is strongly influenced, quinazoline derivatives become the main products and the benzophenone derivative a minor product.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 800-809 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The photochemical activity of nitrazepam, clonazepam and flunitrazepam has been investigated. These closely structurally related compounds decompose photochemically in an oxygen-poor medium, resulting in photoreductive dimerisation and photoreduction of the nitro-group to successively the nitroso, the hydroxylamino and finally the amino analogue of the nitro-compound. The photoreductive dimerisation compound is a result of a coupling reaction between the respective nitroso and hydroxylamino derivatives. In an oxygen-rich medium, however, the 7-nitro-1,4-benzodiazepines are relatively photostable. It appears that the quenching of excited clonazepam and nitrazepam leads exclusively to the formation of singlet molecular oxygen, while in the case of flunitrazepam, beside singlet molecular oxygen, also another reactive oxygen-dependent species is formed. In addition the photochemical activity of methylnitrazepam, methylclonazepam and desmethylflunitrazepam has been investigated. It appears that a relationship exists between the 7-nitro group in the 1,4-benzodiazepine nucleus and the photochemical behaviour.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 828-832 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 10
    Publication Date: 2016-05-06
    Description: In this study, we explored the existence of a transcriptional network co-regulated by E2F7 and HIF1α, as we show that expression of E2F7, like HIF1α, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1α. Our genome-wide analysis uncovers a transcriptional network that is directly controlled by HIF1α and E2F7, and demonstrates both stimulatory and repressive functions of the HIF1α -E2F7 complex. Among this network we reveal Neuropilin 1 ( NRP1 ) as a HIF1α-E2F7 repressed gene. By performing in vitro and in vivo reporter assays we demonstrate that the HIF1α-E2F7 mediated NRP1 repression depends on a 41 base pairs ‘E2F-binding site hub’, providing a molecular mechanism for a previously unanticipated role for HIF1α in transcriptional repression. To explore the biological significance of this regulation we performed in situ hybridizations and observed enhanced nrp1a expression in spinal motorneurons (MN) of zebrafish embryos, upon morpholino-inhibition of e2f7/8 or hif1α . Consistent with the chemo-repellent role of nrp1a, morpholino-inhibition of e2f7/8 or hif1α caused MN truncations, which was rescued in TALEN-induced nrp1a hu10012 mutants, and phenocopied in e2f7/8 mutant zebrafish. Therefore, we conclude that repression of NRP1 by the HIF1α-E2F7 complex regulates MN axon guidance in vivo .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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