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  • 1
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    Berlin : Springer
    Call number: B0200:34
    Keywords: Proteins / analysis ; Proteins / Databases ; Post-translational modification
    Pages: xviii, 243 p. : ill. (some col.)
    ISBN: 3540627758
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    B0200:34 departmental collection or stack – please contact the library
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  • 2
    ISSN: 1432-1041
    Keywords: nadolol ; nifedipine ; tachycardia ; cardiovascular response ; healthy volunteers ; pharmacokinetics ; exercise heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p〈0.05) and nadolol (p〈0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p〈0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: nifedipine ; plasma concentrations ; distribution ; debrisoquine phenotype ; retard preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variations in plasma nifedipine concentrations have been reported and one study has suggested the existence of a subpopulation of poor metabolisers of this drug. We have studied the variability of 12 h plasma nifedipine concentrations in 64 hypertensive patients on long-term nifedipine Retard 20 mg twice daily. A slightly skewed unimodal distribution with a modal concentration of 15 to 30 ng/ml was obtained. No relationship between 12-h plasma levels and debrisoquine hydroxylation phenotype was found.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: Key wordsTerfenadine ; Grapefruit juice ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (Cmax) and the time to maximum concentration (tmax) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml−1 · h), as was the Cmax (median values 7.2 vs 2.1 ng · ml−1). The tmax was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at Cmax was −13 to +38 ms. Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19–22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0–12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0–12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-9071
    Keywords: Dictyostelium discoideum ; extracellular matrix ; cellulose ; cell-ECM interactions ; slime ; glycoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In this review, we detail the current understanding of the extracellular matrix (ECM) of the migratory slug phase of the cellular slime mould,Dictyostelium discoideum. We describe some structural and non-structural molecules which comprise the ECM, and how these molecules reflect both plant and animal ECM systems. We also describe zones of the multicellular slug that are known to make ECM components, including the role of the prestalk cells and the slug epithelium-like layer. Finally, we review the contributions of studies on mutant to our understanding of the ECM ofD. discoideum, and relate this to differentiation and development in more complex eukaryotic systems.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1619-1560
    Keywords: Selectiveα-blocker ; Selectiveβ-blocker ; Blood pressure ; Lipids ; Exercise ; Essential hypertension ; Clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of six weeks of treatment with the selective peripheralα 1-adrenoceptor blocker terazosin, or the selectiveβ 1-adrenoceptor blocker atenolol on blood pressure, exercise performance and blood lipid profile were compared in a single-blind, randomized, crossover study of 17 patients with mild-to-moderate essential hypertension. Although both drugs significantly reduced blood pressure at rest, atenolol caused a larger fall in supine blood pressure (11/11 and 7.5/7.0 mmHg, atenolol and terazosin, respectively;p 〈 0.001). Both treatments controlled the pressor response to exercise, although a greater reduction in diastolic blood pressure was observed at the end of exercise on terazosin (74.0 ± 5.7 and 91.6 ± 4.0 mmHg, terazosin and atenolol, respectively;p 〈 0.01). Alpha1-blocker therapy was not associated with any measurable improvement or deterioration in cardiopulmonary performance and exercise duration. Unlike atenolol, terazosin therapy had the potentially beneficial effect of reducing serum total cholesterol levels and increasing the high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol ratio.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2018-12-05
    Description: Hmt1p is the predominant arginine methyltransferase in Saccharomyces cerevisiae . Its substrate proteins are involved in transcription, transcriptional regulation, nucleocytoplasmic transport and RNA splicing. Hmt1p-catalyzed methylation can also modulate protein-protein interactions. Hmt1p is conserved from unicellular eukaryotes through to mammals where its ortholog, PRMT1, is lethal upon knockout. In yeast, however, the effect of knockout on the transcriptome and proteome has not been described. Transcriptome analysis revealed downregulation of phosphate-responsive genes in hmt1 , including acid phosphatases PHO5 , PHO11 , and PHO12 , phosphate transporters PHO84 and PHO89 and the vacuolar transporter chaperone VTC3 . Analysis of the hmt1 proteome revealed decreased abundance of phosphate-associated proteins including phosphate transporter Pho84p, vacuolar alkaline phosphatase Pho8p, acid phosphatase Pho3p and subunits of the vacuolar transporter chaperone complex Vtc1p, Vtc3p and Vtc4p. Consistent with this, phosphate homeostasis was dysregulated in hmt1 cells, showing decreased extracellular phosphatase levels and decreased total P i in phosphate-depleted medium. In vitro , we showed that transcription factor Pho4p can be methylated at Arg-241, which could explain phosphate dysregulation in hmt1 if interplay exists with phosphorylation at Ser-242 or Ser-243, or if Arg-241 methylation affects the capacity of Pho4p to homodimerize or interact with Pho2p. However, the Arg-241 methylation site was not validated in vivo and the localization of a Pho4p-GFP fusion in hmt1 was not different from wild type. To our knowledge, this is the first study to reveal an association between Hmt1p and phosphate homeostasis and one which suggests a regulatory link between S-adenosyl methionine and intracellular phosphate.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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  • 10
    Publication Date: 2018-12-15
    Description: Hmt1p is the predominant arginine methyltransferase in Saccharomyces cerevisiae . Its substrate proteins are involved in transcription, transcriptional regulation, nucleocytoplasmic transport and RNA splicing. Hmt1p-catalyzed methylation can also modulate protein-protein interactions. Hmt1p is conserved from unicellular eukaryotes through to mammals where its ortholog, PRMT1, is lethal upon knockout. In yeast, however, the effect of knockout on the transcriptome and proteome has not been described. Transcriptome analysis revealed downregulation of phosphate-responsive genes in hmt1 , including acid phosphatases PHO5 , PHO11 , and PHO12 , phosphate transporters PHO84 and PHO89 and the vacuolar transporter chaperone VTC3 . Analysis of the hmt1 proteome revealed decreased abundance of phosphate-associated proteins including phosphate transporter Pho84p, vacuolar alkaline phosphatase Pho8p, acid phosphatase Pho3p and subunits of the vacuolar transporter chaperone complex Vtc1p, Vtc3p and Vtc4p. Consistent with this, phosphate homeostasis was dysregulated in hmt1 cells, showing decreased extracellular phosphatase levels and decreased total P i in phosphate-depleted medium. In vitro , we showed that transcription factor Pho4p can be methylated at Arg-241, which could explain phosphate dysregulation in hmt1 if interplay exists with phosphorylation at Ser-242 or Ser-243, or if Arg-241 methylation affects the capacity of Pho4p to homodimerize or interact with Pho2p. However, the Arg-241 methylation site was not validated in vivo and the localization of a Pho4p-GFP fusion in hmt1 was not different from wild type. To our knowledge, this is the first study to reveal an association between Hmt1p and phosphate homeostasis and one which suggests a regulatory link between S-adenosyl methionine and intracellular phosphate.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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