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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 401-402 
    ISSN: 1573-8744
    Keywords: hysteresis ; proteresis ; pharmacodynamic modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The authors propose the word “proteresis” to designate the clockwise hysteresis, i.e., when an effect increases more rapidly than the observed drug concentrations. Such a phenomenon has been recently described for aspirin and nicotine. Indeed hysteresis means “which comes after,” while “proteresis,” the greek symmetrical word, means “which comes earlier,” a more appropriate term for the described situation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 24 (1996), S. 265-282 
    ISSN: 1573-8744
    Keywords: compliance ; MEMS ; population pharmacokinetics ; Markov chain model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract For population pharmacokinetic analysis of multiple oral doses one of the key issues is knowing as precisely as possible the dose inputs in order to fit a model to the input-output (dose-concentration) relationship. Recently developed electronic monitoring devices, placed on pill containers, permit precise records to be obtained over months, of the time/date opening of the container. Such records are reported to be the most reliable measurement of drug taking behavior for ambulatory patients. To investigate strategies for using and summarizing this new abundant information, a Markov chain process model was developed, that simulates compliance data from real data from electronically monitored patients, and data simulations and analyses were conducted. Results indicate that traditional population pharmacokinetic analysis methods that ignore actual dosing information tend to estimate biased clearance and volume and markedly overestimate random interindividual variability. The best dosing information summarization strategies consist of initially estimating population pharmacokinetic parameters, using no covariates and only a limited number of dose records, the latter chosen based on an a priori estimate of the half-life of the drug in the compartment of interest; then resummarizing the dose records using either population or individual posterior Bayes parameter estimates from the first population fit; and finally reestimating the population parameters using the newly summarized dose records. Such summarization strategies yield the same parameter estimates as using full dosing information records while reducing by at least 75% the CPU time needed for a population pharmacokinetic analysis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 28 (1994), S. 141-148 
    ISSN: 1059-910X
    Keywords: X-ray microanalysis ; Respiratory epithelium ; Secretory cells ; Cryofixation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: In respiratory epithelium, the mucus is densely packed inside the secretory granules (SG) of secretory cells (SC) before being released by exocytosis in the airway lumen. We have previously shown that the frog palate is a representative model of respiratory epithelium and that rapid cryofixation is a very effective technique in preserving the integrity of the mucus SG. The concentration of phosphorus (P), sulphur (S), and calcium (Ca) were analysed inside the SG of the SC of frog palate after quick freezing, cryosubstitution, and embedding in Lowicryl resin at low temperature. The experiments were carried out using X-ray microanalysis conducted with energy dispersive spectrometry (EDS) at 100 kV. The quantitation was carried out using the continuum method with reference to Agar standards. The cryofixation permitted us to distinguish two types of SG depending on whether they were electron dense (serous cells) or electron-lucent (mucous cells). A significant (P 〈 0.001) difference in the S concentration was observed between the individual serous (239 ± 79 mmol.kg-1) and the mucous SG (161 ± 48 mmol.kg-1). No significant difference could be identified in the Ca concentration between the two SG phenotypes. In the serous SG, the P content was high (41 ± 17 mmol.kg-1) compared with the mucous SG where it was not measurable. The comparison of the three element concentrations in each type of secretory cells showed that significant differences in concentration of S and Ca concentration could be observed from one SC cell to another. A significant correlation (r = 0.76, P 〈 0.01) was observed between the S concentration and the topographical position of the SG inside the SC, the more proximal to the lumen, the higher the S concentration, suggesting that the maturation of the SG involves an increase in the protein content possibly due to a maturation process before the mucus exocytosis. Therefore, these results suggest that the elemental composition of granules varies according to the phenotype of the secretory cells and that changes in the S content from one SG to another or even inside the same cell may reflect a differential state in the functional activity of the secretory cells. © 1994 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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