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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Analytical chemistry 44 (1972), S. 2109-2111 
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: Caco-2 ; cell culture ; renin inhibitors ; permeability ; peptide transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 13 (1996), S. 32-37 
    ISSN: 1573-904X
    Keywords: albumin ; nanospheres ; manufacturing ; glutaraldehyde ; cross-linking ; central composite design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to develop a new method to produce albumin particles in the sub-200-nanometer range with a narrow size distribution and in a controlled and reproducible manner. Methods. A new emulsion crosslinking method was developed using ultrasound and static mixing as homogenization steps and a central composite design was used to evaluate the influence of different process parameters on particle size, polydispersity and yield. Results. Response surface analysis allowed the location of the most important factors. Of all the factors investigated, only the albumin concentration and the aqueous phase volume showed a significant influence on response parameters. Albumin nanospheres with sizes below 200 nm in diameter and very narrow size distributions were obtained in high yields (〉80%). Conclusions. This study describes a new preparation method for albumin nanoparticles which are suitable for future drug targeting studies.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 16 (1999), S. 766-771 
    ISSN: 1573-904X
    Keywords: cell culture ; keratinocytes ; androgen metabolism ; testosterone ; transdermal delivery ; 5α-reductase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-904X
    Keywords: cell culture ; keratinocytes ; estradiol ; ethanol ; metabolism ; transdermal delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of our study was to investigate the kinetics of β-estradiol (E2) metabolism in the human keratinocyte cell line HaCaT and to estimate the effect of the potential inhibitor ethanol on the biotransformation reaction. Methods. The formation rates of estrone (E1) in dependence on substrate concentrations were determined in HaCaT cells using tritium labelled E2. Experiments were conducted with and without addition of dehydroepiandrosterone (DHEA) and ethanol. Possible toxic effects on the cells due to ethanol were investigated by cytotoxicity tests. Results. The metabolism of E2 in HaCaT cells exhibited Michaelis-Menten kinetics with Km and Vmax values of 3.5 μM and 216 pmol × mg−1 protein × h−1, respectively. The reaction was inhibited by DHEA and ethanol. The alcohol showed a reversible competitive inhibition mechanism for concentrations of 4 to 8% (v/v). Lower ethanol concentrations had no effect, whereas levels ≥10% significantly decreased cell viability leading to a different inhibition mechanism. Conclusions. The HaCaT cell line seems to be a suitable model for studying enzyme kinetics equivalent to the human skin. The concentration dependent inhibitory effect of ethanol observed in this cell line may be relevant for the transdermal E2 application in patients.
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  • 6
    ISSN: 1573-904X
    Keywords: nasal cell culture models ; differentiation ; histochemical characterization ; lectin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate different in-vitro cell culture models for their suitability to study drug transport through cell monolayers. Methods. Bovine turbinate cells (BT; ATCC CRL 1390), human nasal septum tumor cells (RPMI, 2650; ATCC CCL 30), and primary cell cultures of human nasal epithelium were characterized morphologically and histochemically by their lectin binding properties. The development of tight junctions in culture was monitored by actin staining and transepithelial electrical resistance measurements. Results. The binding pattern of thin-sections of excised human nasal respiratory epithelium was characterized using a pannel of fluorescently-labelled lectins. Mucus in goblet cells was stained by PNA, WGA and SBA, demonstrating the presence of terminal N-acetylglucosamine, N-acetylgalactosamine and galactose residues respectively in the mucus of human nasal cells. Ciliated cells revealed binding sites for N-acetylglucosamine, stained by WGA, whereas Con A, characteristic for mannose moieties, labelled the apical cytoplasm of epithelial cells. Binding sites for DBA were not present in this tissue. Comparing three different cell culture models: BT, RPMI 2650, and human nasal cells in primary culture using three lectins (PNA, WGA, Con A) as well as intracellular actin staining and transepithelial electrical resistance measurements we found, that only human nasal epithelial cells in primary culture showed differentiated epithelial cells, ciliated nasal cells and mucus producing goblet cells, which developed confluent cell monolayers with tight junctions. Conclusions. Of the in-vitro cell culture models studied, only human nasal cells in primary culture appears to be suitable for drug transport studies.
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  • 7
    ISSN: 1573-904X
    Keywords: human nasal epithelium ; primary cell culture ; differentation ; drug metabolism ; drug transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A human nasal epithelial cell culture model has been adapted to observe transport and metabolism of drugs, e.g., peptides. Human nasal epithelial cells, isolated by protease treatment of human nasal conchae, grew to confluency after 6-8 days using DMEM supplemented with 1% nonessential amino acids, 1% glutamine, 10% FCS and 1% antibiotics. These cultures expressed microvilli and actively beating cilia as documented by light microscopy and scanning electron microscopy (SEM). Tight junctions were confirmed by dome formation and positive actin staining using FITC-labelled phalloidin. Preliminary transport studies, carried out with FITC-labelled Dex-tran (FD 4, MW 4400) and Sulforhodamine (SR 101, MW 607), demonstrated the intact barrier function of the cultured monolayer, grown on filter membranes. In addition, the cultured cells metabolized Leu-Enkephalin to Des-Tyr-Leu-Enkephalin demonstrating the presence of aminopeptidase, a naturally occurring enzyme in the human nasal mucosa.
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  • 8
    ISSN: 1573-904X
    Keywords: peptide transport ; permeation enhancers ; micellar systems ; cell monolayers ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effects of five different permeation enhancer systems on the transport properties of a peptidomimetic thrombin inhibitor, CRC 220, were investigated in monolayers of a human intestinal cell line (Caco-2). Methods. The transepithelial transport rates and additionally the cytotoxic properties of these enhancers were characterized using the following tests: measurement of the transepithelial electrical resistance (TEER), the MTT-transformation, the protein content and the release of cytosolic lactate dehydrogenase (LDH), as well as FITC-phalloidin and propidium iodide staining. Results. All permeation enhancer systems showed concentration-dependent effects on cell permeability and toxicity. The most prominent effects on peptide transport were seen at the highest concentration (40 mM), yielding the rank order, NaTC 〉 NaTC/Cholesterol 〉 Solulan C24 〉 NaTC/Oleic acid 〉 NaTC/PC18. Using the TEER after 120 min exposure as the most sensitive parameter describing cytotoxicity, the following order was obtained: Solulan C24 〉 NaTC 〉 NaTC/ PC 18 = NaTC/Cholesterol 〉 NaTC/Oleic acid 〉 NaTC/PC. Generally, efficient enhancement of peptide transport was associated with a noticeable influence on cell viability under in-vitro conditions. Conclusions. Taking into account permeation and cytotoxicity as a function of concentration, both NaTC at 15 mM and the mixed micellar system NaTC/oleic acid at 0.75 mM offer interesting enhancement properties, showing an 18-fold increase in CRC 220 transport rates. The effects on cell viability and cytotoxicity were comparatively low and of reversible nature.
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  • 9
    ISSN: 1573-904X
    Keywords: structure-permeation relationship ; lipophilicity ; hydrogen bonding ; peptide-transport ; Caco-2 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 115 (1982), S. 3096-3106 
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Thiono and Dithio Esters, XXIX. Reactions of Diazo Compounds with ThiooxalatesDimethyl tetrathiooxalate (1) reacts with all diazo compounds 2 investigated to form 1,3-dithioles 3 in high yield. Complex mixtures of products, however, are obtained from O,O-dimethyl dithiooxalate (6) and diazo compounds. The reactions of 6 with diazomethane, diazoethane, 2-diazopropane and diphenyldiazomethane were investigated more in detail.
    Notes: Tetrathiooxalsäure-dimethylester (1) bildet mit allen untersuchten Diazoverbindungen 2 in einheitlicher Reaktion die 1,3-Dithiole 3. Komplexe Produktgemische entstehen hingegen bei der Umsetzung von Dithiooxalsäure-O, O-dimethylester (6) mit Diazoverbindungen. Näher untersucht wurde die Reaktion von 6 mit Diazomethan, Diazoethan, 2-Diazopropan und Diphenyl-diazomethan.
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