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  • 1
    Electronic Resource
    Electronic Resource
    Design of Potent Phosphorothioate Antisense Oligonucleotides Directed to Human Interleukin 10 Gene Product and Their Evaluation of Antisense Activity in U937 Cells (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1163-1171 
    Details
    ISSN: 1573-904X
    Keywords: antisense oligonucleotide ; interleukin-10 ; antisense effect ; melting temperature ; secondary structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The two objectives of this study were to design potent phosphorothioate antisense oligonucleotides (AS-S-oligos) directed against the human interleukin-10 (IL-10) gene product and to reveal the DNA sequence which best activates antisense effects. Methods. The design of potent AS-S-oligo was performed by using melting temperature (Tm) value of a DNA/RNA hybrid calculated by the nearest neighbor method and a secondary structure of human IL-10 mRNA suggested by RNA folding algorithms. U937 cells were used to estimate the antisense effect of the AS-S-oligos. Results. Of the eight candidates selected as potent AS-S-oligos on the basis of having higher Tm values and favorable secondary structures of the IL-10 mRNA, AS-S-oligos directed against the translated (AS367-S-oligo) and 3′-untranslated (AS637-S-oligo) region of IL-10 mRNA showed the strongest inhibitory effects on IL-10 production and this inhibition was dose- and time-dependent. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that the antisense effects of AS-S-oligos originated from a specific reduction of target IL-10 mRNA by hybridization with AS367- and AS637-S-oligos. In addition, these AS-S-oligos did not affect human tumor necrosis factor-∝ (TNF-∝) production in the cells stimulated by lipopolysaccharide (LPS). Strong positive correlations between the inhibitory effect of AS-S-oligos on the IL-10 production and not only Tm values calculated by nearest neighbor method but also Tm values determined by absorbance versus temperature profiles were demonstrated except for AS25-S-oligo and AS1249-S-oligo. Conclusions. These findings suggest AS367- and AS637-S-oligos powerfully inhibit IL-10 production in U937 cells via an antisense mechanism. In addition, it is suggested efficiency of AS-S-oligo directed against the sequence of the target gene product can be explained by these Tm values and the proposed secondary structures of the target gene product.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018964625977
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  • 2
    Electronic Resource
    Electronic Resource
    Interactions Between Aminoglycosides and Phospholipids Using Liposomes: A Possible Mechanism of Nephrotoxicity (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 362-366 
    Details
    ISSN: 1573-904X
    Keywords: aminoglycoside ; nephrotoxicity ; phospholipid ; liposome ; aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Interactions of aminoglycosides with phospholipids were estimated by the increase in turbidity of liposomes consisting of various phospholipids. The turbidity of liposomes containing negatively charged phospholipids was increased by gentamicin, the highest increase in turbidity being observed for phosphatidylinositol-4,5-diphosphate-containing liposomes. The extent of turbidity was dependent on the concentration of acidic phospholipid in the liposomal membrane as well as the number of amino groups of the aminoglycosides. The release of glucose from glucose-entrapped liposomes depended on the concentration of gentamicin. The turbidity of liposomes containing lipids extracted from rat renal cortex was also increased by aminoglycosides depending on the number of amino groups. From electron microscopic observations, the increase in turbidity of liposome suspensions was caused by liposome fusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015919129091
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of Dextran Sulfate on Renal Accumulation of Gentamicin (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 644-647 
    Details
    ISSN: 1573-904X
    Keywords: gentamicin ; dextran sulfate ; nephrotoxicity ; infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 µg/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin–dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015830614244
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  • 4
    Electronic Resource
    Electronic Resource
    Activation of Fc Receptor-Mediated Phagocytosis by Mouse Peritoneal Macrophages Following the Intraperitoneal Administration of Liposomes (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 518-521 
    Details
    ISSN: 1573-904X
    Keywords: liposome ; macrophage ; phagocytosis ; Fc receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effects of liposomes on the phagocytic activity of mouse peritoneal macrophages were investigated using IgG-opsonized sheep red blood cells (SRBC). The highest ingestion index of opsonized SRBC via Fc receptors of macrophages from BALB/c mice was observed for macrophages harvested on day 4 following the intra-peritoneal injection of liposomes (2.27 µmol lipid/mouse). An increase in the ingestion index was observed irrespective of liposomal charge. Binding parameters of Fc receptors of macrophages from liposome- or saline-injected mice were determined using horseradish peroxidase-conjugated IgG, and an increase in the number of binding sites with the same binding constant was observed in macrophages from liposome-injected mice. The activation mechanism of mouse peritoneal macrophages by liposomes differed from that by lipopolysaccharides. Liposomes thus appear to contribute to the activation of immune response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018958314378
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  • 5
    Electronic Resource
    Electronic Resource
    Uptake of Phosphatidylserine Liposomes by Rat Peyer's Patches Following Intraluminal Administration (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 549-552 
    Details
    ISSN: 1573-904X
    Keywords: liposome ; phosphatidylserine ; Peyer's patches ; uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Uptake of the nonabsorbable marker 6-carboxyfluorescein was investigated both free and encapsulated in liposomes as a function of their surface charge and hydrodynamic diameter in rat Peyer's patch and nonpatch tissue. Significant uptake of the marker occurred only when encapsulated in liposomes consisting of at least 25 mol% phosphatidylserine and was highest in Peyer's patches. 6-Carboxyfluorescein encapsulated in liposomes equal to or greater than 374 nm was preferentially taken up by Peyer's patches. There was a trend to higher uptake in lower intestinal segments. These findings were supported by fluorescence microscopic observations. Uptake by Peyer's patches was specific for negatively charged liposomes as judged from competition studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018945902276
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  • 6
    Electronic Resource
    Electronic Resource
    Stability of Liposomes in Vitro and Their Uptake by Rat Peyer's Patches Following Oral Administration (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1228-1231 
    Details
    ISSN: 1573-904X
    Keywords: liposome ; oral administration ; Peyer's patch ; oral vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To evaluate the usefulness of liposomes as a carrier for the targeted delivery of antigens to gut-associated lymphoid tissue, liposomal stability and uptake by rat Peyer's patches were investigated. Liposomes composed of distearoylphosphatidylcholine, phosphatidylserine, and cholesterol (DSPC-liposome), or dipalmitoylphosphatidylcholine, phosphatidylserine, and cholesterol were stable in acidic solution (pH 2.0), diluted bile, and pancreatin solution. Following the oral administration of liposomes to rats, rhodamine B-PE incorporated in the lipid phase of DSPC-liposomes was preferentially taken up by Peyer's patches in the lower ileum. The uptake of rhodamine B-PE from DSPC-liposomes larger than 374 nm in mean diameter was high. Orally administered DSPC-liposomes of a large diameter thus appear to serve effectively as a vehicle for delivering antigens to Peyer's patches.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018936806278
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  • 7
    Electronic Resource
    Electronic Resource
    Induction of Apoptosis in WEHI 231 Cells by Cationic Liposomes (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 515-520 
    Details
    ISSN: 1573-904X
    Keywords: apoptosis ; cationic liposome ; B cell ; WEHI 231 ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Liposomes are of considerable interest as drug carriers andimmunoadjuvants. However, few investigators have studied thechanges exerted by liposomes in the cells with which they interact.The purpose of this study was to investigate whether liposomes induceapoptosis in B cells. Methods. The mouse immature B cell line WEHI 231 cells and mousesplenic B cells were treated with liposomes, and the induction ofapoptosis was evaluated by monitoring changes in DNA content, DNAfragmentation and chromatin condensation by flow cytometry, agarosegel electrophoresis and by morphological investigation. Results. Cationic liposomes induced apoptosis in WEHI 231 cells, butneutral and anionic liposomes did not. A contact time of 30 minbetween WEHI 231 cells and cationic liposomes was sufficient toinduce apoptosis, and 80% of the cells showed hypodiploid DNAcontent. Apoptosis induced by cationic liposomes composed ofstearylamine was inhibited by addition of the oxidant scavenger,N-acetyl-cysteine. Conclusions. Cationic liposomes induced apoptosis in WEHI 231 cells,and the production of reactive oxygen species is important in theregulation of apoptosis induced by cationic liposomes. It is well knownthat cationic liposomes show cytotoxicity, and apoptosis may be oneof the causes of this toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007552529280
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  • 8
    Electronic Resource
    Electronic Resource
    Preparation of Asialofetuin-Labeled Liposomes with Encapsulated Human Interferon-γ and Their Uptake by Isolated Rat Hepatocytes (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 542-546 
    Details
    ISSN: 1573-904X
    Keywords: liposome ; targeting ; asialofetuin ; hepatocytes ; interferon-gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The selective delivery of human recombinant interferon (IFN)-γ to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN-γ was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [32P]IFN-γ was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [32P]IFN-γ were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4°C) was one-fifth of the uptake (estimated at 37°C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN-γ into hepatocytes in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015833220179
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  • 9
    Electronic Resource
    Electronic Resource
    Liposomal Induction of a Heat-stable Macrophage Priming Factor to Induce Nitric Oxide in Response to LPS (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1389-1392 
    Details
    ISSN: 1573-904X
    Keywords: liposomes ; macrophages ; nitric oxide ; heat-stable macrophage priming factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated. Methods. Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (LPS). Peritoneal washing fluid was also collected from the mice injected with liposomes. NO production was evaluated by measuring the concentration of nitrite in the macrophage culture supernatant by Griess reagent. Results. NO production stimulated by LPS was observed in peritoneal macrophages obtained from the liposome-treated mice, but liposomes did not activate macrophages directly to induce NO in response to LPS. NO production was higher in the liposomes composed of phospha-tidylcholine than that of negatively charged liposomes composed of phosphatidylserine. Peritoneal washing fluid obtained from mice injected with liposomes has a capacity to induce NO production in the macrophages from naive mice. This capacity was not diminished by heat-treatment at 100°C for 5 min. Conclusions. Peritoneal macrophages were activated to produce NO in response to LPS following intraperitoneal injection of liposomes. They did not activate macrophages directly, and the induction of heat-stable macrophage priming factor, but not cytokines, is suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016034303012
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