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1.
Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers 总被引:2,自引:0,他引:2
Permeability coefficients across monolayers of the human colon carcinoma cell line Caco-2, cultured on permeable supports, are commonly used to predict the absorption of orally administered drugs and other xenobiotics. This protocol describes our method for the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model. A few modifications that have been introduced over the years are incorporated in the protocol. The method can be used to trace the permeability of a test compound in two directions, from the apical to the basolateral side or vice versa, and both passive and active transport processes can be studied. The permeability assay can be completed within one working day, provided that the Caco-2 monolayers have been cultured and differentiated on the permeable supports 3 weeks in advance. 相似文献
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Köping-Höggård M Issa MM Köhler T Tronde A Vårum KM Artursson P 《The journal of gene medicine》2005,7(9):1215-1222
BACKGROUND: The available methods for administration of gene delivery systems to the lungs of small animals via nebulization have several drawbacks. These include lack of control over the delivered dose and a negative impact on the stability of the formulation. This paper describes a new nebulization catheter device for the administration of plasmid-based gene delivery systems (polyplexes) as aerosols to the mouse lung in vivo. METHODS: The physical stability of naked pDNA and polyplexes formulated with chitosan oligomers and PEI was examined following nebulization with the catheter device. We also examined the in vitro transfection efficiency of the polyplexes recovered after nebulization. Lung distribution and gene expression after administration of the selected gene delivery systems to the mouse lung were also investigated. RESULTS: In contrast to previously described nebulization methods, the structural integrity of the unprotected naked pDNA was maintained following nebulization by the catheter device, which indicates relatively mild nebulization conditions. In addition, the nebulization procedure did not affect the physical stability of the formulated polyplexes. Small volumes of the pDNA aerosol (10-20 microl) were delivered in a highly controlled and reproducible manner. The aerosol droplet size varied with the molecular weight of the polycations. Aerosol delivery via this method resulted in improved lung distribution of pDNA polyplexes and a six-fold increase in the efficiency of gene delivery in vivo over that seen with the commonly used intratracheal instillation method. CONCLUSION: The use of the nebulization catheter device provides a promising alternative for aerosol gene delivery to the mouse lung. 相似文献
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The elimination from the blood of 51Cr-labelled mouse erythrocytes modified with trinitrophenyl (TNP) groups was followed in mice. After 24 hours, when a stable concentration of the labelled erythrocytes has been attained, monoclonal anti-TNP-antibodies were given intravenously, either in free, soluble form, or bound to microparticles containing immobilized protein A. The anti-TNP-antibodies induced a rapid elimination of the TNP- and 51Cr-labelled erythrocytes. Over the 8-hours time period studied, the elimination rate was significantly faster when the antibodies were administered bound to the particles. After the elimination of the target cells, the radioactivity was found in the liver, spleen and bone marrow. These results and relevant control experiments indicate that a solid carrier 1. can be directed to a specific target cell with a specific antibody and 2. can induce a rapid elimination of the target cell from the circulation. 相似文献
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Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. 总被引:30,自引:0,他引:30
Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10(-8) to 5 x 10(-5) cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10(-6) cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10(-6) cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10(-7) cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption. 相似文献
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Attachment of different soil bacteria to arbuscular mycorrhizal fungal extraradical hyphae is determined by hyphal vitality and fungal species 总被引:2,自引:0,他引:2
Attachment of certain bacteria to living arbuscular mycorrhizal fungal extraradical hyphae may be an important prerequisite for interactions between these microorganisms, with implications for nutrient supply and plant health. The attachment of five different strains of gfp-tagged soil bacteria (Paenibacillus brasilensis PB177 (pnf8), Bacillus cereus VA1 (pnf8), Pseudomonas fluorescens SBW25 :: gfp/lux, Arthrobacter chlorophenolicus A6G, and Paenibacillus peoriae BD62 (pnf8)) to vital and nonvital extraradical hyphae of the arbuscular mycorrhizal fungi Glomus sp. MUCL 43205 and Glomus intraradices MUCL 43194 was examined. Arthrobacter chlorophenolicus did not attach to hyphae, whereas the other bacterial strains did to a varying degree. Only P. brasilensis showed greater attachment to vital hyphae than nonvital hyphae of both Glomus species tested. Pseudomonas fluorescens showed a higher attachment to vital compared with nonvital Glomus sp. MUCL 43205 hyphae, whereas this relationship was opposite for attachment to G. intraradices. Both B. cereus and P. peoriae showed higher attachment to nonvital hyphae. This study provides novel evidence that under laboratory conditions soil bacteria differ in their ability to colonize vital and nonvital hyphae and that this can also be influenced by the arbuscular mycorrhizal fungal species involved. The significance of bacterial attachment to mycorrhizal fungal extraradical hyphae is discussed. 相似文献
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Tømmeraas K Köping-Höggård M Vårum KM Christensen BE Artursson P Smidsrød O 《Carbohydrate research》2002,337(24):2455-2462
The trimer 2-acetamido-2-deoxy-D-glucopyranosyl-beta-(1-->4)-2-acetamido-2-deoxy-D-glucopyranosyl-beta-(1-->4)-2,5-anhydro-D-mannofuranose (A-A-M) was reductively N-alkylated onto a fully de-N-acetylated chitosan (F(A)<0.001, DP(n)=25) to obtain branched chitosans with degree of substitution (DS) of 0.070, 0.23 and 0.40, as determined by 1H NMR spectroscopy. The apparent pK(a) values of the primary and secondary amines of the chitosans substituted with the trimer A-A-M were determined by monitoring the chemical shift of the H-2 of GlcN, and were determined as 6.5-6.9 for the primary (unsubstituted) amines and as 5.0-5.2 for the secondary (substituted) amines. The intrinsic pK(a) values (pK(int)) were found to be 7.3-7.4 for the substituted and 8.7 for the unsubstituted amines. The chitosan branched with A-A-M (DS 0.40) was found to be soluble in aqueous solution over the entire pH range. SEC-MALLS (size-exclusion chromatography with a multi-angle laser light scattering detector) further showed that addition of branches did not affect the molar hydrodynamic volume of the chitosan. 相似文献
8.
Satish Srinivas Kitambi Enrique M. Toledo Dmitry Usoskin Shimei Wee Aditya Harisankar Richard Svensson Kristmundur Sigmundsson Christina Kalderén Mia Niklasson Soumi Kundu Sergi Aranda Bengt Westermark Lene Uhrbom Michael Andäng Peter Damberg Sven Nelander Ernest Arenas Per Artursson Julian Walfridsson Karin Forsberg Nilsson Lars G.J. Hammarström Patrik Ernfors 《Cell》2014
9.
ABSTRACT: Backgroud Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila) causes the disease tickborne fever (TBF) in domestic ruminants and has for decades been one of the main scourges for the sheep industry in the coastal areas of Norway. Current control strategies are based on reduction of tick infestation by chemical acaricides. METHODS: In the present study, we investigated if frequent pour-on applications of pyrethroids would reduce tick infestion rate and seroprevalence of A. phagocytophilum infection in sheep. Forty lambs, one month old, of the Norwegian White Sheep breed were used. The lambs belonged to the experimental sheep flock at the Department of Production Animal Clinical Sciences. None of the lambs had been on I. ricinus infested pasture before turnout (day 0). All lambs were twins and twenty lambs were treated with a pour-on pyrethroid (Bayticol(R), Bayer A/S, DK-2300) with a dose of 5 ml on days 0, 14, 28, 42, 56, 70, 84, 98, 112 and 128. Twenty lambs were untreated controls. The lambs were collected every fourteen days on pasture for treatment. In addition, the lambs were examined for ticks, blood sampled, weighed, and rectal temperature was recorded. Results and conclusion A significant reduction in tick infestion rate was detected on treated lambs. However, the present results indicate that frequent acaricide treatment does not reduce the seroprevalence to A. phagocytophilum on tick-infested pasture. 相似文献
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