共查询到20条相似文献,搜索用时 12 毫秒
1.
Fiorenzo Battaini Stefano Govoni Stefano Di Giovine Marco Trabucchi 《Naunyn-Schmiedeberg's archives of pharmacology》1986,332(3):267-270
Summary The release of dopamine was investigated in rat striatal slices exposed in vitro to neurotensin. This peptide increased basal and K+-evoked dopamine release. Moreover neurotensin antagonized the flunarizine-induced inhibition of K+-stimulated dopamine release. The K+-evoked 45Ca2+ accumulation was also inhibited by flunarizine. This effect was antagonized by neurotensin. The results suggest that dopamine release in rat striatum is regulated by different molecular events also of peptidergic nature having as possible mechanism of action an influence on calcium ion movements. 相似文献
2.
Micronized prednisone was used to study the effect of powder mixing on drug-excipient interactions and their effect on in vitro dissolution from uncompacted, hand-filled capsules. Two powder formulations contained CaHPO4 X 2H2O (dibasic calcium phosphate dihydrate) as a filler and potato starch or sodium starch glycolate as a disintegrant. The third powder formulation contained pregelatinized starch as a disintegrant/filler. The lubricant in these formulations was magnesium stearate. When drug, CaHPO4 X 2H2O, and the disintegrant were thoroughly mixed and hand filled into capsules without compaction, only approximately 70% of the drug dissolved in 30 min. The incomplete dissolution of the drug was caused by the formation of agglomerates and the inclusion of the drug particles by these agglomerates. In contrast, when a mixture of drug and pregelatinized starch was used, complete dissolution of the drug was achieved after 30 min due to the absence of agglomeration and inclusion. Prolonged mixing of the formulation containing CaHPO4 X 2H2O with magnesium stearate resulted in a decrease in the dissolution rate. The total amount of the drug dissolved at the end of 30 min was reduced from 70 to 20%. The decrease in the rate of drug dissolution resulted from drug-excipient interactions which caused flaking of the magnesium stearate particles. The adhesion of these flakes to the drug particles and drug-excipient agglomerates resulted in hydrophobic coating which reduced water penetration. The rate of drug dissolution was not affected when drug and pregelatinized starch were mixed with magnesium stearate for a prolonged time due to the absence of magnesium stearate flaking and film formation. 相似文献
3.
1. Nitric oxide (NO) is produced and/or regulates transport in many segments of the nephron, including the proximal convoluted tubule, proximal straight tubule, thick ascending limb, cortical collecting duct and inner medullary collecting duct. 2. Endothelin (ET) is produced and/or regulates nephron transport in many of the segments that produce NO or in which transport is regulated by NO. 3. Four potential interactions between NO and ET are: (i) NO and ET may be antagonistic; (ii) NO and ET may be complementary; (iii) the effects of ET may be mediated via NO; and (iv) the effects of NO may be mediated by ET. 4. In conclusion, direct studies examining the interactions between NO and ET are few. However, circumstantial evidence suggests there may be many interactions between NO and ET in the regulation of nephron transport. In particular, recent data obtained from the collecting duct and thick ascending limb indicate that the effects of ET may be mediated by the production of NO and stimulation of its second messenger cascade. 相似文献
4.
Plaisant F Dommergues MA Spedding M Cecchelli R Brillault J Kato G Muñoz C Gressens P 《Neuropharmacology》2003,44(6):801-809
Tianeptine is an antidepressant with proven clinical efficacy and effects on hippocampal plasticity. Hypoxia increased lactate dehydrogenase (LDH) release from cortical neuronal cultures, and tianeptine (1, 10 and 100 microM) inhibited LDH release as efficiently as the N-methyl-D-aspartate (NMDA) antagonist, MK-801. However, tianeptine did not block apoptosis in cultured cortical neurones caused by NMDA, but reduced apoptosis when interleukin-1beta (IL-1beta) was included with NMDA. In 5-day old mice, intracerebral injection of ibotenate induced reproducible lesions in cortex and white matter. Lesion size was markedly reduced by co-administration of MK-801 (1 mg/kg i.p.) but neither by tianeptine or its enantiomers administered acutely (1, 3 or 10 mg/kg i.p.) nor by tianeptine administered chronically (10 mg/kg i.p. for 5 days). Chronic administration of IL-1beta (10 ng/kg i.p. for 5 days) prior to ibotenate injection exacerbated lesion size in cortex and white matter, and this exacerbation was prevented by chronic pre-treatment with tianeptine (10 mg/kg i.p.) or by acute administration of tianeptine (10 mg/kg i.p.) concomitantly with ibotenate. Thus tianeptine has neuroprotective effects against hypoxia in tissue culture and against the deleterious effects of cytokines in cortex and white matter, but not against NMDA receptor-mediated excitotoxicity. 相似文献
5.
MDCK cells are cultured using wide-ranging conditions and can produce variable results. To develop a standard protocol for studying saquinavir transport using MDCKII cells, stably transfected MDCKII cells overexpressing human Pgp (MDCKII-PGP) and MDCKII wild-type cells (MDCKII/wt) were used to evaluate the combined effects of seeding density (6.9 x 10(5) or 5 x 10(4) cells/cm2), substratum (polycarbonate +/- collagen coating) and saquinavir presence on monolayer integrity, Pgp expression, and saquinavir transport. The saquinavir efflux ratio (ratio of BL --> AP/AP --> BL permeability) for MDCKII-PGP cells (6.9 x 10(5) cells/cm2) was 57 with variable mannitol permeabilities. Consistent mannitol permeabilities and higher saquinavir efflux ratios were obtained with 5 x 10(4) cells/cm2 on polycarbonate (78) or collagen-coated polycarbonate (126). The MDCKII/wt saquinavir efflux ratio was 9. Saquinavir presence increased paracellular permeability for all treatments relative to cells seeded onto collagen-coated membranes. Collagen coating caused increased Pgp expression and saquinavir efflux ratios correlated (r2 = 0.96) with Pgp expression levels [MDCKII-PGP (on collagen-coated polycarbonate) > MDCKII-PGP (on polycarbonate) > MDCKII/wt (on collagen-coated polycarbonate)]. These results directly and quantitatively link interrelated differences in cell culture conditions to changes in monolayer integrity, transporter expression, and active transport; and emphasize the critical application of controls in cell culture models. 相似文献
6.
Marucci M Ragnarsson G von Corswant C Welinder A Jarke A Iselau F Axelsson A 《International journal of pharmaceutics》2011,411(1-2):43-48
The release mechanism of metoprolol succinate pellets coated with a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC), is mechanistically explained. The kinetics of drug release and HPC leaching were followed for drug doses. The coating was initially not permeable to the drug, and release started only after a critical amount of the HPC had been leached out. Drug release occurred mainly through pores created in the coating by the HPC dissolution. Single-pellet release experiments were also performed. The coating thickness and size of each pellet were measured. In order to quantitatively characterize the transport properties of the coating of the individual pellets, and to determine the effective diffusion coefficient (D(e)) of the drug in the coating, a mechanistic model was used to fit the single-pellet release data. It was found that D(e) increased with time due to an increase in the amount of HPC leached. It was also found that D(e) was dependent on the coating thickness, and increased more slowly with a thicker coating. This agreed well with the finding that the HPC leaching rate decreased with increasing film thickness. 相似文献
7.
Ruey-Shiuan Tsai Nabil El Tayar Pierre-Alain Carrupt Bernard Testa 《International journal of pharmaceutics》1992,80(1-3):39-49
The lipophilicity (expressed by log Poct) and H-bond donor acidity (expressed by Δ log Poct-hep) of the dopaminergic agonist piribedil in different ionization states were investigated in order to assess its capacity for crossing membranes. The present study showed that piribedil has a relatively high lipophilicity (log Poct = 2.84) and is a non- or very weak H-bond donor (Δ log Poct-hep = 0.75), implying optimal properties for transmembranal transport. Based on its microscopic ionization behaviour as studied by 13C-NMR spectroscopy and (log P − log P+) value (5.04) (a measure of the stability of the ionic vs neutral species in a lipidic phase), protonation proved to be very unfavourable in water-saturated octanol due to the hindrance of solvation by the two bulky groups adjacent to the piperazinyl amino group. In addition, transport of piribedil across a lipophilic membrane was studied according to first-order kinetics in a three-compartment model. The effects of lipophilic counterions on the partitioning behaviour and transfer kinetics were examined and shown to be non-existent at equimolar concentrations. 相似文献
8.
The transport of molecules and/or larger corpuscular material into the cells takes place in plasma membrane and plasma membrane-derived vesicles and vacuoles. Transmembrane and intracellular transport of various materials plays an essential role in the final cellular effects of the drugs. Cytoskeletal network forms a three-dimensional array in the cytoplasm of cells and is closely related to the plasma membrane. Thus, the cytoskeleton significantly affects various processes such as endocytosis, organization and fluidity of the membrane, activity of ion channels, or localization of intracellular organelles. The interactions of the cytoskeletal system with cellular transport of drugs are the scope of this article. 相似文献
9.
Gnegy ME 《European journal of pharmacology》2003,479(1-3):83-91
Amphetamine elicits its locomotor-activating and drug-reinforcing effects by releasing the catecholamines dopamine and norepinephrine into the synapse. Amphetamine is a substrate of the plasmalemmal transporters for both dopamine and norepinephrine. As such, it binds to the transporters in conjunction with Na+ and Cl-, facilitating a conformational change leading the transporter to face inward. The subsequent binding of intracellular catecholamine results in an outward transport and release of the catecholamine into the synapse. Both inward and outward transport through the catecholamine transporters are regulated by protein kinases, particularly protein kinase C, but the effect of the enzyme on the two processes appears to be asymmetric. The purpose of this review is to discuss the evidence showing that protein kinase C activation facilitates outward transport through the catecholamine plasmalemmal transporters which may mediate amphetamine action in intact tissue. 相似文献
10.
Pentachlorophenol (PCP) has been widely used as a pesticide, and topical exposure to a chemical mixture can alter its dermal absorption. The purpose of this study was to evaluate the influence of single and binary solvent systems (ethanol, EtOH, and water), a surfactant (6% sodium lauryl sulfate, SLS), and a rubifacient/vasodilator (1.28% methyl nicotinate, MNA) on PCP membrane transport, and to correlate these effects with physiochemical characteristics of the PCP mixtures. Partitioning, diffusion, and absorption parameters of (14)C-PCP at low (4 microg/cm(2)) and high (40 microg/cm(2)) doses were assessed in porcine skin and silastic membranes in vitro. In these 8-h, flow-through diffusion studies, PCP was dosed with the following vehicles: 100% EtOH, 100% water, 40% EtOH + 60% water, 40% EtOH + 60% water + SLS, 40% EtOH + 60% water + MNA, and 40% EtOH + 60% water + SLS + MNA. PCP absorption ranged from 1.55-15.62% for the high dose and 0.43-7.20% for the low dose. PCP absorption, flux, and apparent permeability were influenced by PCP solubility, and PCP apparent permeability was correlated with log PC (r2 = 0.66). Although PCP was very soluble in pure ethanol (100%), this vehicle evaporated very rapidly, and PCP absorption in ethanol was the lowest with this vehicle when compared to pure water (100%) or aqueous ethanol mixtures in general. MNA had no significant effect on membrane absorption or relative permeability R(P) in aqueous ethanol solutions, but the presence of the surfactant, SLS, significantly reduced PCP absorption and R(P) in both membrane systems. In conclusion, these studies demonstrated that modification in mixture composition with either a solvent and/or a surfactant can influence PCP diffusion in skin. Physicochemical interactions between these mixture components on the skin surface and stratum corneum contributed significantly to PCP transport, and these interactions were identified by simultaneously assessing chemical diffusion in biological and inert membrane systems. 相似文献
11.
Alginate-polylysine-alginate microcapsules: effect of size reduction on capsule properties 总被引:2,自引:0,他引:2
Strand BL Gåserød O Kulseng B Espevik T Skjåk-Baek G 《Journal of microencapsulation》2002,19(5):615-630
Alginate-polylysine-alginate capsules containing insulin-producing cells have been used as a bio-artificial pancreas in the treatment of diabetes mellitus. In a search for microcapsules with improved diffusion characteristics, a high voltage system was developed that produces 250,000 beads/min with a diameter of 160 microm +/- 3-5%. The diameter of the beads could be varied between 160-700 microm depending on the needle diameter and construction, the voltage, the distance between the electrodes and the flow of alginate solution. Ca-alginate beads with diameters of 200 and 500 microm were produced by the high voltage electrostatic system. The 200 microm beads were sensitive to poly-L-lysine (PLL) exposure and had to be washed in ion-free solution to avoid collapse. The 200 microm beads swelled more than the 500 microm beads in the washing and PLL treatment. Also, the porosity of the capsules changed with size, but capsules impermeable to tumour necrosis factor (TNF) could be made by exchanging PLL with poly-D-lysine (PDL) for the 500 microm beads. The 200 microm beads were impermeable to IgG after PLL exposure. Islets of Langerhans were encapsulated in alginate-PLL-alginate capsules and evaluated by measuring protruding islets and insulin production. Islets in microcapsules made by the high voltage electrostatic system did not function differently from islets in larger microcapsules made by an air jet system. In conclusion, alginate capsules made by a high voltage electrostatic system enable large-scale production of small capsules with a narrow size distribution that can meet the functional properties of larger capsules by small changes in the encapsulation procedure. 相似文献
12.
Maheshwari Manish Jahagirdar Harshal Paradkar Anant 《European journal of pharmaceutical sciences》2005,25(1):41-48
This study deals with development of melt sonocrystallization technique for ibuprofen agglomerates and characterization of their physicochemical, micromeritic and compressional properties. Melt sonocrystallization process was developed for ibuprofen in which ibuprofen melt was poured in deionized water maintained at 25 degrees C and simultaneously subjected to ultrasonic energy. The agglomerates obtained were evaluated using Scanning electron microscopy (SEM), Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transformed infrared spectroscopy (FTIR), intrinsic dissolution rate, BET analysis, solubility, image analysis, Heckel plot analysis and friability studies. The irregular agglomerates with porous surface were obtained. The agglomerates comprised of crystals having different crystal habits such as needles, plates, and some hollow tubes. Solubility, specific surface area and intrinsic dissolution rate increased with the treatment of ultrasonic energy. SEM and XRPD confirmed crystal habit changes. Improvement in compressional properties and reduction in sticking was observed due to the change in crystal habit. Crystal habit changes and lattice defects during processing have caused favorable changes in the physicochemical and compressional properties of the drug. 相似文献
13.
Artigues C Richard V Roussel C Lallemand F Henry JP Thuillez C 《Journal of cardiovascular pharmacology》2000,35(3):468-473
Although adhesion of monocytes to endothelial cells is considered as one of the initial factors leading in the long term to the development of atherosclerosis, the effects of hypertension on monocyte-endothelial cell interactions are still largely unknown. Thus we evaluated whether hypertension affects adhesion of monocytes on rat carotid endothelium, and whether this adhesion may be modified by long-term treatment with L-arginine, the physiologic precursor of nitric oxide (NO). Hypertension was induced in Dahl rats using a sodium-rich diet (8%), in the absence or the presence of L-arginine (1.25 g/L in drinking water). After 1 month, the carotid arteries were isolated, opened longitudinally, and incubated in the presence of 2 x 10(6) monocytes previously rendered fluorescent by incubation with tetramethyl rhodamine isothiocyanate (TRITC), and adherent cells were counted under fluorescence microscopy. In parallel, the production of NO was evaluated in vitro in isolated aorta and isolated hearts. Hypertension markedly increased adhesion of monocytes on carotid endothelium, and this was reduced by L-arginine. Hypertension also reduced an index of NO release at the level of the aorta and the coronary circulation. This impaired release of NO was partially prevented by L-arginine. Thus hypertension was associated with an increased adhesion of monocytes, which is probably due at least in part to a decreased production of NO. The increased adhesion was partly reduced by L-arginine, possibly secondary to an increased production of NO. Such an increased adhesion of monocytes may contribute the increased cardiovascular risk in hypertension. 相似文献
14.
Cocaine and alcohol interactions in the rat: effect on cocaine pharmacokinetics and pharmacodynamics
The effect of alcohol coadministration on cocaine pharmacokinetics and pharmacodynamics was investigated in awake, freely moving rats. Cocaine plasma and brain extracellular fluid (ECF) concentration-time profiles were characterized after intraperitoneal (ip) administration of 30 mg/kg cocaine to rats that were pretreated with either normal saline or alcohol at 5 g/kg in a balanced crossover experimental design. The neurochemical response to cocaine administration, measured as the change in dopamine concentration in the nucleus accumbens (N ACC) and the change in the mean arterial blood pressure were monitored simultaneously. Intragastric alcohol administration significantly increased cocaine systemic bioavailability after ip administration from 0.550 +/- 0.044 to 0. 754 +/- 0.071. Also, the absorption rate constant increased from 0. 199 +/- 0.045 to 0.276 +/- 0.059 min-1 due to alcohol coadministration; however, this increase was not significant. Alcohol inhibition of cocaine metabolism caused an increase in cocaine elimination half-life from 26.3 +/- 3.6 to 40.0 +/- 8.1 min. Also, cocaine tissue distribution was enhanced by alcohol, resulting in a significant increase in cocaine volume of distribution. Analysis of the brain cocaine concentration-neurochemical effect relationship by the sigmoid-Emax pharmacodynamic model showed that Emax increased from 850 +/- 200 to 1550 +/- 640% of baseline due to alcohol coadministration, whereas EC50 decreased from 3400 +/- 580 to 2000 +/- 650 ng/mL, indicating higher cocaine potency in the presence of alcohol. The estimates of the indirect inhibitory pharmacodynamic model used to examine the plasma cocaine concentration-change in blood pressure relationship were not significantly different after the two treatments. These results indicate that alcohol significantly alters cocaine absorption, distribution, and elimination, resulting in higher and prolonged cocaine plasma concentration. Alcohol coadministration also potentiates the neurochemical response to cocaine administration. 相似文献
15.
Microcapsules based on polyelectrolyte complexation, where the inner phase involves a blend of alginate and sodium cellulose sulphate (SCS), have mechanical and transport properties which are relatively insensitive to the chemical composition of the rigid polyanion. Specifically, the bursting force of 400- and 1000 microm microcapsules increase slightly with the degree of substitution of the SCS, though the molar mass of the SCS appears to influence the transport properties more strongly than its composition. The concentration of the sodium chloride in the gelling batch can be varied rather extensively, with optimum properties at approximately half (i.e. 0.5 M) the level typically employed for the formation of cell-containing microcapsules. This indicates that the microcapsule properties can be tuned for biocompatability, without concern that changes to the polymer microstructure or reaction process conditions would adversely influence the bursting force or molar mass cut-off of the capsules. The alginate-SCS blend, which is typical equimass, can be slightly increased in favour of the SCS (to 55 wt%) if one seeks to mechanically optimize the system. The substitution of the oligocation polymethylene-co-guanidine with pDADMAC seems strongly undesirable. Similarly, the replacement of SCS with sulphoethylcellulose, while possible, offers no important advantages. The overall optimum conditions appear to be for a SCS with a DS of 2, prepared at 1.2 wt% of total cation with alginate. The ideal ratio, for mechanical and transport properties, of SCS to alginate is 55:45 (wt:wt), which represents a subtle modification from the classical formulation with very good biocompatability. 相似文献
16.
M Raghoebar W B Van den Berg C A Van Ginneken 《Drug metabolism and drug interactions》1989,7(4):351-401
The need for experimental models to study cellular pharmacokinetics and mechanisms of cell association of drugs in relation to the (patho)physiology is obvious. These models, although never identical to the in vivo physiological environment, can provide fundamental insights with respect to cellular transport mechanisms of drugs in vivo. This knowledge contributes to the development of drug targeting. The human polymorphonuclear leukocyte (PMN) was chosen in our studies as model and target cell because of its involvement in the action of different groups of drugs. First, the physiology and transport characteristics of the PMN has been described. Secondly, the mechanisms of association of some drugs with the PMN are considered. The possible contribution of cellular pharmacokinetics to drug targeting to the PMN is discussed. 相似文献
17.
Transdermal drug delivery using microneedles (MNs) depends on the rate of drug transport through the viable epidermis. Therefore, minimising the distance between the drug-loaded surface and the microcirculation in the dermis where the drug is absorbed into the body is significant in improving drug delivery efficiency. A quantifiable relationship between MN design parameters and skin diffusion properties is therefore desirable, which is what this study aims to achieve. A framework is presented to quantitatively determine the effects of design parameters on drug diffusion through skin, where the effects of compressive strain on skin due to insertion of MN are considered. The model is then used to analyse scenarios of practical importance. For all scenarios analysed, predicted steady-state flux was found to be lower when effect of MN strain on diffusion coefficient was accounted for. For example, simulations results indicated increasing tip radius from 5 to 20 μm and flux increased from 6.56 × 10(-6) to 7.02 × 10(-6) mol/(m(2) s) for constant diffusion coefficient. However, if the effect of strain on diffusion coefficient is considered, the calculated flux increases from 5.30 × 10(-6) to a peak value of 5.32 × 10(-6) mol/(m(2) s) (at 10 μm) and decreases to 5.29 × 10(-6) mol/(m(2) s). This paper contributes by reporting a framework to relate MN geometry to permeability with inclusion of the possible effects the MN design may pose on the diffusion coefficient. 相似文献
18.
Zolnerciks JK Booth-Genthe CL Gupta A Harris J Unadkat JD 《Journal of pharmaceutical sciences》2011,100(8):3055-3061
P-glycoprotein (P-gp)-based drug interactions are a major concern in the clinic and in preclinical drug development, especially with respect to the intestinal absorption of drugs and distribution of drugs across the blood-brain barrier. Thus, there is significant interest in developing in vitro (e.g., cell culture) and in vivo models (e.g., rodents) to predict such interactions. In order to generate accurate predictions from these models, however, an understanding of the magnitude of substrate- and species-dependent differences in P-gp inhibition is required. We have used a sensitive flow cytometry assay to measure the ability of various drugs to inhibit the initial rate of accumulation of two fluorescent drug analogs (probe substrates), 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s -indacene (BODIPY)-verapamil and BODIPY-prazosin, into Lewis lung carcinoma-porcine kidney 1 (LLC-PK1) cells expressing human or rat P-gp. The inhibition of P-gp-mediated efflux of these two fluorescent substrates by several drugs, including quinidine and itraconazole, was found to be substrate- and/or species-dependent. These data suggest that to provide accurate prediction of clinically significant P-gp drug interactions, multiple P-gp substrates will need to be used in both in vitro and in vivo (including human) drug interaction studies. In addition, extrapolation of P-gp-based drug interaction in rodents to humans must be conducted with caution. 相似文献
19.
Daneshtalab N Lewanczuk RZ Russell AS Jamali F 《Journal of clinical pharmacology》2006,46(11):1344-1355
Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and controlled rheumatoid arthritis (n = 12) and healthy subjects (n = 12) received losartan (100 mg). Blood pressures were measured, and samples were taken for pharmacokinetic and inflammatory mediator concentration determination. Active disease significantly increased arthritic index, nitric oxide, and Creactive protein. Although no between-group difference in plasma losartan concentration-time curves was observed, concentrations of the active metabolite, EXP 3174, were significantly reduced by arthritis. This, however, was not accompanied by reduced clinical response. One subject produced no detectable concentrations of EXP 3174 likely due to insufficient CYP2C9 activity. Despite reduced concentrations of the active metabolite, AT1R antagonists potency does not appear to be reduced by inflammation. 相似文献
20.
The effects of Ca and Mg on drug-receptor interactions were examined, using the taenia of the guinea pig and the rat vas deferens. The agonists, butyltrimethylammonium, histamine and noradrenaline protected their receptors from the block by the β-chloroethylamines in normal Locke-Ringer solution Ca-free Locke-Ringer solution and Mg-free Locke-Ringer solution but not in Locke-Ringer solution free of both Ca and Mg. On the other hand, the competitive antagonists, benactyzine methobromide and diphenhydramine protected their receptors from the block by the β-chloroethylamines in all the variations of Locke-Ringer solution used in this paper. These results indicate that Ca and Mg ions are involved in the combination of agonists with their receptors, but they are not involved in the combination of the competitive antagonists and β-chloroethylamines with their receptors. Mg ions may substitute for Ca ions in the agonist-receptor interactions. 相似文献