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61.
62.
Recent toxicological studies indicate that nanoparticles or ultrafine particles (< 100 nm) are more toxic than fine particles (< 2 microm) because of their greater surface area. It is well known that alveolar macrophages play an important role in the first defense against various environmental particles and microorganisms. This is accomplished by binding to a macrophage receptor with collagenous structure (MARCO), one of several scavenger-type receptors expressed on the cell surface of macrophages. MARCO has been shown to mediate the ingestion of unopsonized environmental particles such as TiO(2) and Fe(2)O(3) (1.3 microm in diameter). However, very little is known about the cellular uptake of nanoparticles. In the present study, we investigated whether MARCO mediates the uptake of nanoparticles by using fluorescent-tagged polystyrene particles (20 nm, 200 nm, and 1 microm in diameter). COS-7 cells were transfected with either MARCO cDNA or an empty vector, and the association of the particles with the cells were observed by fluorescence microscopy and atomic force microscopy. MARCO-transfected cells associated with all three sizes of particles in a time-dependent manner, while no obvious binding of particles occurred after 5 h to the empty vector-transfected cells. The uptake of particles by MARCO-transfected cells was partially inhibited by polyG. These results suggest that macrophages associate with nanoparticles (20 nm) at least in part through MARCO and that MARCO plays a role in clearing nanoparticles which can deposit in the alveolar region. 相似文献
63.
Han W. Kim Wolfgang G. Rehwald Elizabeth R. Jenista David C. Wendell Peter Filev Lowie van Assche Christoph J. Jensen Michele A. Parker Enn-ling Chen Anna Lisa C. Crowley Igor Klem Robert M. Judd Raymond J. Kim 《JACC: Cardiovascular Imaging》2018,11(12):1758-1769
Objectives
This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal.Background
The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible.Methods
A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31).Results
In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p < 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03).Conclusions
The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI. 相似文献64.
65.
目的:探讨秦皮甲素在大鼠各肠段的吸收动力学特征。方法:以大鼠在体肠灌流模型从吸收部位、药物浓度考察秦皮甲素的肠吸收动力学情况。结果:秦皮甲素在大鼠各肠段吸收有差异,十二指肠、空肠、回肠中的Ka依次为0.185 0,0.186 5,0.065 7 min-1。结论:秦皮甲素在小肠吸收迅速完全,其吸收呈一级吸收动力学特征且吸收机制为被动转运,适于制成缓释给药系统。 相似文献
66.
67.
异烟肼的体外透皮实验研究 总被引:1,自引:0,他引:1
异烟肼在体外透皮吸收实验中,能透过离体兔皮,月桂氮酮能明显促进其透皮吸收,其中以5%浓度为最佳。 相似文献
68.
The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency 下载免费PDF全文
AIMS: To investigate the absorption profile and estimate the bioavailability of three doses of recombinant human growth hormone (rhGH) smaller than 2 IU in females with GH deficiency (GHD). A second aim of the study was to compare the mean 24 h GH concentrations after s.c. injection of rhGH with the physiological mean 24 h GH concentration of healthy females of comparable age, height, and BMI. METHODS: Fourteen female patients with substituted GHD, and 14 healthy females of comparable age, height, and BMI were studied. All GHD patients underwent 24 h GH sampling after s.c. injection of rhGH in doses of 0.6, 1.2, or 1.8 IU. In addition, these patients underwent a 4 h GH sampling after i.v. injection of rhGH (1 IU). In healthy subjects, blood was withdrawn every 10 min for 24 h to determine the physiological GH profile. RESULTS: A s.c. dose of 0.6 IU resulted in a mean and maximum GH concentration of 0.95+/-0.04 mU l(-1) and 2.62+/-0.09 mU l(-1). A doubling (or tripling) of the rhGH dose resulted in a doubling (or tripling) of the mean and maximum GH concentration. The time of maximum GH concentration was reached on average after 261+/-27 min. Mean GH concentration in healthy females was comparable with the mean GH concentration after a s.c. dose of 1.2 IU. Mean availability of the s.c. injected dose was 63%+/-4%. CONCLUSIONS: A dose of 1.2 IU resulted in a mean GH concentration comparable with the mean physiological GH concentration in healthy females of comparable age, height, and BMI. 相似文献
69.
He Yan-Ling Murby Susan Gifford Larry Collett Andrew Warhurst Geoff Douglas Kenneth T. Rowland Malcolm Ayrton John 《Pharmaceutical research》1996,13(11):1673-1678
Purpose. This study was undertaken to examine the structural determinants of oral bioavailability in the rat of a set of oligopeptides comprising D-amino acids, which were taken to be absorbed paracellularly based on a pronounced sensitivity of permeability to electrical resistance in Caco-2 cell monolayers.
Methods. The study series comprised eleven D-oligopeptides, designed not to be recognised by peptidases or transport proteins, and to have molecular weights between 222 and 406 daltons with different net electrical charges and composition of D-amino acids. All the peptides were [3H]-radiolabelled and analyzed by HPLC with radiometric detection. Bioavailability was estimated based on 24-hr urinary excretion of unchanged peptide after oral and intravenous administrations.
Results. As expected, the series proved metabolically stable. Bioavailability was independent of oral dose when varied by a factor of 10,000, suggesting passive absorption. Whereas bioavailability decreased sharply from 30% to 1% with increasing molecular weight, net charge showed little, if any, effect on bioavailabilty.
Conclusions. This D-oligopeptide model series served as a useful probe for the structural requirements for paracellular absorption in vivo. A critical determinant of bioavailability is molecular size, expressed as molecular weight in this study; net charged appeared of much lesser importance. 相似文献
70.
《Nanotoxicology》2013,7(1):30-42
AbstractTo date, knowledge gaps and associated uncertainties remain unaddressed on the effects of nanoparticles (NPs) on plants. This study was focused on revealing some of the physiological effects of magnetite (Fe3O4) NPs on perennial ryegrass (Lolium perenne L.) and pumpkin (Cucurbita mixta cv. white cushaw) plants under hydroponic conditions. This study for the first time reports that Fe3O4 NPs often induced more oxidative stress than Fe3O4 bulk particles in the ryegrass and pumpkin roots and shoots as indicated by significantly increased: (i) superoxide dismutase and catalase enzyme activities, and (ii) lipid peroxidation. However, tested Fe3O4 NPs appear unable to be translocated in the ryegrass and pumpkin plants. This was supported by the following data: (i) No magnetization was detected in the shoots of either plant treated with 30, 100 and 500 mg l?1 Fe3O4 NPs; (ii) Fe K-edge X-ray absorption spectroscopic study confirmed that the coordination environment of Fe in these plant shoots was similar to that of Fe-citrate complexes, but not to that of Fe3O4 NPs; and (iii) total Fe content in the ryegrass and pumpkin shoots treated with Fe3O4 NPs was not significantly increased compared to that in the control shoots. 相似文献