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961.
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A De Ascentiis R Bettini G Caponetti PL Catellani MT Peracchia P Santi P Colombo 《Canadian Metallurgical Quarterly》1996,13(5):734-738
PURPOSE: Delivery of nasal powders of granulated beta-cyclodextrin by insufflation was studied in order to find the relationship between powder properties and delivery behavior. METHODS: Three nasal powder formulations, prepared by granulating beta-cyclodextrin with different binders, were delivered from a powder insufflation device, in which the dose to be emitted was loaded in a gelatin capsule. The delivery sequence of powder was recorded and characterized using an image analysis program. RESULTS: Particle size was the main parameter affecting nasal powder delivery, both as to the amount of dose sprayed and the aspect of cloud produced. Between 50-150 mu m of particle size a substantial change in delivery behavior of powders was observed. Powder of around 100 mu m in size showed useful insufflation characteristics for nasal delivery. Bioavailability of nasal formulations of progesterone/beta-cyclodextrin powders was discussed in term of delivery behavior. CONCLUSIONS: The formulation approaches for improving nasal delivery of powders require the use of size optimized carriers. Insufflation of powders over 50 mu m can favour the particle deposition by impaction, whereas for powders below 50 mu m, deposition by sedimentation is moved. beta-cyclodextrin is a suitable carrier for achieving high systemic availability following nasal administration of powder formulations. 相似文献
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967.
PL Nicklin WJ Irwin IF Hassan M Mackay HB Dixon 《Canadian Metallurgical Quarterly》1995,1269(2):176-186
The X-AG system, a sodium-dependent, acidic amino-acid transport system has been implicated in the transport of L-aspartate and L-glutamate across monolayers of human Caco-2 cells, an in vitro model of intestinal absorption. This system, which shares many properties with the L-glutamate carrier present in the human jejunum, is highly saturable (> 95% at 50 microM), vectorial (apical-to-basolateral > basolateral-to-apical) and sodium-, pH- and temperature-dependent. L-Aspartate was also transported against a 10-fold reverse concentration gradient. These data are consistent with a major (saturable) carrier-mediated pathway superimposed onto a minor non-saturable (diffusional) pathway. The carrier has an absolute sodium-dependence and the Michaelis constants for the sodium-dependent transport component (Km) for L-aspartate and L-glutamate were 56 +/- 3 microM and 65 +/- 6 microM, respectively. Cross-inhibition studies showed that strong interaction with the carrier was limited to close analogues of the natural substrates. Potent inhibitors included L-aspartate, D-aspartate (Ki, 70 microM), L-glutamate (Ki 180 microM) and threo-beta-hydroxy-DL-aspartate (Ki, 55 microM), while partial inhibitors included alpha-methyl-DL-aspartate, D-glutamate, L-asparagine, L-proline and L-alanine. Replacement of the side-chain -COO- group (aspartate) with -SO-3 (L-cysteate, Ki, 65 microM) or -(H)P(O)O- (DL-3-(hydroxyphosphoryl)alanine, Ki, 60 microM) maintained strong interaction with the carrier while -As(O)(OH)O- (DL-3-arsonoalanine, Ki, 1100 microM) and -P(O)(OH)O- (DL-3-phosphonoalanine, Ki, 3270 microM) were much more weakly bound, with the larger, but probably less ionised, arsono analogue being more tightly bound than the phosphono compound. The corresponding analogues of glutamate (homologous extension of the methylene chain) showed negligible interaction. We conclude that Caco-2 monolayers are a relevant experimental model for the study of the transport of acidic amino acids and their analogues in man. 相似文献
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G Ciotti O Gabrielli I Carloni AM Gangale M Bevilacqua F Principi GG Garzetti PL Giorgi 《Canadian Metallurgical Quarterly》1995,47(4):107-110
The aim of this study is the biometrical and morphological evaluation of the ovaries by sonography and the study of the haemodynamics of the ovarian artery flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume and the mean pulsatility index have been evaluated. A significant difference in the ovarian volume has been found between patients and controls. No index between the two groups. We conclude that the doppler ultrasound needs a larger number of cases to evaluate its validity in girls with precocious puberty. 相似文献
970.
Atrial fibrillation occurring after open heart surgery largely depends on heterogeneous dispersion of refractoriness. To investigate the contribution of the autonomic nervous system in this phenomenon, we studied the regional distribution of neurally induced atrial electrophysiological events. Electrical stimulation of the right atrial fat pad, acetylcholine injection into the sinus node artery, and stimulation of the right and left vagosympathetic trunks were compared with respect to detailed atrial mapping. Unipolar electrograms were recorded from 127 atrial sites before and after neural stimulation or acetylcholine injection (10(-7) mol) in 8 anesthetized dogs. Regional changes in atrial repolarization were estimated by epicardial isointegral maps generated from computed values of the area under each electrogram and plotted on an atrial grid. The anatomical distribution of the sinus node artery was assessed by intra-arterial injection of microspheres. The effects of right and left vagal and right atrial fat pad stimulation extended contralaterally. Acetylcholine injected into the sinus node artery affected the lower left atrium whereas no microspheres could be found in this region upon microscopic examination. Therefore, this effect was possibly related to cholinergic activation of neuronal cell bodies located in the right atrial wall and projecting to the lower left atrium, supporting the hypothesis that local circuit neurons were involved in the activation of the intrinsic nervous system of the heart. 相似文献