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61.
The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation
of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions
were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy
(FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various
disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration
time and percentage friability, a 32 randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming
agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate.
The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility
between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the
better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression
analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining
rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding
the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic
drug. 相似文献
62.
Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae 总被引:2,自引:0,他引:2
Vps30p/Apg6p is required for both autophagy and sorting of carboxypeptidase Y (CPY). Although Vps30p is known to interact with Apg14p, its precise role remains unclear. We found that two proteins copurify with Vps30p. They were identified by mass spectrometry to be Vps38p and Vps34p, a phosphatidylinositol (PtdIns) 3-kinase. Vps34p, Vps38p, Apg14p, and Vps15p, an activator of Vps34p, were coimmunoprecipitated with Vps30p. These results indicate that Vps30p functions as a subunit of a Vps34 PtdIns 3-kinase complex(es). Phenotypic analyses indicated that Apg14p and Vps38p are each required for autophagy and CPY sorting, respectively, whereas Vps30p, Vps34p, and Vps15p are required for both processes. Coimmunoprecipitation using anti-Apg14p and anti-Vps38p antibodies and pull-down experiments showed that two distinct Vps34 PtdIns 3-kinase complexes exist: one, containing Vps15p, Vps30p, and Apg14p, functions in autophagy and the other containing Vps15p, Vps30p, and Vps38p functions in CPY sorting. The vps34 and vps15 mutants displayed additional phenotypes such as defects in transport of proteinase A and proteinase B, implying the existence of another PtdIns 3-kinase complex(es). We propose that multiple Vps34p-Vps15p complexes associated with specific regulatory proteins might fulfill their membrane trafficking events at different sites. 相似文献
63.
Somitogenesis requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta-Notch pathway and hairy- (h) and Enhancer of split- [E(spl)] related genes. With the aim of unravelling the complex mechanism of somite pre-patterning, we have conducted an extensive search for h/E(spl)-related genes in the third release of the Danio rerio genomic sequence. We identified 14 new h/E(spl) genes and analysed them by in situ hybridisation for their potential role in the somitogenesis process. We describe here the functional analysis of one of these genes, which we have named her11. her11 is a paralogue of her1 and, similar to her1, is arranged in a head to head fashion with another her gene, namely the previously described her5. It shares an expression in the midbrain-hindbrain boundary with her5, but is in addition cyclically expressed in patterns overlapping those of her1 and her7 and complementary to those of hey1. Furthermore it is expressed in the anterior half of the most caudally formed somites. We show that Delta-Notch pathway genes and fused somites (fss) are necessary for the control of her11 expression. However, some aspects of the her11 regulation suggest that at least one additional as yet unknown gene of the Delta-Notch cascade is required to explain its expression. Morpholino-oligonucleotide-mediated knockdown of her11 shows that it is involved in the zebrafish somitogenesis clock via an interaction with her1 and her7. We have also studied the role of hey1 by morpholino injection, but could not find a direct function for this gene, suggesting that it reflects the output of the clock rather than being a core component of the mechanism.Edited by B. Herrmann 相似文献
64.
Assembly of the 30S ribosomal subunit occurs in a highly ordered and sequential manner. The ordered addition of ribosomal proteins to the growing ribonucleoprotein particle is initiated by the association of primary binding proteins. These proteins bind specifically and independently to 16S ribosomal RNA (rRNA). Two primary binding proteins, S8 and S15, interact exclusively with the central domain of 16S rRNA. Binding of S15 to the central domain results in a conformational change in the RNA and is followed by the ordered assembly of the S6/S18 dimer, S11 and finally S21 to form the platform of the 30S subunit. In contrast, S8 is not part of this major platform assembly branch. Of the remaining central domain binding proteins, only S21 association is slightly dependent on S8. Thus, although S8 is a primary binding protein that extensively contacts the central domain, its role in assembly of this domain remains unclear. Here, we used directed hydroxyl radical probing from four unique positions on S15 to assess organization of the central domain of 16S rRNA as a consequence of S8 association. Hydroxyl radical probing of Fe(II)-S15/16S rRNA and Fe(II)-S15/S8/16S rRNA ribonucleoprotein particles reveal changes in the 16S rRNA environment of S15 upon addition of S8. These changes occur predominantly in helices 24 and 26 near previously identified S8 binding sites. These S8-dependent conformational changes are consistent with 16S rRNA folding in complete 30S subunits. Thus, while S8 binding is not absolutely required for assembly of the platform, it appears to affect significantly the 16S rRNA environment of S15 by influencing central domain organization. 相似文献
65.
In some cases vaccination is unreliable. For example vaccination against pertussis has comparatively high level of primary and secondary failures. To evaluate efficiency of vaccination we introduce the idea of effective vaccination rate and suggest an approach to estimate it. We consider pertussis in New Zealand as a case study. The results indicate that the level of immunity failure for pertussis is considerably higher than was anticipated. 相似文献
66.
Modulation of YY1 activity by SAP30 总被引:3,自引:0,他引:3
Huang NE Lin CH Lin YS Yu WC 《Biochemical and biophysical research communications》2003,306(1):267-275
67.
Motomu Nishioka Katsuya Nakai Masato Miyake Yasuo Asada Masahito Taya 《Biotechnology letters》2001,23(14):1095-1099
Synechococcus sp. MA19, grown autotrophically under phosphate-limited conditions at 50 °C, produced poly--hydroxybutyrate (PHB) when intracellular phosphate content was 0.043–0.076mmol per g of cellular components. In the culture for 260h using Ca3(PO4)2 as a phosphate source, strain MA19 accumulated PHB at 55% (w/w) of the dry cells and the amount of PHB produced was 2.4gl–1 which was almost twice that without Ca3(PO4)2 addition. 相似文献
68.
69.
The purpose of this study was to investigate the physicochemical properties of nonpareil beads coated with Eudragit RS 30 D containing ibuprofen as a multifunctional agent. The influence of the concentration of ibuprofen in the film coating and the effect of the coating level on drug release from coated beads was determined in pH 7.2 phosphate buffer solution. The influence of storage time at 23 degrees C and 60 degrees C on the release of ibuprofen from coated beads was also investigated. The thermal properties of the films were determined using a differential scanning calorimeter. Scanning electron microscopy was employed to image the surface morphology of the coated beads. Infrared spectroscopy was used to study the interaction of Eudragit RS 30 D and ibuprofen. Results from the dissolution studies demonstrated that increasing the amount of ibuprofen in the polymeric film reduced the rate of drug release, mainly because of a more complete coalescence of the polymeric particles of the latex dispersion. The glass transition temperature (Tg) of Eudragit RS 30 D films decreased and the surface of the coated beads became smoother as the concentration of ibuprofen was increased. Hydrogen bonding between the polymer and ibuprofen was demonstrated by Fourier transform infrared spectroscopy. No significant differences were found in drug dissolution between the coated beads stored at 23 degrees C for 12 months and those stored at 60 degrees C for 12 hours. The results of this study demonstrated that the ibuprofen plasticized the Eudragit RS 30 D. Furthermore, the dissolution rate of ibuprofen can be controlled and changes in the drug release rate can be minimized by using the drug-induced plasticization technique with this polymer. 相似文献
70.