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The objective of this study was to evaluate organogels as potential injectable drug-delivery systems for drospirenone (DRSP). Recently, studies on organogel characterization with focus on the parenteral injection are rarely to find in the literature. DRSP organogels contained the drug suspended in medium-chain triglycerides and were stabilized by various organogelators. The DRSP organogels were assessed in comparison to non-stabilized DRSP microcrystal suspensions (MCSs). Furthermore, rheological properties of the organogels, in particular the elastic modulus (G′), the complex viscosity (η*) and the elasticity, were evaluated with respect to the long-term stability, syringeability/injectability and in vitro release. DRSP organogels showed significantly improved storage stability compared to non-stabilized MCSs with regard to sedimentation and particle growth. Furthermore, all of the DRSP organogels showed shear-thinning behavior. Thus, ejection from syringes was possible by an autoinjector using 23G needles comparable to non-stabilized MCSs. Nevertheless, DRSP organogels exhibited significantly more sustained drug release than non-stabilized MCSs most likely caused by partial recovery of the organogelator structures at 37?°C after destruction. Consequently, DRSP organogels were evaluated to be superior to conventional non-stabilized MCSs. Silica organogels, which provided the highest elasticity, moderate G' and η* and avoided most efficiently particle growth, are slightly more preferable compared to the other DRSP organogels. 相似文献
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采用组织学、形态学及电化学等技术方法,研究了人工养殖条件下美洲鲥鱼雌性亲鱼卵巢发育和性类固醇激素的周期变化规律。结果表明,美洲鲥鱼属于非同步分批产卵类型;根据卵巢外部形状大小及色泽等的不同,可将美洲鲥鱼卵巢发育过程分为6个时期;根据卵母细胞的形态结构、卵黄物质的积累和滤泡细胞的变化,将卵子发生划分为6个时相;卵巢周期变化过程中,肝脏指数(HSI)和肥满度(CF)变化不显著,性腺指数(GSI)与血浆中雌二醇(E2)水平表现出与性腺发育协同一致的变化规律。 相似文献
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Palmer Abraham A.; Miller Mark N.; McKinnon Carrie S.; Phillips Tamara J. 《Canadian Metallurgical Quarterly》2002,116(1):126
Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Mohammad Ali Faramarzi Nadia Zolfaghary Mojtaba Tabatabaei Yazdi Sina Adrangi Hossein Rastegar Mohsen Amini Mohsen Badiee 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2009,84(7):1021-1025
BACKGROUND: A large number of bacterial, fungal and microalgal species are able to bio‐transform steroid compounds. Among them, fungi from the Mucor genus have been shown to mediate hydroxylation, oxidation, and desaturation by the double bond formation and epoxidation of various steroid substances. Mucor racemocus has not been studied for its ability to modify androst‐1,4‐dien‐3,17‐dione, a pharmaceutically important steroid precursor. RESULTS: The filamentous fungus M. racemosus was applied for bioconversion of androst‐1,4‐dien‐3,17‐dione (ADD, I ) in a 5‐day fermentation. Microbial metabolites were purified chromatographically and identified on the basis of their spectral data as 17β‐hydroxyandrost‐1,4‐dien‐3‐one ( II ), 14α‐hydroxyandrost‐1,4‐dien‐3,17‐dione ( III ), 15α‐hydroxyandrost‐1,4‐dien‐3,17‐dione ( IV ), 15α,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( V ), 14α,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( VI ), and 6β,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( VII ). CONCLUSION: Observed modifications included hydroxylation at C‐6β, C‐14α, C‐15α positions and 17‐carbonyl reduction. The best fermentation conditions for production of hydroxysteroid‐1,4‐dien‐3‐one derivatives were found to be 25 °C at 150 rpm for 5 days with a substrate concentration of 0.5 g L?1. Copyright © 2009 Society of Chemical Industry 相似文献
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The Saccharomyces cerevisiae gene YOL151W/GRE2 is widely used as a model gene in studies on yeast regulatory responses to osmotic and oxidative stress. Nevertheless, information concerning the physiological role of this enzyme, a distant homologue of mammalian 3-beta-hydroxysteroid dehydrogenases, is scarce. Combining quantitative phenotypic profiling and protein expression analysis studies, we here report the involvement of yeast Gre2p in ergosterol metabolism. Growth was significantly and exclusively reduced in gre2Delta strains subjected to environmental stress straining the cell membrane. Furthermore, whereas no compensatory mechanisms were activated due to loss of Gre2p during growth in favourable conditions (synthetic defined media, no stress), a striking and highly specific induction of the ergosterol biosynthesis pathway, represented by the enzymes Erg10p, Erg19p and Erg6p, was observed in gre2Delta during growth in a stress condition in which lack of Gre2p significantly affects growth. Involvement of Gre2p in ergosterol metabolism was confirmed by application of an array of selective inhibitors of lipid biosynthesis, as gre2Delta displayed vastly impaired tolerance exclusively to agents targeting the ergosterol biosynthesis. The approach outlined here, combining broad-spectrum phenotypic profiling, expression analysis during conditions reducing the growth of the mutant and functional confirmation by application of highly selective inhibitors, may prove a valuable tool in gene functional analysis. 相似文献
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Paula Bracco Hein J. Wijma Bastian Nicolai Jhon Alexander Rodriguez Buitrago Thomas Klünemann Agustina Vila Patrick Schrepfer Wulf Blankenfeldt Dick B. Janssen Prof. Dr. Anett Schallmey 《Chembiochem : a European journal of chemical biology》2021,22(6):1099-1110
CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation. 相似文献
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The aggregation pheromone of the German cockroach,Blattella germanica, consists of attractant and arrestant, which can be detected by olfactometer and choice-chamber assay, respectively. Both were extracted from the frass-contaminated filter paper being used as a shelter. They were separated by solvent partition withn-butanol and water. The arrestant from then-butanol phase was purified by open column chromatography and then successive HPLC isolated two major arrestant components. Spectral evidence from SI-MS, HR-EI-MS, and NMR experiments with pulse techniques provided possible structures as 1-(6-chloro-4,5-epoxy-5-stigmast-3-yl)--d-glucopyranoside and 1-(6-chloro-5-hydroxy-5-stigmast-3-yl)--d-glu-copyranoside, denoted as blattellastanoside-A and blattellastanoside-B, respectively. They represented arrestant activity as median effective doses (ED50) at 0.044 (A) and 3.2 (B) nmol on 1.0 cm2 of Whatman No. 1 filter paper. 相似文献