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991.
Matteo Piazza Chiara Baruffa Jerrold Weiss Francesco Peri 《Biochemical pharmacology》2010,80(12):2050-2056
The identification of the bacterial endotoxin receptors for innate immunity, most notably the Toll-like receptor 4 (TLR4), has sparked great interest in therapeutic manipulation of innate immune system. We have recently developed synthetic molecules that have been shown to inhibit TLR4 activation in vitro and in vivo. Here we present the synthesis and the biological characterization of a new molecule, the cationic amphiphile 3,4-bis(tetradecyloxy)benzylamine, with a structure strictly related to the previously developed TLR4 modulators. This compound is able to inhibit in a dose-dependent manner the LPS-stimulated TLR4 activation in HEK cells. In order to characterize the mechanism of action of this compound, we investigated possible interactions with the extracellular components that bind and shuttle LPS to TLR4, namely LBP, CD14, and MD-2. This compound inhibited LBP/CD14-dependent LPS transfer to MD-2.TLR4, resulting in reduced formation of a (LPS-MD-2-TLR4)2 complex. This effect was due to inhibition of the transfer of LPS from aggregates in solution to sCD14 with little or no effect on LPS shuttling from LPS/CD14 to MD-2. This compound also inhibited transfer of LPS monomer from full-length CD14 to a truncated, polyhistidine tagged CD14. Taken together, our findings strongly suggest that this compound inhibits LPS-stimulated TLR4 activation by competitively occupying CD14 and thereby reducing the delivery of activating endotoxin to MD-2.TLR4. 相似文献
992.
《Journal of microencapsulation》2013,30(1):85-94
AbstractThe efficacy of magnetic albumin microspheres in the targeted delivery of an anti-cancer agent, doxorubicin hydrochloride, has been investigated in rats. Using the tail as a target organ, the animals were intra-arterially administered with either 0.12mg/kg of free drug, or 0.04mg/kg of microsphere entrapped drug in the presence of a 8000 Gauss magnet applied for 30 min at the target-site. In each group, the animals were sacrificed over a 48 h period and their various tissues analysed for drug concentration using HPLC. It was found that compared to the free drug, a one-third dose of microsphere entrapped drug resulted in almost eight times higher drug exposure (AUCo-) at the target site. In addition, the drug delivery to all the non-target tissues, including liver and heart, was substantially reduced. The study confirms the efficacy of magnetic albumin microspheres in the targeted delivery of chemotherapeutic agents. 相似文献
993.
Rania A. Sayed Ahmed R. Mohamed Wafaa S. Hassan Manal S. Elmasry 《Sustainable Chemistry and Pharmacy》2022
Sulfacetamide sodium as an antibacterial agent is co-formulated with prednisolone acetate in Phenamide-P® ophthalmic suspension to cure the ophthalmic infections correlated with inflammatory disorders. For the first time, two innovative, sensitive, specific, and robust chromatographic platforms were developed and their conditions were optimized for rapid analysis of the aforementioned drugs either in the absence or presence of sulfanilamide; a major impurity and degradation product of sulfacetamide sodium. The first platform is HPLC/UV in which separation of the three analytes was performed on a kinetex C18 column (4.6 × 100 mm, 2.6-μm) with isocratic elution using methanol: deionized water pH 3 (adjusted with orthophosphoric acid) in a ratio of (40:60 by volume) as a green mobile phase. The flow rate of the mobile phase was 1 mL/min and the UV detector was set at 262 nm. The second platform is HPTLC/densitometry in which the three analytes were separated on silica gel 60-F254 TLC plates using a developing system of chloroform: acetone: ammonia (6:2:0.1 by volume) and their developed bands were detected at 262 nm. The detection and quantitation limits were found in ranges of (0.01–0.03 μg/mL) and (0.03–0.09 μg/mL) for the HPLC platform while were found in ranges of (0.007–0.01 μg/band) and (0.02–0.04 μg/band) for the HPTLC platform, respectively. The suggested platforms were applied for the determination of sulfacetamide sodium and prednisolone acetate in spiked rabbit aqueous humor without interference by the matrix of aqueous humor. Greenness assessment was performed using eco-scale and GAPI tools revealing the excellent greenness of suggested platforms. According to ICH recommendations, the suggested platforms were validated producing satisfactory results within the accepted limits. The suggested platforms can be successfully applied for routine analysis of the aforementioned drugs not only in QC laboratories but also in the bioavailability centers due to the short analysis time of these platforms. 相似文献
994.
目的 探讨醋酸去氨加压素(DDAVP)治疗儿童单症状性夜间遗尿症(MNE)的临床疗效.方法 将158例MNE患儿按随机数字表法分为试验组及对照组,每组79例.两组均进行行为心理治疗,试验组加用DDAVP.比较两组患者临床疗效、停止治疗后1个月及3个月复发率、治疗前后最大尿流率等指标.结果 试验组患儿临床治疗总有效率高于对照组(P<0.05);停止治疗后1个月及3个月试验组的复发率均低于对照组(均P<0.05).两组最大尿流率及尿量均随观察时间延长而减少(P<0.05),且治疗后试验组以上指标均低于对照组(P<0.05).结论 DDAVP治疗儿童MNE疗效显著. 相似文献
995.
目的:研究注射醋酸甲孕酮(DMPA)妇女月经改变的相关因素。方法:将390例受试者分为哺乳组和非哺乳组两组,对多种数据进行回归分析。结果:注射DMPA次数越多,体质指数越大,哺乳时间越长,发生问经的可能性越大,而经量多的妇女越容易发生不规则流血。注射期间持续阴道流血不闭经妇女和闭经妇女在初潮、经期、周期、经量、注射次数、是否哺乳六个指标上均有显著性差异。结论:本研究为注射前预测妇女月经改变提供了一定的咨询参考。 相似文献
996.
《Expert opinion on pharmacotherapy》2013,14(8):1359-1366
Background: Medroxyprogesterone acetate (MPA) is a synthetic, orally active derivative of the natural steroid hormone progesterone, widely used in oncology both in the endocrine treatment of hormone-related cancers and as supportive therapy in the cachexia syndrome. Objective: The anticachectic mechanisms of medroxyprogesterone, beyond its endocrine activity, are described to explain its therapeutic efficacy in the treatment of cachexia. Methods: After reviewing its pathophysiology and preclinical studies, the main clinical trials on the use of medroxyprogesterone acetate in cancer cachexia, are reviewed. Results/conclusions: Progestagens, including MPA, are at present the only approved drugs in Europe for the clinical treatment of cancer-related anorexia/cachexia syndrome. Placebo-controlled trials on the effect of MPA on cachexia have generally reported an improvement of both anorexia and body weight as well as of quality-of-life parameters. However, the weight gain was due to increased body fat, while fat-free mass was not significantly influenced by MPA treatment. Moreover, very recently the combination of MPA with other new anticachectic agents has been suggested as a way of ameliorating their efficacy in the treatment of cachexia. 相似文献
997.
IntroductionNew drugs have recently been developed, through a better understanding of the mechanisms involved in the progression of prostate cancer, including castrationresistant ones (CRPC). This article aims to describe the mechanisms of action of these new hormonal treatments and their major clinical outcomes and development programs.Materials and MethodsA bibliographic research in French and English using Medline® and Embase® using the keywords “castration-resistant prostate cancer”, “abiraterone acetate”, “orteronel”, “enzalutamide”, and “clinical trials” was performed.Resultsthe androgen signaling pathway remains the cornerstone of advanced cancers management. Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17. Others act as antagonists of the androgen receptor: the enzalutamide, RNA-509 and ODM201. Finally, galeterone combines the two effects.ConclusionProgress conferred by these molecules in terms of overall survival and quality of life in patients with metastatic CRPC, suggest that their use at earlier stages of the disease could reduce morbidity and mortality from prostate cancer. Determining the best strategy for sequence or combination therapy to optimize the use of these new molecules should be investigated. 相似文献
998.
甲孕酮联合长春瑞滨顺铂治疗晚期非小细胞肺癌临床观察 总被引:1,自引:0,他引:1
目的:观察甲孕酮合并NP方案(长春瑞滨+顺铂)化疗及单用NP方案化疗治疗晚期非小细胞肺癌患者的疗效及不良反应。方法:75例接受化疗的晚期非小细胞肺癌患者随机分为单用化疗组(对照组)36例及化疗并用甲孕酮组(治疗组)39例,治疗周期均为21天,2个周期后评价疗效。结果:治疗组、对照组有效率(CR+PR)分别为43.59%(17/39例),41.67%(15/36例),中位疾病进展期分别为4.0、3.6个月,中位生存期分别为9.1、8.9个月;1年生存率分别为38.5%、38.9%;差异无统计学意义(P〉0.05);主要不良反应是Ⅲ~Ⅳ度骨髓抑制、恶心呕吐。治疗组的白细胞减少(7.69%)、血红蛋白下降(0)、血小板减少(7.69%)发生率与对照组(25.00%、19.44%、13.89%)比较差异有统计学意义(P〈0.05);治疗组的恶心呕吐发生率为0,显著低于对照组(13.89%)。化疗后治疗组生活质量改善明显并优于对照组,差异具有统计学意义(P〈0.05)。结论:甲孕酮合用长春瑞滨联合顺铂治疗晚期NSCLC疗效较高,毒副反应轻,患者耐受良好。 相似文献
999.
Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood.
Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC).
Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS.
Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation.
Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity. 相似文献
1000.
The hallmark of prion disease-induced neurodegeneration is the accumulation of PrPSc , a misfolded form of PrPC . In addition, several lines of evidence indicate a role for the immune system and, in particular, inflammation in prion disease pathogenesis. In this work, we tested whether Copaxone, an immunomodulatory agent currently used for the treatment of multiple sclerosis, can affect prion disease manifestation in scrapie-infected hamsters. We show here that Copaxone exerted no effect on prion disease incubation time when treatment commenced 2 weeks after i.p. prion infection. However, when Copaxone was mixed with the initial prion inoculum or administered to hamsters weekly starting on the day of infection, prion disease incubation time was prolonged by 30 days. This suggests that Copaxone may affect the initial infection process. In vitro experiments indicate that Copaxone significantly reduced PrPSc binding to both Chinese hamster ovary (CHO) cells and heparin beads and also binds to heparin by itself. Interestingly, Copaxone also abolished PrPSc accumulation in scrapie-infected cells. We propose that Copaxone delays prion infection by competing with the PrPSc –glycosaminoglycans interaction. Whether the immunomodulating activity of Copaxone is related to its heparin binding and anti-prion properties remains to be established. 相似文献