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Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.  相似文献   
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对加强药品配送机构监督管理的思考   总被引:1,自引:0,他引:1  
吴公平 《中国药事》2007,21(7):462-463
国家食品药品监督管理局在《关于全面开展加强农村药品监督网络建设促进农村药品供应网络建设工作的指导意见》中明确指出:“为配合药品配送、连锁进县到乡,各省(区、市)食品药品监督部门可以进行建立区域性药品配送站的研究和指导。在进行研究和探索过程中,鼓励将基层的药品批发企业改组成区域性药品配送站”。  相似文献   
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邬玲玲 《护理研究》2006,20(24):2250-2251
岗前培训有助于提高护士技能[1]。医务人员由于职业原因引起可能致命感染(乙型肝炎、丙型肝炎、艾滋病),感染者多数为护士或临床实验工作者,暴露方式主要为暴露于病人的血液,多为针刺伤[2]。而实习护士自我防护意识不足,操作生疏,发生针刺伤比率大,约40.3%[3]。标准防护主张医护人员要严格执行消毒隔离制度和操作规程,充分利用各种屏障防护用具和设备,减少各种危险行为,最大限度地保护医护人员和病人安全。我院从2001年7月起对实习护生进行上岗前标准防护知识及操作培训,现报道如下。1材料与方法1.1研究对象2001年7月—2003年5月,来我院进行…  相似文献   
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A case of untreated fusarial onychomycosis leading to serious consequences is reported. Fusarium solani is a widespread fungus and an occasional human pathogen. It usually invades rapidly in immunocompromised hosts, and often results in a poor outcome despite treatment. We report a woman with diabetes mellitus who had untreated fusarial infection of the nails, which developed into subcutaneous fusariosis, superinfected by bacteria, and then evolved into osteomyelitis that subsequently resulted in septic shock. Early management of mycotic nails in immunocompromised hosts is crucial to prevent life‐threatening disease.  相似文献   
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We have developed a unique, family-oriented approach to lowering plasma cholesterol concentrations in persons with familial hyperlipidemias. The approach includes individual clinic visits and group nutrition classes and uses dietary goals outlined in The New American Diet. A series of 13 nutrition classes is presented to small groups, usually composed of relatives from pedigrees with familial hypercholesterolemia or other familial hyperlipidemias. Dietary action goals, cooking demonstrations, food tasting, and finger-stick plasma cholesterol determinations are important components of the classes. Problem-solving discussion is encouraged in the group. Over the past 4 years, 143 hyperlipidemic individuals, along with at least 94 unaffected family members, have participated in 31 groups, which have met for at least six classes. Many clinic participants lower plasma cholesterol by 20% or more. Keys to the success of this program include emphasizing dietary therapy, using the family setting for nutrition intervention, providing hands-on experience with food and recipes, promoting problem solving for dietary action goals, measuring blood cholesterol during classes, and encouraging long-term follow-up for participants with physicians and dietitians.  相似文献   
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BACKGROUND AND PURPOSE: Thyroidectomy is a common treatment for thyroid disorders in Taiwan, and constitutes a significant percentage of medical expenses. This study investigated the characteristics of thyroidectomy in Taiwan. METHODS: A total of 21 senior general surgeons from 16 medical centers and 5 regional hospitals participated. One surgeon from each hospital reviewed the hospital's medical records of thyroid operations performed in the year 2001. Medical records for 3846 thyroidectomies were retrospectively analyzed, including surgical indications and modalities, complications, pathology reports, and the use of antibiotics. RESULTS: Most of the patients were women (85%). Indications for surgery included proven malignancy (9%), suspicious malignancy (30%), evident compression symptoms (20%), hyperthyroidism (20%), and cosmetic reasons (12%). The majority of patients (78%) underwent a surgical procedure with lobectomy or bilateral thyroidectomy; 13% had unilateral partial thyroidectomy. Prophylactic antibiotics were administered in 46% of procedures, and continued postoperatively in 12%. Postoperative complications occurred in 12% of patients. Hypocalcemia was the most common complication (8%), and its incidence was significantly correlated with the frequency of total thyroidectomy (p < 0.01). Complete pathology reports for the thyroidectomized specimens were available in only 65% of the cases. The frequency of cosmetic reasons for surgery, unilateral subtotal resection, routine antibiotic administration, and incomplete pathology reports were significantly higher in regional hospitals than in medical centers. CONCLUSIONS: Reduction in the high rates of cosmetic reasons for surgery, unilateral partial thyroidectomy, incomplete pathology reports, and use of antibiotic prophylaxis are needed to improve the quality of thyroidectomy in Taiwan.  相似文献   
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