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排序方式: 共有2047条查询结果,搜索用时 15 毫秒
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Alf Lamprecht Hiromitsu Yamamoto Hirofumi Takeuchi Yoshiaki Kawashima 《European journal of pharmaceutics and biopharmaceutics》2005,59(2):367-371
5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process. 相似文献
3.
A Nonell S Kerk F Lederbogen D Kopf B Hamann S Lewicka M Deuschle 《Experimental and clinical endocrinology & diabetes》2004,112(1):59-61
Preclinical research suggests adrenal beta-adrenergic receptors to be involved in the regulation of steroid synthesis. In a group of healthy male volunteers, we compared ACTH-induced cortisol and dehydroepiandrosterone (DHEA) secretion after pre-treatment with orciprenaline, propranolol or placebo. Neither baseline nor ACTH-induced steroid secretion differed between these conditions. Our data do not support the hypothesis that the adrenal beta-receptor plays a major role in steroid secretion in humans. 相似文献
4.
Postural changes of body equilibrium on a moving force plate were examined for sinusoidal movements, saccades and frequency whilst different stimuli were applied under various visual conditions. If a dynamic stimulus was used, the stabilization of vision shows a distinct visual-vestibular conflict which provokes postural disequilibrium. This is the cause of motion sickness during car driving. This disequilibrium is also the cause of the motor insecurity experienced during walking and reading at the same time. 相似文献
5.
P Bálványossy K Dévay L Alf?ldi 《Magyar traumatológia, orthopaedia és helyreállító sebészet》1990,33(2):140-141
Authors describe a case of isolated posttraumatic neuropraxy of the musculocutaneous nerve. With the presentation of this very rare case attention is called, based on literary date, to the fact that the above injury can be mixed with the distal tendon rupture of the biceps. 相似文献
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A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. 总被引:2,自引:0,他引:2
Alf Lamprecht Hiromitsu Yamamoto Hirofumi Takeuchi Yoshiaki Kawashima 《Journal of controlled release》2005,104(2):337-346
Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient. 相似文献
8.
Kossard S. Hamann I. Wilkinson B. 《世界核心医学期刊文摘》2006,2(3):9-30
背景:荨麻疹性皮炎可能是代表一种反应模式的亚型的有用术语,病理学家通常将该反应模式命名为皮肤过敏反应。“荨麻疹性皮炎”这一术语不常用,需要定义以明确其临床相关性。目的:定义荨麻疹性皮炎并与其他荨麻疹性反应模式相鉴别,回顾皮肤科医师对荨麻疹性皮炎的临床诊断与组织 相似文献
9.
躯干运动和负重时对足底支撑面侧向横移的姿势控制 总被引:3,自引:0,他引:3
目的:本研究假设自主运动命令和姿势控制信号间有冲突,因此设计在附加重物和不同自主任务的同时给予足底一个模拟受滑的干扰(横移)来观察姿势变化并分析其是否受冲突命令或者力学参数的影响.方法:受试者在执行各种不同的自主任务时,随机给予足底支撑面一个左侧或右侧的横移干扰.这些不同的自主任务包括不负重静止站立、静止站立单手负重5kg、负重5kg站立并躯干静止侧屈15°、负重5kg动态地提重物和放重物5项任务.测量和分析下列参数:中心压力的侧位移(COP)、躯干和股部在冠状面上的角位移和腹内压(IAP).结果:干扰离开质量(向右)、始反应超射的幅度、达到终平衡的时间和达到平衡前COP位移的次数都增加,这种情况可以看作是为了再获得平衡的姿势反应效率降低,因此,如果质量的重力效果能对抗干扰,则再获得平衡的反应效率甚至可以被增进.结论:提重和负重是危害姿势反应效率的因素,因为提重和负重改变了重力效果,加大了对躯干的干扰.在动态条件下躯干的运动不是被横移干扰增强就是被横移干扰抵消,并没有显著地影响改变最终平衡位置姿势校正的效应.因此附加任务的同时给一个支持面上的横移干扰,姿势控制的效应可以被抵消.这个减低的效应可以引起脊柱周围结构的负荷增加和增加受伤的危险性.但是,在恰当地放置负重的位置时,反而可以增进躯干控制和协助恢复姿势平衡. 相似文献
10.
G. F. Hamann 《Der Radiologe》1997,37(11):843-852
Summary
This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of
the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization
is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy
failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation
of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity,
edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and
reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple
concept of a cascade of ischemic effects which would be easy to block seems to be less applicable. A time window of approximately
6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. The recently
introduced treatment regimen with optimized basic treatment, recanalization using thrombolysis and neuroprotection by different
agents is presented. Different modes of a possible intervention are discussed. Modern concepts of stroke therapy including
stroke-unit care and thrombolysis with add-on neuroprotection seem to have potential for improving the outcome of acute stroke
patients.
相似文献