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31.
Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals. 相似文献
32.
G. I. Bisharova L. I. Kolesnikova V. V. Malyshev 《Bulletin of experimental biology and medicine》1998,126(3):947-949
A comparative study of the parameters of free-radical lipid peroxidation and antioxidant system was performed in children
living in the North for various time periods. Intense lipid peroxidation was shown to be the key factor in the pathogeneses
of several diseases caused by disturbances in the cellular membrane. Decreased resistance of red blood cells to peroxidative
hemolysis is a phenomenon characterizing the adaptation-violating processes.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 342–344, September, 1998 相似文献
33.
J. Åberg B. Abrahamsson M. Grind G. Nyberg B. Olofsson 《European journal of clinical pharmacology》1997,52(6):471-477
Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release
(ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol
CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine
and metoprolol when administered as ER formulation.
Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of
drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis
in six subjects.
Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%)
except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in
the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced
for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding
pharmacodynamics was detected between the fixed combination and the corresponding free combination.
Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after
once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets
and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered
as the fixed combination.
Received: 29 October 1996 / Accepted in revised form: 21 March 1997 相似文献
34.
35.
Angel J. Amante Herwig-Ulf Meier-Kriesche Linda Schoenberg B. D. Kahan 《Transplant international》1997,10(3):217-222
The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use
for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose
to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations
after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling
from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor
the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly
greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (Cav) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de
novo administration of CyA-ME than with CyA-GC.
Received: 13 September 1996 Accepted: 7 January 1997 相似文献
36.
37.
R. Schall F. O. Müller H. K. L. Hundt L. Duursema G. Groenewoud M. Van Dyk A. M. C. Van Schalkwyk 《Biopharmaceutics & drug disposition》1994,15(6):493-503
Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailablity of two 10 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat® XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat® XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat® Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat® XL) have better controlled-release properties than the Adalat® Retard product, and are suitable for once-a-day administration. 相似文献
38.
目的:制备结合凝血酶原复合物(PCC)的阴离子脂膜微泡,评价微泡的理化性质。材料和方法:采用机械振荡直接连接法,分两组(于机械振荡之前或之后加入),制备结合PCC的阴离子脂膜微泡,观察并检测洗涤前后微泡的理化性质。结果:微泡与PCC的结合率及Ⅸ因子活性:两组间比较无明显差异(P>0.05),但洗涤后结合率由洗涤前的95%降为80%,活性由90%降为19%。结论:直接连接法可制备结合PCC的阴离子脂膜微泡,微泡与PCC结合率较高,且洗涤前能保持Ⅸ因子较高的活性。 相似文献
39.
Lipid peroxidation in the brain cortex, striatum, hippocampus, and hypothalamus of rats of the KLA and KHA lines which were distinguished by their strategies of adaptive behavior was investigated following emotional-painful stress. Significant long-term changes in lipid peroxidation were shown to occur in the brain. These had a phase character and depended on the behavioral characteristics of the animals. The investigated brain regions were characterized by different reactions of lipid peroxidation to the stress. The induced depressive-like states (on the 21st day after the stress) in rats of the KLA and KHA lines were distinguished by the largest changes in lipid peroxidation in the striatum and hypothalamus and in the striatum and hippocampus, respectively. One could conclude on the basis of these results that both identical and different mechanisms of formation and development of depression existed in the animals with different behavioral strategies. 相似文献
40.
原发性肉碱缺乏致脂质沉积性肌病的临床与病理特点 总被引:1,自引:0,他引:1
目的 分析原发性肉碱缺乏致脂质沉积性肌病(LSM)的临床与病理特点。方法 回顾性分析4例可能LSM患者的临床资料。结果 本组患者为亚急性或慢性起病,主要表现为近端肌无力,疲劳不能耐受;血清肌酶有不同程度的升高;肌电图示肌源性损害;病理检查示肌纤维内可见大量细小空泡和裂隙形成;MGT染色无破碎红纤维,油红O染色显示空泡为大量脂滴充填;受累纤维以Ⅰ型纤维为主。电镜证实肌纤维内脂滴堆积,可伴有线粒体的轻度增多。改善能量和糖皮质激素治疗有效。结论原发性肉碱缺乏致LSM是一种以易疲劳和肌无力为主要临床表现的脂质代谢障碍性肌病,病理改变以肌纤维内脂滴堆积为主,一般不伴有线粒体结构的明显异常。糖皮质激素治疗可获得良好疗效。 相似文献