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61.
Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells 总被引:5,自引:0,他引:5
Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC50 values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier. 相似文献
62.
Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy 总被引:2,自引:1,他引:1
Fabio Minicucci †Giancarlo Muscas ‡Emilio Perucca §Giuseppe Capovilla Federico Vigevano ¶Paolo Tinuper 《Epilepsia》2006,47(S5):9-15
Summary: Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits. 相似文献
63.
采用中药与行为干预综合治疗的方法对140名轻、中度精神发育迟滞的儿童进行分组康复观察。结果发现中药加行为干预组治疗后智力商数(IQ)及能力的变化最大,明显优于单用中药组和单纯行为干预组(P<0.01);与对照组相比有非常显著的差异(P<0.001)。从而为精神发育迟滞儿童的康复治疗提供了新的途径。 相似文献
64.
A case of partially reversible chronic renal failure due tolong-term NSAID use is discussed. An analysis of this and similarcases recently reported indicates many similarities betweenchronic NSAID nephropathy and analgesic nephropathy. 相似文献
65.
M. Schmutz K. Klebs V. Baltzer 《Journal of neural transmission (Vienna, Austria : 1996)》1988,72(3):245-257
Summary The influence of antiepileptics on the evolution of rat amygdaloid kindling was studied.Under placebo conditions clonic convulsions and a spike-wave EEG pattern developed. Diazepam, clonazepam, clobazam and phenobarbital were most effective in suppressing the evolution of kindling; the effects of valproate sodium, ethosuximide and acetazolamide were somewhat less pronounced in this respect. Carbamazepine, oxcarbazepine and phenytoin, on the other hand, enhanced kindling development, i.e. the increase in duration of after-discharge was faster than in the placebo group. The results indicate that under the above experimental conditions drugs with no anti-absence component can be distinguished from those with an anti-absence component. The mechanism of action underlying the observed effects is not yet known; the hypothesis that under special conditions protective inhibitory neuronal activity can develop to absence type seizures is proposed. 相似文献
66.
Laurent P. Rivory Michael S. Roberts Susan M. Pond 《Journal of pharmacokinetics and pharmacodynamics》1992,20(1):19-61
An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances.This study was supported by the National Health and Medical Research Council of Australia. 相似文献
67.
门诊抗菌药物使用调查 总被引:2,自引:1,他引:1
目的了解医院门诊抗菌药物应用情况,为临床合理应用抗菌药物提供依据。方法抽查2006年1月至11月份门诊处方18163张,统计抗菌药物使用情况,并评价其合理性。结果含抗菌药物处方5809张,占总处方数31.98%。头孢菌素类药物使用率最高,其次为喹诺酮类。给药途径主要为口服给药。结论抗菌药物应用基本合理,但使用中存在一些问题,应引起重视。 相似文献
68.
笔者结合单位的做法和体会,对医疗单位等在特殊药品使用管理中存在的问题,提出特殊药品的管理应法制化、职责化、程序化、档案化及提高业务素质、奖优罚劣的管理方法。 相似文献
69.
桂枝汤各组分作用的比较 总被引:1,自引:0,他引:1
以急性毒性、镇痛及体温降低作用为指标比较了桂枝汤及其组方中五味中药的作用。证实桂枝汤的镇痛作用主要由桂皮和芍药所致;降温作用主要因桂皮和甘草所致。在方剂中各味中药可产生协同效应。桂枝汤毒性主要由桂皮和甘草所致。方剂中各药的毒性均较单独用药降低。表明桂枝汤组方后各味中药的疗效增强而毒性降低。 相似文献
70.
Classification of drugs for teratogenic risk 总被引:2,自引:0,他引:2