一种新型人TNFα对人肝癌裸鼠移植瘤的抗瘤作用

用人肝癌Ｂｅｌ７４０２瘤株建立了人肝癌裸鼠移植瘤模型，探讨新型重组人ＴＮＦａ对这种移植瘤的抗瘤作用，结果表明，ｒｈＴＦａＤ１１ａ和原型重组人ＴＮＦａ的抑瘤率在３０％左右时，后者后用的活性产闰数是前者的２倍；两者用量相同时，前者的抑产经比后者提高２３个百分     

改进虎杖、鸡血藤炮制方法的研究

对虎杖、鸡血藤作了切制、干燥时间和成品、主要成分及水浸出物的比较。结果表明,趁鲜切片优于传统切块、再切片,既能提高饮片的规格质量和成分含量,亦能减少重复劳动,节约能源,避免药材的浪费。     

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers

Background : Nonsteroidal anti–inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo–oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. Methods : Ten healthy male volunteers were given ketoprofen 1.4 mg kg^-1, ketorolac 0.4 mg kg^-1 and diclofenac 1.1 mg kg^-1 in saline i.v. on three different occasions, at more than one–week intervals, in a randomized double–blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. Results : Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 μg–ml^-1) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 ng ml^-1) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 μM and 6 μM) induced platelet aggregation and ketoprofen in ADP (6 μM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. Conclusion : Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.     

Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells

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.     

Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

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.     

轻、中度精神发育迟滞儿童的中药和行为干预综合治疗探讨

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。     

Partially Reversible Chronic Renal Failure Due to Long-term Use of Non-steroidal Anti-inflammatory Drugs

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.     

Inhibition or enhancement of kindling evolution by antiepileptics

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.     

Axial tissue diffusion can account for the disparity between current models of hepatic elimination for lipophilic drugs

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.