当药水提物对大鼠中性白细胞活性氧生成和兔血小板聚集的影响

目的 研究当药水提物对大鼠中性白细胞性细胞内内Ca^2 浓度增加、活性氧生成及兔血小板聚集的影响。方法 用酵母多糖、FMLP和A23 187活化大鼠中性白细胞,用化学发光法测定活性氧,用荧光光度法测细胞内Ca^2 浓度,用比浊法测血小板聚集。结果 当药水提物浓度依赖性地抑制酵母多精、FMLP和A23 187诱导的大鼠中性白细胞内Ca^2 浓度增加及活性氧生成;也抑制花生四稀酸、胶原及ADP诱导的兔血小板聚集。和吲哚美辛比较,当药水提物抑制活性氧生成的作用较强而抑制血小板聚集的作用较弱,其作用远强于swertiamarin。结论 当药水提物是极强的中性白细胞活性氧生成抑制剂,其作用强于swertiamarin。     

进行期银屑病患者活性氧代谢变化探讨

目的：探讨进行期银屑病患者活性氧代谢变化。方法：采用细胞化学发光分析技术测定患者及健康对照组外周血淋巴细胞化学发光强度（ Ｌｙｃｌ）及多形核白细胞化学发光强度（ Ｐ Ｍ Ｎｃｌ）,同时测定血浆超氧化物歧化酶（ Ｓ Ｏ Ｄ）、全血谷胱甘肽过氧化物酶（ Ｇ Ｓ Ｈ Ｐｘ）以及血浆丙二醛（ Ｍ Ｄ Ａ）含量。结果：银屑病患者 Ｌｙｃｌ及 Ｐ Ｍ Ｎｃｌ较对照组显著增强（ Ｐ＜ ０．０５）,血浆 Ｓ Ｏ Ｄ活力明显增强（ Ｐ＜ ０．０５）, Ｍ Ｄ Ａ 浓度较对照组明显增高（ Ｐ＜ ００５）。全血 Ｇ Ｓ Ｈ Ｐｘ 活力较对照组显著下降（ Ｐ＜ ０．０５）。结论：进行期银屑病患者细胞功能改变,机体活性氧代谢增强,抗氧化功能下降,组织细胞损伤加快。活性氧损伤可能是该病患者皮损炎症的重要原因。     

Reactive oxygen species in NMDA receptor-mediated glutamate neurotoxicity

In search of endogenous protective substances that inhibit neurotoxic action of glutamate and nitric oxide (NO), we found that brain-derived neurotrophic factor (BDNF), acting on TrkB receptor tyrosine kinase, inhibited neurotoxicity induced by glutamate and NO donors in cultured cortical neurons. In co-cultures of the mesencephalon and striatum, projection of mesencephalic dopamine neurons to the striatum attenuated N-methyl-d-aspartate (NMDA)-induced cytotoxicity in dopamine neurons themselves. Growth factors such as neurotrophins, which the target cells in the striatum would synthesize and secrete, may offer the protection of dopamine neurons against glutamate neurotoxicity.     

Reactive oxidant species in piriform cortex extracellular fluid during seizures induced by systemic kainic acid in rats

Kainic acid (KA) administered systemically to rats produces seizures and brain damage. We measured an increase in reactive oxidant species (ROS) during KA-induced seizures in the extracellular fluid (ECF) of the piriform cortex, a brain region known to be subsequently damaged. Intracerebral microdialysis samples were collected and assayed for isoluminol-dependent chemiluminescence before and after injection of KA (16 mg/kg, ip). Hydrogen peroxide (H₂O₂) concentrations were calculated from catalase-sensitive chemiluminescence, the difference between total and catalase-resistant chemiluminescence. During generalized tonic-clonic seizures, both total and catalase-resistant chemiluminescence increased significantly in samples from brain ECF. Catalase-resistant chemiluminescence, most likely produced by ascorbic acid, increased for a full hour during sustained seizure activity. H₂O₂ concentrations showed a trend towards elevation during seizures. Increased ROS suggest that oxidative stress occurs in brain ECF during sustained seizure activity.     

Polymorphic karyotypes in related Acremonium strains

Summary A restriction fragment length polymorphism (RFLP) analysis was performed on six related Acremonium strains. With respect to the restriction fragment pattern, all strains of A. chrysogenum were indistinguishable from each other but showed distinctive differences from those of A. strictum, A. flavum and Cephalosporium polyvaleurum. Using pulsed-field gel electrophoresis, we obtained different chromosome patterns from most of the Acremonium strains. Remarkably, the pattern varies in three related A. chrysogenum strains which also differ in their rate of cephalosporin C biosynthesis. The electrophoretic karyotyping was confirmed by the location of rDNA genes on separate chromosomes. Our data indicate that chromosome translocations in industrial strains may be responsible for increased -lactam synthesis.     

Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR.

The freshwater, bloom-forming cyanobacterium (blue-green alga) Microcystis aeruginosa produces a peptide hepatotoxin, which causes the damage of animal liver. Recently, toxic Microcystis blooms frequently occur in the eutrophic Dianchi Lake (300 km2 and located in the South-Western of China). Microcystin-LR from Microcystis in Dianchi was isolated and purified by high performance liquid chromatography (HPLC) and its toxicity to mouse and fish liver was studied (Li et al., 2001). In this study, six biochemical parameters (reactive oxygen species, glutathione, superoxide dismutase, catalase, glutathione peroxide and glutathione S-transferase) were determined in common carp hepatocytes when the cells were exposed to 10 microg microcystin-LR per litre. The results showed that reactive oxygen species (ROS) contents increased by more than one-time compared with the control after 6 h exposure to the toxin. In contrast, glutathione (GSH) levels in the hepatocytes exposed to microcystin-LR decreased by 47% compared with the control. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxide (GSH-Px) increased significantly after 6 h exposure to microcystin-LR, but glutathione S-transferase (GST) activity showed no difference from the control. These results suggested that the toxicity of microcystin-LR caused the increase of ROS contents and the depletion of GSH in hepatocytes exposed to the toxin and these changes led to oxidant shock in hepatocytes. Increases of SOD, CAT and GSH-Px activities revealed that these three kinds of antioxidant enzymes might play important roles in eliminating the excessive ROS. This paper also examined the possible toxicity mechanism of microcystin-LR on the fish hepatocytes and the results were similar to those with mouse hepatocytes.     

Pharmacodynamic differences between species exemplified by the novel anticancer agent CHS 828

When a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell‐lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies. Drug Dev. Res. 61:218–226, 2004. © 2004 Wiley‐Liss, Inc.     

冬虫夏草及其伪劣商品的鉴别

冬虫夏草为名贵滋补药。明代即出口日本，现畅销国际市场，是中国传统的出口商品，享有极高的声誉。近年来国内外市场需求增大，而产量小，价格上扬，伪品、掺杂品增多。本文提出实用鉴别方法，以利保证冬虫夏草的质量。