灯盏生脉胶囊干预急性进展性脑梗死的前瞻性研究

目的：探讨灯盏生脉胶囊对急性进展性脑梗死（acute progressive cerebral infarction，APCI）的干预作用及外周血单个核细胞（peripheral blood mononuclear cells，PBMC）趋化因子受体1（CX3C-chemokine receptor 1,CX3CR1）、锌指蛋白A20表达的变化。方法：将起病7 d以内的100例APCI患者分为对照组和试验组，每组各50例患者，所有病例均采用常规治疗，试验组除常规治疗外还给予灯盏生脉胶囊治疗。分别于入院时、病程d 7,d 14和d 30检测两组患者Scandinavian卒中量表评分(Scandinavian stroke scale，SSS)、PBMC CX3CR1及锌指蛋白A20表达的变化；于入院时、病程d 30检测两组患者梗死灶体积。结果：对照组病程d 7,d 14及d 30 SSS均明显低于试验组（P＜0.05）；试验组病程d 30梗死灶体积及病程d 7,d 14及d 30 PBMC CX3CR1的表达均明显低于对照组（P＜0.05）。结论：灯盏生脉胶囊可通过下调PBMC CX3CR1的表达而改善其预后。     

灯盏生脉胶囊干预急性进展性脑梗死的前瞻性研究

目的：探讨灯盏生脉胶囊对急性进展性脑梗死（acute progressive cerebral infarction，APCI）的干预作用及外周血单个核细胞（peripheral blood mononuclear cells，PBMC）趋化因子受体1（CX3C-chemokine receptor 1,CX3CR1）、锌指蛋白A20表达的变化。方法：将起病7 d以内的100例APCI患者分为对照组和试验组，每组各50例患者，所有病例均采用常规治疗，试验组除常规治疗外还给予灯盏生脉胶囊治疗。分别于入院时、病程d 7,d 14和d 30检测两组患者Scandinavian卒中量表评分(Scandinavian stroke scale，SSS)、PBMC CX3CR1及锌指蛋白A20表达的变化；于入院时、病程d 30检测两组患者梗死灶体积。结果：对照组病程d 7,d 14及d 30 SSS均明显低于试验组（P＜0.05）；试验组病程d 30梗死灶体积及病程d 7,d 14及d 30 PBMC CX3CR1的表达均明显低于对照组（P＜0.05）。结论：灯盏生脉胶囊可通过下调PBMC CX3CR1的表达而改善其预后。     

灯盏生脉胶囊干预急性进展性脑梗死的前瞻性研究

目的：探讨灯盏生脉胶囊对急性进展性脑梗死（acute progressive cerebral infarction,APCI）的干预作用及外周血单个核细胞（peripheral blood mononuclear cells,PBMC）趋化因子受体1（CX3C-chemokine receptor 1,CX3CR1）、锌指蛋白A20表达的变化。方法：将起病7 d以内的100例APCI患者分为对照组和试验组,每组各50例患者,所有病例均采用常规治疗,试验组除常规治疗外还给予灯盏生脉胶囊治疗。分别于入院时、病程d 7,d 14和d 30检测两组患者Scandinavian卒中量表评分(Scandinavian stroke scale,SSS)、PBMC CX3CR1及锌指蛋白A20表达的变化;于入院时、病程d 30检测两组患者梗死灶体积。结果：对照组病程d 7,d 14及d 30 SSS均明显低于试验组（P＜0.05）;试验组病程d 30梗死灶体积及病程d 7,d 14及d 30 PBMC CX3CR1的表达均明显低于对照组（P＜0.05）。结论：灯盏生脉胶囊可通过下调PBMC CX3CR1的表达而改善其预后。     

灯盏生脉胶囊干预急性进展性脑梗死的前瞻性研究

目的：探讨灯盏生脉胶囊对急性进展性脑梗死（acute progressive cerebral infarction,APCI）的干预作用及外周血单个核细胞（peripheral blood mononuclear cells,PBMC）趋化因子受体1（CX3C-chemokine receptor 1,CX3CR1）、锌指蛋白A20表达的变化。方法：将起病7 d以内的100例APCI患者分为对照组和试验组,每组各50例患者,所有病例均采用常规治疗,试验组除常规治疗外还给予灯盏生脉胶囊治疗。分别于入院时、病程d 7,d 14和d 30检测两组患者Scandinavian卒中量表评分(Scandinavian stroke scale,SSS)、PBMC CX3CR1及锌指蛋白A20表达的变化;于入院时、病程d 30检测两组患者梗死灶体积。结果：对照组病程d 7,d 14及d 30 SSS均明显低于试验组（P＜0.05）;试验组病程d 30梗死灶体积及病程d 7,d 14及d 30 PBMC CX3CR1的表达均明显低于对照组（P＜0.05）。结论：灯盏生脉胶囊可通过下调PBMC CX3CR1的表达而改善其预后。     

卒中后抑郁患者外周血单核细胞趋化因子受体1、锌指蛋白A20的表达及甲状腺功能的改变

目的:研究卒中后抑郁(PSD)患者外周血单核细胞(PBMC)趋化因子受体1(CX3CR1)、锌指蛋白A20表达及甲状腺功能的变化。方法:PSD组为46例PSD患者,对照组为50例同期住院的老年缺血性卒中患者。入院后d 14分别检测两组患者的外周血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)浓度及PBMC CX3CR1和锌指蛋白A20表达的变化。结果:对照组外周血清FT3和TSH浓度较PSD组显著升高,差异有统计学显著性(P<0.05);PSD组外周血清FT4浓度和PBMCCX3CR1表达较对照组明显升高,差异有统计学显著性(P<0.05)。PSD组汉密尔顿(HAMD)评分与FT4浓度和PBMC CX3CR1表达成显著正相关(P<0.05),与FT3及TSH浓度成显著负相关(P<0.05)。结论:外周血清FT3,FT4,TSH浓度及PBMC CX3CR1表达与PSD关系密切,可能是老年PSD患者重要的分子标志物。     

灯盏生脉胶囊抗大鼠局灶性脑缺血-再灌注损伤作用研究

目的 研究灯盏生脉胶囊抗大鼠局灶性脑缺血 再灌注损伤的作用。方法将58只雄性SD大鼠随机分为4组，即假手术组10只，0.9%氯化钠溶液组和灯盏生脉胶囊高、低剂量组各16只。假手术组行假手术，其他3组制作大脑中动脉缺血 再灌注模型。假手术组和0.9%氯化钠溶液组于术前72，48，24，0.5 h及术后22 h灌胃给予0.9%氯化钠溶液，灯盏生脉胶囊低、高剂量组在相同时点分别按0.36和0.72 g·kg 1剂量灌胃给予灯盏生脉胶囊内容物悬浊液4 mL；各组大鼠均在最后一次给药后2 h处死，于脑缺血2 h和再灌注2和22 h分别进行神经行为学评分，再灌注22 h后测定大鼠血清乳酸脱氢酶活性及脑梗死体积百分比，观察脑组织病理学改变。结果再灌注2 h后，灯盏生脉胶囊高剂量组神经行为学评分［(1.75±0.68)分］较0.9%氯化钠溶液组［(2.31±0.79)分］明显降低（P＜0.05）；再灌注22 h后，灯盏生脉胶囊高剂量组神经行为学评分［(1.63±0.89) 分］明显低于0.9%氯化钠溶液组［(2.38±1.09)分］（P＜0.05）。再灌注22 h后，灯盏生脉胶囊高剂量组血清乳酸脱氢酶活性［(1 331.89±366.85) U·L 1］明显低于0.9%氯化钠溶液组［(1 799.56±325.92) U·L-1］（P＜0.05），灯盏生脉胶囊高剂量组脑梗死体积百分比［(9.73±5.66)%］亦明显低于0.9%氯化钠溶液组［(18.31±6.96)%］（P＜0.05）。灯盏生脉胶囊低、高剂量组鼠脑组织缺血周围区细胞周围水肿、神经元变性和间质破坏较其他各组轻。结论灯盏生脉胶囊有一定的抗大鼠局灶性脑缺血 再灌注损伤作用，作用机制可能在于抑制缺血半暗带恶化。高剂量作用更明显。     

灯盏生脉胶囊对冠心病心绞痛患者血浆内皮素和降钙素基因相关肽的影响

目的：探讨灯盏生脉胶囊对冠心病心肌缺血的治疗作用。方法：对60例冠心病心绞痛患者用灯盏生脉胶囊口服治疗,观察治疗效果和治疗前后血浆内皮素（ET）、降钙素基因相关肽（CGRP）含量,并与25名健康人对比。结果：冠心病心绞痛患者临床症状有明显缓解,缺血性心电图ST明显改善,血浆ET水平显著下降（P〈0.01）,CGRP明显升高（P〈0.01）。结论：灯盏生脉胶囊能抑制血浆ET过量释放,同时提高血浆CGRP浓度,具有良好的抗心肌缺血作用,对冠心病心绞痛有较好的疗效。     

CX3CR1在炎症性肠病(IBD)中的表达及意义

目的探讨趋化因子受体CX3CR1在炎症性肠病患者肠组织中的表达以及与疾病活动的相关性。方法收集45例确诊的IBD患者及30例正常人的肠组织标本。用免疫组化技术检测CX3CR1蛋白的表达,并进一步分析其与IBD的关系。结果 CX3CR1在正常中表达阳性率为13.3%(4/30),明显低于IBD组77.8%(35/45)、IBD活动期组87.5%(28/32)及IBD缓解期组53.8%(7/13);其中后二者又在统计学上有显著差异性,同时活动期组淋巴细胞CX3CR1较其他组明显高表达。结论 CX3CR1在IBD中显著高表达,且CX3CR1蛋白与IBD的严重程度相关。提示CX3CR1可能在IBD的发生发展中发挥重要作用。     

高效液相色谱法测定灯盏生脉胶囊中咖啡酸的含量

目的建立高效液相色谱法测定灯盏生脉胶囊中咖啡酸的含量。方法选用C18柱（EliteODS24.6mm×260mm,5μm）,甲醇：四氢呋喃：0.2%磷酸溶液（14：14：72）为流动相,流速1.0ml.min-1,检测波长335nm,柱温30℃,进样量为20μl。结果咖啡酸在20.64～206.4μg.ml-1浓度范围内与峰面积呈良好的线性关系,回归方程A=1.704×105C＋1.080×105,r=0.9999,平均回收率为97.8%,RSD为1.15%（n=6）。结论高效液相色谱法可用于灯盏生脉胶囊中咖啡酸的含量测定。     

基于CX3CL1/CX3CR1轴探讨槲皮素对大鼠血管平滑肌细胞增殖的抑制作用

摘要：目的:基于人趋化因子Fractalkine （CX3CL1）/人趋化因子Fractalkine受体（CX3CR1）轴探讨槲皮素对大鼠血管平滑肌细胞（VSMC）增殖的抑制作用。方法:设VSMC细胞组、西拉普利组(100.0μg·ml-1)、槲皮素低、高剂量组(槲皮素终浓度分别为100.0,200.0μg·ml-1);各组每孔设6个平行样,培养72 h。培养结束后,CCK-8溶液试剂测定细胞增殖水平,结晶紫染色测定单克隆形成数目,流式细胞仪分析细胞凋亡水平,RT-PCR法及Western-Blot法测定细胞CX3CL1、CX3CR1基因和蛋白水平。结果:与VSMC细胞组比较,西拉普利组、槲皮素低、高剂量组吸光度（A）值、存活率、单克隆形成数目、CX3CL1、CX3CR 1mRNA和蛋白表达水平降低,而凋亡率升高（P<0.05）。与西拉普利组比较,槲皮素低剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平升高,而凋亡率降低（P<0.05）;槲皮素高剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平降低,而凋亡率升高（P<0.05）;且槲皮素高剂量组A值、存活率水平、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平低于槲皮素低剂量组,而凋亡率高于槲皮素低剂量组（P<0.05）。结论:在100.0～200.0μg·ml-1的范围内,槲皮素能抑制大鼠血管平滑肌细胞增殖,促进大鼠血管平滑肌细胞凋亡;其机制可能与槲皮素能抑制大鼠血管平滑肌细胞CX3CL1、CX3CR1 mRNA和蛋白表达水平进而抑制CX3CL1/CX3CR1轴的激活有关。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.