尼美舒利联合多柔比星对人膀胱癌T24细胞的作用

［摘要］目的探讨尼美舒利联合多柔比星对人膀胱癌T24细胞的协同作用。方法通过噻唑蓝（MTT）法和流式细胞仪Annexin V FITC/PI荧光染色法检测不同浓度尼美舒利及其与多柔比星联合对T24细胞的生长抑制作用和凋亡率。结果25 μmol•L 1尼美舒利作用24，72 h细胞生长抑制率分别为11.10%和31.59%；浓度400 μmol•L 1时，抑制率分别升为38.40%和89.61%。单用多柔比星（0.25 mg•L 1） 作用48 h抑制率为30.01%；合用25，100，400 μmol•L 1尼美舒利抑制率分别升为70.53%，83.32%和89.39%。100 μmol•L 1尼美舒利作用12 h时细胞凋亡率为14.55%，作用24 h时凋亡率升为24.65%。结论尼美舒利能抑制膀胱癌T24细胞的增殖并诱导其凋亡，与多柔比星具有协同作用。     

吡柔比星与多柔比星的急性心脏毒性比较

［摘要］目的观察吡柔比星（THP）或多柔比星（ADM）联合化疗方案治疗恶性肿瘤疗效及急性心脏毒性。方法128例癌症患者分为ADM组63例,THP组65例; THP组又分为THP老年组15例,THP普通组50例。THP剂量为60 mg•（m2） 1, ADM为50 mg•（m2） 1,THP老年组将总量分为二次静脉滴注,其余均为总量一次静脉滴注;用药期间静脉滴注维生素C 4 g•d 1,老年THP组 加用参麦注射液100 mL•d 1。结果THP组（老年组+普通组）和ADM组有效率分别为55.4%和55.6%,两组比较差异无显著性（P＞0.05）。两组化疗后出现心电图异常8例,占6.2 %,其中ADM组6例,THP 2例。结论THP或ADM联合化疗方案治疗恶性肿瘤疗效相当,THP急性心脏毒性较低;对老年人,既往有高血压或心绞痛病史,化疗前心电图异常者应选择THP。     

雷公藤多苷抗炎作用的研究

摘要目的研究雷公藤多苷的抗炎作用。方法①对小鼠毛细血管通透性的影响： 小鼠60只,随机分为空白对照组,模型组,雷公藤多苷0.3,0.6,1.2 g•kg－1组,吲哚美辛10 mg•kg－1组,共6组,各10只,灌胃给药5 d后,均静脉注射0.5%伊文思蓝溶液0.01 mL•g－1,小鼠处死后,收集腹腔冲洗液,测定吸光度（A值）;②对大鼠角叉菜胶足肿胀的影响：大鼠50只,随机分为空白对照组,雷公藤多苷0.25,0.50,1.00 g•kg－1组,地塞米松4 mg•kg－1组,共5组,各10只,造模后,连续灌胃给药7 d,测定右后肢容积。结果空白对照组,模型组,雷公藤多苷0.3,0.6,1.2 g•kg－1组,吲哚美辛10 mg•kg－1组小鼠腹腔冲洗液A值分别为0.24±0.16,1.41±0.60,0.99±0.45,0.93±0.45,0.88±0.58,0.52±0.38,显示雷公藤多苷对小鼠毛细血管通透性有一定抑制作用。末次给药5 h后空白对照组,雷公藤多苷0.25,0.50,1.00 g•kg－1组,地塞米松4 mg•kg－1组大鼠足肿胀率分别为（36.3±13.7）%,（26.3±13.9）%,（37.9±14.5）%,（32.5±12.4）%,（17.2±10.9）%。结论雷公藤多苷具有一定的抗炎作用。     

.舍曲林辅助治疗精神分裂症阴性症状40例

［摘要］目的观察舍曲林对精神分裂症阴性症状的疗效和安全性。方法以阴性症状为主的住院精神分裂症患者80例,随机分为治疗组与对照组,各40例。治疗组：利培酮起始剂量1 mg•d 1,po,平均（4.5±1.3） mg•d 1,联合舍曲林50～100 mg•d 1,平均（66.2±23.7） mg•d 1,po;对照组：利培酮起始剂量1 mg•d 1,平均（4.9±1.1） mg•d 1,po。疗程8周。采用阳性与阴性症状量表（PANSS）、不良反应量表（TESS）评定疗效和不良反应。结果4周末两组PANSS总分、阳性因子分、阴性因子分及8周末两组PANSS总分和各因子分与治疗前比较均差异有显著性或极显著性（P＜0.05或P＜0.01）。8周末治疗组PANSS总分及阴性因子分明显低于对照组（P＜0.05或P＜0.01）。结论舍曲林辅助治疗精神分裂症阴性症状有较好的疗效,且安全性好。     

两种药用植物总黄酮体外抗氧化活性比较

目的研究藤茶总黄酮和铁包金总黄酮的体外抗氧化活性。方法建立体外二苯代苦味酰基自由基（DPPH•）、氧自由基（O－2•）和羟自由基（•OH）发生体系，检测藤茶总黄酮和铁包金总黄酮对DPPH•、O－2•和•OH的清除作用。结果藤茶总黄酮对DPPH•、O－2•、•OH的清除作用比铁包金总黄酮和维生素C强，其三种体系的半数抑制浓度（IC50）分别为（3.32±0.18），（227.41±184.45），（5.22±3.75） mg•L－1。铁包金总黄酮对DPPH•、O－2•、•OH的清除作用弱于维生素C，其DPPH•体系的IC50为（36.41±9.68） mg•L－1。结论藤茶总黄酮具有抗氧化活性，但铁包金总黄酮不能单独作抗氧化剂。     

氯沙坦卡托普利对糖尿病肾病蛋白尿的作用

目的;探讨糖尿病肾病患者联合应用小剂量氯沙坦和卡托普利的疗效.方法;21例糖尿病肾病患者随机分为治疗组10例,服氯沙坦50 mg•d 1、卡托普利50～75 mg•d 1,对照组11例,服卡托普利75～150 mg•d 1.结果;治疗组治疗前后尿蛋白分别为(0.96±0.40),(0.63±0.20) g•d 1,对照组治疗前后尿蛋白分别为(1.00±0.38),(0.71±0.15) g•d 1.治疗糖尿病肾病患者蛋白尿疗效治疗组明显优于对照组.结论;联合小剂量氯沙坦疗效好,副作用小,患者易接受.     

液相色谱-串联质谱法测定肾移植患者的麦考酚酸血浆浓度及其药动学研究

目的 建立液相色谱-串联质谱（LC-MS/MS）法评价免疫抑制剂麦考酚酸酯（MMF）在术后2～3周肾移植患者中连续口服的药动学特点. 方法 受试者口服MMF（0.75 g,bid）,2～3周后用LC-MS/MS法测定血浆中活性代谢物麦考酚酸（MPA）的浓度,并用非房室模型计算药动学参数. 结果 MPA在0.1～51.2 μg•mL^-1 范围内线性关系良好,批内、批间RSD＜10%,准确度在90%～110%,方法学验证符合生物样品分析方法的要求. MMF的体内代谢呈明显的个体差异,药动学参数：AUC0 t为（36.65±11.42） mg•h•L^-1; AUC0 ∞为（43.34±18.02） mg•h•L^-1; Cmax为（15.89±5.77） mg•L-1; t _max为（1.08±0.47） h; t_1/2为（3.34±1.63） h; MRT0 t为（3.42±1.12） h; Vd为（194.88±156.45） L; CL为（41.02±18.19） L• h^-1. 结论 LC MS/MS法用于MPA血浆浓度测定,操作简便,结果灵敏、特异性好.     

丙泊酚联合东莨菪碱治疗重症破伤风的疗效

目的探讨丙泊酚联合东莨菪碱治疗重症破伤风的疗效。方法将31例重症破伤风患者随机分为两组，对照组在基础治疗基础上肌内注射地西泮10 mg,q1h,适时应用冬眠合剂（氯丙嗪、异丙嗪各50 mg，哌替啶100 mg），症状缓解后根据病情适当延长地西泮注射间隔时间；治疗组给予丙泊酚0.3～0.4 mg•kg－1•d－1，联合应用东莨菪碱0.05～0.12 mg•kg－1•d－1。比较两组疗效。 结果治疗组痉挛缓解时间（11.2±1.9）d，住院时间（19.7±1.6）d；均短于对照组［分别为（15.1±1.5）和（25.3±1.2）d］（均P＜0.05），治疗组并发症少于对照组。结论丙泊酚联合东莨菪碱治疗重症破伤风有较好的疗效和安全性。     

喹硫平治疗精神分裂症30例

目的 考察喹硫平治疗精神分裂症的有效性及安全性. 方法 将60例精神分裂症患者分为治疗组和对照组, 每组30例.治疗组给予喹硫平, 初始剂量100 mg&#8226;d^-1, 2周内加至400~800 mg&#8226;d^-1, 以后3周内视病情及不良反应调整剂量, 最大剂量1 200 mg&#8226;d^-1, 平均（728.3±199.9） mg&#8226;d^-1.对照组给予利培酮, 起始剂量1 mg&#8226;d^-1, 2周后加至治疗量3~6 mg&#8226;d^-1, 平均（4.9±0.9） mg&#8226;d^-1.疗程均为8周.两组根据情况给予苯海索、氮类药或普萘洛尔等对症处理, 以阴性和阳性症状量表（PANSS）、不良反应量表（TESS）分别评定疗效、病情严重程度和不良反应. 结果 治疗组与对照组的显效率均为70.0%, 有效率分别为90.0%和86.7%.两组在治疗前PANSS评分差异无显著性, 在治疗8周末, 两组PANSS评分较治疗前显著下降, 均差异有极显著性（均P< 0.01）.两组比较差异无显著性（P＞0.05）.治疗组的不良反应较对照组少而轻.结论 喹硫平可显著改善精神分裂症症状, 且不良反应发生率低, 是一种安全有效的抗精神病药物.     

丹参对HepG2细胞胰岛素抵抗状态的影响

［摘要］ 目的采用高胰岛素体外诱导培养HepG2细胞，建立胰岛素抵抗（IR）的细胞模型；探讨丹参对胰岛素敏感性的影响。方法细胞培养分4组：Ⅰ组为模型组，含5×10-7 mol&#8226;L-1胰岛素；Ⅱ组为对照组，不含胰岛素；Ⅲ组以12 mg&#8226;mL-1丹参溶液处理IR模型细胞；Ⅳ组以3.2 μg&#8226;mL-1罗格列酮处理IR模型细胞。采用3H D 葡萄糖掺入技术，观察丹参对HepG2细胞葡萄糖掺入率的影响。结果①高胰岛素诱导培养的HepG2葡萄糖掺入率明显低于未用高胰岛素诱导的HepG2细胞（对照细胞）的葡萄糖掺入率（P＜0.01）。②含有丹参的胰岛素抵抗HepG2细胞的葡萄糖掺入率明显高于不含丹参的胰岛素抵抗HepG2细胞（对照细胞）葡萄糖掺入率（P＜0.05）。结论①将HepG2置于5×10－7 mol&#8226;L-1胰岛素环境中16 h，该细胞对胰岛素的生物学效应产生抵抗。②丹参对细胞水平的胰岛素抵抗病理状态的进展有一定的阻止作用。     

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.