黄芪与刺五加水提物对弱精子症患者精子体外运动参数的影响

目的研究黄芪和刺五加水提物对弱精子症患者体外精子运动活力的影响。方法将30例弱精子症患者的精子经上游优化法处理后分为8份,其中两份分别加入刺五加水提物和黄芪水提物,使其终浓度分别为10和20mg.mL-1;另取5份将10 mg.mL-1刺五加水提物和20 mg.mL-1黄芪水提物按体积比为4:1,2:1,1:1,1:2和1:4加入;另外1份加入Ham’s F10培养液作对照。分别于孵育15,30和60 m in后应用计算机辅助的精子分析系统(CASA)观察精子各运动参数。结果刺五加水提物和黄芪水提物联用能不同程度地提高弱精子症患者精子的体外运动能力。加入刺五加和黄芪水提物后,精子活率(Mot)、前向运动精子百分率[(A+B)%]、曲线运动速度(VCL)、直线运动速度(VSL)和平均路径速度(VAP)均较对照组显著提高(均P<0.05)。10 mg.mL-1刺五加水提物和20 mg.mL-1黄芪水提物体积比为1:1,共同孵育60 m in作用效果最明显。结论刺五加和黄芪水提物联用能明显改善弱精子症患者精子的体外运动能力。     

麝香草酚和香荆芥酚对痢疾杆菌和肠炎常见菌的体外抗菌效应

目的研究麝香草酚和香荆芥酚对痢疾杆菌和肠炎常见菌的体外抗菌作用，证实此两种物质为牛至的主要有效抗菌成分。方法采用稀释法体外测试麝香草酚和香荆芥酚对痢疾杆菌4菌株和致病性大肠埃希菌等71个菌株的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。结果麝香草酚对痢疾杆菌的MIC为0.125～0.250 mg·mL^-1，MBC为0.250～0.500 mg·mL^-1;对71株肠炎常见菌的MIC为0.031～0.500 mg·mL^-1，MBC为0.062～1.000 mg·mL^-1。香荆芥酚对痢疾杆菌的MIC为0.125～0.500 mg·mL^-1，MBC为0.250～1.000 mg·mL^-1;对71株肠炎常见菌的MIC为0.062～0.500 mg·mL^-1，MBC为0.125～1.000 mg·mL^-1。结论麝香草酚和香荆芥酚是牛至的主要有效抗菌成分，体外对痢疾杆菌和肠炎常见菌均具有较强的抑菌和杀菌作用     

红曲霉菌对姜黄素的转化及产物自由基清除和抗脂质过氧化作用的研究

目的 研究红曲霉菌对姜黄素的微生物转化及转化总产物的自由基清除和抗脂质过氧化的作用,并对转化产物进行了初步分析。方法 用本实验室保存的红曲霉菌对姜黄素进行微生物转化,同时设立菌株对照和底物对照;研究转化总产物对DPPH自由基的清除能力;研究转化总产物对食饵性高脂血症小鼠肝脏和血清MDA、SOD、GSH-Px等过氧化脂质的影响。用乙酸乙酯提取转化产物,用TLC、HPLC-DAD (Agilent Zorbax Extend C₁₈柱,0.1%乙酸和乙腈梯度洗脱,流速1.0 mL·min^-1)对转化产物进行了初步分析。结果 姜黄素转化总产物在10 000~400 mg·mL^-1(相当于含姜黄素100~4 mg·mL^-1)内有很强的自由基清除能力,总产物浓度在100 mg·mL^-1还保留了47.46%的清除能力;而底物对照物在10 000、2 000 mg·mL^-1时有一定的清除能力,但浓度在400 mg·mL^-1时自由基清除能力已明显减弱,100 mg·mL^-1以下已基本消失。转化总产物500,200,100 mg·kg·d^-1(相当于姜黄素5,2,1 mg·kg·d^-1)均能降低高脂血症小鼠肝脏和血清的过氧化脂质,而菌株对照组(500 mg·kg·d^-1)和底物对照组(500 mg·kg·d^-1,相当于姜黄素5 mg·kg·d^-1)抗脂质过氧化作用不明显。研究超氧化物歧化酶、谷胱甘肽过氧化物酶,发现姜黄素转化产物对此二酶的作用不明显,其抗氧化作用可能并非通过改变此二酶的活性。转化产物经HPLC-DAD分析,发现可能存在6个转化产物,其保留时间分别为16.3,22.1,23.2,28.0,33.0,36.1 min,其光谱图与姜黄素存在明显差异。结论 姜黄素经红曲霉菌转化后形成了由6个代谢产物组成的新组合型天然姜黄素类似物群,其自由基清除能力和抗脂质过氧化作用显著增强。     

艾叶与复方艾叶水提液体外抗菌作用比较

目的 考察艾叶与复方艾叶水提液的体外抗菌作用。方法 测定艾叶水提液与复方艾叶水提液对常见妇科阴道致病菌（金黄色葡萄球菌、大肠埃希菌、肺炎双球菌、表皮葡萄球菌、白念珠菌）的最低抑菌浓度与最低杀菌浓度。结果 艾叶水提液对金黄色葡萄球菌、大肠埃希菌、肺炎双球菌、表皮葡萄球菌、白念珠菌等5种妇科常见致病菌的最低抑菌浓度分别为6.25, 25.00 ，6.25，12.50，25.00 mg·mL^-1（按生药含量计）；用相同剂量的黄柏与苦参代替部分艾叶的复方提取液对上述5种致病菌的最低抑菌浓度分别为25.00，50.00，12.50，50.00，25.00 mg·mL^-1（按生药含量计）。结论 艾叶水提液具有明显的体外抗菌作用, 复方艾叶水提液的抗菌作用较相同剂量的艾叶水提液有所下降。     

水解原位萃取分离刺五加异秦皮啶

目的 对刺五加80%体积分数乙醇提取物采用水解原位萃取的方法将结合态异秦皮啶转化成游离态异秦皮啶。方法 确定的工艺条件为每克80%体积分数乙醇浸膏按固液比1∶100加入0.6 mol·L^-1盐酸,加入同体积的1,2-二氯乙烷,搅拌下85 ℃回流水解2.5 h。结果 在此条件下,刺五加根皮、茎皮和根茎混合异秦皮啶分别由原来的0.042 4、0.011 2和0.005 3 mg·mL^-1增加到1.264 1、0.441 2和0.260 0 mg·mL^-1,分别增加28.81、38.39和48.06倍;根木质部和茎木质部由水解前检测不到异秦皮啶增加到0.023 3和0.009 7 mg·mL^-1。结论 将水解原位萃取法分离异秦皮啶工艺与目前常用的传统酸水解-有机溶剂萃取工艺进行了对比,水解温度由原来的100 ℃降低到85 ℃,处理时间由原来的14.5 h降低到2.5 h,溶剂使用量仅为原来的3/4。     

不同有机溶剂对人精子体外运动参数的影响比较

目的研究常用有机溶剂对正常男性精子体外运动活力的影响。方法取正常男性精子,采用上游优化法处理,制备成精子悬液并分成4组,前3组分别加入二甲亚砜,使二甲亚砜终浓度分别为0.5%,1%和2%,pH值均为7.5,渗透压为290 mosm.(kg.H2O-1),D组加入等量Ham’s F10培养液作对照。分别于孵育15,30,45和60 m in后采用CASA进行分析。参照上述方法,考察有机溶剂甘油、聚乙二醇、吐温80对精子体外运动活力的影响。甘油终浓度分别调至1%,5%和10%,聚乙二醇终浓度分别调至1%,5%和10%,吐温80终浓度分别调至1%,5%和10%。结果2%二甲亚砜作用于精子60 m in能导致精子全部死亡,10%甘油作用60 m in后对精子运动参数抑制率达73.8%,10%聚乙二醇400作用于人精子60 m in可致其全部死亡,10%吐温80作用60 m in后对精子运动参数抑制率达95.5%。加入不同浓度二甲亚砜、甘油、聚乙二醇400和吐温80的各组前向运动精子百分率、曲线运动速度、直线运动速度和平均路径速度均较空白对照组显著降低(均P<0.05)。结论高浓度有机溶剂体外可抑制正常男性精子存活率和运动活力。     

响应面法优化丹参醇沉工艺的研究

目的 以原儿茶醛为指标优化丹参醇沉工艺。方法 首先采用Plackett-Burman设计对影响丹参醇沉操作的因素进行筛选,所选取的8个相关因素为：丹参水提浓缩液密度、一次醇沉加醇速度、一次醇沉液乙醇终浓度、一次醇沉浓缩液密度、二次醇沉加醇速度、二次醇沉液乙醇终浓度、氢氧化钠溶液的浓度和二次醇沉液的pH值。在此基础上,采用响应面法在线性范围内对影响醇沉操作的关键因素(丹参水提浓缩液密度、一次醇沉浓缩液密度和pH值)作了进一步的研究与探讨。结果 通过对二次项回归方程求解得知,上述自变量中丹参水提浓缩液密度为1.15 mg·mL^-1、一次醇沉浓缩液密度为1.26 mg·mL^-1和pH值为7.68时,原儿茶醛含量达到最佳值为0.512 mg·mL^-1。结论 优化工艺的原儿茶醛提取含量高,可用于丹参醇沉过程中原儿茶醛的含量控制。     

戒毒康对吗啡依赖豚鼠离体回肠戒断性收缩的影响

目的 研究戒毒康对吗啡依赖豚鼠离体回肠催促戒断反应的抑制作用。方法 连续递增皮下注射吗啡,建立豚鼠身体依赖性模型,利用MD2000 Super Lab 生物信息采集系统观察戒毒康对纳洛酮催促诱发吗啡身体依赖性豚鼠离体回肠的戒断性收缩的抑制作用。结果 戒毒康高(0.6 mg·mL^-1)、中(0.3 mg·mL^-1)、低(0.15 mg·mL^-1)3个剂量对吗啡依赖豚鼠离体回肠纳洛酮催促戒断性收缩的抑制率分别为：78.8%,46.8%,30.0%,并呈剂量相关性,其中高剂量组和中剂量组与模型组比较,有显著性差异。结论 戒毒康在一定程度上能抑制吗啡依赖豚鼠离体回肠体外纳洛酮催促戒断性收缩。     

阿奇霉素分散片人体药动学及生物等效性研究

目的 研究阿奇霉素分散片健康人体的药动学与生物等效性。方法 20名男性健康志愿者随机交叉口服阿奇霉素分散片受试制剂和参比制剂各500 mg,采用高效液相色谱-质谱法(LC-MS)测定血药浓度。以DAS 2.0软件计算其药动学参数,考察其生物等效性。结果 受试制剂和参比制剂阿奇霉素AUC_0-168分别为(8.98±1.74) mg·h·mL^-1和(8.75±1.60) mg·h·mL^-1,C_max分别为(0.81±0.14) mg·mL^-1和(0.80±0.14) mg·mL^-1,t_1/2分别为(48.16±11.10) h和(51.1±7.60) h,T_max分别为(1.80±0.86) h和(1.82±0.92) h,受试制剂相对于参比制剂的生物利用度为(103.4±20.2)%。结论 阿奇霉素分散片受试制剂和参比制剂具有生物等效性。     

HPLC-ELSD测定妥布霉素滴眼液的含量

目的 建立高效液相色谱-蒸发光散射检测器检测法(HPLC-ELSD)测定妥布霉素滴眼液的含量。方法 选用耐酸性的Agilent Zorbax SB-C₁₈(4.6 mm×250mm,5 μm)色谱柱;流动相为0.2 mol·L^-1三氟乙酸溶液-甲醇(92∶8),柱温为35 ℃,流速为0.8 mL·min^-1,进样体积为10 mL;ELSD检测器漂移管温度为45 ℃,雾化气体压力为3.5 bar,信号增益(GAIN)为5。结果 妥布霉素在55.6～1 396.7 mg·mL^-1内,其峰面积的对数与浓度的对数呈良好的线性关系(r = 0.999 7),检测限和定量限分别为0.15 mg·mL^-1和0.45 mg·mL^-1。结论 方法专属性强,准确可靠,适用于妥布霉素滴眼液产品质量控制。     

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.

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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.