硝苯地平片的非水溶液中方波伏安法快速测定

建立了方波伏安法，于非水溶液中测定硝苯地平片的含量。在0.5mol／L高氯酸四丁铵（TBAP）的乙腈溶液中，硝苯地平在铂电极上有一灵敏的氧化峰，峰电流与其浓度在1×10^-7～2×10^-4mol／L范围内线性关系良好，检出限为1×10^-7mol／L。     

马来酸氯苯那敏在GCE和MWCNT／GCE上的电催化氧化及电分析方法

目的：研究马来酸氯苯那敏（chlorphenamine maleate，CPM）在玻碳电极（GCE）及多壁碳纳米管修饰玻碳电极（MWCNT／GCE）上的电化学行为、电化学动力学和电化学分析方法。方法：采用循环伏安法（CV）、计时库仑法（CC）、计时电流法（CA）、线性扫描伏安法（LSV）。结果：与GCE相比，CPM在MWCNT／GCE上氧化峰电流明显增大，氧化峰电位负移90mV，表明MWCNT／GCE对CPM电化学氧化具有良好的催化作用。同时研究了实验条件对CPM电化学行为的影响。CPM在GCE及MWCNT／GCE上在扫描速度10～1000mV·s。范围内氧化峰电流（Ipa）与扫描速度平方根（v^1/2）成正比，其电化学氧化反应是一受扩散控制的电极过程。研究了CPM在GCE及MWCNT／GCE上氧化峰电流与浓度分别在5．0×10^-5～1．5×10^-3mol·L^-1范围内呈良好的线性关系，检出限分别为1．0×10^-5,5．0×10^-6mol·L^-1。RSD在0．56％～1．8％之间，加样回收率在99．5％～103．8％之间。同时分别测定了CPM在GCE及MWCNT／GCE上的电极过程动力学参数：电荷转移系数（α）分别为0．77，0．90；扩散系数（D）分别为5．60×10^-8，6．48×10^-8cm^2·s^-1；电极反应速率常数（kf）分别为2．02×10^-3，5．45×10^-3s^-1。结论：该方法灵敏度高，操作简单，可用于CPM的电化学测定。     

RP—HPLC法同时测定鸡冠花中槲皮素、木犀草素和山奈酚的含量

目的建立鸡冠花中槲皮素、木犀草素和山柰酚的含量测定方法。方法反相高效液相色谱法，色谱柱ZORBAX SB-C18（150mm×4．6mm，5μm）；检测波长360nm；甲醇-0．2%磷酸（45：55）为流动相；柱温30℃；流速1．0mL·min^-1。结果槲皮素、木犀草素和山柰酚的回归曲线分别为：Y=1504．412X＋9．9756，Y=1991．745X＋8．6051，Y=567．591X＋2．5397，它们分别在5．5×10^-2～19．3×10^-2mg·L^-1，4．6×10^-2～16．1×10^-2mg·L，12．6×10^-2～43．9×10^-2mg·L^-1范围内线性关系良好，相关系数r=0．99992～0．99998，加样回收率分别为94．68％，91．03％和103．08％，RSD分别为0．35％，1．01％和0．55％。样品分别含槲皮素、木犀草素和山柰酚0．176，0．262和0．105mg·g^-1。结论方法简便可行，重复性好，数据及结果可靠。     

酶竞争性抑制剂对固定化青霉素酰化酶的影响

利用酶竞争性抑制剂与酶活性中心具有特异性亲和作用，将青霉素酰化酶和一定浓度苯乙酸混合，投入表面修饰环氧基团的磁性微球进行酶固定化。结果表明，在碱性缓冲液系统中，磁性微球带负电荷；加入苯乙酸后，固定化酶活力比对照组提高了13．6％。溶液酶Km为1．188×10^-5mol／L，固定化酶Km＇为5．879×10^-4mol／L，苯乙酸竞争性Ki为2.685×10^-4mol／L。     

尼莫地平对过氧化氢诱导猪脑基底动脉氧化应激损伤的保护作用

目的：探讨尼莫地平对过氧化氢（H2O2）诱导猪脑基底动脉损伤的保护作用。方法：采用去内皮离体血管环灌流的方法，建立H2O2损伤模型。比较正常对照组，H2O2（2×10^-4mol／L）损伤组，维生素C（10^-4mol／L）组，尼莫地平高、中、低剂量（5×10^-6、5×10^-7、5×10^-8mol／L）组血管环对KCl、苯肾上腺素的张力；检测各组血管组织匀浆中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—PX）活性及丙二醛（MDA）含量。结果：（1）H2O2损伤组与正常对照组比较，血管环对KCl、苯肾上腺素的收缩反应明显增加；尼莫地平高、中、低剂量组呈剂量依赖性抑制KCl、苯肾上腺素对血管环的收缩反应。（2）H2O2损伤组MDA含量升高，SOD、CAT、GSH—PX活性降低，与正常对照组比较，差异有统计学意义（P〈0．05）。尼莫地平高、中、低剂量均能降低组织中MDA含量，增强SOD、CAT、GSH-PX，的活性，与H2O2损伤组比较，差异有统计学意义（P〈0．05）。结论：钙通道阻断剂尼莫地平具有抗氧化应激作用，能预防H2O2对脑基底动脉血管的氧化损伤。     

高效液相色谱法测定萜烯树脂中有机溶剂残留量

目的：建立苯、甲苯、苯乙烯在萜烯树脂中残留量的高效液相色谱测定法。方法：采用高效液相色谱法，色谱柱：ZORBAX SB-C18柱（5μm，4．6mm×250mm，Agilent）；流动相：甲醇-水（60：40）；流速：1mL·min^-1；检测波长：261nm；柱温：30℃；进样量：10μL；结果：在考察的浓度范围内呈现良好的线性关系。苯：（10．015～50．075ng，Y=1043．3X-58．3），甲苯：（20．042～501．5ng，Y=1995．8X＋1322．3），苯乙烯：（2．0234～505．85ng，Y=42059.9X-16659．6）；回收率：苯为98．18％，RSD=1．80％，n=6；甲苯为99．12％，RSD=0．77％，n=6；苯乙烯为99．28％，RSD=0．75％，n=6；最低检测限：苯为2×10^-1ppm；甲苯为1×10^-1ppm；苯乙烯为2×10^-2ppm。结论：该法操作简便、准确、灵敏，重现性好，可用于萜烯树脂中苯、甲苯、苯乙烯的残留量检测。     

毛细管电泳-电致化学发光法测定维U颠茄铝胶囊中硫酸阿托品的含量

目的：建立一种快速测定硫酸阿托品的电化学发光分析新方法。方法：基于硫酸阿托品对二联吡啶钌在铂电极上的电致发光信号有增敏作用，与毛细管电泳结合，建立一种快速、灵敏、准确的测定制剂中硫酸阿托品含量的方法。结果：在优化的实验条件下，硫酸阿托品在1．0×10^-4～1．0×10^-6mol·L^-1范围内呈良好线性（r=0．9978）；检出限（3σ）为3．0×10^-7mol·L^-1，回收率为87％～91％，RSD小于5％。峰高和迁移时间的RSD分别为4．3％和1．2％（n=6）。结论：本法与高效液相色谱法相比，具有检出限低和线性范围宽的优点，可用于维U颠茄铝胶囊的质量控制及相关药物的含量检测。     

HPLC法测定双氯芬酸钠缓释片的有关物质

目的：应用高效液相色谱法测定双氯芬酸钠缓释片中有关物质。方法；色谱条件：C8柱，甲醇-磷酸盐缓冲液（0.01mol／L磷酸和0．01mol／L）磷酸二氢钠等量混合，用氢氧化钠试液调pH值至3．0）（6：4）为流动相，检测波长为254nm.结果：该方法双氯芬酸钠的检测限为4．5×10^-4μg；进样的精密度RSD为1．7％。结论：本法简便、灵敏、准确。     

102例癫痫患者卡马西平唾液浓度与血药浓度测定及其相关性研究

目的：探讨癫痫患者卡马西平唾液浓度与血药浓度的相关性。方法：选择我院2007年9月至2009年3月住院患者102例,服药达稳态血药浓度后,采集肘静脉血2mL,并同时收集自然状态下分泌的唾液1mL,用反相高效液相色谱法同时测定唾液浓度与血药浓度。数据分析采用SPSS11．5统计学软件。结果：以卡马西平浓度（C）、峰面积（A）作线性回归,分别得到血清浓度与唾液浓度的回归方程：C=1．34×10^-5A-0．25（r=0．9958）和C=4．07×10^-6A-0．30（r=0．9921）;唾液浓度（y）与血药浓度（x）回归方程为y=2．54×10^-1x-1．09×10^12（n=102,r=0．8985,P〈0．01）其比值为24．89％±3．90％。结论：HPLC法测得卡马西平唾液浓度与血药浓度具有显著的相关性,CBZ唾液／血清药物浓度比不受性别、年龄影响,其间无相关性;可以用唾液代替血清对卡马西平作治疗药物监测。     

N-乙酰半胱氨酸对猪急性肝衰竭血清肿瘤坏死因子-α、白介素-1β的影响

目的探讨N-乙酰半胱氨酸（NAC）对猪急性肝衰竭血清肿瘤坏死因子1α、白介素-1β的影响。方法随机将16只雌性中国实验小型猪分为正常对照组（2只），急性肝衰竭组（6只）和药物治疗组（8只）；急性肝衰竭组和药物治疗组分别应用D-氨基半乳糖（1．2g/kg）静脉滴注制备药物性急性肝衰竭动物模型，正常对照组未给予任何处理：药物治疗组给予NAC治疗．急性肝衰竭组同期给予相同剂量的生理盐水：分别测定3组动物血清生化指标以及肿瘤坏死因子、白介素-1β水平。结果急性肝衰竭组和正常对照组相比，血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBil），水平显著升高，PTA显著降低，凝血酶原时间（PT）明显延长，细胞因子肿瘤坏死因子-α，白介素-1β水平显著升高，差异有统计学意义（P〈0．01）。药物治疗组和急性肝衰竭组ALT水平12h（89．5±23．5）U／L和（77．2±18．5）U／L，P〈0.05；24h分别为（242．6±30．5）U／L和（211．1±34．0）U／L，P〈0．05。TBil水平12h分别为（13．1±2．5）μmol／L和（7．8±1．5）μmol／L，P〈0．05；48h分别为（86．2±10．5）μmol／L和（79．7±10．7）μmol／L，P〈0．05。药物治疗组和急性肝衰竭组相比，TNF-α水平24h分别为（19．3±4．2）pg／ml和（24．0±5．3）pg／ml；48h分别为（26．1±3．8）pg/ml和（29．2±8．7）pg/ml、IL-1β24h分别为（15．2±3．4）pg／ml和（18．5±3．6）pg／ml；48h分别为（20．1±5．2）pg／ml和（24．3±6．3）pg／ml，水平均有下降，差异具有统计学意义（P〈0．05）。结论NAC可改善猪急性肝衰竭肝脏功能，可减少体内肿瘤坏死因子-α、白介素-1β炎症细胞因子的生成，抑制炎症反应的快速发展．稳定机体的内环境。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.