水飞蓟果实、果皮及其提取物质量评价法的研究

目的建立水飞蓟果实、果皮及其提取物综合质量评价方法。方法用UV法在 2 87nm下测定水飞蓟素的含量 ;并以HPLC法测定指标成分水飞蓟宾的含量 :采用HypersilC1 8(2 5 0mm×4 6mm ,5 μm)色谱柱 ;以甲醇 乙腈 磷酸二氢铵缓冲液 (2 4∶2 4∶5 0 ,pH =5 )为流动相 ;流速为1 0mL min ;柱温为 4 0℃ ;检测波长为 2 87nm。结果UV法和HPLC法线性分别在 8 0 4～4 0 2 μmol L和 0 2 76～ 1 3 8μg;加样回收率 :UV法 98 5 % ,HPLC法 97 3 % ;水飞蓟果实、果皮中水飞蓟素和水飞蓟宾含量分别为 3 88%和 1 3 2 %、8 0 1 %和 2 77% ;3种水飞蓟提取物中水飞蓟素含量均在 80 %以上 ,但水飞蓟宾含量在 2 8 7%～ 3 2 8% ,有明显差异。结论 2法合用可用于水飞蓟原料药材及提取物的质量综合评价和控制     

高效液相色谱法测定水飞蓟提取物中水飞蓟宾的含量

目的建立一种用反相高效液相色谱测定水飞蓟提取物中水飞蓟宾含量的方法。方法以Shim-packVP-ODS(250mm×4.6mm,5μm)为分析柱;以甲醇-水-乙腈-磷酸(45∶50∶5∶0.5,体积比)为流动相。结果测得平均回收率为102.3%,RSD为0.75%。结论方法准确可靠、简便,适用于水飞蓟提取物中水飞蓟宾的含量测定。     

梯度高效液相色谱法分离测定利加隆片中水飞蓟宾的含量

目的测定利加隆片中水飞蓟宾的含量.方法采用高效液相色谱法.流动相为甲醇-水系统;以梯度洗脱.流速为1ml/min;检测波长为288nm;色谱柱为Shimpack CLC C18柱(150mm ×6mm,5μm).结果水飞蓟宾的平均回收率为98.89%,RSD=1. 21%;共分离到9个光谱图相似的物质.结论该方法快速准确,适合于该类制剂中水飞蓟宾的含量测定.     

高效液相色谱法测定肝安胶囊中水飞蓟宾的含量

目的建立高效液相色谱法测定肝安胶囊中水飞蓟宾的含量。方法使用Agilent Zorbax SB—C18柱（4．6mm×250mm,5μm）,流动相：1％冰醋酸-甲醇=50：50,流速：1．0ml／min,柱温：30℃,检测波长：287nm,测定10批肝安胶囊中水飞蓟宾的含量。结果水飞蓟宾在10．28～123．36μg／ml（r=1）浓度范围内线性关系良好,回收率为97．00％（RSD=0．68％）。10批肝安胶囊中水飞蓟宾含量为11．11～16．65mg／粒。结论该方法简便、准确、重复性好,可以用于肝安胶囊的质量控制。     

水飞蓟素羟丙基-β-环糊精包合物在大鼠体内的生物利用度

目的:研究水飞蓟素的羟丙基-β-环糊精包合物在大鼠体内的相对生物利用度。方法:给大鼠口服单剂量水飞蓟素羟丙基-β-环糊精包合物(受试样品)和水飞蓟宾胶囊剂(参比样品),用反相高效液相色谱法测定大鼠血浆中水飞蓟宾的浓度,并采用3P97程序进行统计学分析。结果:口服水飞蓟素后大鼠血浆药物浓度-时间曲线符合二室模型。受试样品中水飞蓟宾的Cm ax,tm ax,t1/2,AUC0-∞分别为(0.9±0.3)mg.L-1,(0.50±0.21)h,(12.6±3.7)h,(4.2±0.9)h.mg.L-1,参比样品中水飞蓟宾的Cm ax,tm ax,t1/2,AUC0-∞分别为(0.4±0.3)mg.L-1,(1.0±0.6)h,(31.2±15.0)h,(3.0±0.8)h.mg.L-1。受试样品中水飞蓟宾的相对生物利用度为(142.0±38.4)%。结论:与参比样品相比,受试样品的生物利用度较高。     

HPLC法测定水飞蓟宾胶囊中水飞蓟宾的含量

目的建立高效液相色谱法测定水飞蓟宾胶囊中水飞蓟宾的含量。方法色谱柱：Inertsil ODS-SP（4.6mm×250mm,5μm）;流动相为甲醇-水-冰醋酸（45∶55∶1.0）,检测波长为287nm,流速为1mL.min-1。结果水飞蓟宾对照品在10.13μg.mL-1~101.30μg.mL-1浓度范围内与峰面积呈良好线性关系（r=0.9998）,平均回收率99.72%,RSD%=0.55%（n=9）。结论本方法操作简便、准确、重复性好,可作为该制剂的定量分析方法。     

高效液相色谱梯度洗脱法测定水飞蓟素自微乳化制剂中水飞蓟宾的含量

目的:建立一种用HPLC梯度洗脱法测定水飞蓟素自微乳化制剂中水飞蓟宾含量的方法.方法:采用Symmetry Cts色谱柱(3.9 mm×150 mm,5 μm);流动相为混合溶剂A[水-磷酸(100:0.5)]和混合溶剂B[甲醇水-磷酸(80:20:0.5)];流速:0.8 mL·min-1;检测波长:288 nm;柱温:40℃.结果:水飞蓟宾在0.293 7～0.881 μg范围内线性关系良好(r=0.999 6),方法的精密度为99.30%,加样回收率为99.88%(RSD为0.699%,n=9).结论:建立的方法准确度高,重复性好,本实验为水飞蓟素自微乳化制剂质量标准的制定提供了方法学依据.     

RP-HPLC测定大鼠血浆中水飞蓟宾的浓度

目的　测定大鼠血浆中水飞蓟宾的浓度。方法　用RP -HPLC。样品以叔丁基甲醚提取 ,色谱柱为PoresphereC18柱 (4.0mm× 2 5 0mm ,5 μm) ,流动相为甲醇 水 0 .0 5mol·L-1磷酸二氢钾 (2 0∶10∶7) ,流速为 1.0ml·min-1,检测波长为 2 88nm ,温度为室温。结果　大鼠血浆中成分对水飞蓟宾的测定无干扰 ;在 0 .0 0 6 1～ 3.12 5 μg·ml-1浓度范围内呈现良好的线性关系 ,r=0 .9992 ;血浆中水飞蓟宾的最低检测浓度为 6ng·ml-1,平均回收率为10 7.0 0 % ,日内RSD≤ 8.19% ,日间RSD≤ 13.78%。结论　该法样品处理简便 ,灵敏度高 ,结果准确。     

HPLC-DAD法同时测定复方益肝灵胶囊中水飞蓟宾和五味子醇甲的含量

目的：建立同时测定复方益肝灵胶囊中水飞蓟宾和五味子醇甲含量的方法。方法：色谱柱：Agilent Zorbax SB-Aq（250 mm×4.6 mm,5μm）;流动相：甲醇-0.2%磷酸水溶液,梯度洗脱;检测波长：水飞蓟宾为287 nm,五味子醇甲为250 nm。结果：水飞蓟宾在0.099 7~1.994 0μg（r=0.999 9）线性关系良好,平均加样回收率99.5%（RSD=0.5%,n=6）;五味子醇甲在0.100 1~2.002 0μg（r=1.000 0）线性关系良好,平均加样回收率97.4%（RSD=1.5%,n=6）。结论：本法简便、可靠、准确,可用于复方益肝灵胶囊的含量测定。     

HPLC法测定水飞蓟素及制剂中水飞蓟宾的含量

目的：建立了利用简单流动相组成测定水飞蓟素及制剂中水飞蓟宾的高效液相色谱法。方法：色谱柱为Inertsil—C8（4．6mm×250mm，5μm）；流动相为水（用磷酸调节pH值为4．0）-乙腈-甲醇（50：30：20）；流速为0．8mL·min^-1；检测波长为288nm。结果：可以使水飞蓟素及其制剂中的水飞蓟宾和异水飞蓟宾达到基线分离；水飞蓟宾在0．1504—0．9024μg范围内线性良好，r〉0．9999。结论：该方法流动相组成简单，分离效果好，快速准确，并且具有较好的重复性，可用于水飞蓟素原料及制剂的检测。     

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.     

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.