补阳还五注射液对大鼠血液流变学及大鼠实验性血栓的影响

目的观察补阳还五注射液对大鼠血液流变学及实验性血栓的影响。方法用冰水浴刺激及肾上腺素应激法建立大鼠急性血瘀模型,观察补阳还五注射液静脉注射给药10、5、2.5 g.kg-1对大鼠血液流变学的影响;用大鼠动静脉旁路法建立实验性血栓模型,观察补阳还五注射液静脉注射给药10、5、2.5 g.kg-1对大鼠实验性动脉血栓的影响;体外法观察补阳还五注射液对腺苷二磷酸(ADP)诱导家兔体外血小板聚集率的影响。结果补阳还五注射液能降低全血黏度和血浆黏度;能对抗大鼠的实验性动脉血栓的形成,抑制ADP诱导家兔血小板聚集作用。结论补阳还五注射液具有较好的降低血液黏度、降低血小板的聚集率及抑制实验性血栓形成的作用。     

灯盏花乙素苷元不同给药剂量的大鼠药动学比较

目的:比较灯盏花乙素苷元不同剂量给药的大鼠药动学。方法:12只大鼠随机均分为2组,分别单剂量灌胃给予灯盏花乙素苷元在20和200 mg·kg~(-1),用高效液相-电化学色谱法(HPLC-ECD)测定给药后不同时间血浆中灯盏花乙素苷元及其代谢物灯盏花乙素的浓度,计算AUC_(0-24h)。色谱柱为Kromasil C_(18)柱(150 mm×4．6 mm,5μm);流动相为pH 2．6的50 mmol·L~(-1)磷酸盐缓冲液-甲醇-四氢呋喃(60:40:10);流速为1．0 mL·min~(-1);分析电压为100 mV。结果:灯盏花乙素苷元20 mg·kg~(-1)剂量给药时,原型药完全被代谢,血浆中只检测到代谢产物灯盏花乙素;200 mg·kg~(-1)剂量给药时,血浆中代谢产物灯盏花乙素和原型药灯盏花乙素苷元共存。灯盏花乙素苷元200 mg·kg~(-1)剂量时,代谢产物灯盏花乙素的AUC值相仅较20 mg·kg~(-1)剂量时提高3倍(1934．83 vs 536．51 ng·mL~(-1)·h)。结论:大小剂量下灯盏花乙素苷元的药动学行为呈非线性。     

山丹冠心片对急性血瘀模型大鼠血液流变学及家兔血小板聚集的影响

目的观察山丹冠心片对急性血瘀模型大鼠血液流变学的改善作用和对二磷酸腺苷(ADP)诱导家兔血小板聚集功能的抑制作用。方法采用大鼠皮下注射盐酸肾上腺素加冰水(0℃)的方法,造成大鼠急性血瘀模型,测定不同切变率的全血黏度,血浆黏度等血液流变学指标;采用ADP做诱导剂的方法,测定家兔血小板最大聚集率。结果山丹冠心片低、中、高剂量组对急性血瘀模型大鼠血液流变学多项指标具有明显的改善作用。可明显降低其全血高、中、低切黏度,红细胞聚集指数和红细胞电泳时间,与模型对照组比差异有显著意义(P<0.01或P<0.001)。山丹冠心片中、高剂量组对ADP诱导的家兔血小板聚集有明显的抑制作用,与空白对照组比差异有显著意义(P<0.05或P<0.01)。结论本品具有明显的活血化瘀作用。     

天舒滴丸对急性血瘀模型大鼠血液流变学和血栓形成的影响

目的研究天舒滴丸对急性血瘀模型大鼠血液流变学、血小板聚集及血栓形成的影响。方法 SD大鼠随机分为对照组、模型组、天舒胶囊(4.0 g/kg)组、天舒滴丸(1.0、2.0、4.0 g/kg)组,ig给药3 d后,采用肾上腺素配合冰浴制备大鼠急性血瘀模型,分别测定全血黏度,血浆黏度,红细胞压积,血沉,体外形成血栓的长度、湿质量、干质量,血小板聚集率等指标。结果天舒滴丸能明显降低急性血瘀模型大鼠全血和血浆黏度,明显降低血栓长度、血栓湿质量和干质量,抑制模型大鼠血小板聚集率的升高。结论天舒滴丸能够改善急性血瘀模型大鼠血液流变性,抑制血小板聚集及血栓形成。     

红景天苷对大鼠实验性血栓形成的影响及其作用机制

目的研究红景天苷对大鼠实验性血栓形成的影响及其作用机制。方法①采用体外血栓法,观察红景天苷对大鼠体外血栓长度和干、湿重的影响;②建立血瘀模型,观察红景天苷对血瘀大鼠血液黏度、红细胞比容、血小板聚集率和凝血时间的影响。结果①红景天苷5.0mg/kg和10.0mg/kg缩短体外血栓长度(P<0.05),降低体外血栓湿重和干重(P<0.05)。②红景天苷5.0mg/kg和10.0mg/kg可明显降低红细胞比容、血液黏度(P<0.05,P<0.01),降低血小板聚集率,延长凝血时间(P<0.05,P<0.01)。结论红景天苷具有抗血栓形成作用,其机制与降低血液黏度改善血液流变性有关。     

UPLC-MS/MS联用法分析灯盏花乙素在胃肠道的代谢物

目的：研究灯盏花乙素在胃肠道的代谢物。方法：分别用盐酸、β-葡糖醛酸苷酶水解灯盏花乙素，并用健康志愿者的肠内菌对灯盏花乙素进行转化，用超高效液相．串联质谱联用法分析代谢物。结果：灯盏花乙素可被盐酸、β-葡糖醛酸苷酶水解为苷元，可被肠内菌群转化为苷元。健康受试者口服灯盏花乙素后，血浆中能检测到灯盏花乙素苷元。结论：健康受试者口服灯盏花乙素后，在吸收进入血液之前，胃肠道内灯盏花乙素与其苷元并存，而苷元更易于吸收，以总苷元为检测对象研究灯盏花乙素药代动力学是合理的。     

心适注射液抗动脉血栓作用机制及其对大鼠血液流变学的研究

目的:研究心适注射液对大鼠血液流变学的作用及其抗动脉血栓作用机制。方法:以胶原蛋白-肾上腺素诱发小鼠体内血栓形成与冰水浴造成血瘀模型,观察体内、外血栓形成、血小板黏附率及血液流变学的改变。结果:心适注射液各剂量组均明显降低小鼠体内血栓形成以及大鼠血小板黏附率,改善急性血瘀模型大鼠血液流变学,抑制大鼠血栓形成。结论:心适注射液能改善急性血瘀模型大鼠血液流变学,有效地对抗动脉血栓的形成。     

偏瘫康复散对急性应激血瘀大鼠血液流变学及血栓形成的影响

目的研究偏瘫康复散对急性应激血瘀大鼠血液流变学及血栓形成的影响。方法急性应激血瘀大鼠模型采用在二次注射肾上腺素1mg·kg-1之间将大鼠浸入冰水内5min的方法建立。利用此模型观察偏瘫康复散对模型大鼠全血黏度、全血还原黏度、血浆黏度、红细胞压积、红细胞变形性、红细胞聚集性等血液流变学指标和体外血栓的作用。结果偏瘫康复散可显著改善急性应激造成血瘀模型血液流变学参数;偏瘫康复散0.75g·kg-1显著缩短血栓长度(P<0.05),偏瘫康复散0.75,1.50和3.00g·kg-1显著减轻血栓湿重、干重(P<0.05)。结论偏瘫康复散有显著抗试验性血栓形成和显著活血化瘀作用。     

滁菊总黄酮对寒凝血瘀证家兔血液流变学的影响

目的 观察滁菊总黄酮对寒凝血瘀证家兔血液流变学的影响。方法 采用皮下注射肾上腺素加冰水浸泡复制寒凝血瘀证家兔模型,观察滁菊总黄酮对寒凝血瘀证家兔全血粘度、血浆粘度,红细胞沉降速率和红细胞压积,红细胞聚集指数和刚性指数,以及ADP诱导血小板聚集率的影响。结果 滁菊总黄酮能够改善寒凝血瘀证家兔全血粘度和血浆粘度,降低红细胞沉降速率和红细胞压积,降低红细胞聚集指数和刚性指数,抑制ADP诱导的血小板聚集。结论 滁菊总黄酮能够改善寒凝血瘀证家兔血液流变学异常。     

复方辛芍对急性血瘀模型大鼠血小板聚集及血液流变学的影响

目的观察复方辛芍对急性血瘀模型大鼠血小板聚集、凝血时间及血液流变学的影响。方法用冰水刺激制备“血瘀”模型，检测主要流变学指标；以ADP为诱导剂，观察其对体外血小板聚集的作用。结果（1）复方辛芍能显著降低血瘀大鼠血小板最大聚集率。（2）复方辛芍可以延长血瘀大鼠的凝血时间。（3）复方辛芍有降低血瘀大鼠低切变率下的全血黏度（5s^-1、1S^-1）、血浆黏度、增强红细胞变形和抑制红细胞聚集的作用。结论对急性血瘀模型大鼠，复方辛芍有抑制血小板聚集、延长凝血时间和改善血液流变学异常的作用。     

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.

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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.     

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.     

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.