鸡冠花对致热复合出血模型大鼠的凉血止血效应机制研究

目的 研究鸡冠花对血热出血模型大鼠的药理作用,初步探讨其止血机制并筛选其凉血止血活性部位.方法 建立大鼠致热复合出血模型,监测10 h内大鼠直肠温度变化,测定大鼠血浆凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血酶时间(APTT)和血浆纤维蛋白原(FIB)含量及24 h内全血黏度的变化,观察对胃、肺、肝及子宫等脏器组织的影响.结果 与模型组比较,鸡冠花生品组、乙酸乙酯和正丁醇部位组均能明显降低干酵母所致大鼠体温升高(P<0.01);鸡冠花炭品、鸡冠花乙酸乙酯及正丁醇部位能不同程度缩短模型大鼠TT、PT、APTT时间(P<0.01或0.05);鸡冠花生品及乙酸乙酯部位组和炭品组均能明显升高大鼠FIB含量(P<0.01).鸡冠花生品组和炭品组均能降低模型大鼠低切变率下全血黏度(P<0.05),鸡冠花正丁醇部位能降低模型大鼠全血的高、中及低切黏度(P<0.05).结论 鸡冠花生品及乙酸乙酯和正丁醇部位具有凉血止血功效,鸡冠花炭品具有止血功效,鸡冠花和鸡冠花炭通过不同环节而发挥止血作用.     

不同来源黄芩炮制品的解热作用比较研究

目的 比较二倍体黄芩、四倍体黄芩、甘肃黄芩的解热作用。方法 将Wistar大鼠110只,随机分为11组。药物组分别给予不同来源的黄芩生品、酒炙品水煎液灌胃,连续给药2 d。第3天,除空白组外,其余各组大鼠腹腔注射脂多糖100 μg·kg^-1造模。2 h后,继续灌胃1次。造模1,2,3,4 h分别检测大鼠肛温,动物处死后采血,检测大鼠血清中IL-1β、PGE₂含量。结果 与模型组比较,黄芩各药物组大鼠在造模2,3,4 h时ΔT显著低于模型组,且大鼠血清中IL-1β、PGE₂含量显著降低（P<0.05）;与道地产区河北产黄芩组比较,甘肃黄芩Ⅰ组（生品）、Ⅱ组（酒炙品）大鼠2,3,4 h时ΔT均显著高于河北产黄芩组（P<0.05）;同时,二倍体黄芩、四倍体黄芩、甘肃黄芩的Ⅰ组（生品）、Ⅱ组（酒炙品）大鼠血清中IL-1β、PGE₂含量均显著高于河北产黄芩Ⅰ组、Ⅱ组（P<0.05）。结论 二倍体黄芩、四倍体黄芩、甘肃黄芩均有解热作用,但甘肃黄芩解热作用与道地黄芩有一定差异。不同来源黄芩生品与酒炙品对发热大鼠的解热作用无显著性影响。     

消瘀止血片治疗凝血障碍性出血性疾病的药效学研究

目的探讨消瘀止血片治疗凝血障碍性出血性疾病的作用机制。方法用消瘀止血片高剂量、中剂量、低剂量给大鼠连续灌胃5d,对照组给予等体积生理盐水(NS)。分别观察该药对正常大鼠的血小板数量、血小板功能及凝血系列的影响,以及对华法林致凝血功能障碍大鼠凝血系列的影响。结果本药各剂量组均可缩短正常大鼠的部分凝血活酶时间(APTT)(P<0.01);高、中剂量可缩短正常大鼠凝血酶时间(TT)、凝血酶原时间(PT)(P<0.05);对华法林致凝血功能障碍大鼠,本药高、中剂量组可缩短TT、PT、APTT(与模型组相比,P<0.05或P<0.01)。消瘀止血片对动物的血小板数量无显著影响,但各剂量组均可促进二磷酸腺苷(ADP)诱导的血小板最大聚集率,与对照组相比差异有统计学意义(P<0.01或P<0.05)。结论消瘀止血片可缩短大鼠PT、TT和APTT,增强血小板聚集,有促进止血、凝血作用。     

云南红药对功能失调性子宫出血模型大鼠血浆血栓烷A_2和前列环素含量的影响

目的考察云南红药对子宫出血模型大鼠血浆血栓烷A2(TXA2)和前列环素(PGI2)含量的影响,进一步探讨该药物止血的作用机制。方法采用妊娠大鼠ig给予米非司酮和米索前列醇,造成早孕大鼠不完全流产复制功能失调性子宫出血模型,模型大鼠ig给予云南红药0.4,0.2和0.1 g.kg-1,连续7 d。观察其对子宫出血的治疗作用,并检测血浆TXA2和PGI2的含量。结果与正常对照组相比,功能失调性子宫出血模型组大鼠的凝血酶原时间(PT),活化部分凝血活酶时间(APTT)和凝血酶时间(TT)明显升高,血浆纤维蛋白原(FIB)显著降低(P<0.05,P<0.01);与功能失调性子宫出血模型组比较,云南红药0.4和0.2 g.kg-1组能明显缩短子宫出血模型大鼠的PT,APTT和TT,能明显增加子宫出血模型大鼠的FIB(P<0.05,P<0.01);云南红药0.4 g.kg-1能明显缩短子宫出血模型大鼠的PT和TT(P<0.05),但对APTT和FIB没有明显影响。与正常对照组比较,模型组大鼠血浆TXA2的含量明显降低,而PGI2的含量明显升高(P<0.01);与模型组相比,云南红药0.4和0.2 g.kg-1能明显增加子宫出血模型大鼠血浆TXA2的水平以及明显降低PGI2的水平(P<0.05,P<0.01),而云南红药0.1 g.kg-1组无显著差异。结论云南红药对子宫出血模型大鼠的凝血指标具有显著作用,其作用机制可能与调节TXA2/PGI2系统有关。     

地榆烘法制炭前后止血作用比较

目的 比较地榆烘法制炭前后的止血作用。方法 昆明小鼠60只,随机分为6组：对照组,云南白药（阳性药,0.667 g/kg）组,地榆高、低剂量（8、2 g生药/kg）组,地榆炭高、低剂量（8、2 g生药/kg）组,每天ig给药1次,连续给药3 d,于末次给药1 h后检测小鼠出血时间、凝血时间,血凝仪检测凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血活酶时间（APTT）,进行血小板计数。结果 与对照组比较,高剂量地榆和烘制的高、低剂量地榆炭显著缩短小鼠的出血时间、凝血时间、PT、TT和APTT;高、低剂量地榆和高剂量地榆炭显著提高血小板计数;与地榆高剂量组比较,高剂量地榆炭能显著缩短小鼠的PT、TT、出血和凝血时间,对血小板数量和APTT的影响差异不显著。结论 地榆烘法制炭后止血作用增强。     

益气活血风静胶囊对大鼠及家兔血液流变学的影响

目的：研究益气活血风静胶囊对大鼠及家兔的血液流变学的影响。方法：采用SD大鼠及家兔分别灌胃给药14 d及10 d,检测SD大鼠及家兔血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）及血小板聚集率。另采用SD大鼠,大脑中动脉阻塞（MCAO）大鼠造模后灌胃给药5 d,检测MCAO大鼠PT、APTT、TT、FIB及脑组织含水量。结果：与空白组比较,益气活血风静胶囊高、中剂量组及阳性对照组,能显著延长大鼠血浆的PT、TT、APTT （P<0.05）,并能显著降低FIB的含量（P<0.05或P<0.01）,显著降低以二磷酸腺苷（ADP）诱导的大鼠血小板聚集率（P<0.05）。与空白组比较,益气活血风静胶囊高、中、低剂量组及阳性对照组能显著延长家兔血浆的PT、TT、APTT （P<0.05或P<0.01）,并能显著降低FIB的含量（P<0.01）,显著降低以ADP诱导的大鼠血小板聚集率（P<0.05或P<0.01）。MACO大鼠模型组给药后,与假手术组比较,模型组大鼠PT、APTT、TT明显缩短（P<0.05）,FIB含量升高（P<0.05）,脑组织含水量明显增加（P<0.01）;与模型组比较,益气活血风静组和人参有效部位组能延长大鼠血浆PT、APTT、TT时间（P<0.05或P<0.01）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）,牡丹皮有效部位组大鼠TT延长（P<0.05）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）。结论：益气活血风静胶囊具有显著的抗凝血以及抑制以ADP诱导的血小板聚集的作用,并对MCAO大鼠有较好的活血作用。     

香椿子水煎剂的抗血栓作用研究

目的:研究香椿子水煎剂的抗血栓作用。方法:测定正常大鼠凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)。复制大鼠静脉血栓模型并称取血栓湿重。复制血瘀证模型大鼠,并测定其血浆血栓素B(2TXB2)和6-酮前列腺素F1α(6-keto-PGF1α)含量以及血浆纤溶酶原激活物(t-PA)、纤溶酶原激活抑制物(PAI)含量。结果:280、700、980 mg·kg-1剂量下香椿子水煎剂均可延长大鼠PT、TT、APTT。700、980 mg·kg-1剂量下香椿子水煎剂可使静脉血栓模型大鼠血栓湿重显著降低(P<0.01)。香椿子水煎剂对血瘀证模型大鼠血浆TXB2含量无显著影响,700、980 mg·kg-1剂量下香椿子水煎剂能显著升高模型大鼠血浆6-Keto-PGF1α含量(P<0.01),但对t-PA、PAI含量无显著影响。结论:香椿子水煎剂有较强的抗血栓作用。     

凝血四项检测对诊断病毒性肝炎的结果观察及临床意义

目的探讨凝血功能检测对诊断病毒性肝炎的结果变化和临床意义。方法对118例病毒性肝炎患者及40例健康对照组分别检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)以及纤维蛋白原含量(FIB),并对其结果进行回顾性分析。结果病毒性肝炎患者中急性肝炎、慢性肝炎、重症肝炎及肝硬化患者检测PT、APTT和TT结果与对照组比较,均高于对照组;FIB结果与对照组比较,只有急性肝炎高于对照组,其他均小于对照组。急性肝炎与对照组比较,其PT、TT和FIB均(P<0.05),APTT则(P<0.01);慢性肝炎与对照组比较,其PT和TT均(P<0.05),APTT则(P<0.01);慢性肝炎与对照组比较,其PT和TT均(P<0.05);APTT亦为(P<0.01);重症肝炎和肝硬化与对照组比较结果均(P<0.01)。结论病毒性肝炎检测凝血功能指标,对准确地反映病毒性肝炎患者的凝血功能状态、疗效观察及判断预后都有一定的价值。     

泮托拉唑联合凝血酶对上消化道出血治疗效果及对凝血功能指标的影响

目的:观察泮托拉唑联合凝血酶对上消化道出血患者临床效果及凝血功能指标的影响。方法:选择2019年1月至2020年10月驻马店市中心医院收治的上消化道出血患者86例,按随机数字表法分为两组,各43例。在常规治疗基础上,对照组给予泮托拉唑治疗,观察组给予泮托拉唑联合凝血酶治疗,共治疗7 d。比较两组临床疗效、凝血功能指标、止血时间、输血量及不良反应。结果:观察组临床总有效率为97.67%,高于对照组的81.40%,差异有统计学意义(P<0.05)。两组治疗后凝血酶时间(TT)、部分凝血酶活时间(APTT)、凝血酶原时间(PT)均短于治疗前,且观察组TT(17.49±1.20)s、APTT(34.15±2.89)s、PT(12.03±0.84)s,短于对照组,差异有统计学意义(P<0.05)。观察组止血时间(29.83±3.66)h,短于对照组,输血量(523.26±31.53)mL,少于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率相比,差异无统计学意义(P>0.05)。结论:泮托拉唑联合凝血酶治疗上消化道患者,能有效缩短TT、APTT、PT及止血时间,减少输血量,临床治疗安全有效。     

参芪止血胶囊止血作用的实验研究

目的观察参芪止血胶囊止血的作用机制。方法以雌性SD大鼠为研究对象，将其随机分为正常组，参芪止血胶囊低、中、高剂量组（以下简称参低、中、高组）和宫血宁组。测定大鼠出血时间（BT），凝血时间（CT），凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）并进行比较分析。结果与正常组比较，参芪止血胶囊能够显著缩短BT、CT、PT和APTT的时间（P〈0．05，P〈0．01），与宫血宁组比较，参中组缩短BT、CT上有统计学意义。结论参芪止血胶囊能有效止血。     

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.