丹红注射液对大鼠脑缺血再灌注损伤的保护作用

目的：研究丹红注射液对大鼠缺血再灌注损伤的保护作用。方法：采用线栓法建立大鼠脑缺血再灌注模型,观察丹红注射液对脑缺血再灌注损伤大鼠的神经功能评分、脑组织中一氧化氮合酶（NOS）、一氧化氮（NO）、超氧化物歧化酶（SOD）、丙二醛（MDA）等的影响。结果：丹红注射液可显著降低脑缺血再灌注大鼠的神经功能评分,减轻脑组织损伤程度;提高SOD活力,降低MDA和NO、NOS水平。结论：丹红注射液对大鼠缺血再灌注损伤具有明显的保护作用。     

强力宁对大鼠脑缺血再灌注损伤的保护作用

目的：观察强力宁（QLN）对大鼠急性脑缺血再灌注损伤的作用。方法：采用大鼠急性不完全性脑缺血再灌注损伤模型,测定脑组织含水量,丙二醛（MDA）,超氧化物歧化酶（SOD）及三磷酸腺苷酶（ATPase)的含量,结果：QLN（20mg.kg^-1)能显著对抗缺血再灌注大鼠脑组织含水量,MDA含量的升高（P＜0．05,P＜0．012）,SOD及ATPase活性的降低（P＜0．05,P＜0．01）,结论：QLN具有保护脑缺血再灌注性损伤的作用,机制与降低脑脂质过氧化和增强氧自由基清除酶的活性,改善ATP酶的功能有关。     

复方灯盏花滴丸对大鼠急性脑缺血再灌注损伤的保护作用

目的：研究复方灯盏花滴丸对大鼠急性脑缺血财灌注损伤的保护作用。方法：采用4-动脉阻断法复制大鼠急性脑缺血再灌注模型。观察不同剂量的复方灯盏花滴丸对脑组织含水量，病理组织学改变及血清中肌酸激酶（CK），乳酸脱氢酶（LDH），超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量的影响。结果：复方灯盏花滴丸可显著降低脑含水量。减轻脑组织的病理损害；显著降低血清中CK，LDH的活性及MDA含量，并且可明显提高血清中SOD活性。结论：复方灯盏花滴丸对大鼠急性脑缺血再灌注损伤有显著保护作用。其机制可能与抗脂质过氧化作用有关。     

牛黄、栀子配伍对大鼠局灶性脑缺血再灌注不同时段脂质过氧化损伤的影响

目的：通过检测牛黄、栀子及二者配伍对大鼠局灶性脑缺血再灌注不同时段脂质过氧化损伤的影响，探讨治疗缺血性中风在该作用环节不同时段的作用特点，研究其配伍阻抑脑缺血级联反应的时序特征。方法：用线栓法建立大鼠大脑中动脉缺血再灌注模型，观察牛黄、栀子及二者配伍对缺血再灌注24h和72h两个时段大鼠神经症状、脑组织超氧化物歧化酶(superoxide dismutase，SOD)活性和丙二醛(malondialdehyde，MDA)含量的影响。结果：牛黄、栀子均能显著改善两个时段大鼠神经功能缺损症状，配伍后作用更为显著；牛黄对缺血再灌注24h、72h脑组织SOD活性和MDA含量均未见明显影响；栀子可明显升高缺血再灌注24h脑组织SOD活性、降低MDA含量，但对再灌注72h脑SOD活性和MDA含量未见明显影响；二者配伍可使缺血再灌注72h脑组织SOD活性显著升高、MDA含量降低，但对再灌注24h脑组织SOD活性和MDA含量的影响并不显著。结论：中药配伍的作用不是简单的效应累加，在同一效应环节上还表现为不同时段的配伍作用特征。     

消旋四氢巴马汀对局灶性脑缺血 再灌注损伤模型大鼠的保护作用

目的 观察消旋四氢巴马汀（THP）对局灶性脑缺血 再灌注损伤大鼠的保护作用。方法用改良LONGA法制作大鼠局灶性脑缺血 再灌注损伤模型,缺血前15 min 腹腔注射THP10.0,5.0,2.5 mg•kg 1,观察缺血3 h再灌注3 h后大鼠神经功能障碍、脑梗死范围、血清乳酸脱氢酶（LDH）和肌酸激酶（CK）含量,脑组织钙、水、丙二醛（MDA）和超氧化物歧化酶（SOD）含量,以及脑超微结构。结果THP能剂量依赖性降低神经功能行为评分,缩小脑梗死范围,抑制血清LDH、CK活力升高;THP10.0 mg•kg 1可明显减轻脑水肿,减轻脑超微结构损害,提高脑组织SOD活性,降低MDA含量和脑组织钙聚集。结论THP对局灶性脑缺血 再灌注损伤模型大鼠有一定保护作用,其作用机制可能与抑制脑组织钙聚集、抗脂质过氧化反应有关。     

TNHH对大鼠全脑缺血再灌注损伤的抗氧化性保护作用

目的观察TNHH对大鼠全脑缺血再灌注损伤的抗氧化性保护作用。方法以改良的四血管阻塞法(Pulsinelli four-vessel occlusion model)建立大鼠全脑缺血模型,于缺血30 min,再灌注48 h后进行脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)测定。结果TNHH能显著降低大鼠缺血损伤脑组织中MDA含量,降低MPO活性,提高SOD活性。结论TNHH对大鼠全脑缺血再灌注损伤的具有明显的抗氧化作用。     

D-R聚甘酯对局灶性脑缺血大鼠的保护作用

目的研究D-聚甘酯(多糖类化合物)对大鼠局灶性脑缺血再灌注损伤(RI)的保护作用及其可能机制。方法用改良Longa法,建立大鼠局灶性脑缺血2 h再灌注损伤模型,观察D-聚甘酯对脑缺血再灌注大鼠的脑组织中丙二醛(MDA)含量及对超氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(GSH-PX)活性的影响。结果模型组大鼠在RI 24 h、RI 72 h及RI 144h时,MDA含量明显高于假手术组;而SOD和GSH-PX活性降低。D-聚甘酯可降低MDA含量,升高SOD和GSH-PX活性,尤其是在RI 144 h。结论 D-聚甘酯对脑缺血再灌注损伤有保护作用,其机制可能与抗缺血性脑组织中的自由基有关。     

丹参酮ⅡA纳米制剂对大鼠全脑缺血再灌注损伤的保护作用

目的：观察丹参酮ⅡA纳米制剂对大鼠全脑缺血再灌注损伤的保护作用。方法：采用三动脉夹闭法制备大鼠全脑缺血再灌注损伤模型,以丹参酮ⅡA纳米制剂灌胃给药,观察丹参酮ⅡA纳米制剂对脑组织的丙二醛（MDA）含量、超氧化物歧化酶（SOD）活力和脑组织Na^＋-K^＋-ATPase活性水平的影响。做脑组织病理切片检查和透射电镜观察。结果：丹参酮ⅡA纳米制剂（25mg／kg）能使脑组织MDA含量下降（P〈0．01）,SOD活性明显升高（P〈0．05）,Na^＋-K^＋-ATP活性显著上升（P〈0．01）,病理切片和透射电镜观察显示丹参酮ⅡA纳米制剂能在不同的水平上抑制细胞和线粒体的损伤。结论：丹参酮ⅡA纳米制剂对全脑缺血再灌注损伤具有很好的保护作用。     

麝香醒脑滴丸对脑缺血再灌注损伤的保护作用

目的：探讨麝香醒脑滴丸（Shexiang Xingnao dropping pills,SXD）对大鼠脑缺血再灌注损伤的保护作用及其机制。方法线栓法建立大鼠局灶性脑缺血（MCAO）再灌注模型,按 Bederson 的方法对 MCAO 再灌注0、4、8、22 h 时大鼠的神经功能损伤进行评分;测定脑梗死百分比、脑指数、脑含水量;检测血浆中血小板聚集率和脑组织超氧化物歧化酶（SOD）、乳酸脱氢酶（LDH）活性以及丙二醛（MDA）含量;HE 染色观察脑组织病理变化。结果与模型组比较,SXD（0．42、0．84 g·kg －1）对MCAO 再灌注大鼠的神经功能损伤评分有一定的改善作用,能减少脑梗死百分比、脑含水量、脑指数和血小板聚集率,提高脑组织 SOD 和 LDH 活性,降低脑组织中 MDA 含量,减轻脑组织皮质神经元的损伤。结论SXD 对脑缺血再灌注损伤具有一定的保护作用,其机制可能与抗氧自由基损伤及抑制血小板聚集等有关。     

香丹注射液对大鼠脑缺血再灌注损伤的保护作用

目的研究香丹注射液对脑缺血再灌注损伤的保护作用,为该药的临床应用提供实验依据。方法将Wister大鼠50只随机分为5组：假手术组、模型组、香丹注射液高、中、低剂量组,其中香丹注射液高、中、低剂量组分别腹腔注射香丹注射液2g/（kg.d）、4g/（kg.d）、8g/（kg.d）,假手术组和模型组给予等容量生理盐水。连续腹腔注射14d,末次腹腔注射1h后,麻醉,固定,线拴法制备MCAO模型。缺血2h后,再灌注24h后观察香丹注射液对缺血再灌注大鼠神经功能评分;检测香丹注射液对脑缺血再灌注大鼠血清及脑组织中一氧化氮（NO）、超氧化物歧化酶（SOD）、丙二醛（MDA）等的影响。结果香丹注射液可显著降低脑缺血再灌注大鼠的神经功能评分,减轻脑组织损伤程度;提高SOD活力,降低MDA含量和NO水平。结论香丹注射液对大鼠脑缺血再灌注损伤有明显的保护作用,作用机制主要与抗自由基损伤有关。     

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.     

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.     

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.     

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.