西红柿凝集素修饰脂质体对小鼠口服吸收胰岛素的促进作用西红柿凝集素修饰脂质体对小鼠口服吸收胰岛素的促进作用

目的研究西红柿凝集素修饰的胰岛素脂质体在小鼠胃肠道吸收作用。方法采用碳二亚胺交联法制备西红柿凝集素(TL)修饰的磷脂酰乙醇胺(PE),将TL-PE掺入胰岛素脂质体中制成凝集素修饰脂质体并证实TL凝集活性不受影响。分别对正常小鼠及糖尿病模型小鼠灌胃给予350 u·kg^-1胰岛素的修饰脂质体溶液,用葡萄糖酶试剂盒测定小鼠血糖,并与同剂量普通胰岛素脂质体比较。结果正常小鼠中,西红柿凝集素修饰脂质体在4 h血糖降至初始水平的(85±5)%,8 h降至(54±11)%,12 h为(57±6)%。胰岛素普通脂质体几乎没有降糖作用,与生理盐水对照组相当。糖尿病模型小鼠中,西红柿凝集素修饰脂质体在4 h血糖降至初始水平的(38±13)%,8 h降至(50±15)%,12 h为(50±16)%。结论西红柿凝集素修饰的脂质体可能通过与细胞表面特异性受体的结合作用促进大分子药物的胃肠吸收。     

荆豆凝集素修饰脂质体对小鼠口服吸收胰岛素的促进作用

目的研究荆豆凝集素(UEA1)修饰的胰岛素脂质体在小鼠胃肠道的吸收作用。方法采用碳二亚胺偶联法制备荆豆凝集素修饰的磷脂酰乙醇胺(PE)，将PE-UEA1参入胰岛素脂质体中制成凝集素修饰脂质体，并证实UEA1凝集活性不受影响。分别对正常小鼠及糖尿病模型小鼠灌胃给予350 u·kg^-1胰岛素的修饰脂质体溶液，用葡萄糖酶试剂盒测定小鼠血糖，并与同剂量普通胰岛素脂质体比较。结果对于正常小鼠，荆豆凝集素修饰脂质体在4 h使血糖降至初始水平的(84±15)%，8 h降至(78±11)%，12 h为(90±12)%。胰岛素普通脂质体几乎没有降糖作用，与生理盐水对照组相当。对于糖尿病模型小鼠，荆豆凝集素修饰脂质体在4 h使血糖降至初始水平的(73±7)%，8 h降至(74±9)%，12 h为(86±9)%。结论荆豆凝集素修饰的脂质体可能通过与M细胞表面特异性受体的结合促进大分子药物的胃肠吸收。     

凝集素修饰乳酸-羟基乙酸共聚物纳米粒的制备及体外黏附性能评价

本文分别以麦胚凝集素、西红柿凝集素和天门冬豌豆凝集素为表面修饰材料，采用碳化二亚胺法制备了不同凝集素修饰的乳酸-羟基乙酸共聚物纳米粒。分别考察了活化剂的用量、活化时间、凝集素的用量、孵化时间对凝集素修饰纳米粒的影响，由此确定最佳制备条件。福林-酚法测定凝集素的修饰率为(18.97±2.9)%～(20.15±2.4)%，纳米粒表面的凝集素浓度为(9.46±1.45)～(10.05±1.19) μg·mg^-1。采用黏蛋白结合法对纳米粒的体外黏附性能进行评价，结果表明纳米粒与黏蛋白溶液在室温下孵化60 min后结合反应达到平衡，此时不同凝集素修饰纳米粒的黏蛋白结合量分别为15.5%，12.1%和11.8%，是普通纳米粒黏蛋白结合量的2.4～3.2倍。经Langmuir方程拟合计算得到各结合速率常数分别为2.373×10^-3，1.536×10^-3和1.714×10^-3 (μg·min/mL)^-1。不同凝集素修饰纳米粒与黏蛋白的结合可被该凝集素的特异性单糖抑制。实验结果表明，与普通纳米粒相比，凝集素修饰纳米粒与黏蛋白的体外黏附能力显著增强，预计其口服后可与胃肠黏膜表面产生黏附作用，从而延长制剂在胃肠道内的滞留时间。     

红藻琼枝麒麟菜中凝集素的提取、纯化及其性质研究

目的 从琼枝麒麟菜中分离纯化凝集素，并测定其生物活性。方法 采用缓冲低温提取，40％－90％（NH4）2SO4分级盐析沉淀，Sephadex G-75凝胶过滤层析进行纯化：SDS－PAGE检测其纯度和测定分子量；考察该凝集素凝血活性的血型专一性，糖抵制性及高温，酸，碱处理下的稳定性。结果 琼枝麒麟菜中有凝集素，分子量为29000。该凝集素对人A，B，O和AB4种类型血细胞均显凝血活性，该活性对高温，酸，碱处理有较好的稳定性。结论 琼枝麒麟菜中存在凝集素，其生物活性显著。     

凝集素修饰透黏膜微粒给药系统

通过对近年来相关文献的检索,本文介绍了凝集素修饰的微球、纳米粒和脂质体,以及凝集素对不同微粒系统的修饰机制,综述凝集素修饰微粒给药系统在透黏膜给药中的应用,认为凝集素修饰微粒给药系统有较好的应用前景。     

荆豆凝集素修饰牛血清白蛋白脂质体的黏附性评价

目的对荆豆凝集素修饰牛血清白蛋白脂质体的黏附性进行评价。方法采用逆向蒸发法制备了荧光标记的普通脂质体和荆豆凝集素修饰的脂质体,通过小鼠胃肠道组织和荧光标记脂质体的离体孵化法考察了制剂的体外黏附性;通过制剂灌胃后的在体实验法考察了其体内黏附性。结果荆豆凝集素修饰的脂质体在小鼠胃、不含派伊尔氏结(peyer's patches,PPs)小肠和结肠中的黏附量与普通脂质体组相比没有明显差异(P>0.05),但在有PPs小肠区域,黏附脂质体量显著增加(P<0.05),且黏附时间可达24 h以上。结论荆豆凝集素修饰的脂质体可以长时间特异性黏附于小鼠含有PPs的小肠部位,从而增强口服黏膜免疫的靶向性和长效性。     

福建11种海洋贝类凝集素的研究

用绵羊、家兔、家鸡、麻鸭和人的A,B,AB,O型血等8种红细胞对11种海洋贝类的凝集素进行凝血活性检测,同时进行凝集素的糖抑制和热稳定性试验,结果表明,有10种贝类凝集素对绵羊红细胞有凝集活性,有6种对家兔红细胞有凝集活性,对家鸡,麻鸭和人B型血细胞铡全无凝集活性,对人的其它3种血型的细细胞只有个别的有凝集活性,某些种类的凝集对兔红细胞的凝集活性可分别被一种或几种糖抑制,6种贝类的凝集素在90度,10min热处理后仍然对兔红细胞有凝集活性,显示出较高的热稳定性     

荆豆凝集素修饰的牛血清白蛋白脂质体的免疫学性质

目的对荆豆凝集素修饰的牛血清白蛋白脂质体进行免疫学评价。方法 3组小鼠分别于0、7、14、21 d口服免疫牛血清白蛋白溶液(bovine serum albumin,BSA)、BSA脂质体及荆豆凝集素修饰的BSA脂质体,建立ELISA法测定小鼠在7、14、21、28、35及42 d时体内产生的系统及黏膜免疫应答。结果与BSA溶液组相比,将抗原包裹于脂质体、尤其是荆豆凝集素修饰的脂质体中免疫小鼠后,可在小鼠血清及小肠分泌液中检测到较高的IgG及IgA水平。其中,免疫后42 d,凝集素修饰脂质体组的IgG和IgA水平分别为BSA溶液组产生相应抗体值的4.33倍和4.74倍。结论荆豆凝集素修饰脂质体口服免疫小鼠后可同时诱导机体产生黏膜及系统免疫应答,可以作为口服疫苗的载体。     

血浆置换治疗重型肝炎183例临床分析

目的:探讨血浆置换(PE)治疗重型肝炎的临床疗效.方法:对183例重型肝炎患者进行PE治疗,比较血浆置换前后的肝功能﹑凝血功能﹑血氨以及血液学参数的变化.结果:血浆置换后患者的肝功能、凝血功能、血氨与治疗前相比有显著性差异(P＜0.01),治疗前后血液学参数无显著改变(P＞0.05).结论:血浆置换是治疗重型肝炎的一种...     

新生儿全身炎症反应综合征血浆AT-Ⅲ、D-dimer水平的研究

目的:通过研究AT-Ⅲ、D-dimer的水平,探讨新生儿凝血功能紊乱在全身炎症反应综合征/多器官功能障碍综合征(SIRS/MODS)中的表现.方法:对87例SIRS新生儿及40例非SIRS新生儿血浆AT-Ⅲ活性、D.dimer含量进行检测.结果:SIRS组与正常对照组和非SIRS对照组比较,AT-Ⅲ活性明显减低,D-dimer含量明显升高;SIRS组AT-Ⅲ、D-dimer异常发生率明显高于非SIRS对照组(65.5%、56.3%vs 12.5%、10.0%,P<0.05);SIRS合并MODS与SIRs未合并MODS者比较,AT-Ⅲ活性明显减低,D-dimer含量明显升高;死亡组与存活组比较,AT-Ⅲ活性明显减低,D-dimer含量明显升高.结论:SIRS新生儿存在凝血机制异常,合并MODS者,凝血功能紊乱越显著,病死率越高.     

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.