板蓝根中苯甲酸的抗内毒素作用

目的研究板蓝根中苯甲酸的抗内毒素作用。方法将苯甲酸配成0.25%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测苯甲酸体内抗内毒素作用;脂多糖致小鼠死亡实验测定苯甲酸保护作用及苯甲酸对脂多糖致小鼠过度释放肿瘤坏死因子（TNF-α）和一氧化氮（NO）的影响研究苯甲酸的抗内毒素作用。结果0.416 mg.mL^-1苯甲酸可使4 EU内毒素降解为0.926 EU,破坏率为78%;0.25%苯甲酸溶液可使内毒素引起的家兔体温升高显著降低,使同等剂量脂多糖引起的小鼠死亡率从70%降为20%;板蓝根中的苯甲酸可抑制脂多糖致小鼠血清中TNF-α和NO的过度释放,其抑制率呈剂量依赖性。结论从板蓝根中提取分离出的苯甲酸有抗内毒素作用。     

板蓝根中4(3H)-喹唑酮的抗内毒素作用

目的 研究板蓝根中4(3H)-喹唑酮(QZO)的抗内毒素作用.方法 鲎试验法测定抗内毒素;内毒素致家兔发热实验检测其体内抗内毒素作用;脂多糖致小鼠死亡实验测定QZO的保护作用及其对脂多糖致小鼠过度释放肿瘤坏死因子(TNFα)和一氧化氮(NO)的影响,研究QZO的抗内毒素作用.结果 0.832 mg·ml-1QZO可使4 EU内毒素降解为1.19 EU,破坏率71.31%;0.5%QZO溶液可使内毒素引起的家兔体温升高显著降低,使同剂量脂多糖引起的小鼠死亡率从70%降为30%;板蓝根中的QZO可抑制脂多糖致小鼠血清中TNFα和NO的过度释放,抑制率呈剂量依赖性.结论 从板蓝根中提取分离出的QZO有抗内毒素作用.     

板蓝根中水杨酸的抗内毒素作用

目的:研究板蓝根中水杨酸的抗内毒素作用。方法:将水杨酸配成0.25%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测水杨酸体内抗内毒素作用;脂多糖致小鼠死亡实验测定水杨酸保护作用及水杨酸对脂多糖致小鼠过度释放肿瘤坏死因子(TNFα)和一氧化氮(NO)的影响实验,研究水杨酸的抗内毒素作用。结果:0.416g.L-1水杨酸可使4EU内毒素降解为1.08EU,破坏率为74.07%;0.25%水杨酸溶液可使内毒素引起的家兔体温升高显著降低、使同等剂量脂多糖引起的小鼠死亡率从70%降为25%;板蓝根中的水杨酸可抑制脂多糖致小鼠血清中TNFα和NO的过度释放,其抑制率呈剂量依赖性。结论:从板蓝根中提取分离出的水杨酸有抗内毒素作用。     

黄芩中黄芩苷的抗内毒素作用

目的 探讨黄芩中黄芩苷的抗内毒素作用。方法将黄芩苷配成0.5%水溶液，鲎实验法进行抗内毒素定量测定；内毒素致家兔发热实验检测黄芩苷体内抗内毒素作用；脂多糖致小鼠死亡实验测定黄芩苷保护作用及黄芩苷对脂多糖致小鼠过度释放肿瘤坏死因子（TNF）和一氧化氮（NO）的影响实验，研究黄芩苷的抗内毒素作用。结果0.833 g· mL 1黄芩苷可使4 EU内毒素降解为0.546 EU，破坏率为87.45%；0.5%黄芩苷溶液可显著降低内毒素引起的家兔体温升高，同等剂量脂多糖引起的小鼠死亡率从70.0%降为10.0%；黄芩中的黄芩苷可抑制脂多糖致小鼠血清中TNF和NO的过度释放，其抑制率呈剂量依赖性。结论 从黄芩中提取分离出的黄芩苷有抗内毒素作用。     

板蓝根对脂多糖刺激鼠释放炎性细胞因子的影响

目的探讨板蓝根抗内毒素活性部位F022对脂多糖(LPS)刺激鼠单核细胞释放炎性细胞因子的影响。方法取BALB/C小鼠腹腔内单核细胞,实验设计为6组。其中,实验组根据F022浓度分为1%、0.5%、0.25%、0.125%4组,分别加入板蓝根F022部位液后再加入LPS液;LPS阳性组仅加入LPS液;阴性组加入1%F022液。之后检测细胞培养上清液中3种炎性细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)和一氧化氮(NO)水平。结果LPS可刺激鼠单核细胞过度释放炎性细胞因子TNF-α、IL-6和NO;与阳性组比较,实验组炎性细胞因子水平降低,且呈剂量依赖性。结论板蓝根抗内毒素活性部位F022对LPS刺激鼠单核细胞过度释放炎性细胞因子具有抑制作用。     

板蓝根抗内毒素活性有效部位研究(Ⅰ)

目的探讨板蓝根F022部位抗内毒素活性.方法用板蓝根F022部位溶液分别做对内毒素致兔发热影响、对LPS致鼠巨噬细胞释放TNFα和NO的影响、对LPS刺激鼠体内组织moesin mRNA表达的影响来检测其抗内毒素活性.结果经预先给予板蓝根F022部位可抑制(40 EU·kg 1)致兔发热反应,与内毒素模型组比,TRI 4和ATmax差异均有显著性(P＜O.01);可抑制LPS刺激鼠巨噬细胞分泌TNFα和NO,且有剂量依赖性;可抑制LPS刺激鼠肝、脾、肾组织中moesin mRNA表达,且与模型组相比差异均有显著性(P＜O.01).结论板蓝根F022部位从多途径显示抗内毒素活性,该部位为板蓝根抗内毒素活性物质.     

消炎退热颗粒清热解毒作用研究

目的：观察中成药消炎退热颗粒（DPZG）对家兔发热模型、小鼠急性耳廓肿胀模型、小鼠内毒素血症模型的作用,探讨其清热解毒的作用和机理。方法：采用脂多糖（lipopolysaccharides,LPS）耳缘静脉注射建立家兔发热模型,评价其解热作用;采用二甲苯致小鼠急性耳廓肿胀模型评价其抗炎作用;建立小鼠内毒素血症模型,观察DPZG对于D-氨基半乳糖（ACTD）敏化小鼠LPS致死攻击的影响,评价其抗内毒素的作用;以Elisa法检测DPZG对内毒素血症模型小鼠血清中TNF-α、IL-1β等炎症因子水平的影响,Western blot法检测小鼠肝、脾、肾组织中膜突蛋白（moesin）以及磷酸化P38 MAPK表达。结果：与模型组比较,DPZG对家兔体温升高有显著抑制作用,与阿司匹林趋同;可显著降低二甲苯致小鼠急性耳廓肿胀程度;可显著升高内毒素血症模型小鼠存活率;显著降低小鼠血清中TNF-α、IL-1β水平和小鼠肝脾肾组织内p-P38MAPK和膜突蛋白（moesin）的表达,效果明显优于中成药对照药蒲地蓝消炎口服液（PBKH）。结论：消炎退热颗粒有显著清热解毒作用,主要作用方式是解热、抗炎、抗内毒素,且效果明显优于PBKH。其作用机制可能与抑制IL-1β、TNF-α、Moesin以及p-P38 MAPK的表达有关。     

板蓝根抗内毒素活性部位研究(Ⅱ)

目的探讨板蓝根F022部位抗内毒素活性.方法用板蓝根F022部位溶液分别作对LPS致小鼠死亡的影响、对LPS诱导P38MAPK活性的影响及其化学成分丁香酸对内毒素的破坏作用,检测其抗内毒素活性.结果板蓝根F022部位可降低LPS致小鼠死亡率;可抑制LPS诱导鼠单核细胞分泌P38丝裂原活化蛋白激酶活性且有剂量依赖性;板蓝根F022部位的丁香酸成分可破坏内毒素,破坏率达83.16%.结论体内外有多项实验显示板蓝根F022部位有抗内毒素活性,该部位为板蓝根抗内毒素活性物质.     

板蓝根抗内毒素活性物质筛选

目的从板蓝根氯仿提取部位(F02)4个不同极性组分(F021、F022、F023和F024)中筛选出抗内毒素活性最强的部位.方法用板蓝根不同组分对内毒素致小鼠死亡保护作用及对内毒素致鼠巨噬细胞分泌炎性因子肿瘤坏死因子(TNFα)、白细胞介素-6(IL-6)的影响作比较研究.结果 F02、F021、F022、F023和F024组对2.42 mg·kg-1内毒素致小鼠死亡有保护作用,死亡率分别为30%、50%、20%、50%和60%.对内毒素刺激鼠巨噬细胞分泌TNFα和IL-6有抑制作用,LPS浓度为50 ng·mL-1时,抑制率TNFα分别为76.54%、30.86%、78.60%、36.63%、2.06%,IL-6分别为75.85%、18.45%、77.68%、21.41%、3.64%;LPS浓度为100 ng·mL-1时抑制率TNTα分别为49.65%、16.86%、66.97%、13.39%、7.16%,IL-6分别为59.78%、1.28%、61.86%、2.08%、1.44%.结论板蓝根氯仿提取部位第F022组分抗内毒素活性最强,该部位为板蓝根抗内毒素活性物质.     

肉苁蓉多糖的巨噬细胞活化作用

目的观察肉苁蓉多糖(CDPS)对巨噬细胞的活化作用。方法采用中性红法测定吞噬活性;Griess试剂法测定NO释放量;L929细胞法及小鼠胸腺细胞法测定TNF-α及IL-1释放。结果CDPS在6.25～50mg.L-1剂量范围内可剂量依赖性地增强BALB/c小鼠腹腔巨噬细胞吞噬中性红能力和促进NO释放;在2.8～100mg.L-1剂量范围内可使正常和免疫抑制的RAW264.7细胞NO释放明显增加;在0.56～7.2mg.L-1或3.6～10mg.L-1范围促进RAW264.7细胞TNF-α或IL-1产生,均具有良好的量效关系。结论CDPS可明显提高巨噬细胞吞噬及分泌功能,活化巨噬细胞。肉苁蓉免疫增强作用可能与此有关。     

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.     

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.