全麻复合硬膜外阻滞对体外循环病人血浆内皮素、心钠肽和肌钙蛋白Ⅰ的影响

目的 研究全麻复合硬膜外阻滞及术后硬膜外镇痛对换瓣病人血浆内皮素（ET）、心钠肽（ANP）和肌钙蛋白Ⅰ（CnT-Ⅰ）的影响。方法 20例行二尖瓣置换术病人随机分成异氟醚吸入全麻复合硬膜外组（GEA组）和异氟醚吸入全麻组（GA组）。GEA组行硬膜外镇痛,GA组行术后静脉镇痛。观察麻醉前、手术后4、24、72h及第7天血浆ET、ANP和CnT-Ⅰ的变化水平。结果 术后第1、3天两组病人的ET浓度较麻醉前均有显著性降低（P〈0．05）,GEA组降低的幅度明显大于GA组（P〈0．05）;GA组病人的ANP自术后第1天起显著升高（P〈0．05）,GEA组则无明显变化（P〉0．05）;两组病人的CnT—Ⅰ水平在术后4h及术后第1天均较术前显著性增高（P〈0．05）,但组间无显著性差异;GEA组病人术后清醒及拔管时间明显均早于GA组（P〈0．05）。结论 全麻复合硬膜外阻滞能有效降低血浆ET及ANP的水平,促进病人术后恢复。     

心钠素对肝硬化患者血浆内皮素血管紧张素Ⅱ的影响

目的：应用外源性心钠素（ANP），观察其对直硬化患者血浆内皮素（ET）、血管紧张素Ⅱ（ATⅡ）等缩血管物质的影响。方法：应用心血通注射液（心钠素）治疗41例肝硬化患者，用放免法分别检测治疗前后血浆ANP、ET、ATⅡ的水平，同时检测20例健康人，结果：肝硬化组比正常组血浆ANP、ET、ATⅡ水平明显升高（P＜0．05），肝硬化患者血浆ANP与ET呈负相关，与ATⅡ无显著相关。外源性心钠素能降低childA级和／或B级ET、ATⅡ的水平（P＜0．05，P＜0．01），对childC级无抑制作用。结论：肝硬化患者血管扩张因子与血管收缩因子之间失衡，促进腹水及门脉高压的形成，外源性心钠素能部分调节它们之间的紊乱关系，对肝硬化失代偿期的治疗有重要价值。     

慢性阻塞性肺疾病患者血浆脑肽钠和内皮素水平的变化

目的 测定慢性阻塞性肺疾病（COPD）急性加重期（AECOPD）和稳定期患者血浆脑肽钠（BNP）和内皮素（ET）水平的变化,以探讨BNP和ET在COPD发病机制中的作用。方法检测28例AECOPD患者,24例COPD稳定期患者和26名健康对照者的血浆脑肽钠和内皮素含量。结果AECOPD组分别与对照组和COPD组比较,血浆BNP和ET水平明显升高（P〈0．01,P〈0．05;P〈0．01,P〈0．05）,COPD患者与对照组比较,血浆BNP和ET水平明显升高（P〈0．05;P〈0．05）。结论COPD患者血浆ET和BNP的变化参与COPD的炎症过程,它们的变化可能与其疾病本身和疾病程度有关。     

急性有机磷中毒患者血浆内皮素和降钙素基因相关肽水平的变化

目的 通过观测正常人和有机磷中毒患者（AOPP）血浆内皮素（ET）和降钙素基因相关肽（CGRP）水平异常变化,探讨内皮素和CGRP在AOPP发病过程中的变化及意义。方法 用放射免疫法测定血浆内皮素和CGRP水平。结果 轻度、中度、重度中毒组的ET水平与对照组比较有明显增高（P〈0．01）．而CGRP水平与对照组比较有明显降低（P〈0．05或P〈0．01）;而中度、重度组的ET水平较轻度组有明显增高（P〈0．01）．而中度、重度组的CGRP水平较轻度组有明显有明显降低（P〈0．05）;同时发现ET与CGRP水平呈负相关（P〈0．05）。结论 AOPP患者血浆ET和CGRP含量的变化与中毒程度有关,可做为判断预后和中毒程度的指标．同时也为临床抢救提供新的思路。     

米力农治疗心力衰竭的疗效及其对神经内分泌的影响

目的：探讨米力农治疗充血性心力衰竭的疗效及其对患内皮素（ET），心钠素（ANF），血浆肾素活性（PRA），血管紧张素Ⅱ（Ang-Ⅱ）的影响。方法：充血性心力衰竭病人48例，以米力农10mg加入5%葡萄糖注射液250ml中静滴6h，每日1次，共7天。治疗前后分别测定心功能，ET，ANF，PRA，Ang-Ⅱ，并加以比较。结果：米力农的临床总有效率为91.7%，对左室收缩和舒张功能均有明显改善。治疗后ET，ANF明显下降，PRA，Ang-Ⅱ无明显变化。结论：米力农短期应用能改善心力衰竭患心功能和部分神经内分泌异常。     

心钠素、肾素-血管紧张素-醛固酮系统在慢阻肺病、肺心病的变化及相互关系

本文应用放免法测定了正常人16例、肺气肿13例、肺心病51例血浆心钠素(ANP)、肾素活性(PRA)、血管紧张素Ⅱ(AT Ⅱ)、醛固酮(Aldo)的浓度,结果发现①肺气肿组血浆 ANP 水平明显低于正常对照组;②肺心病不同心功能血浆 ANP 水平不同,心功能Ⅰ、Ⅱ、Ⅲ级肺心病患者的血浆 ANP 浓度各组之间有明显差异;③肺心病组血浆 PRA,AT Ⅱ、Aldo 的水平明显高于肺气肿组;④血浆 ANP 与 PRA 有一定的正相关。     

睾酮对去势的肾血管性高血压大鼠肾素-血管紧张素系统及血压的影响

目的探讨去势对肾血管性高血压大鼠肾素-血管紧张素系统及血压的影响,及给予去势的肾血管性高血压大鼠不同剂量的十一酸睾酮后肾素-血管紧张素系统及血压的变化。方法成年雄性Wistar大鼠（180-220g）32只．行左侧肾动脉结扎手术,4周后肾血管性高血压大鼠造模成功。随机分为对照组,单纯去势（双侧睾丸切除）组,小剂量睾酮（TU）组（去势后皮下注射TU13．7μg/g）和大剂量．TU组（去势后皮下注射TU625μg／g）。30d后,测量血压（BP）。测血压后,取血检测血清总睾酮（TT）、血浆肾素活性（RA）、血管紧张素Ⅱ（AngⅡ）。取左侧肾脏,检测组织肾素活性（RA）,血管紧张素Ⅱ（AngⅡ）。结果单纯去势组血清TT水平明显低于对照组（P〈0．01）,小剂量TU组血清TT水平低于对照组（P〈0．05）,大剂量TU组血清TT水平明显高于对照组（P〈0．01）。单纯去势组的血浆RA、AngⅡ水平明显低于对照组（P〈0．01）,小剂量TU组的血浆RA、AngⅡ水平低于对照组（P〈0．05）,大剂量TU组的血浆RA、AngⅡ水平明显高于对照组（P〈0．01）。单纯去势组肾组织的RA、AngⅡ水平明显低于对照组（P〈0．01）,小剂量TU组肾组织的RA、AngⅡ水平低于对照组（P〈0．05）,大剂量TU组肾组织的RA、AngⅡ水平高于对照组（P〈0．05）。单纯去势组BP明显低于对照组（P〈0．01）,小剂量TU组BP低于对照组（P〈0．05）,大剂量TU组BP明显高于对照组（P〈0．01）。结论雄性肾血管性高血压大鼠去势及去势后给予不同剂量的十一酸睾酮可产生不同水平的TT,同时也使血浆及组织局部的肾素-血管紧张素系统、血压发生变化。去势及去势后给予十一酸睾酮可能通过血浆及组织局部的肾素-血管紧张素系统影响肾血管性高血压大鼠的血压。     

术后镇痛对冠心病患者肾素-血管紧张素-醛固酮系统的影响

目的 比较胸段硬膜外阻滞（TEA）镇痛与静脉镇痛（GA）对冠心病患者术后肾素-血管紧张素-醛固酮系统（R-A-A-S）的影响。方法 60例择期行胸部、上腹部手术的冠心病患者，随机分为TEA组和GA组。分别于术前1d、术毕清醒后1h和术后第1天同一时间点抽取静脉血测定血浆肾素活性（PRA）、血管紧张素Ⅱ（AⅡ）及醛固酮（ALD）的浓度，采用视觉模拟评分法评定镇痛效果。结果 镇痛评分无明显差异。术后PRA、AⅡ及ALD值与术前比较TEA组差异元显著意义（P〉0．05）。GA组明显升高（P〈0．05），组间比较差异有显著意义（P〈0．05）。结论 TEA镇痛不会对冠心病患者术后R-A-A-S产生不良影响，能有效地防止和治疗围术期心肌缺血和心肌梗死。     

美托洛尔对高血压患者肾素系统活性的影响

目的研究美托洛尔的降压疗效及其对肾素-血管紧张素-醛固酮系统及血管内皮功能的影响。方法对49例初诊原发性高血压患者口服美托洛尔4周。观察治疗前后血压及血浆肾素、血管紧张素、醛固酮、内皮素和一氧化氮浓度的变化。结果美托洛尔治疗4周后,诊室收缩压和舒张压的下降幅度分别为16．70mmHg和7．52mmHg（P〈0．01）;肾素、血管紧张素、醛固酮降低,一氧化氮水平升高（P〈0．05）;而内皮素、一氧化氮／内皮素比值无明显变化。结论美托洛尔能够有效的抑制肾素、血管紧张素、醛固酮系统及改善血管内寿功能,达到降低血压和保护靶器它的目的．     

弥漫性硬皮病患者血浆置换后血浆肾素,血管紧张素Ⅱ的变化

26例弥漫性硬皮病患者行血浆置换治疗。观察治疗前及治疗后半个月、3个月、9个月、18个月的血浆肾素、血管紧张Ⅱ（ATⅡ）的变化，并与26例青霉胺治疗者对照、治疗前血浆肾素、ATⅡ均显著高于正常（P＜0．01），血浆置换（PF）组治疗半个月后显著下降（P＜0．05），治疗后各阶段与青霉胺组比较显著性降低（P＜0．05～P＜0．01）。156次PE操作发生低血压6次，经处理后恢复正常。     

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.

---

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.