浅低温心脏不停跳心内直视手术对心肌酶学和超微结构的影响

目的 探讨浅低温不停跳心内直视手术对心肌保护的效果。方法20例单纯房间隔缺损或室间隔缺损患随机分成两组，其中浅低温不停跳组(Ⅰ组)12例、低温停跳组(Ⅱ组)8例。两组均切开右心房置入冠状静脉窦(CS)灌注管，不停跳组分别于体外循环(CPB)前(T1)、CPBl5min(T2)、CPB停止时(T3)及停止后15min(T4)取冠脉血和右心房心肌，停跳组分别于转流前(T1)、主动脉阻断时(T2)、主动脉开放时(T3)、主动脉开放后15min(T1)取冠脉血和右心房心肌。测定冠状静脉血中超氧化物歧化酶(SOD)、肌酸激酶(CK)、乳酸脱氢酶(LDH)的活性和丙二醛(MDA)的含量，测定心肌组织匀浆中钙-ATP酶(Ca2^ -ATPase)、一氧化氮合酶(NOS)的活性，观察两组心房肌超微结构的变化。结果体外循环开始后各时段两组LDH、CK均呈上升趋势，停跳组明显高于不停跳组。体外循环开始后停跳组SOD明显低于不停跳组而MDA明显高于不停跳组。停跳组心肌组织Ca^2 -ATPase、NOS活性较不停跳组低。结论与传统的冷停跳心脏手术相比浅低温不停跳手术具有很好的心肌保护作用。     

浅低温体外循环心脏不停跳下心内直视术临床分析

目的　通过测定心脏不停跳与心脏停跳手术两组患者的血浆肌钙蛋白 ( c Tn- )值 ,评价心脏不停跳手术对心肌保护的效果。方法　随机选择 2 0例先天性心脏病患者于浅低温体外循环下施行心脏不停跳心内直视手术作为实验组 ,同期随机选择 2 0例施行常规心脏停跳心内直视手术作为对照组 ,测定两组患者术前、术中、术后各时相的血浆 c Tn- 值进行比较研究。结果　两组术前 c Tn- 值差异无显著性 ,转机后两组 c Tn - 值均升高 ,对照组比实验组增高明显 ,差异有显著性 ( P<0 .0 5)。结论　浅低温体外循环心脏不停跳手术可明显减轻心肌缺血再灌注损伤 ,对心肌起到良好的保护作用。     

体外循环心脏停跳与不停跳心内直视手术心肌缺血再灌注损伤心肌肌钙蛋白动态变化研究

目的 探讨体外循环心脏停跳与不停跳心内直视手术心肌缺血再灌注损伤心肌肌钙蛋白I(cTnI)动态变化与心肌细胞损伤程度的相关性.方法 2004年6月至2007年3月,40例先天性心脏病矫治手术中,性别、年龄、体重、身高、心胸比率及左心室功能无明显差别.男28例、女12例,房间隔缺损20例、室间隔缺损20例.分成两组,每组20例,Ⅰ组为停跳组(室缺组),Ⅱ组为不停跳组(房缺组).两组病人分别于体外循环转机前、转机中、停机及术后1、6、12、24、48、72、96 h取静脉血,检测心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、天冬氨酸氨基转移酶(AST)、α-羟丁酸脱氢酶(HBDH),同时描记心电图及用超声测量24、72、168 h心脏射血分数(EF).结果 cTnI停跳组显著增高(P＜0.01),不停跳组变化不明显(P＞0.05).AST、LDH、CK、CK-MB、HBDH停跳组术后24 h内明显增高,不停跳组AST、LDH、CK、CK-MB、HBDH活性也发生变化,两组差异有显著意义(P＜0.05).EF在停跳组恢复减慢,差异无显著性(P＞0.05),心电图无明显改变.结论 cTnI可以作为先天性心脏病矫治术中评价缺血再灌注损伤的敏感特异性指标,其血浆浓度的改变与心脏缺血再灌注损伤程度呈正相关.     

浅低温体外循环间断灌注的心肌保护效果观察

探讨浅低温体外循环温血间断灌注心肌保护的临床效果,提高瓣膜置换、冠脉搭桥手术的成功率。方法①浅低温体外循环温血高钾持续灌注心肌保护为对照组(A,n=53);②浅低温体外循环温血高钾间断灌注心肌保护为实验组(B,n=75)。观察两组临床结果并进行比较。结果体外循环时间、主动脉阻断时间B组明显少于A组;库血用量和24h胸腔引流量B组明显少于A组;主动脉开放前血钾浓度B组明显低于A组;主动脉开放后心脏自动复跳率B组明显高于A组。结论浅低温体外循环温血高钾间断灌注保护心肌效果显著,方法简单可行。     

磷酸肌酸温血心停搏液终末灌注对心肌保护作用的临床研究

目的研究外源性磷酸肌酸（CP）对风湿性心脏病心瓣膜替换术患者在体外循环期间心肌再灌注损伤的保护作用。方法将46例风湿性心脏病体外循环心瓣膜替换术患者随机分为治疗组和对照组各23例。治疗组在开放主动脉前30min，在圣·托马斯（STH2）液中加入外源性磷酸肌酸终末温血半钾灌注，对照组应用常规圣·托马斯液。分别测定所有患者术前、主动脉开放2h、6h、24h、48h各时点中心静脉血中的红细胞压积（HCT）、乳酸脱氢酶（LDH）、磷酸肌酸激酶（CK）、磷酸肌酸激酶同工酶（CK-MB）及心脏肌钙蛋白T（cTnT）。记录术毕心脏自动复跳率和术后多巴胺用量。结果治疗组术后多巴胺用量明显少于对照组（P〈0．01）；术后6h、24h、48h的LDH、CK、CK-MB及cTnT水平均明显低于对照组（P〈0．01）；治疗组患者术毕心脏自动复跳率明显高于对照组。结论磷酸肌酸加入心停搏液中能显著提高心肌保护作用。     

浅低温体外循环心脏不停跳心内直视手术的临床应用

目的 对１３２例心脏不停跳心内直视手术临床应用的研究,探讨该手术的优点和意义。方法 １９９５年７月￣１９９７月１０应用浅低温体外循环疏脏不停跳心内直视手术行先心病矫治术１０９例,后心病瓣膜置换和（或）成形术２０例,心脏粘液瘤摘除术３例。术中不阻断主动脉,不灌注心停跳液,心脏有持续供血,术中缓慢跳动。结果 术后１３０例治愈出院,术后早期死亡２例（１．５％）。结论 心脏不停跳心内直视手术,使心肌在手术     

温血诱导心脏停搏及间断灌注在成人心内直视手术中的应用

目的 探讨温血诱导心脏停搏及间断温血灌注技术在成人心内直视手术中对心肌的保护作用。方法 将60例成人患者随机分成2组：温血诱导停搏及温血间断灌注组（实验组）;冷晶体诱导停搏及冷晶体间断灌注组（对照组）;2组主动脉阻断时间无明显差异。体外循环前、后60例患者分别抽血测定乳酸脱氢酶（LDH）,磷酸肌酸激酶（CK),电子显微镜观察缺血后心肌超微结构变化。结果 发现冷晶体组LDH、CK值均高于温血灌注组,显微镜观察缺血后心肌超微结构温血组优于冷晶体组。结论 温血诱导心脏停搏及间断灌注技术对成人心肌作用较为明显。     

浅低温体外循环不停跳心内直视术的心肌保护

目的:探讨浅低温体外循环不停跳心内直视术的心肌保护。方法:30例心内直视术病人随机平均分为心脏停跳和不停跳两组。停跳组降温致食管温度(25±1.35)℃,并从升主动脉根部灌注冷高钾停跳液,灌注量15ml/kg,同时在心脏表面及心腔内冰盐水浸泡,致心脏停跳,阻断升主动脉。不停跳组降温至食管温度(31±1)℃,只阻断上下腔静脉,不阻断主动脉,控制心率在40～70次/分。结果:两组病例术中血液动力学均较稳定,差异无显著性。但两组CK-MB、CK、LDH、α-HBDH均较术前增高,尤以停跳组明显,两组比较差异有显著性。结论:心内直视术麻醉采用浅低温心脏不停跳体外循环技术对心肌具有较好的保护作用,但仍然存在需要进一步解决的问题。     

心脏不停跳心内直视手术(附50例报告)

心肌保护是体外循环心内直视手术的关键,心脏不停跳正是出于这种理念,其机理是心脏不停跳直视手术不阻断升主动脉,不使用心脏停搏液,使心脏得到持续的氧合血灌注的一种手术广泛,保持着较接近生理状态的有氧代谢,酸硷平衡和电解质代谢,故能避免由于阻断升主动脉,灌注高钾停跳液而引起的心肌缺血和再灌注损伤的产生,能有效的防止术后低心排和严重的心律失常发生,本组2例瓣膜置换病人EF 33～38%,心功能Ⅳ级,由于不停跳病变心肌没有遭到高K+,低温,停搏,定额等非生理性,避免了再灌注损伤,有效的防止已病变的心肌进一步损害,故术后恢复良好.     

心脏不停跳与停跳对心肌超微结构和心肌酶的影响

目的 通过比较心脏停跳与不停跳条件下心内手术对心肌酶和心肌超微结构的影响以确定较好的手术方式和心脏保护方法。方法 对常温（３４℃～３７℃）不阻断升主动脉心脏不停跳和冷晶体间断灌注心脏低温保护方法心脏停跳下进行心内手术。结果 不停跳组心肌微结构和心肌酶几乎无变化,而停跳组有显著变化。结论 心脏不停跳行心内手术是值得推广的心肌保护方法。     

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.     

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.     

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.