氧合血与冷晶体心肌停搏液保护心肌的临床研究

目的：比较氧合血心肌停搏液与冷晶体心肌停搏液对心肌的保护效果。方法：心脏瓣膜直视术病人120例，随机分为氧合血心肌停博液组（I组）、冷晶体心肌停博液组（Ⅱ组）各60例。I组采用4：1高钾冷血停搏液（4℃-8℃）灌注诱导心肌停跳，术中每隔20min用4：1高钾冷血停搏液维持，在开放升主动脉钳之前用温血灌注。Ⅱ组采用4℃冷晶体心肌停搏液灌注，术中每20min复灌1次。结果：I组心脏自动复跳率明显高于Ⅱ组（P＜0．001）；术后低心排综合征和室性心律失常的发生率明显低于Ⅱ组（P＜0．01）；术后应用心肌正性肌力药物量及时间明显少于Ⅱ组（P＜0．05）。结论：氧合血心肌停博液较冷晶体心肌停搏液具有更好的保护心肌效果。     

温血停跳液在小儿复杂先天性心脏病矫正术中的应用

40例患复杂性先天性心脏病的患儿防机分成温血停跳（BCP）组和冷晶体停跳（CCP）组，两组进行比较。主动脉阻断前和开放后由冠状静脉窦取血标本测磷酸肌酸激酶（CK－MB）、乳酸脱氢酶1（LDH1）和乳酸脱氢酶2（LDH2）。主动脉阻断前和开放前由左心尖取心肌作超微结构检查并作立体学分析。记录血流动力学情况。结果表明温血停跳液比冷晶体停跳液有更好的心肌保护作用。     

不同温度含氧血停跳液的临床应用价值

目的：评价三组不同温度含氧血停跳液的临床应用价值,方法：选择30例病人,分为三组,手术中分别实施温血停跳组（n=10)(34-36℃）;中低温停跳组（n=10)(24-28 ℃）;低温停跳组（n=10）（15－20℃）,分别在不同的时点测量血清磷酸肌酸激酶值,分析动静脉血气值,推算心肌耗氧摄取率和血流动力学改变,并行心肌活检病理学检查,行统计学处理,结果：血液动力学改变,温血组复苏后心率偏慢,与中低温组和低温组比较有统计学意义（P＜0．05）,低温组复苏后心率偏快,与温血组和中低温组比较（P＜0．05,静脉压偏高,与前两组比较P＜0．05。血清CK水平;温血组与中低温组比较无显著差异（P＞0．05）。低温组血清CK水平与前两组比较有显著差异（P＜0．05）;甚至在24小时后仍高,持续时间长,提示低温对心肌的损害是明显的,病例活组织检查也证实低温组的心肌线粒体细胞器损害以及空泡样变,比温血组和中低温组严重,结论：不同温度含氧血停跳液都有临床使用价值,但低温含氧血停跳液更有临床应用价值。     

温血心停跳液续灌与冷晶体间灌临床研究

目的 探讨温血心停跳液和冷晶体心停跳液对心肌的保护作用。方法 选择主动脉阻断时间大于60min的心脏手术20例。分别应用温血心停跳液持续灌注（Warmblood Continuous cardioplegia WBCC）（10例）和冷晶体心停跳液间断灌注（Coldcrystalloid intermittent cardioplegia CCIC）（IC例）的结果进行分析。,记录术前、术后6、12、24、48、72h血浆CPK、CK—MB、LDH、LDH．变化。结果两组在心脏直视手术中心脏停跳良好。围术期血液动力学指标、平均动脉压、中心静脉压、心率无明显差异。WBCC的血浆CPK、CK-MB、LDH、LDH1的水平均明显低于CCIC组（P〈0．05）。酶的释出量大为减少,并于72h内降至正常。恢复比CCIC组早。结论 WBCC能保护心脏停跳过程中有氧代谢的进行,减轻再灌注损伤,心肌酶释放减少。WBCC心肌保护效果优于CCIC。     

三种心脏停跳液对心肌保护的对比研究

为评估三种心脏停跳液的心肌保护作用,将30例风湿性心脏病二尖辦病变随机分为温血停跳液组(温血组)、冷血停跳液组(冷血组)及冷晶体停跳液组(冷晶体液组),每组10例,观察心肌缺血30～50min期间血浆心肌肌钙蛋白T(cTn-T)、内皮素(ET-1)、心钠素(ANP)和心肌超微结构改变。结果表明:①温血组cTn-T在12h出现高峰;冷血组在12h出现高峰,随后的12h内有一平台期;冷晶体液组峰值出现在48h,体外循环后较前二组增高明显;②温血组ET-1在主动脉开放后下降速度最快,并且低于其它二组,其中冷晶体液组含量最高;③温血组在主动脉阻断后15min,ANP含量上升,恢复至正常水平时间最短;冷血组与冷晶体液组ANP在主动脉阻断后迅速下降,主动脉开放后上升并持续至1h;④心脏复跳后3组心肌超微结构均存在不同程度的损伤表现,以冷晶体液组最重,温血组最轻。结论:温血停跳液的心肌保护作用优于冷血停跳液和冷晶体停跳液。     

辛伐他汀对一氧化氮缺乏性高血压大鼠心脏局部肾素血管紧张素系统的影响

目的：观察辛伐他汀对一氧化氮（NO）缺乏性高血压大鼠心脏局部肾素－血管紧张素系统（RAS）的影响。方法：24只Wistar大鼠随机分为正常对照组（C组）、硝基精氨酸甲酯（L－NAME）组（L组）和L－NAME＋辛伐他汀组（L＋S组）。每2wk尾袖法测定动脉收缩压，8wk后测定血清甘油三酯（TG）、总胆固醇（TC）及血清和心肌组织血管紧张素Ⅱ（AngⅡ）水平、血管紧张素转移酶（ACE）活性。结果：L组大鼠血压与同期C组血压相比有极显性差异（P＜0．01），辛伐他汀干预未对增高的血压产生明显影响（P＞0．05）；各组大鼠血清TG和TC水平比较也无显性差别（P＞0．05）。与C组相比，L组大鼠血清ACE活性明显降低（P＜0．01），L组和L＋S组大鼠血浆AngⅡ水平与C组比较无显性差异（P＞0．05），心肌组织中AngⅡ水平和ACE活性则较C组明显增高（P＜0．01）；辛伐他汀干预后L＋S组大鼠血清ACE活性升高，但与L组无显性差异（P＞0．05），心肌ACE活性和AngⅡ水平则均比L组明显降低（P＜0．05）。结论：辛伐他汀可能通过降低局部心肌组织ACE活性抑制NO缺乏性高血压大鼠心脏局部RAS活性，减少AngⅡ生成，这种作用独立于调脂和降压作用之外。     

不同配伍曲马多术后硬膜外病人自控镇痛效应的比较

采用硬膜外病人自控镇痛（PCEA）技术，对不同配伍曲马多术后镇痛效应进行研究。将90例（ASAⅠ～Ⅱ级）手术病例随机分成三组，Ⅰ组（n＝30）用1％曲马多；Ⅱ组（n=30）用1％曲马多＋0．125％布比卡因；Ⅲ组（n=30）用1％曲马多＋0．25％布比卡因；采用双盲法对比观察。结果术后24小时三组病人VAS评级Ⅰ组＞Ⅱ组＞Ⅲ组（P＜0．05）；三组曲马多用量Ⅰ组＞Ⅱ组＞Ⅲ组（P＜0．05）；PCEA总按数／实进数（D／D）比值在0～2范围内的病例数，Ⅲ组＞Ⅱ组＞Ⅰ组（P＜0．05），提示Ⅱ、Ⅲ组镇痛效果较单纯组好。三组病人PCEA期间呼吸、循环无明显变化，无肢体运动障碍；恶心、呕吐等并发症较低。结论：选择曲马多行PCEA镇痛时，复合0．25％的布比卡因其镇痛效果更好。     

左-卡尼汀在心内直视手术中对心肌的保护作用

目的：探讨心内直视手术中外源性左-卡尼汀（L-CN）对心肌的保护作用。方法：选取心内直视手术的患者32例,随机分为实验组和对照组。实验组术中于冷晶体心脏停搏液中按10g／L加入L—CN,行冠状动脉顺行灌注;对照组仅使用冷晶体停搏液灌注。两组均于术前、主动脉阻断开放后2、24、72h各时点采取静脉血,测心肌酶（CK、CK—MB）,肌钙蛋白I（cTnI）和肌钙蛋白T（cTnT）水平。结果：两组患者CK、CK—MB,cTnT、cTnI水平在术前比较。差异无统计学意义（P〉0．05）,于主动脉开放后均有明显的升高。实验组CK、CK—MB升高程度较对照组低（P〈0．05）。实验组cTnT、cTnI升高程度在2、24及72h较对照组低（P〈0．05）,2h尤其明显（P〈0．01）。结论：在心内直视手术中。左-卡尼汀加入心脏停搏液后可明显改善心脏能量供应,有效减少心肌细胞损伤,对心肌起到明显保护作用。     

先天性心脏病直视手术温血持续灌注心肌保护的临床研究

目的 初步评价体外循环含钾温血持续灌注心肌保护方法的临床价值。方法 对31例先天性心脏病患者（温血组）实施室间隔缺损修补术，采用体外循环含钾温血持续灌注的心肌保护方法。30例先天性心脏病患者（冷血组）实施室间隔缺损修补术，采用体外循环冷血间歇灌注心肌保护。观察两组心脏除颤率、开放主动脉后血钾、术后呼吸机辅助时间及心肌正性肌力药物使用情况。结果 温血组与冷血组比较，开放主动脉后心脏除颤率比较差异有显著性（3．2％与26．7％，P〈0．01）；心肌正性肌力药物使用时间差异亦有显著性（P〈0．01）；术后心功能恢复快，无术后高血钾、低心排血量、严重心律失常等严重并发症。结论 体外循环含钾温血持续灌注心肌保护方法可明显减轻心肌缺血与再灌注损伤，先天性心脏病手术中温血持续灌注的心肌保护效果优越，值得推广应用。     

膝关节骨性关节炎氧化应激指标的临床分期检测及分析

目的：检测不同临床分期膝关节骨性关节炎（OA）患者血清及关节液氧化应激指标水平,分析其临床应用价值。方法2011年7月至2013年6月,收集符合美国风湿病学会OA诊断标准（ACR2007）的患者49例（观察组）,临床分期为Ⅰ期者10例,Ⅱ期15例,Ⅲ期13例,Ⅳ期11例。以同时期健康体检志愿者16例（无OA病史、X线检查排除OA诊断）作为对照（对照组）,2组均抽取空腹静脉血和膝关节液。 WST-1法测定过氧化物歧化酶（ SOD）活性,化学法测总抗氧化能力（ T-AOC）、丙二醛（ MDA）和谷胱甘肽（ GSH）水平,统计并分析各指标的波动。结果与对照组相比,观察组血清与关节液T-AOC,MDA均显著增高（ P ＜0崓．01）,SOD,GSH显著降低（ P ＜0．01）。与对照组相比,观察组Ⅰ期OA患者血清及关节液T-AOC水平即显著升高,Ⅱ期两者均进一步升高,Ⅲ期与Ⅳ期之间差异无统计学意义（ P ＞0．05）,但均较Ⅱ期高。观察组血清MDA水平显著升高（ P ＜0．01）,各分期之间MDA差异无统计学意义（ P ＞0．05）;而关节液中,Ⅱ期OA患者较I期MDA水平显著升高,Ⅲ、Ⅳ期MDA水平进一步升高,而2期之间差异无统计学意义（ P ＞0．05）。观察组OA患者血清SOD活力均明显降低（ P ＜0．01）,4期间SOD活力水平差异无统计学意义（ P ＞0．05）;而关节液中,Ⅰ～Ⅳ期SOD水平逐渐下降,Ⅰ期患者SOD水平较对照组即明显下降（ P ＜0．01）,Ⅱ期较Ⅰ期进一步下降,Ⅲ、Ⅳ期之间SOD水平差异无统计学意义（ P ＞0．05）,但均较Ⅱ期低（ P ＜0．01）。对照组与观察组各分期血清GSH水平差异均无统计学意义（ P ＞0．05）;而关节液中,观察组Ⅰ期OA患者GSH水平较对照组升高（ P ＜0．05）,至Ⅱ期GSH水平达到顶点（ P ＜0．05）,Ⅲ、Ⅳ期GSH水平下降,均低于对照组（ P ＜0．05）。结论不同临床分期OA患者血清及关节液氧化应激指标水平不同;关节液及血清氧化应激指标T-AOC、MDA、SOD和GSH可作为评估OA患者病情,判断预后的依据。     

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.     

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.