前列腺素E1在心肺转流中的肺保护作用

目的研究前列腺素E1(PGE1)对心肺转流(CPB)后肺损伤的保护作用.方法30例心脏手术病人随机分为对照组和观察组,每组15例.观察组病人于麻醉诱导时从中心静脉持续泵入PGE1(20～30ng·kg-1·min-1)至CPB结束.分别于转流前、主动脉开放心脏复跳后15 min检测左、右心房血中中性粒细胞(PMN)计数及血浆丙二醛(MDA)浓度,并计算左、右心房差值.记录CPB前、心脏复跳后15 min、CPB结束后2 h、6 h气道峰压及桡动脉血气值,并计算气道阻力(AR)及氧合指数(OI).结果(1)CPB后各时点观察组AR、OI显著低于对照组(P＜0.01).(2)心脏复跳后15 min观察组左、右心房血PMN计数差和MDA浓度差明显低于对照组(P＜0.05和P＜0.01).(3)两组心脏复跳后15 min左、右心房血PNM计数差与MDA浓度差之间呈直线相关(r=0.57,P＜0.05).结论PGE1可减轻CPB引起的PMN在肺内聚集、降低肺内自由基的产生,并减轻由此引起的肺损伤.     

腺苷预处理对体外循环心脏直视手术患者的肺保护作用

目的 观察腺苷预处理对心肺转流(CPB)心脏直视手术患者的肺保护作用.方法 48例心脏瓣膜置换术患者随机分为两组,每组24例.A组CPB前微量泵入腺苷1.5 mg/kg;B组泵入同体积生理盐水.检测两组CPB前、心脏复跳后10 min左、右心房血中性粒细胞(PMN)、血小板(Plt)计数;检测CPB前、主动脉开放后2、6、16 h循环中肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)及IL-10;记录术前、开胸后、停CPB及手术结束时肺顺应性、气道压力及氧合指数(OI).结果 A组停CPB及手术结束时肺顺应性、气道压力及OI优于B组(P<0.05);A组心脏复跳后右、左心房PMN、Plt计数差值的升高低于B组[(0.46±0.52)×109/L vs.(2.41±0.89)×109/L、(9.07±14.22)×109/L vs.(22.67±14.27)×109/L](P<0.05);A组主动脉开放后IL-10水平显著高于B组,而TNF-α、IL-8水平显著低于B组(P<0.05).结论 外源性腺苷可减轻CPB引起的肺损伤.     

右美托咪定预充对心脏手术患者体外循环期间血流动力学的影响

目的:评价右美托咪定预充对心脏手术患者体外循环(CPB)期间血流动力学的影响。方法:将择期行二尖瓣和主动脉瓣置换术的风湿性心脏病患者80例,按随机数字表法分为对照组(C组)和右美托咪定组(D组),各40例。全麻下D组患者预充液中加入右美托咪定1μg/kg,C组患者预充液中加入等量氯化钠溶液。观察两组患者CPB前并行阶段的平均动脉压(MAP)和心率(HR);观察两组患者CPB期间升压药(间羟胺)和降压药(酚妥拉明)的使用量、降压药使用前后的MAP变化和两次用药间隔时间;记录两组患者CPB期间的麻醉药物使用量;于麻醉诱导前5 min(t_1)、CPB前5 min(t_2)、CPB 30 min(t_3)、CPB 60 min(t_4)、CPB结束(t_5)、术后2 h(t_6)、术后12 h(t_7)和术后24 h(t_8)测定两组患者的血清白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平;观察两组患者心脏复跳时间、复跳例数及心律失常(室颤)发生情况,前/后并行循环时间和主动脉阻断时间,心脏复跳后各时段的多巴胺使用量及心动过缓的发生情况。结果:与C组比较,D组患者CPB前并行阶段的MAP明显升高、HR明显降低,间羟胺和酚妥拉明的使用量明显减少,两次用药间隔时间明显延长,CPB期间的咪达唑仑和丙泊酚用量明显减少,差异均有统计学意义(P<0.05)。CPB转流后两组患者血清IL-6和TNF-α水平随时间逐渐升高,至CPB结束时(t5)达到最高;与t_1比较,两组患者在t_3~t_8时点的血清IL-6和t_2~t_8时点的血清TNF-α水平均明显升高;与C组比较,D组患者在t_4~t_7时点的血清IL-6和t_3~t_7时点的血清TNF-α水平均明显降低,差异均有统计学意义(P<0.05)。两组患者心脏复跳时间、复跳例数、复跳后室颤例数、前/后并行循环时间和主动脉阻断时间比较,差异均无统计学意义(P>0.05)。两组患者心脏复跳后多巴胺的使用量随时间逐渐减少,但各时段组间比较差异均无统计学意义(P>0.05)。复跳后两组患者均未见心动过缓现象发生。结论:右美托咪定1μg/kg加入到预充液中可有效预防心脏手术患者CPB开始时的一过性低血压,同时可减轻其CPB期间血压的升高现象。     

戊乙奎醚对体外循环瓣膜置换术后肺损伤的影响

目的探讨戊乙奎醚对心肺转流(CPB)瓣膜置换术后肺损伤的影响。方法 30例CPB瓣膜置换术患者随机均分为戊乙奎醚组(P组)和对照组(C组),分别在CPB前静注戊乙奎醚0.02 mg/kg和同体积生理盐水。于麻醉诱导后CPB前(T0),CPB结束时(T1),CPB结束后8 h(T2),CPB结束后24 h(T3)测定血乳酸(LA)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-8水平。记录T0、T1、T2时的肺顺应性、气道阻力、气道峰值压力。结果与C组相比,P组T1、T2时肺顺应性增高,气道峰值压力降低,T2时气道阻力降低(P<0.05)。两组患者CPB后血LA、TNF-α、IL-6I、L-8水平均高于术前(P<0.05),P组T1、T2时LA、TNF-α、IL-6、IL-8水平较C组降低(P<0.05)。结论戊乙奎醚能改善CPB期间微循环功能,抑制炎性介质的释放,减轻CPB瓣膜置换术后肺损伤。     

还原型谷胱甘肽对体外循环心脏瓣膜置换术患者炎性反应的影响

目的评价还原型谷胱甘肽(GSH)对体外循环(CPB)心脏瓣膜置换术患者炎性反应的影响。方法择期CPB下行心脏瓣膜置换术患者60例,随机数字表法分为对照组和GSH组(均n=30)。两组麻醉诱导及维持方法相同,GSH组于麻醉诱导后静脉注射GSH 100 mg·kg-1,对照组加入等量的氯化钠注射液。于麻醉诱导后(T1)、CPB即刻(T2)、CPB结束(T3)、CPB结束2 h(T4)和6 h(T5)采取中心静脉血样,测定血浆心肌肌钙蛋白Ⅰ(cTnⅠ),肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β和S100β蛋白的浓度。结果与T1时比较,T2^T5时两组血cTn I、TNF-α、IL-6、IL-1β和S100β蛋白的浓度均显著升高(P<0.05);GSH组T2T5时两组血cTn I、TNF-α、IL-6、IL-1β和S100β蛋白的浓度均显著升高(P<0.05);GSH组T2^T5时血cTn I、TNF-α、IL-6、IL-1β和S100β蛋白的浓度均显著低于对照组(P<0.05)。结论 CPB下心脏瓣膜置换术中GSH 100 mg·kg-1可抑制炎性反应,从而减轻心、脑损伤。     

体外循环对患者肺内致炎与抗炎物质的影响

目的研究心肺转流（CPB）对心脏手术患者肺内致炎与抗炎物质的影响。方法择期心脏瓣膜置换患者20例，在CPB前，主动脉开放心脏复跳1、3、5、10min分别采右心房与肺静脉血检测中性粒细胞（PMN）数量、中性粒细胞黏附分子（CD11b）、丙二醛（MDA）、白细胞介素-10（IL-10）水平及过氧化物歧化酶（SOD）活性水平。结果与CPB前比较，主动脉开放心脏复跳后各时点，患者肺静脉血中PMN的数目，CD11b的表达，MDA的含量，SOD活性和IL-10水平均显著性增加（P〈0．05），差异有统计学意义。与右心房比较，心脏复跳后各时点患者肺静脉血中PMN的数目和CD11b的表达明显增加，MDA的含量、SOD活性和IL-10水平在心脏复跳1、3min后显著升高（P〈0．05），差异均有统计学意义。结论体外循环过程中肺内致炎性物质增多，引起抗炎性物质的产生亦随之增加，有利于消除炎性反应对肺的伤害。     

中性粒细胞凋亡延迟及细胞因子释放在体外循环全身炎性反应中的作用

目的探讨中性粒细胞(PMN)凋亡延迟和细胞因子释放对体外循环全身炎性反应的影响和意义。方法30例行体外循环(CPB)心脏直视手术病人分别于麻醉诱导后、CPB结束时、CPB后4h、CPB后8h、术后第1d晨5个时点采集静脉血。用全血细胞计数仪测定PMN数量,流式细胞仪测定PMN凋亡率变化,ELISA法测定血浆白介素6(IL-6)、白介素8(IL-8)浓度变化。结果PMN凋亡率在CPB期间明显降低,与CPB时间呈负相关。PMN数量、IL-6、IL-8血浆浓度在CPB期间明显升高,与其凋亡率呈负相关,与CPB时间呈正相关。结论CPB期间细胞因子IL-6、IL-8释放增多导致PMN的凋亡延迟,PMN数量增加、生存周期延长,从而加剧炎性反应扩散和组织损伤。     

参附注射液对体外循环肺保护作用的临床研究

目的探讨参附注射液(SF)对体外循环(CPB)术后肺保护作用的临床效果。方法将30例进行二尖瓣瓣膜置换术的风湿性心脏病患者随机均分为两组,实验组在CPB前静脉泵注SF1mL/kg至术毕,对照组同期静脉泵注等量生理盐水。在CPB前及CPB后1h分别取左右心房血测定中性粒细胞。于CPB开始前、CPB结束时、CPB结束后1h分别抽取桡动脉血,采用ELISA法测定血清测定肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)。结果 CPB前两组各指标差异均无统计学意义(P>0.05);CPB后两组各项指标差异均有统计学意义(P<0.05)。结论参附注射液对体外循环肺功能有良好的保护作用。     

氨溴索对小儿体外循环炎症介质和呼吸功能的影响

目的探讨氨溴索对小儿心肺转流(CPB)术后炎症介质和呼吸功能的影响。方法31例CPB下行室间隔缺损修补术患儿随机分为氨溴索(A)组(n=15)和对照(C)组(n=16)。A组术前3d及术后2d静脉滴注氨溴索20mg.kg-1.d-1并行雾化吸入;C组使用等量生理盐水。分别在CPB前(T1),CPB结束(T2)和CPB结束后2h(T3)、4h(T4)及18h(T5)采集桡动脉血,测定血浆IL-6、IL-8、TNF-α浓度,计算呼吸指数(RI)和氧合指数(OI)。结果 T2-T5时点,两组血浆IL-6、IL-8和TNF-α浓度均较T1时增加,C组高于A组(P<0.05)。CPB后两组RI和OI均较CPB前升高,C组高于A组(P<0.05)。结论氨溴索能够通过抑制炎症因子的产生减轻小儿CPB引起的肺损伤和功能障碍。     

盐酸戊乙奎醚对体外循环炎性反应的影响

为探讨不同剂量盐酸戊乙奎醚对大鼠体外循环(CPB)致全身炎性反应的影响,将40只健康雄性SD大鼠随机分为假手术对照组(S组)、体外循环组(C组)、盐酸戊乙奎醚低剂量组(PL组)、中剂量组(PM组)和高剂量组(PH组),每组8只。S组进行所有的麻醉和手术操作,但不连接转流管道进行CPB,其余4组进行CPB 60 min,并继续观察2 h。PL、PM、PH组分别在预冲液中加入盐酸戊乙奎醚0.2 mg/kg、0.6 mg/kg、2mg/kg,C组给予相同容积的生理盐水。CPB结束后即刻(T1)、结束后2 h(T2)采集血标本,用放免法检测大鼠血浆肿瘤坏死因子-α(TNF-α)与白介素-6(IL-6)水平。结果表明,与S组比较,C、PL、PM、PH组T1、T2时刻血浆TNF-α、IL-6水平均升高,差异均有统计学意义(P<0.05);与C组比较,PM、PH组T1、T2时刻血浆TNF-α、IL-6水平均降低,差异有统计学意义(P<0.05);与PM组比较,PH组T1、T2时血浆TNF-α、IL-6水平均降低,差异有统计学意义(P<0.05)。结论:中、高剂量的盐酸戊乙奎醚可减轻体外循环后的炎性反应,且高剂量组作用更显著。     

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.     

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.