失血性休克高张盐复苏对急性肺损伤与肠淋巴液致炎作用影响

目的观察并比较高张盐和乳酸林格液复苏对失血性休克大鼠急性肺损伤和肠淋巴液的影响。方法将雄性SD大鼠40只分成4组(n=10),分别为假休克组(组Ⅰ)、休克组(组Ⅱ)、乳酸林格氏液组(组Ⅲ)和高张盐溶液组(组Ⅳ)。复苏后比较肺干湿重比和肺组织学变化,收集并测定肠淋巴液肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)含量,观察肠淋巴液对肺巨噬细胞的刺激作用。结果组Ⅱ和组Ⅲ肺干湿重比和组织中白细胞浸润程度显著高于组Ⅰ和组Ⅳ,组Ⅱ和组Ⅲ大鼠在休克期及复苏后的肠淋巴液TNF-α、IL-1β、IL-6含量及对肺巨噬细胞刺激作用均显著高于组Ⅰ、组Ⅳ。结论高张盐溶液复苏可降低失血性休克大鼠肠淋巴液促炎作用,减轻失血性休克后的急性肺损伤。     

电针足三里对重度失血性休克大鼠肝脏损伤的影响

目的:探讨电针足三里对于重度失血性休克大鼠肝损伤的影响及可能的机制。方法:取60只SD大鼠随机分为对照组(C组)、休克组(S组、SEN组)、复苏组(LR组、LREN1组、LREN2组),采用改良wigger's法复制重度失血性休克模型,检测各组大鼠血浆AST、ALT含量,肝组织TNF-α和MIP-2蛋白表达,MPO活性,电镜下观察肝组织病理学变化。结果:与休克组比较,各复苏组血浆AST、ALT含量,肝组织TNF-α和MIP-2蛋白表达增加,MPO活性降低,肝组织超微结构受损明显;与LR组比较,LREN1组及LREN2组以上损伤减轻,其中LREN2组以上指标降低显著(P<0.05),肝组织病理损伤较轻。结论:休克期电针刺激双侧足三里能减轻重度失血性休克再灌注后肝脏损伤,其机制与降低肝组织TNF-α、MIP-2产生,降低MPO活性有关。     

高张溶液复苏大鼠创伤失血性休克对肺组织I-κBα水平的影响

目的探讨高张溶液复苏大鼠THS对肺组织I-κBα水平及该作用对减轻急性肺损伤的意义。方法实验大鼠分为假创伤失血性休克(Sham)组、大容量等张乳酸钠林格氏液+6%羟乙基淀粉液(RLH)复苏组和小容量高张(7·5%氯化钠)液+6%羟乙基淀粉溶液(HTH)复苏组。采用Westernblot技术检测肺组织I-κBα蛋白含量;以RT-PCR检测ICAM-1mRNA表达水平;以分光光度法测定肺组织MPO活性;光镜下评估肺炎症损伤程度;以干/湿重比代表肺组织水含量。结果与Sham组比较,肺组织I-κBα含量RLH组明显降低(P<0·01),HTH组轻微降低且明显高于RLH组(P<0·01);而ICAM-1mRNA表达水平RLH组明显增高,HTH组仅轻度增高,低于RLH组(P<0·05);RLH组MPO活性和炎症损伤评分也均明显高于HTH和Sham两组(P<0·01),HTH组与Sham组比较差异无统计学意义(P>0·05);肺水含量在RLH组也有所增高。结论HTH可明显抑制大鼠THS复苏后肺组织I-κBα的降低,此作用可能与其抑制THS后ICAM-1表达增高和中性粒细胞在肺部大量聚集、从而减轻急性肺损伤有关。     

葛根素对失血性休克家兔急性肺损伤的保护作用

目的：研究葛根素对实验性失血性休克家兔导致急性肺损伤(ALI)的保护作用。方法：家兔24只，随机分为3组。A组为假手术组，只进行相应的手术操作；B组和C组按照Wiggers改良法制作失血性休克模型，造成ALI，然后在20min内复苏，C组复苏时应用葛根素。测定动脉血浆中肿瘤坏死因子-α(TNF-α)含量、支气管肺泡灌洗液(BALF)中巨噬细胞(PAM)和中性粒细胞(PMN)总数、BAIY中蛋白含量和肺组织中超氧化物歧化酶(SOD)含量；计算肺组织含水率；光镜下观察肺组织形态学改变。结果：与A组比较，复苏后B、C组TNF-α含量、BALF中的蛋白含量和PMN总数、肺组织含水率明显升高，SOD含量明显降低。但C组上述指标的变化程度均低于B组。光镜下见B组肺组织间质水肿、细胞浸润明显，与之相比C组肺组织以上改变明显减轻。结论：葛根素对实验性失血性休克家兔所致的ALI具有保护作用。     

二甲基乙二酰甘氨酸对大鼠肺缺血-再灌注损伤的保护作用

目的探讨二甲基乙二酰甘氨酸(DMOG)对大鼠肺缺血-再灌注损伤(IRI)的保护作用。方法成年SD大鼠24只均分为三组。采用阻断左肺门60min、再灌注120min制备肺IRI模型(IRI组)。DMOG组予腹腔注射DMOG 60mg/kg后制备肺IRI模型,假手术组(S组)仅游离左肺门,但不阻断。处死大鼠,计算肺组织肺湿干重比(W/D),分光光度法检测肺组织中丙二醛(MDA)含量、髓过氧化物酶(MPO)及超氧化物歧化酶(SOD)活性,ELISA法检测血清TNF-α、IL-1β和IL-6水平,RT-PCR和Western blot检测肺组织缺氧诱导因子1α(HIF-1α)mRNA和蛋白表达量。结果与S组相比,IRI组肺组织W/D、MDA、MPO及TNF-α、IL-1β、IL-6、HIF-1α蛋白相对表达量均升高(P<0.05),而SOD降低(P<0.05)。与IRI组相比,DMOG组W/D、MDA、MPO及TNF-α、IL-1β、IL-6水平均降低(P<0.05),而SOD、HIF-1α蛋白相对表达量均升高(P<0.05)。结论 DMOG预处理可以减轻大鼠早期肺IRI,其调控作用主要发生在HIF-1α基因转录后的蛋白水平。     

复方丹参对失血性休克大鼠早期炎症反应的影响

目的探讨复方丹参是否能抑制休克后早期炎症反应,从而防止失血性休克后多器官功能衰竭综合征的发生。方法30只Wistar大鼠随机分为三组,每组10只,分别为假手术对照组(A组)、失血性休克组(B组)和失血性休克丹参治疗组(C组),采用ELISA法测定血清IL-1β、IL-6、TNF-α含量;采用化学反应法测定SOD活性及MDA含量。结果失血性休克组血清IL-1β、IL-6、TNF-α及MDA浓度均显著高于假手术对照组(P均<0.01),SOD活性明显低于假手术对照组(P<0.01)。而丹参治疗组与失血性休克组比较,血清IL-1β、IL-6、TNF-α及MDA浓度显著降低(P均<0.05),而SOD活性显著升高(P<0.05)。结论复方丹参能有效抑制失血性休克后早期炎症因子的表达,增强SOD的活性,从而抑制休克后早期炎症反应。     

下肢缺血预处理对大鼠肺缺血-再灌注损伤的保护作用

目的 研究下肢缺血预处理在大鼠肺组织缺血-再灌注(I-R)损伤中的作用及机制.方法 18只SD大鼠随机均分为假手术(A组)、I-R(B组)和下肢缺血预处理十I-R(C组)三组.实验结束时,取肺组织测定湿/干重比(W/D)、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性和丙二醛(MDA)含量,观察肺组织病理学变化;ELISA法检测血清肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6含量.结果 与B组比较,C组肺组织W/D、MPO活性和MDA、TNF-α、IL-1β、IL-6的含量均明显降低(P＜0.05),SOD活性升高(P＜0.05).光镜下C组肺组织病理学改变较B组明显减轻.结论 下肢缺血预处理可以通过抑制大鼠肺组织I-R后炎症细胞的聚集、氧自由基的产生和促炎细胞因子TNF-α、IL-1β、IL-6的释放而减轻肺I-R损伤.     

七氟醚后处理对失血性休克复苏大鼠海马氧化应激及SIRT1/PGC-1α表达的影响

目的探讨七氟醚后处理对失血性休克复苏大鼠海马氧化应激,以及对沉默信息调节因子1 (silent information regulation 1,SIRT1)和过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)表达的影响。方法♂SD大鼠随机分为假手术组(Sham组)、失血性休克复苏组(Shock组)、七氟醚后处理组(Sevo组)。Sevo组经失血性休克后,于血液回输即刻吸入2.4%七氟醚,Sham组和Shock组在相应时间点吸入95%O_2,5%CO_2混合气体,记录放血即刻(T0)、放血结束即刻(T1)、血液回输即刻(T2)和血液回输结束即刻(T3)的平均动脉压(MAP),并采集动脉血进行血气分析。血液回输结束24 h后,检测海马组织丙二醛(MDA)含量和线粒体超氧化物歧化酶(SOD)活性,Western blot测定海马组织中SIRT1和PGC-1α蛋白的表达。结果与Sham组相比,Shock组MDA含量增加,SOD活性降低,SIRT1和PGC-1α蛋白表达上调(P<0.05);与Shock组相比,Sevo组MDA含量减少,SOD活性增强,SIRT1和PGC-1α蛋白表达上调(P<0.05)。结论七氟醚后处理可减轻失血性休克复苏大鼠海马氧化应激,其机制可能与上调SIRT1和PGC-1α的蛋白表达水平有关。     

低温高渗盐液对创伤失血性休克大鼠血清TNF-α、IL—1β的影响

创伤失血性休克是外科常见的急危重病,创伤失血性休克后各脏器处于缺血、缺氧状态,心肌、肺、肾对缺血缺氧特别明显,早期复苏、如何复苏、复苏后如何避免缺血再灌注损伤至为重要。本文建立创伤失血性休克大鼠动物模型,观察低温高渗液对大鼠不同时段生命征、血浆TNF-α、IL-1β水平及肺脏超微结构的改变的影响。     

羟乙基淀粉200对失血性休克肺损伤的保护作用

目的探讨羟乙基淀粉200(HE200)溶液复苏失血性休克对大鼠肺损伤保护作用及其机制。方法复制SD大鼠失血性休克模型，分别用HE200、羟乙基淀粉40溶液(HE40)、乳酸林格液(RL)复苏大鼠，观察复苏后1h、2h、4h动脉氧分压(PaO2)、血清肿瘤坏死因子(TNF-α)、肺组织核转录因子(NF-kB)、细胞间粘附分子-1(ICAM-1)的表达，肺组织髓过氧化物酶(MPO)活性，肺组织湿干重比值(W/D)。结果失血性休克大鼠复苏后各生物学指标HE200组较其他液体复苏组低，肺损伤程度减轻。结论羟乙基淀粉200溶液通过减轻失血性休克大鼠复苏后炎症反应从而对肺损伤具有保护作用。     

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.     

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.