血必净对急性百草枯中毒大鼠炎性因子影响的实验研究

目的 观察血必净对百草枯急性中毒大鼠炎性因子的抑制作用.方法 72只SD大鼠随机分为对照组、中毒组和血必净组,分别在给药后6h、2h、72h三个时间点,每个时间点每组8只大鼠,中毒组和血必净组一次性以120mg/kg百草枯灌胃,2h后血必净组腹腔注射血必净10ml/kg,对照组和中毒组腹腔注射等体积0.9%氯化钠注射液,1次/d.于给药后6h、24h、72h取大鼠眼眶血,用酶联免疫(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和IL-2.结果 给药后6h中毒组血清TNF-α、IL-1β和IL-2较其他组明显升高(P<0.05),而血必净组较中毒组明显降低(P<0.05);给药后24h中毒组血清TNF-α、和IL-1β较其他组明显升高(P<0.05),而血必净组TNF-α、IL-1β较中毒组明显降低(P<0.05);给药后72h中毒组血清TNF-α仍较其他组明显升高(P<0.05),血必净组TNF-α较中毒组明显降低(P<0.05),而且IL-1β和IL-2已降至对照组水平(P0.05).结论 血必净可以明显抑制急性百草枯中毒大鼠血清TNF-α、IL-1β和IL-2的释放,对急性百草枯中毒大鼠炎性反应具有一定的抑制作用.     

免疫相关细胞因子在不同程度慢性苯中毒中的表达及意义

目的观察慢性苯中毒患者中毒程度与血清细胞因子变化。方法慢性苯中毒患者53例为中毒组(轻度28例、中度12例、重度13例),对照组为20例健康志愿者。采集每一名研究对象上肢静脉血2 ml,分离血清,采用酶联免疫吸附法(ELISA)检测中毒组与对照组血清中白细胞介素1β(IL-1β)、白细胞介素2(IL-2)、白细胞介素3(IL-3)、白细胞介素6(IL-6)、白细胞介素11(IL-11)及促红细胞生成素(EPO)、血小板生成素(TPO)、肿瘤坏死因子α(TNF-α)含量。结果重度中毒组较对照组及轻、中度组IL-1β、IL-3、IL-6明显降低且IL-2、IL-11增高(P0.05);TPO表达增高在轻度中毒组高于对照组,但在中、重度中毒组TPO表达降低(P0.05),重度中毒组较中度中毒组降低明显(P0.05)。中度中毒组EPO表达增高,但在重度中毒组EPO表达降低(P0.05);轻、中、重度中毒组TNF-α均高于对照组(P0.05),重度中毒组表达高于轻、中度中毒组(P0.05)。结论不同程度苯中毒患者血清细胞因子表达不同,TNF-α、IL-2表达增高与IL-1β、IL-6的降低和中毒严重程度密切相关。表明细胞因子网络失调在慢性苯中毒的发生发展过程中有重要作用。     

血必净注射液治疗急性百草枯中毒的实验

目的探讨血必净注射液对急性百草枯大鼠中毒脏器损害的治疗保护机制。方法成年Wistar大鼠随机分为百草枯250 mg/kg剂量染毒对照组、百草枯250 mg/kg剂量染毒 血必静注射液高剂量治疗组(1.72 g生药/kg)、百草枯250 mg/kg剂量染毒 血必静注射液低剂量治疗组(0.86 g生药/kg)3组。取原液加蒸馏水稀释至1 ml灌胃染毒。治疗组于染毒后1 h经鼠尾静脉给予相应剂量的血必静注射液缓慢注射,观察染毒组和治疗组动物表现。染毒8 h后处死动物,留取动静脉血及大鼠肺组织,行动脉血气分析、丙氨酸转氨酶(ALT)、碱性磷酸酶(AKP)、尿素氮(BUN)、肌酐(Cr)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6I、L-10I、L-1β、血小板衍生生长因子(PDGF)和胰岛素样生长因子-1(IGF-1)测定,同时行常规病理观察。结果血必净注射液治疗组大鼠动脉血气指标PaO2、PaCO2、pH值明显好于非治疗染毒组,差异有统计学意义(P<0.05或0.01)。治疗组肝肾损害减轻,表现为ALT升高幅度较小,差异有统计学意义(P<0.05),血肌酐变化治疗组明显小于非治疗组,差异有统计学意义(P<0.05)。细胞因子TNF-αI、L-6血必净治疗组与染毒组比较,差异无统计学意义(P>0.05),而IL-10I、L-1β、PDGF和IGF-1高剂量血必净治疗组均明显小于染毒组,差异有统计学意义(P<0.05),PDGF低剂量治疗组也明显小于染毒组,差异有统计学意义(P<0.05)。病理检查示百草枯染毒8 h后肺泡毛细血管的扩张充血,内皮细胞肿胀,出现大量以中性白细胞为主的炎性细胞浸润,肺泡腔内充血,有蛋白水肿液的渗出。血必净治疗组上述改变明显较轻。结论血必净注射液可抑制部分炎性因子的活力。对百草枯中毒脏器损害有治疗保护作用。     

PPAR-γ受体激活对百草枯中毒致大鼠急性肺损伤的保护作用

目的研究PPAR-γ受体激活对百草枯中毒致大鼠急性肺损伤的保护作用。方法 48只SD雄性大鼠随机平均分成3组,A组(百草枯中毒组):按照20 mg/kg剂量腹腔注射;B组(低剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射3 mg/kg罗格列酮;C组(高剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射10 mg/kg罗格列酮;D组(对照组):1 m L生理盐水腹腔注射。在注射百草枯后24 h和72 h时,每组取出6只,收集血清和肺组织标本。采用Elisa方法检测血清中IL-1β和TNF-α含量测定,行组织切片HE染色进行肺损伤评分,利用Western blot方法检测肺组织中caspase-3和AP-1蛋白表达水平,采用免疫组化方法检测caspase-3蛋白在肺组织中的表达。结果大鼠百草枯中毒后血清炎性细胞因子IL-1β和TNF-α含量明显增加。肺湿重/干重比以及肺损伤评分明显增加。罗格列酮预处理组可以减轻肺组织损伤程度,降低血清中IL-1β和TNF-α含量,减少肺组织中caspase-3和AP-1蛋白的表达。结论应用PPAR-γ激动剂罗格列酮可以抑制百草枯中毒大鼠肺组织中caspase-3和AP-1蛋白表达,抑制炎症反应和凋亡,对百草枯中毒导致急性肺损伤产生保护作用。     

急性百草枯中毒后MODS患者血清TNF-α和IL-10的变化及意义

目的探讨急性百草枯中毒（APP）后多器官功能障碍综合征（MODS）患者血清TNF-α、IL-10的变化及临床意义。方法应用放射免疫技术测定32例APP后MODS患者与30名健康人血清TNF-α、IL-10水平,分析APP后MODS患者血清TNF-α、IL-10水平和急性生理学与慢性健康状况Ⅱ（APACHEⅡ）评分、动脉血氧分压（PaO2）、血尿素氮（BUN）、血肌酐（Scr）等指标的关系。结果APP后MODS患者血清TNF-α、IL-10水平较正常对照组明显升高（P〈0.05）,但死亡组与存活组比较差异无统计学意义（P〉0.05）;血清TNF-α、IL-10水平与APACHEⅡ评分、BUN、Scr呈正相关（P〈0.05）,与Pa02呈显著负相关（P〈0.01）。结论TNF-α、IL-10参与了APP后MODS的发病过程,且与APACHEⅡ评分呈正相关;血清TNF-α、IL-10水平可作为APP后MODS患者多器官功能损害程度评估与预后判断的临床指标之一。     

大剂量盐酸氨溴索治疗急性百草枯中毒肺损伤的临床研究

目的观察大剂量盐酸氨溴索治疗急性百草枯(PQ)中毒肺损伤的临床效果。方法将40例急性百草枯中毒肺损伤患者分为治疗组(20例)和对照组(20例),对照组给予常规治疗,治疗组在对照组治疗基础上加用盐酸氨溴索注射液20 mg/(kg·d)静脉滴注q12h,连用5 d;观察两组动脉血气、HRCT变化,发生多脏器功能障碍综合征(MODS)病例,病死率与死亡病例存活时间。检测两组患者治疗前后血清丙二醛(MDA)、超氧化物歧化酶(SOD)及血清TNF-α、IL-6水平。结果治疗后两组动脉氧分压、氧合指数、HRCT改变等均有所改善(P<0.01或P<0.05),治疗组与对照组比较改善更为显著(P<0.05)。治疗组发生MODS病例数少于对照组(P<0.05),两组病死率比较差异无统计学意义(P>0.05)。两组患者治疗后血清MDA水平均下降,治疗组治疗后MDA水平下降较对照组更为明显(P<0.05);两组患者治疗后血清SOD水平均升高,治疗组治疗后SOD水平升高较对照组更为明显(P<0.05)。与治疗前比较,两组患者血清TNF-α和IL-6水平均显著降低(P<0.01);与对照组比较,治疗组患者TNF-α和IL-6降低更显著(P<0.05)。结论大剂量盐酸氨溴索注射液通过提高机体抗氧化能力,抑制脂质过氧化反应,抑制促炎因子的水平,减轻肺损伤,对急性PQ中毒肺损伤有一定治疗作用。     

丹参川芎嗪对胰腺炎患者血清IL-1β和TNF—α含量的影响

目的:通过检测急性胰腺炎(acute pancreatitis,AP)患者外周血清IL-1β和TNF-α的含量的变化,探讨二者与AP的关系及中药制剂对二者变化的影响。方法:选择AP患者40例,随机分为一般治疗组和参芎组,另选健康体检者做对照组,分别于入院后第1天及第7天抽取外周静脉血2mL,采用双抗体夹心EL ISA法检测血清中IL-1β和TNF-α的含量,同时记录AP患者一般状况及生化指标。结果:入院第1天AP组IL-1β和TNF-α的含量明显增高,与正常对照组比较有显著性差异(P<0.01);治疗7d后,IL-1β和TNF-α含量均下降,参芎组较一般治疗组下降明显(P<0.05)。结论:急性胰腺炎患者血清中IL-1β和TNF-α的含量均增高,应用参芎葡萄糖注射液结合常规治疗可明显降低IL-1β、TNF-α水平,减轻胰腺损伤。     

连续性静脉-静脉血液滤过联合血液灌流对百草枯中毒疗效的研究

目的 探讨连续性静脉-静脉血液净化(CVVH)对口服百草枯急性中毒的疗效,及其对百草枯中毒患者血清炎性因子的影响.方法 回顾分析2010年1月至2016年6月福州总医院第一附属医院急诊科诊治的急性口服百草枯中毒患者62例的临床资料.所有患者均给予包括血液灌流在内的常规治疗(对照组30例),在此基础上给予CVVH治疗的32例为观察组,比较2组患者一般临床资料和预后,分析2组患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、动脉血氧分压、血清肌酐(Cr)和丙氨酸氨基转移酶(ALT)的变化.结果 与对照组相比,观察组第3、7天时TNF-α、Cr和ALT降低(P＜0.05);观察组IL-6、动脉血氧分压在第3天时差异无统计学意义(P＞0.05),第7天差异有统计学意义(P＜0.05).观察组和对照组治疗总有效率分别为71.9％、56.7％(P＞0.05),2组治疗结果为痊愈、好转、有效和死亡人数构成比上差异无统计学意义(P＞0.05).结论 CVVH对急性百草枯中毒患者能清除炎性因子TNF-α和IL-6,可提高百草枯中毒患者治疗总有效率.     

罗格列酮对百草枯致大鼠肺损伤的炎症抑制作用

目的：研究罗格列酮对百草枯致大鼠肺损伤过程中的炎症抑制作用机制。方法将72只SD雄性大鼠随机分成3组,每组24只。模型对照组：腹腔注射百草枯20 mg·kg-1;罗格列酮组：腹腔注射百草枯前1 h,腹腔注射罗格列酮10 mg·kg-1;空白对照组：腹腔注射0.9％氯化钠溶液1 mL。注射百草枯后4,8 h及1,3 d,收集各组大鼠血清和肺组织标本,组织切片苏木精-伊红( HE)染色进行肺损伤评分,采用酶联免疫吸附法( ELISA)检测血清白细胞介素-1β( IL-1β)和肿瘤坏死因子-α( TNF-α)含量,采用免疫组化方法检测NF-κB蛋白在肺组织的表达,利用Western blot法检测肺组织核因子-κB (NF-κB)和激活蛋白(AP-1)蛋白表达水平。结果模型对照组大鼠血清炎性细胞因子IL-1β和TNF-α含量明显增加。罗格列酮组肺组织损伤程度明显降低,血清IL-1β和TNF-α含量减少,肺组织NF-κB和AP-1蛋白的表达降低。结论罗格列酮可以抑制百草枯中毒大鼠肺组织NF-κB和AP-1蛋白表达,减少IL-1β和TNF-α分泌,对百草枯所致大鼠肺损伤炎症有抑制作用。     

氨甲喋呤(MTX)治疗类风湿性关节炎的免疫调节机制

目的:探讨MTX治疗类风湿性关节炎(RA)的免疫学机制,为临床MTX治疗RA提供理论依据。方法:在建立佐剂型关节炎(AA)动物模型基础上,通过关节炎指数评价,血清中细胞因子测定和关节切片的病理学检查,观察MTX对促炎症细胞因子如IL^-1β、TNF-α和抗炎症细胞因子IL-4、IL-10的调控作用。结果:MTX预防组和对照组关节炎指数和发病率的变化均无显著差异(P>0.05)。MTX肌肉注射治疗或外用治疗后,关节炎指数发生较显著的变化与对照组相比有显著性差异(P>0.05)。对照组与MTX预防组、MTX肌肉注射组、MTX外用组血清中细胞因子水平相比,对照组与各组TNF-α和IL-10的水平有明显差异,P<0.05 ,MTX肌肉注射组与MTX外用组的TNF-α水平相差很大,P>0.05。而IL-1β、IL-4的水平各组之间没有明显差异,P>0.05。病理组织学变化中炎症程度:对照组>MTX预防组>MTX肌肉注射组>MTX外用组。结论:本研究结果表明,MTX治疗(肌肉注射和外用)可以降低AA大鼠血清中TNF-α浓度,提高IL-10的浓度,从而抑制或控制RA的发生发展。但MTX治疗对IL-1β和IL-4没有明显作用,这方面的机制尚需进一步研究。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.