白血病患者化疗前后血清IL-2、SIL-2R和TNF-α水平检测的临床意义

目的分析白血病患者化疗前后血清IL-2、SIL-2R和TNF-α含量的变化.方法分别应用MTT比色法,双抗体夹心法和放射免疫分析法对42例白血病患者进行化疗前后血清IL-2、SIL-2R和TNF-α含量检测,并与30例正常健康人作对照.结果白血病患者化疗前IL-2水平明显低于正常人(P＜0.01),而SIL-2R、TNF-α水平则显著地高于正常人(P＜0.01),化疗后6个月复发者IL-2、SIL-2R、TNF-α水平持续异常,未复发者IL-2、SIL-2R、TNF-α水平接近正常.结论观察白血病患者的免疫功能的变化与白血病的发生及预后密切相关.     

褪黑素对内毒素血症大鼠血清炎性因子的影响

目的探讨褪黑素(MT)对脂多糖(LPS)诱导的内毒素血症大鼠炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和抗炎因子IL-10表达的影响。方法雄性SD大鼠48只,分为溶剂对照组、LPS组、LPS+MT组、MT组,每组12只。检测各组大鼠血清超氧化物歧化酶(SOD)和丙二醛(MDA)的含量;应用酶联免疫吸附法(ELISA)检测血清TNF-α、IL-6和IL-10含量。结果 LPS+MT组的血清SOD活性较LPS组明显增高(P<0.01),MDA含量较LPS组明显降低(P<0.01);LPS组大鼠血清TNF-α,IL-6含量明显上升,与对照组比较差异有统计学意义(P<0.01),而给予LPS前后应用MT干预治疗,可显著降低血清TNF-α、IL-6含量,与同时间点LPS组比较均差异有统计学意义(P<0.01)。结论 MT可以降低内毒素血症大鼠血清炎性因子水平。     

Effect of melatonin on the inflammatory factors in serum of rats with endotoxemia

目的 探讨褪黑素(MT)对脂多糖(LPS)诱导的内毒素血症大鼠炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和抗炎因子IL-10表达的影响.方法 雄性SD大鼠48只,分为溶剂对照组、LPS 组、LPS+ MT组、MT组,每组12只.检测各组大鼠血清超氧化物歧化酶(SOD)和丙二醛(MDA)的含量;应用酶联免疫吸附法(ELISA)检测血清TNF-α、IL-6和IL-10含量.结果 LPS+MT组的血清SOD活性较LPS组明显增高(P＜0.01),MDA含量较LPS组明显降低(P＜0.01);LPS组大鼠血清TNF-α,IL-6含量明显上升,与对照组比较差异有统计学意义(P＜0.01),而给予LPS前后应用MT干预治疗,可显著降低血清TNF-α、IL-6含量,与同时间点LPS组比较均差异有统计学意义(P＜0.01).结论 MT可以降低内毒素血症大鼠血清炎性因子水平.     

糖皮质激素对重度颅脑损伤患者血浆TNF-α、 IL-6、IL-8水平的影响

目的 研究糖皮质激素对重度颅脑损伤患者血浆TNF-α、IL-6、IL-8水平的影响.方法 随机将重度颅脑损伤患者分为激素治疗组(18 例)与非激素治疗对照组(18 例),激素组给予地塞米松 10 mg/d,共 7 d.正常组选择健康体检者 18 例.采用 ELSIA法检测两组患者伤后第 1、2、3、7、14 d血浆中 TNF-α、IL-6、IL-8含量.结果 在颅脑损伤第 1、2、3天激素组血浆 TNF-α、IL-6、IL-8水平明显高于正常组(P<0.01),在第 7、14 天明显低于非激素组(P<0.01),但与正常组比较差异无统计学意义(P>0.05).非激素组血浆TNF-α、IL-6、IL-8水平在各时间点均明显高于正常组 (P<0.01).结论 糖皮质激素对损伤早期血浆TNF-α、IL-6、IL-8显著升高无明显影响,但至恢复期使血浆TNF-α、IL-6、IL-8明显降低.     

急性痛风性关节炎患者血清IL-1β、IL-6、IL-18及TNF-α水平的研究

目的探讨急性痛风性关节炎(acute gouty arthritis,AGA)患者血清白细胞介素(interleukin,IL)-1β、IL-6、IL-18及肿瘤坏死因子(tumor necrosis factor,TNF)-α水平的变化及意义。方法用ELISA法测定100例AGA患者(观察组,T)和100名健康查体者(对照组,C)血清IL-1β、IL-6、IL-18及TNF-α水平。观察组与对照组比较采用独立样本t检验,一般生理指标及血生化指标用独立样本t检验,计数资料采用χ2检验。计量资料用(x-±s)表示。采用IBM SPSS 19.0软件包对所有数据进行统计学分析。结果观察组与对照组相比,IL-1β、IL-6、IL-18及TNF-α水平均显著升高,差异有统计学意义(P<0.01)。结论 IL-1β、IL-6、IL-18及TNF-α水平在AGA发病时升高,提示它们参与了炎性反应过程,在炎症机制中发挥了重要作用。     

急性白血病患者血清IL-3、IL-6及IL-8水平的变化及意义

目的 探讨急性白血病(AL)患者治疗前后血清白细胞介素(IL)3、IL-6、IL-8水平的变化及意义.方法 采用酶联免疫法(ELISA),对94例初诊AL患者治疗前后血清IL-3、IL-6、IL-8水平进行检测.结果 急性淋巴细胞白血病(ALL)与急性髓细胞白血病(AML)初诊患者血清IL-3水平均明显低于正常对照组(P＜0.01),而血清IL-6、IL-8水平均明显高于正常对照组(P＜0.01);经治疗ALL完全缓解(CR)患者血清IL-3、IL-6、IL-8水平恢复正常,而AML-CR患者血清IL-3水平较初诊时明显升高(P＜0.01),但仍明显低于正常对照(P＜0.01),IL-6、IL-8水平恢复正常;ALL未缓解(NR)及AML-NR组与初诊组相比无性差异(P＞0.05).AML初诊患者血清IL-3水平与ALL-初诊患者无显著性差异,IL-6水平明显低于ALL患者(P＜0.05),而IL-8水平明显高于ALL患者(P＜0.01).AML各亚型之间血清IL-3水平无显著性差异;M1及M5患者血清IL-6水平明显高于其他亚型(P＜0.01);M4及M5患者血清IL-8水平明显高于其他亚型(P＜0.01).结论 IL-3、IL-6、IL-8与AL发生发展有关,其水平与AL类型有关,观察IL-3、IL-6、IL-8水平的变化可作为判断AL患者病情及疗效的辅助指标.     

5-氨基水杨酸治疗结肠炎的抗氧化作用及对细胞因子表达的影响

目的探讨5-氨基水杨酸(5-ASA)灌肠治疗对三硝基苯磺酸(TNBS)诱导大鼠结肠炎的抗氧化作用及对细胞因子表达的影响。方法建立TNBS结肠炎模型,给予5-ASA灌肠治疗,同时设正常对照组和模型组。于治疗后1、2周,评价结肠大体、组织学损伤及髓过氧化物酶(MPO)活性,检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平,逆转录-多聚酶链反应(RT-PCR)检测结肠组织白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-αmRNA表达水平。结果5-ASA灌肠治疗能明显降低结肠炎大鼠的大体、组织学评分及MPO活性(P<0.05),升高SOD活性(P<0.05),降低MDA水平(P<0.05),降低IL-1β和TNF-α表达水平(P<0.05)。结论5-ASA灌肠治疗TNBS诱导的大鼠结肠炎疗效显著,其机制与抗氧化作用及抑制IL-1β和TNF-α的表达有关。     

慢性阻塞性肺病患者治疗前后细胞因子水平检测的临床意义

目的探讨IL-2、IL-1β、IL-10和TNF2在慢性阻塞性肺病(COPD)患者发病机制中的作用及意义。方法应用放射免疫法对40例COPD患者进行了血清IL-2、IL-1β、IL-10和TNF2水平测定,并与35名正常健康人作比较。结果 COPD患者在治疗前血清IL-2、IL-10水平显著低于正常人组(P<0.01),而IL-1β、TNF2水平又显著地高于正常人组(P<0.01),经治疗2周后与正常人的比较仍差异有显著性(P<0.05),血清IL-2水平与IL-10水平呈正相关(r值分别为0.4902,P值均小于0.01),与IL-1β、TNF2水平呈显著负相关(r值分别为-0.5184,-0.6028,P值均小于<0.01)。结论细胞因子参与COPD的气道炎症过程,观察细胞因子水平的变化可作为监测病情观测疗效和预后判定的重要指标之一。     

慢性支气管炎患者血清IL-6、IL-8和TNF-α水平动态变化研究

目的:研究慢性支气管炎患者血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(INF-α)水平的动态变化及其在慢性支气管炎发病中的作用。方法:检测住院慢性支气管炎患者52例(治疗组)急性期与恢复期血清的IL-6、IL-8和TNF-α水平,并与正常对照组进行比较。结果:治疗组急性期血清IL-6、IL-8和TNF-α水平显著高于恢复期和对照组(P<0.01),恢复期与健康对照组比较差异无显著性(P>0.05);慢性支气管炎并发呼吸衰竭和慢性支气管炎急性发作期患者血清IL-6、IL-8和INF-α的含量明显高于无呼吸衰竭的急性发作期患者(P<0.01),临床症状缓解患者的血清IL-6、IL-8和TNF-α含量仍明显高于对照组(P<0.01),低于急性发作期患者(P<0.01)。结论:血清IL-6与IL-8和TNF-α含量测定可作为评估慢性支气管炎患者病情轻重程度及判断预后的参考指标。     

白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素2和6的影响

目的观察白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素(IL)2、IL-6含量的影响。方法 50只大鼠随机分为正常对照组、模型组、白茅根多糖低剂量组、白茅根多糖高剂量组和地塞米松组,每组10只。复合免疫法建立IgA肾病大鼠模型,于造模后第9周起白茅根多糖高、低剂量组及地塞米松组分别给予白茅根多糖20 mg·kg-1·d-1、10 mg·kg-1·d-1或地塞米松2 mg·kg-1·d-1,灌胃4周。检测各组大鼠尿红细胞、24 h尿蛋白,血清肌酐(Scr)、尿素氮(BUN)、IL-2、IL-6水平,并观察大鼠肾脏病理学改变。结果大鼠IgA肾病模型造模成功,模型组电镜观察见电子致密物沉积、系膜细胞增生、足突融合明显;尿红细胞数、24 h尿蛋白、血Scr、BUN、IL-6水平、IgA沉积水平均高于正常对照组(P<0.05或P<0.01)。各治疗组与模型组比较,尿红细胞数、24 h尿蛋白水平,血Scr、BUN均明显下降(P<0.01),白茅根多糖高剂量组血清IL-2和IL-6水平低于模型组(P<0.05或P<0.01),肾脏组织病理学异常改善。结论白茅根多糖可改善IgA肾病大鼠肾功能、降低IgA在系膜区的沉积,降低血清IL-2和IL-6水平可能是其作用机制之一。     

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.