5-氟脲嘧啶对急性胰腺炎病程中细胞因子的影响

目的：观察5－Fu对急性胰腺炎（AP）病程中TNF－α、IL－6和IL－10的影响。探讨其治疗价值。方法：对5％牛磺胆酸钠溶液（0．1ml/100g)逆行胰胆管注射建立急性死性胰腺炎（ANP）模型，雄性SD大鼠48只，随机平均分为三组：假手术组（Sham组）；ANP组；5－Fu组。ANP模型建立后经股静脉注射5－Fu4.5mg/100g。观察术后3小时、6小时（每时间段8只大鼠）血清TNF－α、IL－6、IL－10、血清淀粉酶和胰腺组织学病理改变。结果：（1）ANP组3h,6h血清淀粉酶明显升高（P＜0．01），同时血清TNF－α、IL－6和IL－10水平均明显高于Sham组（P＜0．001）。（2）5-Fu处理后3h血清淀粉酶及胰腺组织学评分均降低（P＜0．05）；而血清IL－6水平仅在3h时降低（P＜0．01）。结论：TNF－α、IL－6和IL－10在AP病程中起了重要的作用。5－Fu抑制了AP病程中细胞因子的产生，对其治疗有益，抑制细胞因子可能是它治疗急性胰腺炎的另一机制。     

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。     

螺旋藻多糖对小鼠移植性肿瘤化疗后造血恢复及相关细胞因子的影响

目的：研究螺旋藻多糖（polysaccharide from spirulina platensis,PSP)对小鼠移植性肿瘤化疗后造血恢复及相关细胞因子的影响。方法：通过右前肢皮下接种肿瘤细胞形成小鼠移植性实体瘤，给予PSP边疆灌胃10d,d4给予环磷酰胺（CTX）腹腔注射连续3d。于d11，分别了外周细胞，骨髓有核细胞及CFU－S计数，用紫外分光光度计检测骨髓DNA含量，用双抗体夹心ELISA法检测血清中IL-1,IL-3,GM-CSF,TNF含量。结果：CTX可造成明显骨髓抑制，而PSP则提升了外周血细胞，增加了骨髓中有核细胞计数和DNA含量以及促进了CFU－S形成。此外，PSP还增加了血清中IL－1，IL－3，GM－CSF，TNF含量。结论：PSP可能通过促进内源性细胞因子的分泌来实现其促进小鼠移植性肿瘤化疗损伤后的造血恢复。     

CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子表达的影响

目的：探讨CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子的调节作用及气道炎症的抑制作用。方法：采用酶联免疫中附法（ELISA）分别检测CpG-ODN对哮喘小鼠抗原首次激发后24小时和抗末次激发后24小时血清及支气管肺泡灌洗液（BALF）中Th2细胞因子IL－4和Th1细胞因子IFNγ水平的影响，并与激素治疗组和哮喘组对照。结果：（1）抗原末次激发后24小时，CpG-ODN 血清及BALF中IFNγ水平高于哮喘组及地塞米松组（P＜0．001）。（2）抗原首次激发后24小时及抗原末次激发后24小时血清和BALF中IL－4水平低于哮喘组（P＜0．05），与地塞米松组比较无显著性差异（P＞0．05）。（3）抗原末次激发后24小时，CpG-ODN组外周血和BALF中嗜酸性粒细胞计数均低于哮喘组（P＜0．001）。结论：CpG-ODN不仅有具有与地塞米松相同的下调Th2细胞因子表达和抑制嗜酸性粒细胞的作用，而且还具有地塞米松所没有的诱导Th1细胞因子表达的作用。说明其可能通过调节Th1/Th2平衡而达到在早期抑制哮喘发病的目的。     

去脑重体大鼠细胞因子水平的变化

目的 探讨脑垂体对细胞因子水平的影响。方法 采用生物活性法检测去脑垂体大鼠血清细胞因子IL－2、IL－6、TNF水平及应用放射免疫分析法检测垂体GH、TSH、PRL水平。结果 SD大鼠切除脑垂体后血清中GH、TSH、PRL水平均显著下降,血清中细胞因子IL－2、TNF活性均显著性降低,但IL－6无明显改变。结论 切除大鼠脑垂体后将影响了其免疫功能,证明脑垂体分泌正常的GH、TSH、PRL水平对维持正常的细胞因子水平有重要的作用。     

血清炎性生物标记物在子宫内膜异位症患者血清中的表达及意义

目的：探讨炎性因子TNF－α、IL－1β、IL－6、IL－8及CA－125、MMP－3、VEGF在子宫内膜异位症患者血清中表达变化及其意义,分析其与患者EMs病变r－AFS临床分期及EMs患者痛经程度的相关性。方法采用酶联免疫法（ELISA）检测入组患者血清中TNF－α、IL－1β、IL－6、 IL－8,CA－125、MMP－3、VEGF的浓度。分析EMs患者血清中TNF－α、IL－1β、IL－6、IL－8、CA－125、MMP－3、VEGF的浓度与正常对照人群的差异;分析不同分期EMs患者血清中上述标记物的浓度差异;分析EMs患者术前术后血清中上述标记物的表达变化情况;分析EMs患者血清中上述标记物与痛经评分的相关性。结果炎性相关因子TNF－α、IL－1β、IL－6、IL－8及CA－125、VEGF浓度在EMs患者血清中显著升高（ P ＜0．05）,并且随着EMs病变γ－AFS临床分期加重而增加,手术切除病灶后血清中上述指标浓度迅速回落;此外严重痛经EMs患者血清中TNF－α、IL－1β及IL－6的浓度较无痛经EMs患者高（ P ＜0．05）。 EMs患者血清中TNF－α、IL－1β及IL－6浓度与患者痛经严重程度呈正相关（ P ＜0．05）。 MMP3－在EMs患者血清中浓度显著升高（ P ＜0．05）,手术切除病灶后血清中MMP－3迅速下降,然而血清中MMP－3浓度与EMs患者r－AFS临床分期无显著性关联,血清中MMP－3浓度与EMs患者痛经严重程度亦无明显相关性（ P ＜0．05）。结论测定EMs患者血清中TNF－α、IL－1β、IL－6、IL－8及CA－125、MMP3－、VEGF浓度对于EMs的临床诊断具有一定价值,并且可作为无创性辅助检查手段。     

急性白血病患者血清IL-6、IL-8的测定

目的：探讨白细胞介素（interleukin) 6、8在急性白血病中的意义。方法：采用放射免疫法测定细胞因子成员中IL－6和IL－8在急性白血病治疗前和治疗后获得完全缓解患者及正常人血清中表达及其意义。结果：AL治疗前和AL获CR后患者的外周血血清IL－6和IL－8水平明显低于正常对照组。结论：AL发病与免疫应答功能降低有关。     

sIL-2R在急性移植物抗宿主病中的临床研究

目的探讨细胞因子sIL-2R在异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）发病机理中的作用。方法观察20例Allo-HSCT患者aGVHD的发病情况，移植前后定期采集20例患者的外周血，采用双夹心酶联免疫吸附法（ELISA）检测其细胞因子sIL-2R的浓度。结果①异基因造血干细胞移植后20例患者全部获得造血功能重建，中性粒细胞恢复到0．5×10^9／L及血小板恢复到20×10^9／L的中位时间分别为移植后13．5d及18d；②发生aGVHD的患者，sIL-2R浓度较移植前明显升高，sIL-2R浓度在aGVHD阳性组明显高于aGVHD阴性组（P〈0．01）。结论①细胞因子sIL-2R在aGVHD的发病中起重要的正向调节作用，检测异基因造血干细胞移植后患者血清的sIL-2R水平有助于预测aGVHD的发生；②sIL-2R与感染无相关性。     

A群链球菌制剂抗肿瘤效应与细胞因子的关系

目的：从细胞因子水平探讨A群链球菌制剂的抗肿瘤机制。方法：将浓度0.5，0.1，0.02，0.004 KE·mL 1的A群链球菌制剂与肿瘤患者外周血淋巴细胞(PBL)共同孵育，以活性细胞定量(MTT)法检测经24，48，72 h诱导后的PBL对K562及Raji细胞的杀伤效应，并采用酶联免疫吸附(ELISA)法或生物学活性检测法测定其上清液中白细胞介素 12(IL 12)、白细胞介素 2(IL 2)、γ 干扰素(IFN γ)、α 肿瘤坏死因子(TNF α)含量。结果：经不同浓度A群链球菌制剂作用不同时间后PBL对K562及Raji细胞的杀伤效应不同，诱导产生的细胞肿瘤因子也不同。0.1和0.02 KE·mL 1 A群链球菌制剂可增强PBL杀伤肿瘤细胞的能力，其上清液中亦均能检测到较高水平的IL 12、IL 2、IFN γ、TNF α；0.5 KE·mL 1 A 群链球菌制剂不但抑制PBL对肿瘤细胞的杀伤，而且还抑制其分泌细胞因子的能力。结论：A群链球菌制剂诱导肿瘤患者PBL杀伤肿瘤细胞的活性与其浓度有关，抗肿瘤效应与细胞因子的产生有关。     

丹参注射液对β2糖蛋白I诱导产生抗心磷脂抗体的影响

目的：观察丹参注射液对β2糖蛋白I （β2－GP I）诱导的抗心磷脂抗体（anticardiolipin antibody,aCL)产生的影响，以探讨其对抗磷脂综合征的治疗作用及可能的作用机制。方法：60只雌性昆明种小鼠被随机分为六组，A、B、C、D四组经腹腔注射不同剂量的丹参注射液；14天后，A、B、C、E四组多部位皮下注射β2－GP I。E组为造模组；F组为空白对照组。用酶联免疫吸附实验法测定血清中的aCL;以链霉亲和素－生物素复合物法检测外周血T细胞亚群；以四甲基偶氮唑盐（MTT）比色法检测外周血白细胞介素－2（IL－2）生物活性。结果：（1）用药组血清aCL吸光度值均较E组有不同程度降低（P＜0．05或P＜0．01）；药物剂量与aCL吸光度值的变化成负相关（P＜0．01）。（2）与E组相比，A、B、C组均可降低TH／TS比值（P＜0．05或P＜0．01）；D组与F组相比无统计学意义（P＞0．05）；药物剂量与TH／TS比值存在负相关（P＜0．01）。（3）与E组相比，A组对IL－2活性无明显影响（P＞0．05），而B、C组则使之明显降低（P＜0．01）；D组与F组无明显差异（P＞0．05）；药物剂量与IL－2活性存在负相关（P＜0．01）。（4）经双变量直线相关分析，TH／TS比值和IL－2生物活性呈正相关（P＜0．01）。结论：丹参注射液可抑制β2-GP I诱导的aCL的产生，其作用机理可能是抑制TH／TS比值和IL－2生物活性的升高；丹参注射液对正常小鼠无明显作用，提示其具有选择性免疫调节作用。     

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.     

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.