枸杞子,白术对小鼠干扰素诱生的影响

目的：观察枸杞子、白术对小鼠干扰素诱生的影响。方法：将小 发为正常对照组、氢化可的松（氢可）组、枸杞子、氢可＋枸杞子组、白术组、白术＋氢可组；氢可５ｍｇ／只，ｓｃ，枸杞子、白术均为０．５ｇ／只ｉｇ；用新城疫病毒（ＮＤＶ），刀豆蛋白Ａ（ＣｏｎＡ）分别诱生α和γ干扰素，应用微量细胞病变抑制法滴定干扰素，以ｌｏｇ α或γ干扰素滴度为指标。结果：与正常对照组比较，氢可组非常显著抑制α和γ干扰素滴度为指标。     

山芝麻水提取物对小鼠免疫性肝损伤的保护作用

目的观察山芝麻水提取物对小鼠免疫性肝损伤的保护作用。方法将60只小鼠随机分为正常对照组、模型组、日达仙阳性对照组(4.2μg.kg-1.d-1),以及山芝麻高、中、低剂量组(20,10,5 g.kg-1.d-1),各组预防性给药15 d,除正常对照组外,其余各组小鼠尾静脉注射20 mg.kg1刀豆蛋白A(Con A)。12 h后测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)的活性,流式细胞术测定全血中CD3+、CD4+、CD8+T细胞亚群比率,ELISA方法测定血清肿瘤坏死因子(TNF-α)和γ干扰素(IFN-γ)的水平。结果与模型组比较,10,20μg.kg-1.d-1剂量的山芝麻能明显降低Con A介导的肝损伤小鼠血清中AST、ALT的水平,显著提高CD3+、CD4+、CD4+/CD8+比率,明显降低血清中炎性细胞因子IFN-γ和TNF-α的含量。结论山芝麻水提取物对免疫性肝损伤具有保护作用,其机制可能与调整T细胞亚群的活性和减少炎性细胞因子的作用有关。     

西咪替丁抑制再生障碍性贫血小鼠脾细胞产生干扰素γ和肿瘤坏死因子α(英文)

目的:研究西咪替丁对免疫介导再生障碍性贫血小鼠淋巴细胞产生IFNγ和TNFα的影响。方法:亚致死量照射后输注异种淋巴细胞构建再障小鼠,用LPS或PHA-P刺激脾脏细胞产生TNFα或IFNγ,夹心ELISA法检测诱生的IFNγ浓度,用L929细胞毒法测定TNFα水平。结果:(1)再障鼠淋巴细胞诱生的IFNγ和TNFα浓度分别为(137±36)ng/L and(6±3)μg/L,均高于单纯放射组及对照组;(2)用西咪替丁处理淋巴细胞后,再障小鼠淋巴细胞产生的IFNγ和TNFα水平下降,分别为(14±8)ng/L和(2.7±0.6)μg/L。结论:西咪替丁能有效减少再障小鼠脾淋巴细胞IFNγ和TNFα的产生。     

羧甲基茯苓多糖对人外周血淋巴细胞分泌IFN-α和IFN-γ的调节作用及中间体制备

用羧甲基茯苓多糖（CMP）预处理人外周血淋巴细胞（HPBL），经200IU／mlIFN－α启动后，加NDV的促诱生组的α-干扰素（IFN－α）效价比无CMP的常规诱生组高1．2倍；经PHA和／或ConA促诱生组的γ-干扰素（IFN－γ）效价比无CMP的PHA和／或ConA刺激常规诱生组高0．5倍（P＜0.01），尤以CMP＋PHA＋ConA促诱生的IFN－γ效果最佳。说明CMP具有IFN－α和IFN－γ促诱生效应（P＜0．01）。用CMP促诱生的IFN－α和IFN－γ中间体经各项指标检测不仅IFN－α和IFN－γ效价高，而且可达到生物制剂药用标准，经临床试验证明安全有效。     

六味五灵片对刀豆蛋白A诱导的小鼠急性免疫性肝损伤的保护作用研究

目的研究六味五灵片(Liuweiwuling Tables,LWWL)对刀豆蛋白A(concanavalin A,Con A)诱导的小鼠急性免疫性肝损伤的保护作用及机制。方法将小鼠随机分成正常组对照组、模型组、双环醇组(Bicyclol,39 mg·kg~(-1))、六味五灵片低剂量组(8 g·kg~(-1))、六味五灵片高剂量组(16 g·kg~(-1)),各给药组每天给药1次,连续7 d,末次给药1 h后,除正常对照组外,其他各组尾静脉注射Con A(15 mg·kg~(-1))制备小鼠急性免疫性肝损伤模型。HE染色观察小鼠肝组织病理变化;比色法检测小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL);实时定量RT-q PCR测定法检测肝组织中白介素-12(IL-12)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白介素-4(IL-4)、白介素-10(IL-10)mRNA的表达;流式细胞术(FCM)观察脾脏Th1(IFN-γ)/Th2(IL-4)细胞的变化;免疫印迹(Western blot)法检测肝组织中Th1/Th2转录因子T-bet/GATA-3的表达。结果与正常对照组相比,模型组小鼠血清中ALT、AST、TBIL明显升高,小鼠肝组织病理损伤严重,肝细胞大量坏死、凋亡,表明造模成功。与模型组比较,六味五灵片低、高剂量组小鼠血清中ALT、AST、TBIL的水平明显降低;脾脏中Th1细胞减少,Th2细胞增多。肝组织中IL-12、IFN-γ、TNF-α的mRNA表达下降,IL-4、IL-10的mRNA表达上升,GATA-3蛋白表达上调,T-bet蛋白表达无明显变化。结论六味五灵片通过调节Th1/Th2的平衡,保护Con A诱导的急性免疫性肝损伤。     

猪脾细胞干扰素安全性的研究 (一)急性毒性实验和长期毒性实验

<正> 猪脾细胞干扰素是用猪睥细胞在一定条件下经新城病毒(NDV)诱生而得的干扰素。含有α及γ干扰素二种类型。实验证明不仅可在同源细胞表现出抗病毒活性,而且可在异源细胞表现出较高的抗病毒活性。对流行性出血热病毒(EHFV)亦具有抑制作用。     

安络化纤丸联合γ-干扰素治疗小鼠血吸虫性肝纤维化的实验研究

目的 比较中成药安络化纤丸、西药γ-干扰素以及二者联合使用对血吸虫性肝纤维化的治疗作用,初步探讨作用机制. 方法将50只昆明小鼠随机分为5组,正常对照组10只,其余40只以每只感染日本血吸虫尾蚴40条为入选对象,6周后成功建立小鼠血吸虫性肝纤维化模型. 将建模成功的小鼠随机分为4组,每组10只. 感染对照组用0.9%氯化钠溶液灌胃,每次0.75 mL. 安络化纤丸组用0.9%氯化钠溶液配制混悬液灌胃(安络化纤丸20粒加0.9%氯化钠溶液7.5 mL),每次0.75 mL. γ-干扰素组用灭菌注射用水配制溶液皮下注射(γ-干扰素200万U加注射用水4 mL,每次0.1 mL). 联合治疗组用等量的安络化纤丸和γ-干扰素. 上述治疗均为每天1次,疗程8周. 正常对照组给予等量0.9%氯化钠溶液灌胃8周. 肝组织切片,苏木精 伊红(HE)染色观察病理改变. 免疫组化检测肝组织Ⅰ、Ⅲ型胶原及基质金属蛋白酶组织抑制因子-1(TIMP-1)的表达. 结果 安络化纤丸组、γ干扰素组、联合治疗组、感染对照组血吸虫卵结节直径分别为(460.406 5±36.276 8),(433.927 6±44.209 5),(433.430 0±64.928 4),(533.765 8±88.102 2) μm,与感染对照组比较,各治疗组小鼠肝脏病理损害减轻,血吸虫虫卵结节直径明显减小(P<0.05). Ⅰ、Ⅲ型胶原及TIMP-1的表达,各组与感染对照组比较均明显下降;联合治疗组表达最低,与单药治疗组比较,差异有统计学意义(P<0.05). 结论 安络化纤丸联合γ-干扰素治疗血吸虫性肝纤维化的效果优于单药治疗,其作用机制可能与抑制肝星状细胞激活、减少TIMP-1表达有关.     

用预先刺激的小鼠脾细胞生产高滴度的γ干扰素

本文介绍小鼠脾细胞用刀豆素A(ConA)预先刺激,可使细胞体积增大,这些细胞在用ConA再次刺激后,可获得高滴度的γ干扰素(IFN-γ)。实验中所用的动物为8～12周龄的C57BL/6小鼠,分别用不同剂量的ConA刺激小鼠脾细胞群3～8天,然后检测诱生的IFN-γ的滴度。用水泡性口炎病毒的细胞病     

吗啡依赖小鼠免疫功能的变化

以饮用吗啡药水法建立小鼠依赖模型,探讨其免疫机能的改变。发现,与对照组比较,依赖小鼠腹腔巨噬细胞(PMΦ)吞噬中性红能力下降,LPS 10μg·ml~(-1)诱生的IL-1及TNF活性降低。吗啡亦抑制Con A/LPS刺激的胸腺细胞和脾细胞参入[~3H]TdR,使DNFB所致迟发型过敏反应下降。若脾细胞单独或与Con A 3μg·ml~(-1)共同培养24h,成瘾小鼠产生IL-2的能力皆明显弱于对照。但Con A活化3d的脾母细胞对重组IL-2的反应性以及产生抗SRBC的空斑形成细胞数和抗体的水平,在二组之间均未见差异。     

黄芪注射液联合恩替卡韦对乙型肝炎模型小鼠血清炎症因子及肝功能的影响

目的:研究黄芪注射液联合恩替卡韦对乙型肝炎模型小鼠血清炎症因子及肝功能的影响。方法:将60只小鼠随机分为正常对照组(生理盐水)、模型组(生理盐水)、黄芪注射液组(0.5 mL/10 g)、恩替卡韦组(45μg/kg)和联用组(0.5 mL/10 g黄芪注射液+45μg/kg恩替卡韦),各12只。除正常对照组外,其余4组小鼠均建立乙型肝炎模型。成模后,各组小鼠ig给药,每天1次,连续4周。给药结束后,检测小鼠血清中肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素8(IL-8)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆红素(TBIL)水平,观察各组小鼠肝组织的病理学变化。结果:与正常对照组比较,模型组小鼠血清中TNF-α、IFN-γ、IL-8、AST、ALT和TBIL水平均显著升高(P<0.05),肝细胞呈弥散性重度脂肪变性。与模型组比较,各给药组小鼠血清中TNF-α、IFN-γ、IL-8、AST、ALT和TBIL水平均显著降低(P<0.05),肝组织病理学变化得到不同程度改善,且联用组小鼠指标改善程度优于黄芪注射液组和恩替卡韦组(P<0.05)。结论:黄芪注射液联合恩替卡韦有助于下调乙型肝炎模型小鼠血清中炎症因子表达、改善肝功能水平,且两药联用效果优于两药单用。     

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.     

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.     

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.