刺三甲醇提物对AA大鼠血清中炎性因子含量的影响

目的:研究彝药刺三甲醇提物对佐剂性关节炎(AA)大鼠血清中白细胞介素(IL)-1β、IL-6、IL-10、一氧化氮(NO)、肿瘤坏死因子α(TNF-α)和前列腺素E2(PGE2)含量的影响。方法:将60只大鼠随机均分为正常对照组(蒸馏水)、模型组(蒸馏水)、阳性对照(尼美舒利,0.03 g/kg)组和刺三甲高、中、低剂量[7、3.5、1.75 g(生药)/kg]组,除正常对照组外,其余各组大鼠均于右后足趾部sc弗氏完全佐剂(0.1 ml)复制AA大鼠模型,致炎后,各组大鼠ig相应药物,每天1次。30 d后测定大鼠血清中IL-1β、IL-6、IL-10、TNF-α、NO、PGE2含量,并观察大鼠踝关节病理形态学变化。结果:与正常对照组比较,模型组大鼠血清中IL-1β、IL-6、TNF-α、NO、PGE2含量升高,IL-10含量降低,差异有统计学意义(P<0.01);与模型组比较,刺三甲高剂量组大鼠血清中IL-1β、IL-6、TNF-α、NO、PGE2含量降低,IL-10含量升高,差异有统计学意义(P<0.05)。病理结果显示,刺三甲组部分切片滑膜细胞轻度增生、纤维组织轻度增生、炎细胞不同程度浸润、巨噬细胞有轻度增生;正常对照组无此变化。结论:彝药刺三甲醇提物对AA模型大鼠有明显的抗炎作用,其作用机制可能与降低炎症因子IL-1β、IL-6、TNF-α、NO、PGE2的含量,升高抗炎因子IL-10的含量有关。     

乌梅丸治疗溃疡性结肠炎大鼠作用机制初探

目的：探讨乌梅丸治疗溃疡性结肠炎大鼠的作用机制。方法采用2,4-二硝基氯苯（ DNCB）加醋酸复合法制备大鼠溃疡性结肠炎（UC）模型。动物随机分为正常组、模型组、柳氮磺胺吡啶（SASP）组和乌梅丸大、中、小剂量组6组。采用酶联免疫吸附测定（ELISA）法检测大鼠血清白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（ TNF-α）的含量,采用反转录聚合酶链反应（ RT-PCR）法检测大鼠肠道组织中核因子κB（ NF-κB） mRNA和过氧化物酶增殖体激活受体-γ（ PPAR-γ） mRNA的表达水平。结果模型组大鼠血清IL-1β、IL-6、TNF-α的含量及肠道组织NF-κB mRNA的表达水平均高于正常组,而PPAR-γmRNA的表达水平均低于正常组（P＜0．05）。而SASP组及乌梅丸各剂量组IL-1β、IL-6、TNF-α的含量及肠道组织NF-κB mRNA的表达水平均低于模型组,PPAR-γmRNA的表达水平高于模型组（P＜0．05）。结论乌梅丸治疗溃疡性结肠炎可能是通过抑制炎性反应因子和调升NF-κB与PPAR-γ基因的表达实现的。     

草乌甲素对大鼠佐剂性关节炎的影响

目的:了解草乌甲素对佐剂性关节炎(AA)大鼠原发性关节炎的抗炎镇痛作用。方法:用Freund's完全佐剂免疫Wistar大鼠建立AA动物模型,将其随机分为3组,即草乌甲素治疗2组(剂量分别为100μg.kg-1、50μg.kg-1)、注射用水组。于AA动物模型建立当天对实验大鼠进行处理,连续7d,并记录各组大鼠体重、右踝关节周径变化。治疗结束当天记录炎侧踝关节屈关节疼痛试验评分,用ELISA法检测大鼠血清的TNF-α、INF-γ、PGE2、β-内啡肽含量。结果:在100μg.kg-1治疗组中,草乌甲素在治疗第2天即可明显减轻关节肿胀(P<0.05),提高AA大鼠痛阈(p<0.05),显著降低AA大鼠PGE2含量、提升血清β-内啡肽含量(P<0.01);在50μg.kg-1治疗组中,草乌甲素从治疗的第3天起开始减轻关节肿胀(P<0.05),对大鼠PGE2含量、提升血清β-内啡肽含量作用较弱(P>0.05)。100μg.kg-1、50μg.kg-1草乌甲素均可降低AA大鼠血清TNF-α含量(P<0.01),但两者间无统计学差异;草乌甲素对血清INF-γ无明显影响(P>0.05)。结论:草乌甲素明显改善AA大鼠关节的肿胀,这可能与其降低血清TNF-α、PGE2含量有关;草乌甲素提高AA大鼠痛阈可能与降低血清PGE2,提升血清β-内啡肽有关。     

原花青素对佐剂性关节炎大鼠炎性介质的影响

目的 观察原花青素对佐剂性关节炎大鼠炎症介质PGE2、NO和细胞因子IL—β、TNF—α、IL-4、IL-0的影响。方法60只雄性SD大鼠随机分为正常对照组、模型对照组、地塞米松治疗组（2mg／kg）、原花青素小剂量组（1．2mg／kg）、原花青素中剂量组（6mg／kg）、原花青素大剂量组（30mg／kg），每组10只，以完全弗氏佐剂制造大鼠佐剂性关节炎模型。大鼠于致炎后第8天给药，第24天心脏取血，ELISA测血清中IL—β、TNF—α、IL-4、IL—10的含量；并剪下致炎足的对侧足爪，剪碎后浸泡于生理盐水2小时，     

苦参素对佐剂性关节炎大鼠的治疗作用

目的研究苦参素(OM)对大鼠佐剂型关节炎(AA)的影响,并探讨部分作用机制。方法弗氏完全佐剂(FCA)诱导AA大鼠模型,检测大鼠足爪肿胀度、多发性关节炎指数(AI),HE染色观察关节病理学改变,放免法检测血清IL-1β、TNF-α水平。结果 OM(60、120 mg.kg-1)剂量组能明显抑制AA大鼠继发性足肿胀,改善膝关节的病理学病变,使AA大鼠血清IL-1β、TNF-α水平显著下降。结论 OM对AA大鼠有治疗作用,调节体内细胞因子IL-1β、TNF-α的水平可能是其治疗AA的作用机制之一。     

亚油酸及其甲酯对大鼠佐剂性关节炎的治疗作用

目的观察亚油酸和亚油酸甲酯对大鼠佐剂性关节炎的治疗作用。方法用弗氏完全佐剂建立大鼠关节炎模型(AA),观察亚油酸及其甲酯对AA大鼠足肿胀的抑制作用和对血清中IL-1β和TNF-α表达水平的影响。结果亚油酸及其甲酯能显著减轻关节肿胀,并能显著降低血清中IL-1β和TNF-α的含量。结论亚油酸及其甲酯对佐剂性关节炎有一定的治疗作用。     

肿瘤坏死因子受体-抗体融合蛋白对佐剂性关节炎大鼠滑膜中TNF-α、TGF-β1 和 VEGF 表达的影响

目的探讨肿瘤坏死因子受体-抗体融合蛋白对佐剂性关节炎大鼠滑膜中肿瘤坏死因子-α（TNF-α）、转化生长因子-β1（TGF—β1）血管内皮生长因子（VEGF）表达的影响。方法将成年雄性Wistar大鼠随机分为5组,Ⅱ-Ⅴ组建立佐剂性关节炎大鼠（AA）模型,于造模后第12天开始Ⅲ组给予甲氨喋呤灌胃治疗,Ⅳ-V组给予益赛普皮下注射治疗。第28天取膝关节滑膜,常规HE染色,计算滑膜病理积分,免疫组织化学染色检测TNF-α、TGF-β1和VEGF在膝关节滑膜的表达。结果正常对照组大鼠滑膜组织均有少量TNF-α、TGF-β1和VEGF的表达,Ⅱ～Ⅴ组较Ⅰ组均明显增高（P〈0．05）。Ⅳ、Ⅴ组滑膜组织TNF—α表达较Ⅱ组明显减低（P〈0．05）,而Ⅲ组与Ⅱ组无统计学意义（P〉0．05）。Ⅲ～Ⅴ组滑膜组织TGF—β1、VEGF的表达均明显低于Ⅱ组,差异有统计学意义（P〈0．05）。结论可溶性重组人肿瘤坏死因子受体-抗体融合蛋白可明显降低AA大鼠滑膜组织TNF-α、TGF—β1和VEGF表达,对AA大鼠的关节炎症有明显的治疗作用,可能抑制局部组织血管新生。     

藏药翁布总苷对大鼠佐剂性关节炎的治疗作用

目的：研究翁布总苷对佐剂性关节炎（AA）大鼠的治疗作用及部分机制。方法：用弗氏完全佐剂（FCA）诱导大鼠AA模型。足容积法测量继发侧足肿胀度,进行关节炎评分,测定AA大鼠血清中超氧化物歧化酶（SOD）和一氧化氮（NO）的水平,酶联免疫吸附测定法（ELISA）测定脂多糖（LPS）诱导的滑膜腔单核巨噬细胞（AM）产生IL-1、TNF-α和PGE2的水平。结果：致炎后第12天,大鼠继发性关节炎出现,同时灌胃给予不同剂量的翁布总苷及吲哚美辛,连续两周。从第24天起,翁布总苷（1.0、1.5 g/kg）对AA大鼠继发性炎症反应（继发性足肿胀、多发性关节炎）有明显的治疗作用。翁布总苷（1.0、1.5 g/kg）可不同程度纠正AA大鼠血清中低下的SOD水平,降低AA大鼠血清中NO水平,同时降低AA大鼠滑膜腔单核巨噬细胞产生过高的白介素（IL-1）、肿瘤坏死因子（TNF-α）、前列腺素E2（PEG2）。结论：翁布总苷对AA大鼠继发性炎症有治疗作用,其作用机制可能与维持细胞因子网络平衡,减少炎症介质的释放和提高机体抗氧化能力有关。     

茶多酚对胶原诱导性关节炎大鼠足爪组织MMP-2蛋白表达水平的影响

目的：探讨茶多酚对Ⅱ型胶原乳化剂诱导关节炎大鼠的治疗作用及机制。方法 SD大鼠随机分为正常对照组、模型组、地塞米松对照组（2 mg·kg－1·d－1）和茶多酚治疗组（200 mg·kg－1·d－1）,采用Ⅱ型胶原弗氏完全佐剂法（collagen-in-duced arthritis,CIA）建立类风湿性关节炎大鼠模型。记录大鼠足趾体积的变化,酶联免疫法（ELISA）检测大鼠血清IL-1β、PGE2水平,免疫组化法检测大鼠足爪组织基质金属蛋白酶2（MMP-2）蛋白水平的表达。结果与模型组比较,茶多酚治疗组大鼠踝关节肿胀明显减轻（P＜0．05）,大鼠血清IL-Iβ、PEG2水平明显降低（P＜0．05）,足爪组织细胞中MMP-2蛋白表达明显下降（P＜0．05）。结论茶多酚对CIA大鼠关节炎有抑制作用,其机制可能与抑制炎症介质IL-1β、PEG2,下调MMP-2蛋白表达有关。     

佐剂性关节炎大鼠外周血TNF-α、IL-1β、MIF与MLT的昼夜节律

目的：观察佐剂性关节炎（ AA）大鼠外周血肿瘤坏死因子-α（ TNF-α）、白介素-1β（ IL-1β）、巨噬细胞移动抑制因子（ MIF）和褪黑素（ MLT）水平的昼夜变化。方法采用Wistar大鼠复制AA模型,光、暗周期L∶ D=12∶12;于造模后第19天08：00、12：00、16：00、20：00、24：00、04：00共6个时间点采集尾静脉血,采用 ELISA 法检测TNF-α、IL-1β、MIF、MLT含量,余弦法分析其昼夜节律。造模前与造模后6个时间点采用容积测量仪检测大鼠双侧足爪容积。结果 AA大鼠足爪容积未发现明显昼夜变化（ P〉0．05）。昼夜不同时间点外周血细胞因子TNF-α、IL-1β、MIF、MLT水平的波动具有统计学意义（P〈0．05）;4种细胞因子昼夜节律特征相似,即峰值相位均位于夜间（暗期）,其中MIF的峰值出现时间较早,谷值相位均位于白天（明期）。结论 AA大鼠外周血TNF-α、IL-1β、MIF与MLT的表达存在昼夜节律,提示生物钟在类风湿关节炎的病理生理及治疗研究中具有重要意义。     

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.