绞股蓝皂苷调节环磷酰胺诱导免疫功能低下小鼠的免疫调节作用

目的研究绞股蓝皂苷对环磷酰胺诱导的免疫功能低下小鼠的免疫调节作用。方法采用环磷酰胺诱导建立免疫低下小鼠模型,用绞股蓝皂苷低、中及高剂量(60,120和180 mg·kg^-1)灌胃给药,30 d后测定小鼠外周血白细胞数、免疫器官脏器指数和T淋巴细胞CD4+/CD8+比值,用酶联免疫吸附(Elisa)法检测血清中白介素-2(IL-2)、白介素-6(IL-6),白介素-10(IL-10)、干扰素-γ(IFN-γ)及肿瘤坏死因子-α(TNF-α)的水平,实时荧光定量PCR检测脾脏中IL-2、IL-6、IL-10、IFN-γ及TNF-α的mRNA表达。结果绞股蓝皂苷能增强免疫功能低下小鼠的免疫功能,显著提高免疫低下小鼠的外周血白细胞数、胸腺及脾脏指数、CD4+/CD8+比值和血清中细胞因子的水平,并使其在脾脏中mRNA的表达升高从而发挥免疫调节作用。结论绞股蓝皂苷能够增强环磷酰胺诱导的免疫功能低下小鼠的免疫功能。     

HPLC法同时测定苯磺酸氨氯地平片中7个杂质的含量

目的：探讨潞党参口服液对环磷酰胺所致的免疫抑制小鼠的免疫调节作用。方法：240只ICR小鼠随机均分6组：空白组、模型组、香菇多糖（0.2 g·kg-1）组和潞党参口服液低、中、高剂量组（3.3、6.6、13.2 g·kg-1）。连续3天腹腔注射环磷酰胺（50 mg·kg-1）建立免疫抑制小鼠模型，采用香菇多糖和潞党参口服液灌胃进行治疗14天，检测小鼠体质量、免疫器官脏器指数、血清溶血素、脾脏淋巴细胞增殖、腹腔巨噬细胞吞噬能力，以及血清免疫因子IL-2、IL-4和IFN-γ水平，研究潞党参口服液的免疫调节作用。结果：与空白组比较，模型组小鼠体质量、免疫器官脏器指数、血清溶血素水平、脾脏淋巴细胞增殖率、腹腔巨噬细胞吞噬能力以及血清免疫因子IL-2、IL-4和IFN-γ水平均显著降低（P<0.05，P<0.01）；潞党参口服液中、高剂量组和香菇多糖组治疗后，免疫抑制小鼠体质量、免疫器官脏器指数、血清溶血素水平、脾脏淋巴细胞增殖率、腹腔巨噬细胞吞噬能力及血清免疫因子IL-2、IL-4和IFN-γ水平均显著升高，与模型组比较具有统计学意义（P<0.05，P<0.01）。结论：潞党参口服液能够改善环磷酰胺所致免疫抑制小鼠的免疫功能。     

参黄胶囊对环磷酰胺致免疫低下小鼠免疫功能的影响

目的 探讨参黄胶囊对环磷酰胺致免疫抑制模型小鼠免疫功能的作用.方法 分别用环磷酰胺和限食法结合环磷酰胺两种方法建立小鼠免疫抑制模型,分别给予0.26、0.53、1.06 g/kg参黄胶囊,观察其对小鼠外周血T淋巴细胞率、胸腺指数、脾脏指数、白细胞数、巨噬细胞吞噬指数、血清溶血素含量(半数溶血值)的影响.结果 应用环磷酰胺后,免疫抑制模型小鼠外周血T淋巴细胞率、胸腺指数、脾脏指数、白细胞数、巨噬细胞吞噬指数、血清溶血素含量均显著降低.0.26、0.53、1.06g/kg参黄胶囊均可明显提高用限食法结合环磷酰胺致免疫低下(气虚模型)小鼠外周血T淋巴细胞率、胸腺指数和脾脏指数和环磷酰胺致免疫低下小鼠体内白细胞数和巨噬细胞吞噬指数;0.53、1.06 g/kg参黄胶囊可明显促使溶血素生成增加.结论 参黄胶囊可明显改善环磷酰胺致免疫低下小鼠的免疫功能,具有扶正固本、增强机体特异性免疫和非特异性免疫功能作用.     

灵芝多糖对S180荷瘤小鼠血清细胞因子水平与脏器指数的影响

目的:研究灵芝多糖对S180荷瘤小鼠血清细胞因子水平与脏器指数的影响。方法:瘤细胞悬液接种于小鼠右前肢腋窝皮下(0.2 ml/只)以复制S180荷瘤模型。60只KM小鼠随机均分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、环磷酰胺(40 mg/kg,连续3 d)组与灵芝多糖高、中、低剂量(160、80、40 mg/kg,连续10 d)组。灌胃给药,每天1次。ELISA法测定小鼠血清干扰素(IFN)-γ与白细胞介素(IL)2含量,称定瘤质量并计算抑瘤率,称定胸腺和脾脏质量并计算胸腺和脾脏指数。结果:与正常对照组比较,模型组小鼠血清IFN-γ和IL-2含量减少,瘤质量增加,胸腺和脾脏指数降低,差异有统计学意义(P<0.05);与模型组比较,灵芝多糖高、中剂量组小鼠血清IFN-γ和IL-2含量增加,瘤质量减少,胸腺和脾脏指数升高,差异有统计学意义(P<0.05)。结论:灵芝多糖对S180荷瘤小鼠具有一定的抗肿瘤及增强免疫的功能,其机制与调节血清细胞因子水平,降低脏器指数有关。     

黄芪多糖诱导的树突状细胞疫苗对S180荷瘤小鼠Th1/Th2类细胞因子的影响

目的探讨黄芪多糖诱导成熟的树突状细胞(DC)肿瘤疫苗对S180荷瘤小鼠的抗肿瘤作用及作用机制。方法体外培养小鼠骨髓来源的DC,加入黄芪多糖诱导成熟,以S180肿瘤抗原致敏获得DC肿瘤疫苗。建立S180荷瘤小鼠模型,分为模型组、环磷酰胺组、黄芪多糖组、细胞因子组,在荷瘤第5天和第10天分别给予相应治疗。荷瘤第12天摘取肿瘤组织、胸腺、脾脏称质量,计算抑瘤率、胸腺指数、脾脏指数;ELISA法检测小鼠血清白细胞介素(IL)-4、干扰素(IFN)-γ水平。结果黄芪多糖组、细胞因子组的抑瘤率高于环磷酰胺组(64.25%、64.10%vs35.11%),胸腺指数高于环磷酰胺组(1.69±0.26、1.74±0.38 vs 1.45±0.22),脾脏指数高于环磷酰胺组(5.44±0.76、5.31±0.81 vs 3.54±0.52),IL-4水平(ng/L)低于环磷酰胺组(15.66±2.57、14.72±4.84 vs 23.95±6.07),IFN-γ水平(ng/L)高于环磷酰胺组(16.54±3.71、17.20±2.03 vs 10.37±2.19),差异均有统计学意义。结论黄芪多糖诱导的DC疫苗可有效发挥抑瘤作用,其机制可能与提高荷瘤小鼠胸腺指数与脾脏指数,调节细胞因子表达,促进Th1/Th2失衡向Th1细胞占优势的细胞免疫偏移,增强机体的抗肿瘤免疫功能有关。     

抗毒补心胶囊对免疫功能低下小鼠免疫调节的影响

目的:观察抗毒补心胶囊对免疫功能低下小鼠免疫调节的影响。方法:昆明种小鼠60只,随机分成空白对照组,模型组,抗毒补心胶囊高、中、低剂量组,阳性对照组,除空白组外,环磷酰胺(50 mg.kg-1)腹腔注射,连续3 d,建立免疫抑制小鼠模型,分光光度法测定小鼠血清溶血素、溶血空斑形成,ELISA法检测小鼠血清白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的含量。结果:抗毒补心胶囊可提高免疫抑制小鼠溶血素水平升高、促进溶血空斑形成(P<0.05),提高小鼠血清IL-2、IFN-γ和TNF-α的含量(P<0.05)。结论:抗毒补心胶囊对免疫抑制小鼠的免疫功能有较好的调节作用。     

合成鱼腥草素对环磷酰胺模型小鼠免疫功能的影响

对于环磷酰胺所致免疫功能低下模型小鼠 ,灌胃给予合成鱼腥草素 6 0mg/kg、12 0mg/kg能明显增加环磷酰胺所致免疫功能低下模型小鼠的脾脏指数、外周血淋巴细胞ANAE阳性百分率 ;增强单核巨噬细胞吞噬功能、迟发型超敏反应强度及ConA诱导的脾脏T淋巴细胞增殖能力 ;对胸腺指数则无明显影响 ;合成鱼腥草素 12 0mg/kg还能明显增强环磷酰胺模型小鼠血清溶血素的生成及脾脏空斑形成细胞溶血能力 .     

鬼鲉肝脏提取物对小鼠免疫功能的影响△

目的 采用免疫低下小鼠模型研究鬼鲉肝脏提取物对免疫功能的影响。方法 采用环磷酰胺诱导建立免疫低下动物模型,免疫器官重量法测定胸腺指数和脾脏指数,碳粒廓清法测定小鼠单核巨噬细胞的功能,绵羊红细胞免疫法测定小鼠体液免疫功能,采用血细胞计数仪检测小鼠外周血常规,采用ELISA方法测定小鼠血清中TNF-a、IL-1b、IL-2、IL-6的水平,采用流式细胞仪测定脾细胞周期。结果 鬼鲉肝脏提取物可以减缓免疫低下小鼠体重的下降趋势,减少免疫低下小鼠脾脏和胸腺的损伤,促进免疫低下小鼠脾细胞的分裂和增殖,可以增加免疫低下小鼠单核巨噬细胞吞噬功能和血清溶血素含量,并且可以增加免疫低下小鼠白细胞数、中性粒细胞数、淋巴细胞数和单核细胞数和血清中TNF-a、IL-1b、IL-2、IL-6的含量。结论 鬼鲉肝脏提取物可以增强免疫低下小鼠的免疫功能,为综合利用鬼鲉这一生物资源提供了指引。     

短葶山麦冬多糖对免疫抑制小鼠的免疫功能的影响

目的研究短葶山麦冬多糖(LMP)对环磷酰胺致免疫低下小鼠的影响。方法应用环磷酰胺建立免疫低下小鼠模型,连续21天灌胃给予不同剂量(0.5、1.0、2.0g·kg-1)LMP后,测定小鼠胸腺指数、脾脏指数、腹腔巨噬细胞吞噬率、血清溶血素、细胞因子IL-2、TNF-α、IL-6含量、脾淋巴细胞增殖、NK细胞活性等免疫指标。结果 LMP能升高免疫低下小鼠胸脏指数,明显增加小鼠腹腔巨噬细胞吞噬率,增加血清溶血素和细胞因子(IL-2、TNF-α)含量,同时能明显提高脾淋巴细胞增殖能力和NK细胞活性。结论 LMP能够增强免疫抑制小鼠机体免疫功能。     

火棘果红色素提取物的体内免疫活性研究

目的研究火棘果红色素提取物对环磷酰胺所致免疫低下模型小鼠免疫功能的调节作用,为其在畜牧养殖中的应用提供理论依据。方法采用腹腔注射环磷酰胺(cyclophosphamide,CTX)复制免疫功能低下小鼠模型,并考察不同剂量火棘果红色素提取物对免疫抑制小鼠胸腺指数、脾脏指数、腹腔吞噬细胞吞噬功能、血清溶血素生成及溶血空斑形成的影响。结果火棘果红色素提取物中、高剂量组能显著提高免疫功能低下小鼠的脏器指数,增强腹腔巨噬细胞吞噬功能,促进溶血素水平及溶血空斑的形成。结论火棘果红色素提取物具有良好的免疫活性。     

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.

---

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.     

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.     

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.