海洋真菌多糖YCP对小鼠扶正减毒作用的研究

从海洋真菌YC中提取的真菌多糖YCP,选择9,3,1 mg/kg的不同剂量,分别联合60Co放疗和Cy化疗正常小鼠和Heps荷瘤鼠,观察药物对放、化疗的减毒作用。以荷瘤小鼠观察药物对小鼠的扶正作用。结果:YCP(9,3,1 mg/kg)剂量组可显著地对抗由大剂量Cy造成的正常小鼠外周血白细胞,骨髓有核细胞数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)剂量组可显著地抑制由大剂量Cy和60Co照射造成的Heps荷瘤小鼠外周血白细胞,骨髓有核细胞数和脾脏指数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)可显著提高S180荷瘤小鼠的吞噬指数k和血清半数溶血值(P<0.01,P<0.05)。结论YCP可明显对抗由60Co照射,大剂量化疗药Cy引起的正常和荷瘤小鼠的血液和骨髓抑制毒性。YCP可显著提高S180荷瘤小鼠免疫功能。     

银耳孢糖对荷瘤小鼠环磷酰胺化疗的增效作用

目的:研究银耳孢糖(Tremella fuciformis spores polysaccharide,TSP)对环磷酰胺(CTX)化疗H22及S180荷瘤小鼠的增效作用.方法:建立小鼠肝癌H22及小鼠肉瘤S180的体内移植性肿瘤模型,随机分为对照组,TSP小、中、大剂量组,CTX小、大剂量组,TSP(小、中、大剂量) CTX小剂量组,TSP(小、中、大剂量) CTX大剂量组等12组,接种肿瘤次日开始每天分别腹腔给予0.9%氯化钠注射液、TSP(25,50及100 mg·kg-1)、CTX(10,20 mg·kg-1)、TSP(25,50,100 mg·kg-1) CTX 10 mg·kg-1及TSP(25,50及100 mg·kg-1) CTX 20 mg·kg-1,连续12～14 d,称小鼠的瘤重,测定TSP对CTX的增效作用,每批实验重复3次.结果:TSP 25,50,100 mg·kg-1可明显增加CTX(10,20 mg·kg-1)对H22及S180荷瘤小鼠的抑制作用,抑瘤率分别提高6.82～92.01%,3.90～24.27%(P<0.05,0.01);9.50～87.04%,2.41～21.51%(P<0.05,0.01).结论:TSP与CTX合用对抑制荷瘤小鼠H22及S180有明显的增效作用.     

牛磺酸对化疗后S_(180)荷瘤小鼠增效减毒作用的研究

目的研究牛磺酸对环磷酰胺化疗后S180荷瘤小鼠的增效减毒作用。方法取健康昆明小鼠50只,将S180肿瘤细胞种植于小鼠右腋窝皮下,建立移植性肿瘤模型。实验分为五组。腹腔注射给药,每日1次,连续8 d。观察不同剂量牛磺酸(Tau)与环磷酰胺(CTX)联合用药的抑瘤率;脾指数和胸腺指数;检测骨髓有核细胞数和外周血白细胞数;MTT法检测NK细胞杀伤活性和脾淋巴细胞增殖活性。结果与模型组比较,CTX组抑瘤率为56.65%,CTX+Tau低、中、高剂量组小鼠的抑瘤率分别为60.10%,72.41%,86.70%,有统计学意义(P<0.01);与CTX组比较,CTX+Tau各剂量组外周血白细胞数,骨髓有核细胞数,脾指数,胸腺指数,NK细胞活性,淋巴细胞增殖活性增高。尤其是CTX+Tau中、高剂量组作用显著(P<0.05)。结论牛磺酸与环磷酰胺联合用药具有增效减毒作用。     

红芪总多糖对荷S180瘤小鼠的抑瘤作用及其机制的研究

目的研究红芪总多糖(THPS)单用及与环磷酰胺(CTX)合用对荷瘤小鼠的抑瘤作用,并探讨其机制。方法昆明种小鼠90只,随机分10只为正常对照组,其余80只小鼠接种S180瘤株后随机分为荷瘤对照组、CTX组、THPS高、中、低剂量[400、200、100mg/(kg.d)]组及各与CTX合用组共8组。正常对照组和荷瘤对照组给予生理盐水,其余各组给予相应剂量THPS及CTX治疗,观察肿瘤的体积变化。14d后处死小鼠,观察瘤质量、抑瘤率;血球计数仪检测外周血白细胞、血小板、红细胞及血红蛋白;流式细胞仪检测CD3+T细胞和NK细胞。结果与荷瘤对照组相比,中剂量THPS明显抑制小鼠S180瘤质量增长(P<0.01)及体积增加(P<0.05),提高NK细胞水平(P<0.05)。与CTX组相比,THPS与CTX合用后,各剂量组均能明显抑制CTX所致的白细胞数量下降(P<0.01);而只有中剂量的THPS与CTX合用能够降低肿瘤的质量(P<0.05),并能明显抑制CTX所致的CD3+T细胞(P<0.01)和NK细胞(P<0.05)数量下降。结论中剂量的THPS能抑制S180瘤生长,具有降低CTX免疫抑制和骨髓抑制的作用,其机制与提高T细胞和NK细胞介导的免疫应答有关。     

扶正清络胶囊联合环磷酰胺抗S_(180)肿瘤作用研究

目的:观察扶正清络胶囊(FZQL)联合环磷酰胺(CTX)抗S180肿瘤作用及其对CTX的减毒作用。方法:建立S180荷瘤小鼠模型,分为单用CTX组、CTX+FZQL组、单用FZQL组和生理盐水对照组,比较各组间的差别。结果:FZQL治疗组S180肿瘤重明显小于对照组,联合用药组各项实验指标均好于CTX组。结论:FZQL对S180肿瘤有抑制作用,并对CTX有增效、减毒以及提高机体免疫作用。     

复方甘草酸苷注射液对小鼠放、化疗模型减毒作用实验研究

目的 考察复方甘草酸苷注射液(美能注射液)对于放、化疗动物模型骨髓抑制和免疫损伤的减毒作用,探寻本品临床应用的新价值。方法 选择正常及S180荷瘤小鼠,采用放疗(⁶⁰Co照射,5.0 Gy)和化疗(环磷酰胺,100 mg·kg^-1,腹腔注射)方法建立模型,通过体质量、胸腺指数、脾脏指数、白细胞数和骨髓有核细胞数等指标,评价复方甘草酸苷注射液对放、化疗模型减毒作用。复方甘草酸苷注射液设高、中、低剂量组(以甘草酸苷计分别为40,20,10 mg·kg^-1),1次·d^-1,连续静脉注射给药7 d。第8天处死动物,测定体质量、外周血白细胞数、骨髓有核细胞数、胸腺系数、脾脏系数。结果 ①化疗模型中,环磷酰胺可使得正常小鼠和S180荷瘤小鼠胸腺和脾脏的脏器指数显著下降(P<0.01),白细胞数和骨髓有核细胞数显著减少(P<0.05)。复方甘草酸苷注射液高剂量可明显升高2种化疗动物模型白细胞数和骨髓有核细胞数(P<0.05),中低剂量组也有部分改善作用。复方甘草酸苷注射液对胸腺和脾脏的脏器指数改善作用不明显。②放疗模型中,⁶⁰Co照射可使得正常小鼠和S180荷瘤小鼠胸腺和脾脏的脏器指数显著降低(P<0.01),白细胞和骨髓有核细胞数显著减少(P<0.01)。复方甘草酸苷注射液各剂量组对60Co照射引起的正常小鼠和S180荷瘤小鼠各项指标变化均未见明显改善作用。结论 对于环磷酰胺化疗引起的正常小鼠和S180荷瘤小鼠的骨髓抑制,复方甘草酸苷注射液具有明显的改善作用;对于60Co放疗引起的正常小鼠和S180荷瘤小鼠的骨髓抑制,复方甘草酸苷注射液改善作用不明显,提示本品在化疗骨髓抑制防护方面具有一定的应用价值。     

砂生槐种子水提物的S180小鼠体内抗肿瘤及免疫调节作用

目的研究砂生槐种子水提取物(SMSWE)的小鼠体内抗瘤作用,探讨其抗癌及免疫调节的意义。方法以S180荷瘤小鼠为研究对象,分别观察SMSWE各剂量组对S180荷瘤小鼠的抑瘤率、生存期、胸脾指数、T淋巴细胞增殖活性以及白细胞介素-2(IL-2)和肿瘤坏死因子-α(TNF-α)等血清细胞因子的影响和变化。结果SMSWE 1.2~2.4 g.kg-1均可抑制肿瘤的生长和延长小鼠带瘤生存时间(P<0.05),高剂量组的抑瘤率高达41.4%。SMSWE 0.6~2.4 g.kg-1可促进Con A诱导的T淋巴细胞增殖反应,中、高剂量药物组与荷瘤对照组比较具有统计学意义(P<0.05),其血清中IL-2、TNF-α的含量明显高于荷瘤对照组(P<0.05)。结论SMSWE能明显抑制S180小鼠体内肿瘤生长,具有提高荷瘤小鼠细胞免疫功能的作用。     

银耳孢糖对小鼠体内移植性肿瘤及免疫功能的影响

目的 研究银耳孢糖(Tremella fuciformis spores polysaccharide,TSP)对小鼠移植性肿瘤及免疫功能的影响.方法利用小鼠肝癌H22及小鼠肉瘤S180的体内移植性肿瘤模型,腹腔连续给予TSP 12 d,称小鼠体重及肿瘤、脾脏和胸腺重量,测定脾淋巴细胞转化率及NK细胞杀伤活性.同时观察TSP对正常小鼠免疫器官重量和碳粒廓清的影响.结果TSP 25,50,100mg·kg-1对小鼠肝癌H22及小鼠肉瘤S180有一定的抑制作用,抑瘤率分别为17.8%,27.6%,34.9%;32.8%,36.1%,44.0%;TSP 50,100 mg·kg-1能提高荷瘤小鼠脾NK细胞杀伤活性及淋巴细胞转化率(P<0.05).此外,TSP 50,100mg·kg-1亦能明显提高正常小鼠脾脏和胸腺的重量及网状内皮系统吞噬功能(P<0.05).结论 TSP对小鼠移植性肿瘤有一定的对抗作用,其抗肿瘤作用可能与增强机体免疫能力有关.     

扶正消症胶囊对化疗小鼠免疫功能及心脏毒性的影响

目的观察扶正消症胶囊对环磷酰胺(CTX)治疗S180荷瘤小鼠免疫力及心脏毒性的影响。方法将腋下接种S180的小鼠随机分为肿瘤组、CTX组(15 mg·kg~(-1))、CTX[15 mg/(kg·d)]+扶正消症胶囊[大剂量2.04 g/(kg·d)、中剂量1.02 g/(kg·d)和小剂量0.51 g/(kg·d)]组,另设CTX+贞芪扶正胶囊组[15 mg/(kg·d)+4.2 g·kg~(-1)]。除肿瘤组外,其他各组于接种肿瘤细胞24 h后腹腔注射CTX并灌胃给予相应药物,肿瘤组在同样条件下注射等量生理盐水,灌胃等量纯净水,每日1次,连续10 d。末次给药后2 h,摘眼球釆血,离心取血清,酶联免疫法检测血清中IL-2和INF-γ的含量;称取脾脏、胸腺、心脏及肝脏重量并计算脏器指数;称取心脏重量后,进行心脏组织匀浆,离心取上清,酶联免疫法检测心肌酶的含量;无菌制作脾细胞悬液,MTT法检测脾脏中T细胞、B细胞产生抗体的能力,NK细胞杀伤力和腹腔巨噬细胞吞噬力。结果与CTX组比较,CTX+扶正消症胶囊大、中剂量组可明显增加S180荷瘤小鼠化疗后胸腺、脾脏和心脏的脏器指数(P<0.05),CTX+扶正消症胶囊大剂量组能显著提高T免疫细胞活力(P<0.05),CTX+扶正消症胶囊大、中剂量组可显著升高腹腔巨噬细胞吞噬力和NK细胞杀伤力(P<0.05),CTX+扶正消症胶囊各剂量组均可显著提高B细胞产生抗体的能力(P<0.01);CTX+扶正消症胶囊中、大剂量组可增加血清中IL-2、INF-γ、AKP和CPK的含量(P<0.05)。结论扶正消症胶囊能改善化疗小鼠免疫力低下和心脏毒性,提高免疫力。     

安多霖对免疫功能影响的保护作用

目的观察安多霖胶囊（ADL）对受环磷酰胺（CTX）抑制的S180荷瘤小鼠免疫功能的影响。方法采用灌胃给药,观察ADL对S180o荷瘤小鼠注射CTX后引起的碳廓清率、脾淋巴细胞增殖速度减慢;迟发超敏反应和血清溶血素生成受抑制的影响。结果ADL可使S180荷瘤小鼠受CTX抑制的碳廓清率显著改善,受抑制的脾淋巴细胞增殖速度明显加快;受抑制的迟发超敏反应水平明显提高;受抑制的血清溶血素生成明显改善。结论ADL对受CTX抑制的非特异性免疫、细胞免疫和体液免疫均有明显改善作用。     

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.     

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.     

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.     

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.