广谱抗病毒抗生素17997对HSV—1形态学的影响

目的 探讨新一类抗病毒抗生素17997的抗病毒的作用机制。方法 比较不同浓度的17997和ACV对HSV－Ⅰ形态学的影响。结果 在Vero细胞核内和胞浆中发现许多HSV－Ⅰ空心衣壳，当17997的浓度达到几科完全抑制HSV－Ⅰ复制时，仍没有看到明显的细胞损害。结论 17997主要抑制病毒DNA合成，而且没有明显的细胞毒性。     

单纯疱疹病毒1型对抗生素17997的耐药及交叉耐药研究

目的 体外训练单纯疱疹病毒1型（HSV－1）对抗生素17997的耐药突变及体内、外研究抗生素17997与阿昔洛韦（ACV）的交叉耐药。方法 HSV－1在抗生素17997或ACV的存在下连续传代，选择一定代数测定HSV－1野株及训练株的IC50。用HSV－1的ACV耐药株感染兔用膜造模，分别用抗生素17997或ACV局部给药治疗，以局部病损及病毒分离判断疗效。结果 HSV－1在抗生素17997存在下连传41代仍保持对抗生素17997的敏感性，未产生耐药变株；但HSV－1在ACV存在下，仅传一代，就发生耐药变株。抗生素17997与ACV无交叉耐药。抗生素17997对HSV－1 ACV耐药株实验感染角膜炎有明显治疗效果，可减轻病损，降低病毒排出量；阳性对照药ACV无任何疗效。结论 体外HSV－1对抗生素17997不易产生耐药。抗生素17997与ACV体内、外均无交叉耐药。     

广谱抗病毒抗生素17997对HSV-1形态学的影响

目的探讨新一类抗病毒抗生素17997的抗病毒的作用机制。方法比较不同浓度的17997和ACV对HSV_Ⅰ形态学的影响。结果在Vero细胞核内和胞浆中发现许多HSV_Ⅰ空心衣壳。当17997的浓度达到几乎完全抑制HSV_Ⅰ复制时 ,仍没有看到明显的细胞损害。结论17997主要抑制病毒DNA合成 ,而且没有明显的细胞毒性。     

抗病毒抗生素17997体外联合用药研究

目的：研究抗病毒抗生素17997与临床应用的抗病毒药物－阿昔洛韦、病毒唑及入干扰素α的联合用药抗单纯疱疹病毒I型的作用。方法：应用VERO细胞培养法及MTT染色法进行实验及观察结果,以Calcusyn软件计算,分析结果。结果：实验结果显示抗生素17997与阿昔洛韦、病毒唑及人干扰素α在ED50、ED70（或ED75）、ED90条件下均有协同抗单纯疱疹病毒I型的作用,表现在降低ED50值及联合指数＜1。仅抗生素17997与人干扰素α联合组,在ED90条件下,表现为相加或拮抗作用。结论：抗生素17997抗疱疹病毒活性强,在多次单纯疱疹病毒I型实验感染的兔多膜炎模型上显示抗病毒疗效。本研究结果为抗生素17997临床联合用药提供实验依据。     

喷昔洛韦栓的制备及质量控制

喷昔洛韦（penciclovir，PCV）是英国SKB公司开发的开环核苷类抗病毒药物，是前体药物泛昔洛韦（famciclovir，FCV）的代谢产物，有抗单纯疱疹病毒HSV—Ⅰ，HSV—Ⅱ，VZV（带状疱疹）和EB病毒的作用，它的作用机制与阿昔洛韦相似，与阿昔洛韦相比，其抗病毒效果显著，是一种抗病毒谱较广的药物。主要用于治疗单纯疱疹病毒引起的感染，也可用于治疗带状疱疹病毒感染。     

金银花提取物对单纯疱疹病毒性角膜炎的作用

目的考察金银花提取物对单纯性疱疹病毒性角膜炎的疗效。方法建立单纯性疱疹病毒Ⅰ型（herpes simplex virus Ⅰ,HSV Ⅰ）感染Vero细胞的体外模型,以细胞病变效应、治疗指数为观察指标,了解不同浓度金银花提取物体外抗病毒效果;采用HSV Ⅰ感染家兔角膜建立体内病毒感染模型,分别用金银花提取物、阿昔洛韦、0.9%氯化钠溶液治疗15 d,每天经荧光素钠染色角膜后在裂隙灯下观察药物对病毒性角膜炎模型的治疗作用。结果体外实验表明,金银花提取物对感染HSV Ⅰ病毒的Vero细胞具有明显的抗病毒作用,最大无毒浓度为384 mg•L 1,治疗指数为26.56;体内实验结果显示,与模型组相比,金银花提取物和阿昔洛韦均能有效治疗单纯疱疹病毒性角膜炎,减轻角膜病变程度,缩短平均治愈时间,金银花提取物疗效与阿昔洛韦相似。结论金银花提取物对单纯疱疹病毒性角膜炎有显著的疗效。     

卷柏属药用植物提取物体外抗疱疹病毒Ⅰ型的研究

目的 对卷柏属7种药用植物的13种提取物在体外抗疱疹病毒Ⅰ型（HSV—Ⅰ）的作用进行比较研究,并对其抗病毒作用机制进行初步探讨。方法采用13种提取物一定浓度的溶液作用于HSV-Ⅰ感染的Vero细胞,观察比较细胞病变效应（CPE）,72h后MTT法测定细胞存活率。结果在Vero细胞体系中,卷柏属7种药用植物的乙酸乙酯和95％乙醇提取物部位具有一定的抑制HSV-Ⅰ对细胞的致病变作用,使细胞存活率提高。结论多种卷柏属药用植物可作为新的抗HSV—Ⅰ的资源植物。     

格尔德霉素体内外抑制单纯疱疹病毒l型的复制

格尔德霉素(GA)是一种抗生素,它的作用靶点是热休克蛋白Hsp90 N末端的ATP/ADP结合位点.在我们对抗病毒的抗生素筛选中,发现格尔德霉素显著抗单纯疱疹病毒1型(HSV一1).体外在Vero细胞内GA显著抑制HSv-1的复制,IC50为0,093μmol/L,GA对Vero细胞的毒性CC50为350μmol/L,治疗指数可达3763.HSV-1腹腔(ip)感染1h后腹腔(ip)注射GA(0.093～0.37mg/kg)可以将存活率增加到67%～100%,皮下(sc)给药(0.37mg/kg)的存活率为43.8%,都明显高于生理盐水对照组(ipP＜0.001.scP＜0.05).GA对小白鼠的急性LD50为15.5mg/kg(ip).格尔德霉素不影响病毒的吸附、穿人.由于GA在体内外都能抑制单纯疱疹病毒1型,GA可以成为新的抗单纯疱疹病毒感染的药物.     

朱砂七总蒽醌体外抗单纯疱疹病毒的研究

目的研究朱砂七总蒽醌(ZSQ)体外对单纯疱疹病毒的抑制作用。方法运用单纯疱疹病毒I型(HSV-Ⅰ)和Ⅱ型(HSV-Ⅱ),以非洲绿猴肾细胞(Vero细胞)为宿主细胞,通过观察感染病毒后的细胞变性反应(CPE)和MTI比色法,检测ZSQ对单纯疱疹病毒的抑制作用。结果与病毒对照组相比,朱砂七总蒽醌各质量浓度组均能有效地保护感染HSV-I和HSV-Ⅱ病毒的Vero细胞,抑制单纯疱疹病毒的复制,使病毒导致的细胞病变减弱。ZSQ抗HSV-I病毒作用IC50为0.004 7g.L-1,抗病毒有效率达90.83%,治疗指数(TI)为16.62;总蒽醌抗HSV-Ⅱ病毒作用IC50为0.006 7g.L-1,抗病毒有效率达90.06%,治疗指数(TI)为11.66。结论 ZSQ在体外显示出明显的保护宿主细胞、抵抗单纯疱疹病毒感染的活性。     

抗病毒新药法昔洛韦

法昔洛韦（famciclovir，FCV），即6－脱氧喷昔洛韦双乙酸酯，是一种前体药，口服后迅速代谢为具抗病毒活性的代谢物质昔治韦（penciclovir，PCV）。本文着重评述喷昔洛韦对单纯疟疾病毒（HSV）-1、HSV－2和水痘带状浪疹病毒（VZV）的抗病毒活性及法昔洛韦对免疫功能正常患者感染带状疮疹和单疱病毒生殖器疱疹的治疗作用。1抗病毒活性体外试验，PCV对HSV－1、HSV－2和E－B病毒有抑制活性，而对巨细胞病毒（CAIV）的活性很弱。在HSV－1、HSV司和VZV感染的细胞中，PCV在病毒胸音激酶的作用下，生成单磷酸酯，经细胞酶进一步…     

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.