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。     

膦甲酸钠对HepG 2.2.15细胞分泌HBsAg、HBeAg和HBV DNA的抑制作用

膦甲酸钠为广谱抗病毒药物，能直接抑制病毒特异的DNA多聚酶和逆转录酶，对Ⅰ、Ⅱ型单纯疱疹病毒、巨细胞病毒等有抑制作用。临床用于抗乙肝病毒，尤其是用于治疗重型肝炎。本文采用HepG2．2．15细胞模型进行了膦甲酸钠的体外抗乙型肝炎病毒作用的研究。     

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。     

疱疹病毒疫苗

疱疹病毒感染是一种常见病、多发病,估计美国每年发生口唇疱疹者至少9500万,生殖器疱疹者至少200万,因单纯疱疹就医者约160万。疱疹病毒科的主要成员是Ⅰ型和Ⅱ型疱疹病毒(HSV-1、HSV-2)、巨细胞病毒(CMV)、水痘-带状疱疹病毒(VZV)和 EB     

抗病毒药-盐酸万乃洛韦

盐酸万乃洛韦是L-缬氨酸阿昔洛韦酯,本品是阿昔洛韦的前体,水溶性好,进入体内迅速吸收,并水解出母体阿昔洛韦而抑制病毒DNA的合成从而抑制其复制.对单纯疱疹病毒和带状疱疹病毒的抑制作用强,对水痘疱疹病毒、EB病毒以及巨细胞病毒的抑制作用弱.用于治疗水痘带状疱疹及Ⅰ型、Ⅱ型单纯疱疹,包括初发和复发的生殖器疱疹,对于阿昔洛韦治疗无效或不敏感的严重疱疹病毒感染和乙型肝炎也仍然有效.     

无环鸟苷

【化学名】9-(2-羟乙氧甲基)鸟嘌呤【结构式】【作用特点】系高效抗病毒药物,并具有广谱及起效快的特点,本品经体外试验对疱疹病毒Ⅰ、Ⅱ型水痘带状疱疹,巨细胞病毒和E-B病毒有抑制作用,体内试验对家兔单纯疱疹角膜炎、豚鼠皮肤和生殖器疱疹病毒感染以及小鼠疱疹病毒脑炎均有效。【适应症】3％霜剂,适用于皮肤单纯疱疹和带状疱疹,0.1％眼药水,3％眼膏适用于单纯疱疹角膜炎。【不良反应及注意点】本品在用药期间一般未见明显的不良反应,眼局部用药偶见轻微刺激,停药后即可消失,皮肤外用偶有轻度发红、痒感,脱皮等均能很快消失,不影响治疗。     

重组人干扰素α2b阴道片药效学研究

目的：验证重组人干扰素α2b阴道片的抗病毒作用。方法：采用组织细胞培养法和建立小鼠阴道炎动物模型，对不同活性的重组人干扰素α2b及重组人干扰素α2b阴道片进行体内外抗病毒药效学研究。结果：重组人干扰素α2b在体外有抑制单纯疱疹病毒2型的致细胞病变作用；体内抗病毒试验显示重组人干扰素α2b阴道片可明显减轻单纯疱疹病毒2型所致小鼠阴道炎。结论：重组人干扰素α2b及其阴道片在体内外均具有明显抗单纯疱疹病毒2型的作用。     

板蓝根抗病毒有效部位筛选

目的:对板蓝根药材中提取的10个化学部位进行体外抗单纯疱疹病毒(HSV)活性研究,确定板蓝根抗病毒的有效部位。方法:利用溶剂法和色谱法从板蓝根中提取分离出10个粗提和精制部位,用MTT法检测这10个部位体外对HSV-Ⅰ及HSV-Ⅱ型病毒的抑制作用,以病毒抑制率和治疗指数(TI)为评价指标,比较各化学部位体外抗病毒的效果。结果:水提大孔树脂吸附的10%、50%醇洗部位(Ⅷ、Ⅹ)作用最强,对HSV-Ⅰ型病毒的抑制率为分别为53.21%、56.28%,接近阳性对照药阿昔洛韦(62.55%),其TI分别为4.61、18.62。结论:板蓝根不同化学部位的抗病毒作用强度有较大差异。     

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…     

化学抗病毒治疗带状疱疹及有关问题

化学抗病毒治疗带状疱疹及有关问题虞瑞尧（解放军总医院皮肤科北京１００８５３）一、带状疱疹概述１．带状疱疹的流行病学侵犯人类的疱疹病毒现在已知的有５类：单纯疱疹病毒Ⅰ、Ⅱ（ＨＳＶⅠ，ＨＳＶⅡ）；水痘－带状疱疹病毒（Ｖａｒｉｃｅｌｌａ－Ｚｏｓｔｅｒｖｉｒ...     

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.     

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.