海洋硫酸多糖911抗艾滋病毒作用及其机理研究——体内对猴免疫缺陷病毒（SIV）

采用体外细胞培养技术和病毒体内感染模型,通过Ｅｌｉｓａ、定量ＰＣＲ、流式细胞术等方法,研究了海洋硫酸多糖９１１体外对ＨＩＶ－１复制及体内对ＳＩＶ增殖的影响,并初步探讨其作用机制。结果发现９１１可明显抑制ＨＩＶ－１对ＭＴ４细胞的急性感染和Ｈ９细胞的慢性感染,其半数有效浓度（ＥＣ５０）分别为４．４４ｍｇ．Ｌ＾－１和０．３２ｍｇ．Ｌ＾－１;并可明显降低猴血浆中病毒滴度及ＲＮＡ拷贝数,对血液中ＣＤ４＾＋,细胞具有一定的保护作用,同时可升高血液中病毒抗体的含量;并可明显抑制病毒逆转录酶活性,对ＨＩＶ－１无明显直接灭活作用,但可明显干扰ＨＩＶ－１与细胞的吸附,半数有效浓度（ＩＣ５０）为３６．５１μｇ．Ｌ＾－１。提示９１１体内外均可抑制艾滋病毒的增殖,为高效的艾滋病毒增殖抑制剂,其作用机制与干扰病毒与细胞吸附、抑制病毒逆转录     

Alpha momorcharin inhibits HIV 1 replication in acutely but not chronically infected T lymphocytes 1

目的：研究α苦瓜子蛋白（αＭＭＣ）在ＨＩＶ１急性和慢性感染Ｔ淋巴细胞中的抗ＨＩＶ１活性．方法：以合胞体抑制实验,ＨＩＶ１ｐ２４核心抗原表达水平和ＨＩＶ抗原阳性细胞的百分率检测了αＭＭＣ的抗ＨＩＶ活性．结果：αＭＭＣ对ＨＩＶ１ⅢＢ诱导Ｃ８１６６细胞形成合胞体有显著的抑制作用．αＭＭＣ显著地抑制了ＨＩＶ１急性感染Ｔ细胞中ｐ２４抗原的表达水平和减少了ＨＩＶ抗原阳性细胞的百分率．在上述三种测定中,αＭＭＣ的ＥＣ５０分别是００１６,００７和０３２ｍｇ·Ｌ－１．但是,αＭＭＣ不影响慢性感染ＨＩＶ１ⅢＢ／Ｈ９中ｐ２４抗原表达水平．结论：αＭＭＣ是苦瓜子蛋白中唯一的具有抗ＨＩＶ１活性的成份．αＭＭＣ抑制急性感染中ＨＩＶ１的复制而对慢性感染Ｔ细胞中的ＨＩＶ１复制无影响．     

Fas与HIV感染

Ｆａｓ抗原（Ｆａｓ Ａｇ）表达与人类免疫缺陷症病毒（ＨＩＶ）感染引起的艾滋病（ＡＩＤＳ）进程有密切关系。随着ＨＩＶ感染的加重，细胞表面Ｆａｓ Ａｇ表达增加，主要表现在ＣＤ４＾＋和ＣＤ８＾＋细胞。通过Ｆａｓ Ａｇ介导的细胞程序死亡（ＰＣＤ）途径是ＨＩＶ感染引起的Ｔ淋巴细胞免疫缺陷的重要原因，白细胞介素２（ＩＬ－２），ＩＬ－１２等细胞因子以及ＩＬ－１β转化酶（ＩＣＥ）样蛋白酶抑制剂在体外能抑制由Ｆａｓ     

海洋硫酸多糖911抗AIDs作用机制的初步探讨

研究了抗ＡＩＤｓ药物海洋硫酸多糖“９１１”对病毒逆转汞酶及ＨＩＶ－１与细胞吸附的影响,结果表明“９１１”可明显掏病毒逆转录酶活性,对ＨＩＶ－１无明显直接灭活作用,但可明显干扰ＨＩＶ－１与细胞的吸附,半数有效浓度（ＩＣ５０）为３６．５１ｍｇ．Ｌ＾－１。提示９１１的抗ＡＩＤｓ作用与抑制逆转录酶活性和干扰病毒与细胞的吸附有关。     

α—苦瓜子蛋白抑制急性感染而不抑制慢性感染T淋巴细胞中HIV—1？…

目的 研究α－苦瓜子蛋白（α－ＭＭＣ）在ＨＩＶ－１急性和慢性感染Ｔ淋巴细胞中的抗ＨＩＶ－１活性,方法：以合胞体抑制实验,ＨＩＶ－１ｐ２４核心抗原表达水平和ＨＩＶ抗原阳性细胞的百分率检测了α－ＭＭＣ的抗ＨＩＶ活性。结果 α－ＭＭＣＣ地ＨＩＶ－１ⅢＢ诱导Ｃ８１６６细胞形成合胞体有显著的抑制作用,α－ＭＭＣ显著地抑制了ＨＩＶ－１急性感染Ｔ细胞中ｐ２４抗原的表达水平和减少了ＨＩＶ抗原阳性细胞的百分率,在上     

固相萃取高效液相色谱法检测生物样本中甲氨喋呤

目的：建立生物样品中甲氨喋呤（ＭＴＸ）浓度测定方法。方法：固相萃取净化和富集样品,高效液相色谱法测定血清和脑脊液中ＭＴＸ含量。色谱条件：以Ｃ１８柱为分析柱,流动相为甲醇－乙腈－磷酸盐缓冲液（２：７：９１）,流带０．８ｍＬ．ｍｉｎ＾－１,柱温２５℃,检测波长３１３ｎｍ。结果：在０．０５￣８０μｇ．ｍＬ＾－１范围内呈线性,回收率为９０％以上,血清中ＭＴＸ最低检测限为１０ｎｇ．ｍＬ＾－１,脑脊液中最低检     

芒果甙对Ⅱ型单纯疱疹病毒体外复制的抑制作用

采用空斑减数试验与产量减数试验对芒果甙体外抗ＨＳＶ－２作用的研究表明，Ｍａｎ抑制５０％空斑形成的有效浓度（ＥＣ５０）为１１１．７μｇ·ｍｌ＾－１，使病毒产量减少９０％和９９％的有效浓度（ＥＣ９０和ＥＣ９９）分别为３３和８０μｇ·ｍｌ＾－１，治疗指数（ＩＣ５０／ＥＣ５０）为８．１。药物加入和去除试验结果提示Ｍａｎ抗ＨＳＶ－２作用的机制可能是抑制病毒在细胞内复制的晚期。     

HIV-1感染早期重复免疫gp160:对T细胞增殖应答的评价

细胞免疫功能在控制１型人类免疫缺陷症病毒（ＨＩＶ－１）感染中可能起重要作用。作者在长达５年的现场试验中比较了重组ｇｐ１６０疫苗与安慰剂组对ＨＩＶ－１抗原、记忆抗原及有丝分裂原的Ｔ细胞增殖应答。 将受试者随机分为４组,进行疫苗和安慰剂接种,在０、７、３０天分别用ＶａｘＳｙｎ１６０μｇ或磷酸铝安慰剂肌肉注射,之后每２个月注射一次直至６２个月。于接种前及接种后间隔一定时间收集血样、分离外周血单个核细胞（ＰＢＭＣ）用于淋巴细胞增殖试验。部分样品冷藏备用。以［３Ｈ］胸苷掺入法测定对重组ｇｐ１６０及ｐ２４、…     

HIV-1蛋白酶抑制剂ritonavi

抑制艾滋病毒逆转录酶的药物已产生耐药性，其研制停滞不前，抗ＨＩＶ蛋白酶成为治疗艾滋病药物的新的靶点。Ａｂｂｏｔｔ公司于１９９４年报道了以噻唑环取代Ａ－８０９８７吡啶环的新一代药物ｒｉｔｏｎａｖｉｒ（ＡＢＴ－５３８），它具有口服生物利用度高、体外氧化代谢缓慢、抗病毒活性强等特点。ｒｉｔｏｎａｖｉｒ抗ＨＩＶ蛋白酶作用比其母体化合物Ａ－８０９８７强１０倍，抗纯化的重组ＨＩＶ蛋白酶的Ｋｉ值为１５ｐｍｏｌ·Ｌ－１。在ＭＴ４细胞上，它抑制ＨＩＶ的ＥＣ５０为０．０３μｍｏｌ·Ｌ－１，而其产生细胞毒作用浓度高于…     

静脉药瘾者HCV和HIV混合感梁的报千——附37例分析

目的：了解静脉药瘾者中ＨＣＶ和ＨＩＶ混合感染的情况及其相关性。方法：对３７例静脉药瘾者采用ＥＬＩＳＡ法检测抗－ＨＣＶ和抗－ＨＩＶ,统计分析方法为四格表确切概率法。结果：抗－ＨＣＶ阳性率７３．０％,抗－ＨＩＶ阳性率４８．６％,相关性显著,Ｐ＝０．００７９。ＨＣＶ和ＨＩＶ混合感染率４５．９％,其中８２．４％有过共用注射器,７０．６％有性乱行为。结论：静脉药瘾者是ＣＨＶ和ＨＩＶ感染的高危人群,ＨＣＶ和Ｈ     

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.     

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.