知母宁体外抗单纯疱疹病毒Ⅰ型体外活性研究

目的:对知母宁体外抗单纯疱疹病毒Ⅰ型的活性进行研究.方法:采用MTT比色法测定知母宁对Vero细胞的毒性作用.采用中性红染色法,以阿昔洛韦为阳性对照药物,考察不同给药方式与不同药物处理时间下知母宁体外抗单纯疱疹病毒Ⅰ型(HSV-ⅠSm44)的活性.结果:MTT法测得Vero细胞对知母宁的最大耐受浓度与半数中毒浓度(TC50)分别为0.29与3.66mg*ml-1.不同加药方式下,知母宁与阿昔洛韦均对HSV-ⅠSm44表现出综合抑制作用并能抑制病毒吸附后的复制增殖过程,这些作用总体上随药物浓度升高而增强,其中知母宁抗病毒有效率(ER%)最高达76.42%.知母宁预防HSV-Ⅰ病毒吸附的作用较弱,但其在高浓度(2.08mg*ml-1以上)对HSV-Ⅰ具强的直接杀伤作用,最高ER%值为98.86%.随药物处理时间延长,低浓度知母宁抗HSV-Ⅰ的ER%值递减,2.08mg*ml-1以上知母宁的ER%值变化小.在不同药物处理时间下,知母宁及阿昔洛韦组病毒的感染性均较平行设置的病毒对照组减弱,且知母宁组的感染力较阳性药物组更弱.知母宁组病毒感染力下降值△lgTCID50随处理时间增加而增加.结论:知母宁在体外从多个作用点较强地抑制单纯疱疹病毒Ⅰ型活性.     

通窍止咳液体外抗甲型人流感病毒作用研究

目的:研究通窍止咳液体外抗甲型人流感病毒的作用。方法:以利巴韦林作阳性对照药物,采用存留细胞结晶紫染色法测定通窍止咳液不同加药方式对甲型人流感病毒H3N2的体外抑制作用及其时效关系。结果:通窍止咳液对甲型人流感病毒具有良好的综合抑制作用及抑制病毒吸附后的复制增殖作用;通窍止咳液对病毒吸附的预防作用弱,无直接杀伤病毒的作用;随药物作用时间延长,通窍止咳液在低浓度时的抗病毒有效率呈降低趋势,在高浓度时的抗病毒能力基本不变。结论:通窍止咳液具有较好的体外抗甲型人流感病毒的作用。     

知母宁抗流感病毒作用研究

目的:考察知母宁抗流感病毒的作用.方法:采用人流感病毒A型(H1N1)滴鼻感染小鼠,以利巴韦林作为阳性对照药,对知母宁抗病毒活性进行评价.结果:与生理盐水对照组相比,知母宁可改善感染小鼠的临床症状,减少14 d内动物的死亡数,并能延长其平均存活时间.组织病理学检查表明25,50及75 mg/kg的知母宁对小鼠肺部感染均有一定的疗效,随剂量的降低疗效减弱.其中75 mg·kg-1的知母宁治疗作用与利巴韦林(15 mg·kg-1)相似.结论:知母宁具有较强的抗流感病毒A型(H1N1)的活性.     

抗病毒口服液在鸡胚内的抗病毒作用研究

目的观察抗病毒口服液在鸡胚内的抗病毒作用.方法采用鸡胚法(体内及体外)研究了抗病毒口服液对三种病毒(甲3型流行性感冒病毒IFV株、亚甲型流行性感冒病毒鼠适应的FM1株及新城疫鸡瘟病毒NDVⅡ系病毒株)的作用.结果抗病毒口服液对三种病毒株在鸡胚体外有明显的抑制作用或杀灭作用,在鸡胚内对鸡胚尿囊液HA效价有明显抑制趋势,但统计学处理无明显差异.结论抗病毒口服液在体外对甲3型流感病毒株、亚甲型FM1株和NDVⅡ系病毒株有明显的抑制作用,抗甲3型流感病毒和亚甲型FM1株的作用比抗NDVⅡ系病毒株的作用略强,但该药在鸡胚内抗病毒作用仅有抑制趋势.     

中西医结合体外抗甲型流感病毒的实验研究

目的研究中西医结合药物体外对甲型流感病毒的抑制作用。方法体外接种甲型流感病毒鼠肺适应株H1N1于狗肾细胞（MDCK）,观察各组药物体外抗病毒作用。结果根据实验,测得各组药物对甲型流感病毒的选择指数,利巴韦林注射液组为4.68;痰热清注射液组为5.50;达菲组为5.53;中西医结合组为14.48。结论中西医结合组具有明显的体外抗甲型流感病毒的作用。     

腔肠素抗流感病毒研究

目的 对海洋来源的化合物腔肠素进行体外抗流感病毒活性研究。方法 细胞病变效应(CPE)抑制实验评价腔肠素对不同流感病毒株的抗病毒作用。CPE实验检测腔肠素细胞毒性和抗病毒作用方式并结合血凝抑制实验、神经氨酸酶(NA)活性实验及微基因组实验初步探究腔肠素的作用靶点。结果 腔肠素体外对不同流感病毒株均有良好抗病毒作用,其中对PR8的抑制作用最强,IC₅₀为5.0μmol·L^-1且细胞毒较小,CC₅₀为144.1μmol·L^-1。通过不同作用方式以及不同作用时间的实验显示,腔肠素预先处理流感病毒以及在病毒感染后加入均有良好抗病毒作用,并且在病毒吸附后0～3 h的抑制效果较好。用腔肠素预处理病毒后可以呈剂量依赖性地抑制血凝素(HA)的活力。故腔肠素可能是通过与病毒HA相互作用来阻断流感病毒的进入,其作用位点可能为HA蛋白HA2链的72、74位谷氨酸。结论 腔肠素具有良好的体外抗甲型流感病毒效果,为海洋来源的小分子化合物的开发与改造提供了借鉴,为寻找新型抗流感病毒药物提供新思路。     

银翘散主要药物提取物体外抑制流感病毒作用的比较研究

目的:观察并比较银翘散主要药物金银花、连翘、牛蒡子及其配伍提取物体外抗甲型流感病毒FM1株作用.方法:采用血凝试验对中药不同浓度、不同时间点进行体外抗甲型流感病毒的效价测定.结果:金银花、连翘、牛蒡子及其配伍提取物可直接抑制甲型流感病毒FM1株的活性,作用时间从1 h可持续到24 h;各时间点各中药提取物在最大不凝血浓度即金银花25 mg/mL、连翘50 mg/mL、牛蒡子100 mg/mL、配伍组50 mg/mL时均能完全抑制病毒的增殖,其对病毒的抑制作用随着药物浓度的降低而逐渐减弱.结论:金银花、连翘、牛蒡子及其配伍提取物可有效抑制甲型流感病毒FM1株体外增殖.     

松针叶绿素-胡萝卜素软膏的体外抗甲型流感病毒作用研究

目的 观察松针叶绿素-胡萝卜素软膏的体外抗甲型流感病毒作用.方法 接种甲型流感病毒于狗肾传代细胞(MDCK),评价松针叶绿素-胡萝卜素软膏的细胞毒性及体外抗病毒作用.结果 松针叶绿素-胡萝卜素软膏对MDCK细胞的半数中毒浓度(TC50)为56 μg· mL-1,治疗和预防给药方式均有抗甲型流感病毒作用,半数抑制浓度(IC50)分别为30、29μg·mL-1,治疗指数(TI)均为1.9.结论 松针叶绿素-胡萝卜素软膏具有明显的抗流感病毒作用,且在安全浓度范围内呈现一定的量效关系,浓度越高抗病毒作用增强.     

速感宁胶囊抑菌抗病毒作用观察

观察速感宁胶囊的抑菌、抗病毒作用及对免疫功能的影响。结果：速感宁胶囊灌胃给药对小鼠流感病毒性肺炎具有明显的保护作用，可明显降低体内注射肺炎球菌小鼠死亡率；体外抑菌试验表明其对金黄色葡萄球菌、肺炎球菌、甲型溶血性链球菌、乙型溶血性链球菌、流感杆菌均有明显抑制作用；体外抗病毒试验证明，3．75mg／ml对感染流感FMl、柯萨奇病毒S4(CVB4)、腺病毒3型(Adv-3)、单纯疱疹病毒Ⅰ型(HSV-1)的Hep-2或FL(人羊膜细胞)具有明显的保护作用；对小鼠单核巨噬细胞吞噬功能和抗体产生具有明显促进作用。     

金莲花醇提物体外抗甲型流感病毒作用研究

目的研究金莲花醇提物的抗呼吸道甲型流感病毒作用。方法采用鸡胚培养流感病毒,并用鸡红血球凝集试验检测药物对病毒在鸡胚尿囊液中增殖的抑制作用。结果在药物和病毒先在体外直接作用后的共同接种试验中,金莲花醇提物对甲型流感病毒具有体外直接灭活作用;在甲型流感病毒先感染鸡胚后再接种药物试验中,金莲花醇提物可抑制病毒在鸡胚内的增殖。结论金莲花醇提物在体外对甲型流感病毒具有直接杀灭作用,对甲型流感病毒在鸡胚中的增殖具有抑制作用。     

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.

---

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.