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。     

重组干扰素α-2b栓的抗疱疹病毒作用

目的探讨重组干扰素α-2b栓(IFNα-2b栓)的体外、体内抗单纯疱疹病毒Ⅰ型和Ⅱ型作用。方法应用细胞病变抑制法,观察IFNα-2b栓的体外抗病毒作用。建立HSV-2豚鼠阴道炎模型和HSV-1型豚鼠皮肤感染模型,分别用0.75、2.25、6.75 mg.kg-1的IFNα-2b栓治疗,进行豚鼠阴道分泌物的病毒毒力检测及阴道组织的病理组织学等检查,每天记录豚鼠皮肤损伤病变分值情况,观察IFNα-2b栓的体内抗病毒作用。结果体外实验,IFNα-2b栓、重组人干扰素α-2b注射液和阿昔洛韦对单纯疱疹病毒Ⅱ型的IC50分别是(0.59±0.11)、(0.56±0.08)、(21.20±1.90)mg.L-1。体内实验,各给药组中,IFNα-2b栓6.75 mg.kg-1剂量抗病毒作用最强,豚鼠阴道分泌物中病毒毒力显著低于模型组(P<0.01)。阴道组织切片病理结果也表明IFNα-2b栓对豚鼠阴道损伤具有较好的治疗作用。IFNα-2b栓能显著的减轻单纯疱疹I型病毒感染豚鼠的皮肤损伤程度(P<0.01),在相同剂量下,干扰素α-2b栓剂与干扰素α-2b注射液的抗单纯疱疹病毒活性相比较,2.25 mg.kg-1的干扰素α-2b栓剂组与其注射液组的治疗作用相当。结论 IFNα-2b栓在体外及体内均有一定的病毒抑制作用。     

阿昔洛韦联合羟基脲抗疱疹病毒的研究

目的 研究抗肿瘤药物羟基脲（HU）与抗病毒药物阿昔洛韦（ACV）联用抗疱疹病毒的协同增效作用。方法 体外实验应用VERO细胞培养法及MTT染色法进行实验,以Calcusyn软件计算、分析实验结果;体内实验采用单纯疱疹病毒Ⅰ型感染的兔角膜炎实验模型,用临床裂隙灯观察不同用药情况下兔角膜病变,进行Trouzdale评分,并分离病毒、滴定度及病理检查。结果 体外实验结果显示ACV：HU为1：312.5及1：100时,两药为协同作用;ACV：HU为1：50、1：25、1：10时,两药为拮抗作用。配比为1：300的阿昔洛韦和羟基脲联合治疗病毒性角膜炎,其疗效与0.1％的ACV相当。结论 羟基脲对阿昔洛韦抗HSV-Ⅰ活性在一定比例条件下,体内、外均有增效作用。     

抗病毒抗生素17997不同时间给药抗单纯疱疹病毒Ⅰ型的效果

目的：广谱抗病毒抗生素17997，对单纯疱疹病毒Ⅰ型（HSV－Ⅰ）有较好的疗效，本实验通过观察不同给时间的抗病毒效果。方法：以HSV－Ⅰ感染Vero细胞，在感染前4h，感染后0、3、6h给予抗生素17997（10μmol/L），以透射电镜观察Vero细胞内的病毒，比较不同给药时间的抗病毒效果。结果：在病毒感染前4h给药无效，细胞内外有大量病毒颗粒；在感染早期（0.3h）给药效果好，细胞内外均极少见病毒颗粒，胞浆内可见病毒空壳聚集；感染晚期（6h）给药在细胞核内见病毒核壳体及有囊膜病毒颗粒，但细胞浆及细胞外均未见病毒颗粒。结论：抗病毒抗生素17997在病毒复制早期抑制单纯疱疹病毒DNA的合成，晚期可抑制有囊膜单疱疹病毒颗粒从核释放至胞浆。     

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。     

重组人干扰素α-2b脂质体凝胶的皮肤刺激性及抗病毒作用研究

目的考察干扰素α-2b脂质体凝胶外用对皮肤的刺激性及抗病毒作用。方法用健康家兔进行皮肤刺激性试验,用皮肤感染单纯疱疹病毒的豚鼠进行抗病毒试验。结果干扰素α-2b脂质体凝胶对完整皮肤和破损皮肤均无刺激性,对疱疹病毒的皮肤感染具有缩短病程、促进结痂及痊愈的效果。结论干扰素α-2b脂质体凝胶是一种安全有效的外用抗疱疹病毒药物。     

喷昔洛韦体外抗病毒的药效学研究

目的 明确喷昔洛韦(PCV)的抗病毒作用谱及体外抗病毒的作用机理。方法采用组织细胞培养法、MTT法检测PCV对各种病毒的作用,通过改变给药时间、途径,探讨：PCV抗病毒的作用环节。结果：PCV具有明显抗单纯疱疹病毒Ⅰ、Ⅱ型,人巨细胞病毒,汉坦病毒和腺病毒的作用;对单纯疱疹病毒Ⅰ、Ⅱ型和人巨细胞病毒有一定的抑制作用。与阿昔洛韦相比,其抗病毒效果显著。结论PCV是一种抗病毒谱较广的药物。     

IFNα_(1b)与IFNα_(1b)突变体的抗病毒效应的对比分析

目的 进一步研究IFNα1b、IFNα1b突变体干扰素的抗病毒效应。方法 采用微量细胞病变(CPE)抑制法进行抗病毒试验。结果 500、50、5 IU.ml-1 IFNα1b或IFNα1b突变体,在Vero细胞上分别也可抗8、4、2 TCID50的Ⅰ型和Ⅱ型单纯疱疹病毒感染细胞。结论 IFNα1b突变体抗病毒效果较IFNα1b无明显差别。     

干扰素联合阿昔洛韦治疗单纯疱疹病毒脑炎临床效果观察

目的 观察干扰素联合阿昔洛韦治疗单纯疱疹病毒脑炎临床效果.方法 治疗组患儿采用干扰素50～100万U肌内注射,1次/d,联合阿昔洛韦每次10 mg/kg,3次/静脉滴注治疗,对照组阿昔洛韦每次10 mg/kg,3次/d静脉滴注治疗.每天观察记录患儿症状、体征等.结果 治疗组总有效率为95.56%,对照组为78.57%,差异有统计学意义(P<0.05).结论 干扰素联合阿昔洛韦治疗单纯疱疹病毒脑炎临床效果,值得临床推广应用     

阿昔洛韦的临床应用

阿昔洛韦是人工合成的第二代核苷类光谱抗病毒药.阿昔洛韦的抗病毒机理为其进入感染细胞被HSV的特异性胸苷激酶酸化,生成三磷酸型,一方面竞争性抑制病毒DNA多聚酶,另一方面也可掺入病毒DNA中,与DNA末端连结,使病毒DNA合成受阻,从而起到抗病毒的作用.临床用于单纯病毒感染、带状疱疹、免疫缺陷者水痘的治疗及预防、生殖疱疹感染、免疫缺陷者自限性黏膜皮肤单纯疱疹、与免疫调节剂（α-干扰素）联合应用治疗乙型肝炎、降低骨髓移植患者巨细胞病毒感染的发病率.要注意阿昔洛韦的不良反应,临床上要针对疾病、个人状况选择其用药.     

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.