非典型抗精神病药的受体药理学研究进展

介绍非典型抗精神病药作用的新靶点及部分非典型抗精神病药的受体药理学及其临床特征。非典型抗精神病药除作用于D2受体外，还对多巴胺D3，D4，D1受体，5-羟色胺受体以及谷氨酸受体系统等都有作用。这种多受体靶点作用的药理特征，使其具有不同于传统抗精神病药的优点。与传统抗精神病药相比，非典型抗精神病药的锥体外系副作用更小，对阴性症状有效，并可改善认知功能障碍，是一类治疗精神分裂症更安全有效的药物。     

抗血小板药的研究现状

抗血小板药是一类抑制血小板活化,预防血小板参与血栓形成的药物。近10多年来,抗血小板药已被广泛应用于各科血栓性疾病的预防和治疗。本文按抗血小板药的不同作用机制,对各类抗血小板药——环氧化酶抑制剂、磷酸二酯酶抑制剂、血栓素A2抑制剂及其它抗血小板药进行较为系统的、详细的介绍和探讨。     

贝母的药理作用研究概况

综述了国内外贝母药理作用的研究概况:贝母对呼吸系统药理作用;对心血管系统的影响;对胃肠平滑肌作用;对中枢神经系统的影响;以及对兔瞳孔的扩瞳作用;抑菌作用、对细菌或白血病细胞多药耐药的逆转作用、抗炎和抗腹泻作用、抗溃疡和镇痛作用、抗肿瘤作用等方面的初步药理研究;抗乙酰胆碱活性、抑制cAMP磷酸二酯酶活性等基础药理研究.     

他莫昔芬新的作用机制与治疗应用进展

近年研究中发现部份雌激素受体括抗剂他莫昔芬的许多新功效，包括心脏保护作用、抗多种肿瘤及抗多药耐药性、治疗偏头痛、抗真菌及抗病毒作用，这些均与其雌激素受体之外的作用机制——一膜调节机制相关。对雌激素受体分别呈阳性和阴性的人乳癌细胞等多种天然和模型化股性结构的研究’‘’“表明，作为股调节剂，他莫昔芬可以使细胞膜流通性降低，在此基础上还可作为抗氧化剂保护细胞膜不受自由基、过氧化物等伤害，并可保护人体低密度脂蛋白不发生氧化性破坏。1抗多种肿瘤及抗多药耐药性作用双·且抗肿瘤作用机制ti－。‘他莫昔芬（TMX）…     

抗凝和抗栓药发展概况

凝血酶对血凝块的调节有重要作用，是新的抗凝和抗检药的主要作用环节；另一些涉及细胞和非凝血酶的蛋白酶也被视为重要的辅因子。当今正在开发的新的抗凝和抗栓药的作用涉及凝血系统的多个环节。且抗凝和抗栓药常用的抗凝药如肝素，具有抗凝和抗柱作用。用肝素治疗的病例其血液在试管内具有抗凝作用2用阿司匹林治疗的病例其血液则无抗凝作用，但有抗血栓形成作用。抗凝药如肝素和水蛙素的抗凝作用，主要是由于抑制凝血酶的作用；抗检药的作用则是由于抑制凝血酶的生成和其他过程。阿司匹林、葡聚糖和许多首烷醇酸类（e允osano沮s），具有抗…     

甘草次酸逆转肿瘤多药耐药机制的研究进展

甘草次酸属五环三萜类化合物,是中药甘草的重要活性成分,具有抗炎、抗病毒、抗溃疡、免疫调节等广泛的药理活性,近年来发现甘草次酸具有广谱的抗肿瘤作用,其抗肿瘤作用机制也得到了广泛研究。肿瘤多药耐药机制十分复杂,且目前在肿瘤的临床治疗中,仍然是化疗所面临的障碍和挑战。甘草次酸具有药理活性好,低毒性的优点,已经展现出对肿瘤多药耐药的逆转作用,具有在多种化疗药物引起的化学抵抗中成为化疗增敏剂的潜力。本文论述了肿瘤多药耐药的发生机制及甘草次酸逆转肿瘤多药耐药机制研究进展。     

抗组胺药与粘附分子

综述了主要粘附分子的种类、性质、功能及抗组胺药在过敏性炎症中对炎症细胞粘附分子表达的直接调控作用和间接调控作用 ,提示抗组胺药具有多方面抗炎作用。     

多枝雾水葛不同提取部位的抗炎镇痛作用研究

目的 研究多枝雾水葛不同提取物的抗炎镇痛作用.方法 采用二甲苯致小鼠耳肿胀、醋酸致小鼠扭体反应和小鼠热板法观察多枝雾水葛灌胃、外搽使用以及不同提取部位的抗炎、镇痛作用.结果 多枝雾水葛外搽使用的抗炎镇痛效果不明显,灌胃给药具有较强的抗炎镇痛作用,能显著减少醋酸所致的小鼠扭体次数和抑制二甲苯所致的小鼠耳廓肿胀,且其水提物比醇提物的作用更强.对多枝雾水葛水提取物的活性部位研究表明,多枝雾水葛的氯仿部位和水部位都具有较好的镇痛效果,抗炎的有效部位则是氯仿部位和正丁醇部位.结论 多枝雾水葛水提取物灌胃给药具有抗炎镇痛作用,其有效部位是氯仿部位、正丁醇部位和水提取部位.     

非典型抗精神病药治疗精神分裂症的临床应用评价

目的:系统论述非典型抗精神病药治疗精神分裂症临床研究和应用的进展,评价其临床疗效和安全性.方法:通过互联网查阅Medline、Pubmed、Ovid、Science Direct、Proquest及国内外相关专业杂志所公开发表的研究报道进行综合评价和分析.结果与结论:非典型抗精神病药近10年来的临床应用研究进展迅速,除氯氮平外,大多数新型非典型抗精神病药如利培酮、奥氮平、喹硫平、齐拉西酮及阿立哌唑等已成为精神分裂症各种症状维度、不同病期和复发预防的一线临床选择,特别是在不良反应方面克服了经典抗精神病药和氯氮平的诸多严重缺点,同时,各种临床研究结果已被多项应用循证医学方法的系统研究所证实.     

红参-制何首乌药对抗衰老作用的HT22细胞和秀丽隐杆线虫模型初步研究

目的 初步探讨不同提取工艺下红参-制何首乌药对对神经细胞的抗衰作用,为红参-制何首乌药对在抗衰及抗阿尔茨海默病(AD)作用的应用提供数据支撑。方法 分别制备30%和70%乙醇回流提取物,30%和70%乙醇渗漉提取物和水提取物。通过流式细胞术检测不同提取物对HT22细胞中β-半乳糖苷酶含量的影响,初步筛选红参-制何首乌药对神经细胞抗衰效果最佳的提取物,并通过β-半乳糖苷酶染色直观分析该提取物对神经细胞的抗衰效果,用秀丽隐杆线虫寿命试验及瘫痪实验验证其抗衰及抗AD作用。结果 红参-制何首乌药对的不同提取方式均对HT22细胞具有显著的抗衰老作用,其中70%乙醇渗漉提取物效果最佳。对其进行多浓度验证,显示具有剂量依赖性的保护作用。浓度为0.2 mg·mL^-1的70%乙醇渗漉提取物对秀丽隐杆线虫的寿命有明显的延长作用,浓度为0.008mg·mL^-1的70%乙醇渗漉提取物具有缓解瘫痪的趋势。结论 红参-制何首乌药对的70%乙醇渗漉提取物具有明显抗神经细胞衰老的作用,具有抗衰老延长寿命与治疗AD的潜力,应深入研究。     

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.