苦楝化学成份的研究

从苦楝(Melia azedarach L.)果中分得苦楝新醇(Ⅰ),苦楝醇(Ⅱ)、苦楝酮(Ⅲ)、苦楝二醇(Ⅳ)、香草醛(Ⅴ)和香草酸(Ⅵ)。根据波谱(IR,MS,~1HNMR,~(13)CNMR)分析和理化常数测定,确定了它们的结构。其中苦楝新醇(Ⅰ)为新化合物,对菜青小虫有一定的拒食活性。     

苦楝化学成份的研究

从苦楝(Melia azedarach L.)果中分得苦楝新醇(Ⅰ),苦楝醇(Ⅱ)、苦楝酮(Ⅲ)、苦楝二醇(Ⅳ)、香草醛(Ⅴ)和香草酸(Ⅵ)。根据波谱(IR,MS,¹HNMR,¹³CNMR)分析和理化常数测定,确定了它们的结构。其中苦楝新醇(Ⅰ)为新化合物,对菜青小虫有一定的拒食活性。     

苦楝、黄药子抗癌成分的细胞学评价

应用MTT法对天然药物组分Ⅰ（苦楝素）、Ⅱ（苦楝提取结晶）、Ⅲ（黄药子乙素）进行体外抑癌作用的观察，发现组分Ⅰ在浓度04～40ug／ml时与对照组比较，有抑制胃癌（SGC－7901）细胞增殖作用，而对黑色素瘤细胞A375无抑制作用。表明该方法简便、快速、重复性好，可作为药物筛选的常用方法。     

雷公藤中的一种新活性成分——16—羟基雷公藤内酯醇

从雷公藤（Tripterygium wilfordii Hook f.）的叶、根及制剂“雷公藤多甙”中分离出一个新的三环氧二萜内酯化合物－－16－羟基雷公藤内酯醇（L2）。该化合物是一种白色簇状结晶，熔点232－233.5℃，分子式为C20H24O7。根据光谱（UV，IR，MS，^1HNMR,^13CNMR,2d-NMR和Se-lective Long-range DEPT）数据分析，确定了其化学结构，并通过x-射线晶体分析确证了它的立体化学。15－C为“S”构型的手性碳，药理试验表明，16－羟基雷公藤内酯醇具有较强的抗炎、免疫抑制和雄性抗生育活性。另外，还分离到已知化合物雷公藤内酯醇，并通过2d-NMR等光谱分析归属了全部碳和质子的NMR光谱峰。     

苦楝子中三萜成分的研究

目的:对苦楝子的甲醇提取物中的三萜成分进行研究.方法:利用硅胶,常压RP-C18硅胶,葡聚糖凝胶 LH-20以及制备液相色谱分离纯化,通过1D-NMR,2D-NMR以及EI-MS波谱数据鉴定化合物结构.结果:从苦楝子的甲醇提取物中共分离得到4个三萜化合物经鉴定为:Meliasenin B (Ⅰ),Meliasenin ...     

美国更新Mifeprex的标签

Danco公司已修订其堕胎药Mifeprex（mifepristone，米非司酮）（Ⅰ）的美国标签，列入五例用（Ⅰ）及米索前列醇（misoprostol）（Ⅱ）后发生严重细菌性感染及脓毒症致死的新的安全性信息。     

鹰爪种子的木脂素和半萜化学成分

从药用植物鹰爪种子分得4个木脂素：异洋商陆素A（soamericanin A,1)，异洋商陆醇A（isoamericanol A,2)，洋商陆素B（americainin,B,3),鹰爪木脂醇（atabotrycinol,4)和一个半萜 ：（R）－鹰爪三醇[(R)-arttaboriol,5],以及棕榈酸（6），β谷甾醇（7）和胡萝卜苷（8），根据光谱数据（IR，UV，MS，1D，2D－NMR）分析，确定它们的化学结构，其中，鹰爪木脂醇（4）是一个新木脂素，（R）－鹰爪三醇（5）是一个新半萜醇，木脂素化合物1，2和3是首次从该植物分得。     

米非司酮加米索前列醇是减少药物流产花费的较佳选择

一项多国研究小组的研究结果显示，在美国和印度，使用米非司酮（mifepristone）（Ⅰ）加米索前列醇（misoprostol）（Ⅱ）联合药物流产花费较少，或者比单独使用（Ⅱ）花费稍稍多一点。研究者在假设的100名妇女中使用（Ⅰ）加（Ⅱ）或者单独使用（Ⅱ）进行药物流产，     

米非司酮伍米索用于晚期妊娠引产的效果观察

目的：探索米非司酮配伍米索在晚期妊娠引产中的作用及安全性。方法：将62例妊娠37^ 2-42^ 3周的正常孕妇有引产指征随机分成两组，观察组（31例）口服米非司酮200mg（8片）配合米索前列醇50μg阴道上药；对照组（31例）口服蓖麻油鸡蛋餐。结果：两组引产总有效率无显性差异, 观察组引产时间显少于对照组（P＜0．05）。服用米非司酮后宫颈缩短1－3cm,Bishop评分提高5分。与用药前比较，均有显性差异（P＜0．01）。结论：应用米非司酮配伍米索前列醇进行晚期妊娠引产，能促宫颈成熟，发动子宫收缩，并安全、有效、方便，有临床价值。     

卡前列素氨丁三醇治疗产后出血临床疗效观察

目的 探讨卡前列素氨丁三醇治疗产后出血的临床疗效.方法 将产后出血患者120例按数字表法随机分为对照组与观察组各60例.对照组使用缩宫素＋米索前列醇治疗,观察组应用卡前列素氨丁三醇治疗,比较两组临床疗效、产后出血量、不良反应发生率以及治疗后生活质量.结果 观察组总有效率为95.0%,明显高于对照组的75.0%（χ^2=12.288,P＜0.01）;观察组产后2h、24h累计出血量分别为（150.21±44.32） mL、（188.92±55.38）mL,均明显少于对照组的（266.71±66.89）mL、（311.09±72.38） mL（t =5.556、3.297,均P＜0.05）;观察组不良反应发生率为8.3%,明显低于对照组的20.0%（χ^2=12.399,P＜0.01）;根据QLQC-30生活质量评价标准,观察组QLQC-30评分明显高于对照组（均P＜0.05）.结论 卡前列素氨丁三醇应用于预防及治疗产后出血,效果显著,治疗后患者生活质量明显提高,具有较高的临床应用价值.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.