多指标综合评分法优化痛风巴布剂的醇提工艺

目的 优选痛风巴布剂的最佳提取工艺。方法 以青藤碱、总生物碱的含量和干浸膏得率为评价指标,采用正交设计试验,考察乙醇浓度、乙醇用量、提取时间和提取次数对提取结果的影响,确定痛风巴布剂处方药材的最佳提取工艺。结果 痛风巴布剂的最佳提取工艺为65%乙醇,提取3次,每次6倍量溶剂,提取总时间为1.5 h,在该工艺条件下得到的青藤碱含量、总生物碱含量和干浸膏得率分别为2.79 mg·g^-1、1.22%和13.06%。结论 优选的醇提工艺稳定、可行。     

多指标综合评分法优选芩黄凝胶剂提取工艺

目的 优选芩黄凝胶剂的提取工艺。方法 以黄芩苷、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚的转移率为评价指标,采用L9（3⁴）正交法优选芩黄凝胶剂的水提取与醇提取工艺。结果 最佳水提取工艺为加6倍量水,浸泡0.5 h,回流提取2次,每次提取1.5 h;最佳醇提取工艺为加8倍量40%乙醇,回流提取3次,每次提取1.0 h。结论 采用多指标综合评分法优选的芩黄凝胶剂提取工艺合理、可行。     

桂龙巴布贴提取工艺考察

摘 要 目的：优选桂龙巴布贴的最佳提取工艺。方法: 采用单因素筛选法,以挥发油得量为指标,对挥发油提取工艺条件进行优选;采用单因素筛选法和正交设计法,以干浸膏得量和乌头类总生物碱含量的综合评分值为指标,对水提取工艺条件进行优选。结果: 挥发油提取工艺最优条件为加入药材量8倍的水,浸泡1 h后,加热回流提取6 h;水提取工艺最优条件为加水8倍量,提取3次,每次1 h。结论:优选得到的提取工艺简单、稳定、可行,为下一步研究奠定了良好的基础。     

正交试验优化止咳平喘颗粒处方药材的乙醇提取工艺

目的 优选止咳平喘颗粒处方药材的提取工艺。方法 以麻黄碱、连翘酯苷A提取率为指标,以乙醇体积分数、乙醇倍量、提取时间、提取次数为因素,采用L₉(3⁴)正交试验对提取工艺进行优选。结果 最佳提取工艺条件为65%乙醇,回流提取2次,每次8倍量,每次1 h。结论 优选的止咳平喘颗粒处方药材提取工艺条件合理、可行。     

赤丹肝纤颗粒的醇提工艺研究

摘 要 目的： 优选赤丹肝纤颗粒的醇提最佳工艺。方法: 以虎杖苷含量为考察指标,先优选出最佳乙醇浓度,再采用L₉(3⁴)正交试验法,考察提取次数、提取时间及乙醇用量对提取效果的影响。结果: 最佳醇提工艺条件为以70%乙醇为溶媒回流提取2次,每次2 h,每次溶媒量为药材量的5倍。结论: 优选的工艺合理可行、重复性良好、提取效率高,适合于工业化生产。     

星点设计-效应面法优选龙钻通痹方总生物碱提取工艺

摘 要 目的：利用星点设计 效应面法优选龙钻通痹方总生物碱的最佳提取工艺。方法: 以乙醇体积分数、溶剂用量和提取时间为自变量,以提取液中总生物碱（以青藤碱计）、青藤碱含量的加权总评归一值（OD）为因变量,采用星点设计 效应面法优选龙钻通痹方总生物碱的最佳提取工艺。结果: 最佳提取工艺为加入9倍量75%乙醇,回流提取2次,每次130 min。结论:采用星点设计 效应面法优选龙钻通痹方总生物碱的提取工艺方法简便,具有良好的预测性。     

正交试验法优选葛花异黄酮的提取工艺

目的 优选葛花异黄酮的提取工艺。 方法 乙醇回流提取葛花异黄酮,采用紫外分光光度(UV)法和高效液相色谱(HPLC)法测定葛花中总黄酮及鸢尾苷、鸢尾苷元含量。在对乙醇浓度、溶剂用量、提取时间等进行单因素考察基础上,选用L₉(3⁴)正交设计试验优选提取工艺。 结果 葛花异黄酮的最佳提取工艺为第1次加入12倍量70%乙醇提取90 min,第2次加入10倍量70%乙醇提取60 min。 结论 优选的葛花异黄酮提取工艺合理可行,能为实际生产提供参考。     

赤雹根总皂苷提取优化工艺考察

摘 要 目的：优选赤雹根总皂苷的提取工艺。方法: 以赤雹根总皂苷的溶出量为评价指标,以提取次数、提取时间、固液比为考察因素,采用正交试验法优选出赤雹根总皂苷的最佳提取工艺。结果: 最佳提取工艺为70 %乙醇回流提取2次,每次1.5 h,固液比为1∶6。结论:此工艺操作简便,重复性好,稳定可行。     

伤科止痛油提取工艺的优选

摘 要 目的：优选伤科止痛油最佳提取工艺。方法: 以毛蕊花糖苷和没食子酸提取量的综合评分为指标,采用L9（34）正交试验考察乙醇浓度、浸泡时间、提取次数和提取时间对伤科止痛油的提取工艺的影响。结果:最佳提取工艺为用65%乙醇浸泡1 h后,再回流提取3次,第一次1.5 h,第二、三次1 h;毛蕊花糖苷和没食子酸提取量分别为0.870 8、0.717 8 mg·ml-1。结论:优选所得的提取工艺简单易行,科学合理。     

星点设计-效应面法优化镰形棘豆总黄酮的提取工艺

摘 要 目的：优选镰形棘豆总黄酮的提取工艺。方法: 以总黄酮含量为指标,在单因素试验的基础上,采用星点设计 效应面法考察溶剂用量、乙醇体积分数、提取时间对镰形棘豆总黄酮含量的影响。结果: 最佳提取工艺为加入20倍量66%乙醇回流提取2次,每次84 min,在此条件下,总黄酮的含量达23.21 mg·g^-1。结论:采用星点设计 效应面法优选的提取工艺条件稳定可行,预测性好。     

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.

     

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.     

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.     

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.