杠板归抗炎及抑菌活性部位研究

目的研究杠板归抗炎及体外抑菌作用以确定其有效部位。方法采用二甲苯诱发小鼠耳廓炎症、采用新鲜鸡蛋清致小鼠足肿胀评价其抗炎作用；采用试管二倍稀释法评价其抑菌作用。结果杠板归总提部位具有显著的抗炎作用，正丁醇部位有一定的抗炎作用；体外抑菌实验表明，杠板归乙酸乙酯部位对金黄色葡萄球菌、大肠杆菌、粪链球菌、铜绿假单孢菌有明显的抑菌作用，对白色念球菌有一定的抑菌作用。结论杠板归总提部位具有显著的抗炎活性，正丁醇部位有一定抗炎活性，杠板归乙酸乙酯部位抑菌作用明显，证实了杠板归用于炎症治疗的科学性。     

板蓝根乙酸乙酯提取物HPLC指纹图谱及体外抑菌活性的相关性分析

目的考察板蓝根乙酸乙酯提取物的HPLC指纹图谱及体外抑菌活性的相关性。方法HPLC法建立十批不同来源板蓝根的乙酸乙酯提取物的指纹图谱采用微量量热法记录大肠杆菌在板蓝根乙酸乙酯提取物作用下生长代谢的热谱图。运用系统聚类分析法考察不同来源板蓝根之间的差异，结合体外抑菌活性进行相关分析。结果不同来源板蓝根乙酸乙酯提取物的HPLC指纹图谱与体外抑菌活性之间存在很好的相关性。结论采用HPLC指纹图谱和体外抑菌活性相关性分析的方法，可以发现板蓝根乙酸乙酯部位抑菌活性有效成分。     

板蓝根抗内毒素研究

目的：探讨板蓝根抗细菌内毒素作用,方法：分别用细菌内毒素检查法,热原检查法,对内毒素致小鼠毒性保护力,对内毒素致鼠巨噬细胞释放炎性因子抑制作用及内毒素定量检测等方法,比较板蓝根不同提取部位化学成分及药材抗内毒素强度,结果：板蓝根氯仿提取的中的F022抗内毒素作用最强,其中F02207可作为板蓝抗内毒素药物的活性指标成分,结论：F022是板蓝根抗内毒素新药研究的物质基础。     

板蓝根对内毒素性DIC家兔血清LPO、SOD水平的影响

目的：观察板蓝根对内毒素性弥散性血管内凝血(DIC)家兔血清中血清脂质过氧化物(LPO)含量及超氧化物歧化酶(SOD)活力的影响。方法：复制家兔内毒素性DIC模型，采用硫代巴比妥酸显色法测定其血清LPO的含量，以黄嘌呤氧化酶法测定血清SOD活力。结果：板蓝根及板蓝根D部位可显著降低内毒素性DIC家兔血清LPO水平，提高其SOD的活力。 结论：板蓝根D部位具有抗脂质过氧化、清除氧自由基的作用，能够拮抗内毒素的生物效应，是板蓝根发挥抗内毒素活性的物质基础。     

板蓝根抗内毒素活性部位研究(Ⅱ)

目的探讨板蓝根F022部位抗内毒素活性.方法用板蓝根F022部位溶液分别作对LPS致小鼠死亡的影响、对LPS诱导P38MAPK活性的影响及其化学成分丁香酸对内毒素的破坏作用,检测其抗内毒素活性.结果板蓝根F022部位可降低LPS致小鼠死亡率;可抑制LPS诱导鼠单核细胞分泌P38丝裂原活化蛋白激酶活性且有剂量依赖性;板蓝根F022部位的丁香酸成分可破坏内毒素,破坏率达83.16%.结论体内外有多项实验显示板蓝根F022部位有抗内毒素活性,该部位为板蓝根抗内毒素活性物质.     

板蓝根低极性流分的分离及其免疫活性

目的：进行板蓝根低极性流分及其亚流分的分离,并研究其免疫活性。方法：用快速低压干柱柱层析从板蓝根中分离出一个低极性流分及其一组亚流分;用化学发光法检测其对人多形核细胞化学发光的影响。结果：板蓝根低极性流分具有双向免疫活性,在低浓度时具有激活作用,在高浓度时具有抑制作用;而亚流分的免疫活性并未因其纯度的提高而相应提高。结论：板蓝根低极性流分及其亚流分含有抗炎成分。     

板蓝根乙酸乙酯部位体外抗病毒活性研究

目的对板蓝根的乙酸乙酯部位各化学组分进行体外抗单纯疱疹病毒Ⅰ型(HSV1)活性研究。方法利用溶剂法和色谱法从板蓝根中提取分离出20个乙酸乙酯组分,利用四甲基偶氮唑盐比色(MTT)法检测这20个组分体外对HSV1病毒的抑制作用,以细胞存活率、治疗指数(TI)和细胞保护率为评价指标,比较各化学组分的体外抗病毒的效果。结果板蓝根乙酸乙酯8个组分均有明显的抗HSV1病毒作用,对病毒的抑制率均远大于50%。结论板蓝根乙酸乙酯部位中存在直接抗病毒较强的活性成分,对其结构进行深入研究,将有助于阐明板蓝根抗病毒药效物质基础。     

板蓝根清热解毒实质分析

板蓝根具有较强的清热解毒作用。其作用机制表现在其具有抗病毒、抗炎、增强免疫力、解热等功效方面,而这些功效可能与板蓝根的作用部位、化学成分、作用途径等有关。本文对板蓝根的清热解毒作用机制进行阐述。     

板蓝根抗病毒有效部位筛选

目的:对板蓝根药材中提取的10个化学部位进行体外抗单纯疱疹病毒(HSV)活性研究,确定板蓝根抗病毒的有效部位。方法:利用溶剂法和色谱法从板蓝根中提取分离出10个粗提和精制部位,用MTT法检测这10个部位体外对HSV-Ⅰ及HSV-Ⅱ型病毒的抑制作用,以病毒抑制率和治疗指数(TI)为评价指标,比较各化学部位体外抗病毒的效果。结果:水提大孔树脂吸附的10%、50%醇洗部位(Ⅷ、Ⅹ)作用最强,对HSV-Ⅰ型病毒的抑制率为分别为53.21%、56.28%,接近阳性对照药阿昔洛韦(62.55%),其TI分别为4.61、18.62。结论:板蓝根不同化学部位的抗病毒作用强度有较大差异。     

对甲磺酰基苯丙烯酸异羟肟酸和酰脲衍生物的合成及抗炎活性

目的研究对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物的合成及其抗炎活性.方法 将对甲磺酰基苯丙烯酸转化成其异羟肟酸(Ⅳ)和酰脲衍生物(Ⅴ),评价Ⅳ和Ⅴ的抗炎活性以及连续经口服给药对大鼠胃肠道的影响.结果 合成了10个新化合物(Ⅳ1～Ⅳ5和Ⅴ1～Ⅴ5),其结构经IR、1H-NMR和MS确证.小鼠试验表明:Ⅳ1、Ⅳ4、Ⅳ5和Ⅴ1、Ⅴ3、Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当(P＞0.05);大鼠试验显示:Ⅴ3和Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当(P＞0.05),Ⅳ4、Ⅴ3和Ⅴ5的胃肠道损伤显著小于双氯芬酸钠(P＜0.01),与罗非昔布和CMC-Na相当(P＞0.05).结论 对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物抗炎活性较强,胃肠道不良反应小,值得深入研究.     

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.     

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.     

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.     

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.