在醒脑静注射液质量标准中建立“生物活性测定”项的研究

目的:对不同厂家生产的醒脑静注射液的生物活性进行了比较,以探索醒脑静注射液质量标准中建立"生物活性测定"项目的必要性和可行性。方法:选择与该样品功能主治相关的主要药效学试验方法,即对戊巴比妥钠诱导小鼠睡眠的拮抗作用及对盐酸二甲福林致小鼠惊厥的影响。结果:在相同的检测限值下,不同厂家生产的不同规格的样品"生物活性测定"存在明显差异。结论:醒脑静注射液质量标准中建立生物活性测定项是可行的。     

灯盏细辛注射液生物活性限度测定方法适用性研究

目的：探讨灯盏细辛注射液生物活性测定方法的适用性。方法：经预试验,采用小鼠体内血栓形成试验和急性脑缺血试验、大鼠体内和体外血小板聚集试验,观察不同批号灯盏细辛注射液的药理作用,作为生物活性测定方法和限值确定依据。结果：3批样品中有2批样品小鼠30mL·kg^-1可明显增加血栓形成试验偏瘫恢复数,明显延长急性脑缺血试验小鼠存活时间;大鼠10mL·kg^-1可降低体内血小板最大聚集率,另一批反应较弱。3批样品对ADP诱导大鼠体外血小板聚集率有明显抑制作用,体内体外结果作用趋势相近。结论：灯盏细辛注射液三批样品对不同药理模型呈现不同的活性作用差别,考虑均可作为生物活性测定方法。建议选用其中之1～2种方法和10～30mL·kg^-1限值剂量对产品进行质量内部控制,积累数据,为制定正式标准提供依据。     

灯盏花素注射液的生物活性测定方法的建立

目的采用生物活性测定法加强控制灯盏花素注射液的质量。方法取清洁级大鼠,体重180~200 g,雄性,用YLS-14B血栓生成仪,将刺激电流控制在1 mA,电刺激时间定为3 min,建立大鼠单侧颈总动脉血栓形成实验动物模型来评价灯盏花素注射液活血化瘀的功能。结果比较大鼠颈总动脉单侧血栓全阻塞时间,灯盏花素注射液给药组与模型对照组有显著差异(P<0.05),同时延长率>60%,灯盏花素注射液的生物活性符合规定。结论灯盏花素注射液的生物活性动物模型建立成功,可用于测定灯盏花素注射液的生物活性。     

中药注射剂中添加聚山梨酯80的快速检测

目的建立中药注射剂中添加聚山梨酯80的快速检测方法 ,并做了方法学验证。方法采用化学反应,快速、简便地检测出处方中未标示而添加的聚山梨酯80。结果测定了血塞通注射液247批次和灯盏花素注射液141批次,其中6批标示添加了聚山梨酯80和4批未标示添加了聚山梨酯80的灯盏花素注射液样品检测结果为阳性,经HPLC验证确实存在并测出其含量。结论该研究为中药注射剂中添加聚山梨酯80的快速检测提供了思路与方法 。     

正交法考察注射用灯盏花素在不同输液中的稳定性

目的 在4℃、25℃和37℃条件下,考查不同浓度的注射用灯盏花素与5%葡萄糖注射液、葡萄糖氯化钠注射液、氯化钠注射液在不同时间的配伍稳定性.方法 采用正交试验方法将注射用灯盏花素与上述3种输液配成不同浓度的溶液,按4因素3水平进行L9(34)正交试验,采用高效液相色谱法测定各配伍液中的灯盏花乙素含量.结果 配伍液在上述各温度、不同浓度的输液中,0～4h内灯盏花乙素含量均无显著性的变化.结论 注射用灯盏花素可与上述3种输液配伍,与氯化钠注射液配伍使用最佳.     

灯盏花素注射液生产处方及工艺的确定

灯盏花素注射液为菊科植物短萼飞蓬中提取的黄硐类物质,为脑血管扩张剂,能降低脑血管阻力,增加脑血流量,改善微循环,并有对抗血小板聚积的作用。用于治疗缺血性脑血管疾病,如脑血栓形成,脑栓塞、脑溢血等所致后遗瘫疾病人,具有较好疗效。由于灯盏花素注射液疗效确切,适用范围广。九     

2010年某院中药注射剂应用分析

目的 调查医院中药注射剂使用情况,以利规范使用.方法 统计医院各科病区20lO年1月至12月中药注射剂使用数量及销售金额,计算各种中药注射剂的用药频度、日均费用及各科室中药注射剂的用药频率.结果 销售金额居前3位的为注射用灯盏花素、注射用炎琥宁、舒血宁注射液,销售数量居前3位的为注射用灯盏花素、香丹注射液、舒血宁注射液,用药频度居前3位为注射用灯盏花素、血栓通注射液、注射用七叶皂苷钠.日均费用为79.34元,科室中用药频度排前3名的为心血管内科、神经内科、骨科.结论 中药注射剂用药频率各科分布基本合理,但总体上用药频度较高,应加强管理.     

灯盏花素注射液稳定性研究

目的研究灯盏花素注射液的化学稳定性,为保证药效提供依据.方法采用初均速法,分别在40,50,60,70,80,90℃(±1℃)下,恒温加热不同时间,用紫外分光光度计测定灯盏花素注射液各样品的吸收度.结果相关系数r为0.9904,说明lgVo与1/T的线性关系良好,符合一级动力学公式.结论灯盏花素注射液的热解反应活化能为88.93kJ*mol-1,以Arrhenius指数规律推算τ20℃0.9贮存期约6.5a,τ25℃0.9贮存期约3.5a.     

灯盏花素葡萄糖注射液安全性评价

目的:通过多种动物实验对灯盏花素葡萄糖注射液的安全性进行评价,分别进行了灯盏花素葡萄糖注射液的一般药理性实验、局部刺激性实验、急性毒性实验、溶血性实验、被动过敏性试验.方法与结果:通过相关的动物实验结果表明,灯盏花素葡萄糖注射液对实验动物一般生理性活动和精神及神经活动无明显影响,局部刺激反应不明显,成功得出该药对小鼠的...     

灯盏花素治疗脑梗死临床观察

灯盏花素注射液是从中药灯盏花中提取的黄酮类有效成分制成，其有效成分是以灯盏花乙素为主含少量甲素的混合物，具有抗血小板聚集、降低脑血管阻力、降低血浆纤维蛋白原和促进纤溶活性的作用。临床上用于治疗脑血栓、脑栓塞和脑供血不足等缺血性脑血管病。总结我科2003～2004年用灯盏花素注射液治疗脑梗死病人200例，并与维脑路通注射液治疗140例进行对照观察，现将结果报道如下：     

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.