用RP-HPLC法测定人血浆中巴洛沙星浓度并应用于治疗药物监测

目的:建立巴洛沙星血药浓度的RP-HPLC测定方法,并用于巴洛沙星片剂的药动学参数测定,为临床合理用药提供参考.方法:色谱柱为Diamonsil ODS C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-水(含0.04 mol/L磷酸和0.4%三乙胺,pH=4.5):23,77,流速为1.0 mL/min,柱温35℃,检测波长294 nm.内标物为加替沙星.将该方法用于单剂量口服100 mg巴洛沙星片的主要药动学参数研究.结果:该方法的线性范围为0.05～5.00μg/mL(r=0.999 8),方法的日内及日间RSD＜10%.结论:该方法准确,快速、简便,可为临床评价药物治疗效果提供参考.     

高效液相色谱法测定巴洛沙星片含量及有关物质

目的:建立高效液相色谱法测定巴洛沙星片的含量和有关物质。方法:采用 Zorhax SB C_(18)色谱柱(4.6mm×250 mm,5μm);以0.02 mol·L~(-1)磷酸二氢钾-甲醇(60:40,用磷酸调 pH 至3.5)为流动相;流速1.0 mL·min~(-1);检测波长:295 nm;柱温:40℃;进样量:20μL。结果:巴洛沙星线性范围为5～40μg·mL~(-1),r=0.9999;平均回收率为99.8%(RSD=0.56%),n=6。结论:该法简便准确,专属性好,可用于该制剂的质量控制及有关物质测定。     

巴洛沙星有关物质测定方法的改进

目的:建立用高效液相色谱法(HPLC法)测定巴洛沙星降解物质的方法.方法:色谱柱为C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-磷酸盐缓冲溶液(25:75);检测波长为295 nm.结果:HPLC法可测定巴洛沙星的有关物质.结论:HPLC法简单、快速、重现性好.     

巴洛沙星片有关物质测定方法的研究

目的建立RP-HPLC法[1]测定巴洛沙星片的有关物质。方法采用Ecosil C18色谱柱（250 mm×4.6 mm,5μm）,0.05 mol/L磷酸二氢钾溶液（含0.2%三乙胺,用磷酸调节pH值为3.0）为流动相A,乙腈为流动相B,梯度洗脱,流速为1 mL/min,检测波长294 nm。结果采用主成分自身稀释方法测定,方法的专属性强,巴洛沙星在0.195 10~9.752 90μg/mL范围内呈线性,线性方程为A=53.009 7C＋1.508 4,相关系数为：r=0.999 9（n=5）。最低检测限为0.030 pg。结论结果方法准确可靠,重复性好,可用于巴洛沙星片有关物质的测定。     

巴洛沙星的含量测定方法研究

目的对自行研制的巴洛沙星的含量测定方法进行研究。方法分别采用高效液相色谱(HPLC)法、非水溶液滴定法测定巴洛沙星的含量。结果HPLC法测定其含量为99.42%～99.51%,非水溶液滴定法为99.43%～99.57%。结论2种方法测定结果无明显差异,但非水溶液滴定法所耗成本较低且操作简便。     

巴洛沙星片治疗泌尿系统细菌性感染的多中心随机双盲对照临床试验

目的评价巴洛沙星片治疗泌尿系统急性细菌性感染的安全性和有效性。方法采用多中心、双盲双模拟、随机、阳性药物平行对照试验设计。共入选221例,其中可评价疗效病例209例,巴洛沙星组102例,左氧氟沙星组107例。巴洛沙星组予巴洛沙星片200 mg,hid,左氧氟沙星组予左氧氟沙星片200 mg,bid,2组疗程均为7～14 d。结果巴洛沙星组临床总有效率和痊愈率分别为98.0%和87.2%,细菌清除率为100%;左氧氟沙星组临床总有效率和痊愈率分别为100.0%和87.9%,细菌清除率为100%。巴洛沙星组和左氧氟沙星组药物不良反应发生率分别为4.8%和0.9%。2组比较均无显著差异(P>0.05)。结论巴洛沙星治疗急性细菌性泌尿系统感染安全、有效。     

高效液相色谱法测定甲磺酸帕珠沙星注射液中右旋体的含量

目的建立甲磺酸帕珠沙星注射液中右旋异构体含量的高效液相色谱测定方法。方法Shim pakCLC ODS柱 (15 0mm× 6 .0mm ,5 μm) ,流动相为L 异白氨酸硫酸铜溶液 (取L 异白氨酸 1.3g、硫酸铜 1.0g和水 10 0 0ml溶解用 0 .1mol/L盐酸或 0 .1mol/L氢氧化钠调pH至 3.5 ) 甲醇 (75∶2 5 ) ;检测波长 :32 0nm。结果甲磺酸帕珠沙星右旋体在 0 .5～ 10 0 μg/ml浓度范围内呈良好的线性关系 (r=0 .9993) ,平均回收率为 99.5 4 % ,RSD为 1.0 1% (n =9)。结论此法快捷、专属性及重现性好 ,可用于甲磺酸帕珠沙星和D 甲磺酸帕珠沙星杂质的含量测定。     

HPLC法测定滑肠通便片中大黄素的总量

目的 建立滑肠通便片中大黄素的含量测定方法 .方法 采用高效液相色谱(HPLC)法:色谱柱为迪马Diamonsil-C18(5 μm,200 mm×4.6 mm);检测波长:254 nm;甲醇-0.1%磷酸(78∶22)为流动相;进样量: 20 μl;流速:1.0 ml/min;柱温:25℃.结果 大黄素在0.08～0.8 μg范围内呈良好的线性关系,r=1.0, 平均加样回收率为99.0%,相对标准偏差值(RSD)=0.70%.结论 本方法 简便、准确,可用于滑肠通便片的质量控制.     

气相色谱-质谱联用法测定巴洛沙星中乙酸残留量

目的:建立气相色谱-质谱联用(GC-MS)法测定巴洛沙星中残留溶剂乙酸.方法:采用GC-MS法,先采用扫描(SCAN)方式确定乙酸与甲醇酯化反应生成的醋酸甲酯色谱峰的保留时间,再用选择离子监测(SIM)方式检测醋酸甲酯,检测质核比(m/z)分别为29、42、43、59和74时的总离子流强度.色谱柱为DB-WAX毛细管柱(30 mm×0.25mm,0.25um);柱温:40℃保持10 min,再以10℃/min的速度升温至140℃;进样口温度150℃,质谱检测器离子源温度200℃,载气为氦气,柱压为0.105 MPa;顶空进样:平衡温度70℃,平衡时间20 min;进样量0.5 ml;分流比1:20.结果:在10～50ug/ml范围内,溶液浓度与峰面积呈良好的线性关系(r=0.999 9),平均回收率为101.22%,RSD为1.76%(n=9),最低检出限为1ug.结论:该方法准确可靠,重现性良好,可用于巴洛沙星的质量控制.     

单剂量巴洛沙星片在健康人体的药代动力学

目的 研究巴洛沙星片(喹诺酮类抗生素)在健康志愿者体内的药代动力学.方法 采用随机开放的三周期交叉试验设计,健康志愿者12例随机分成3组,分别单剂量交叉口服巴洛沙星100、200、400 mg,以反相高效液相色谱法测定给药后不同时间点巴洛沙星的血浆浓度,血药浓度经DAS软件处理.结果 巴洛沙星的主要药代动力学参数Cmax分别为(0.93±0.30)、(1.97±0.60)、(3.54±0.83)mg·L-1,t1/2分别为(8.78±2.65)、(8.11±1.42)、(7.68±1.31)h,AUC0～t分别为(9.9±1.4)、(20.38±3.20)、(40.02±5.54)mg·h·L-1,AUC0-∞分别为(10.41±1.44)、(21.19±3.16)、(44.07±7.29)mg·h·L-1.结论 单剂量口服巴洛沙星片,其消除半衰期t1/2与给药剂量无关;而Cmax、AUC0-t、AUC0～∞与剂量呈明显相关性,且随给药剂量的增大而增加.表明巴洛沙星在体内为线性动力学特征.     

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.