格拉司琼血药浓度的高效液相色谱分析

目的 :建立人血浆中格拉司琼浓度的反相高效液相色谱测定方法。方法 :液 液萃取法分离纯化血浆样品 ,采用荧光检测器 ,以甲醇 磷酸盐缓冲液 (pH 2 .2 ,0 .0 2mol·L- 1含 3 .0 %三乙胺 ) ( 6 3∶3 7)为流动相 ,色谱柱为Shim PackCLC ODS柱( 150mm× 6 .0mm) ,并阐述了血浆中格拉司琼色谱峰形变和分裂的可能机理。结果 :格拉司琼色谱峰对称、不拖尾 ,萃取回收率达 92 % ,空白血浆和代谢物不干扰测定 ,血药浓度线性范围为 0 .5～ 6 0 .0 μg·mL- 1(r =0 .9995) ,最低检测限 0 .3 μg·mL- 1,方法回收率为 98.43 %～ 10 0 .4% ,日内RSD 2 .3 %～ 3 .8% ,日间RSD 2 .9%～ 4.6 %。结论 :此法简便、准确 ,灵敏度高 ,选择性好。     

猪血浆中格拉司琼质量浓度的LC-MS/MS测定方法及应用

目的建立猪血浆中格拉司琼质量浓度液相色谱-串联质谱(LC-MS/MS)检测方法,考察格拉司琼经皮给药后药物动力学行为。方法色谱柱:Diamonsil C18柱(150 mm×4.6 mm,5μm),流动相:甲醇-5 mmol·L-1醋酸铵-甲酸(体积比为45∶55∶0.1),采用液液萃取法,以多反应监测(multiple reaction monitoring,MRM)扫描方式,测定巴马小型猪经皮给予格拉司琼贴剂后血浆中药物的质量浓度。结果猪血浆中格拉司琼质量浓度在0.020²0.0μg·L-1内线性关系良好,r=0.995 9;日内和日间精密度RSD≤13.4%;格拉司琼的平均提取回收率为63.8%20.0μg·L-1内线性关系良好,r=0.995 9;日内和日间精密度RSD≤13.4%;格拉司琼的平均提取回收率为63.8%⁶6.7%(n=6),基质效应为101.4%66.7%(n=6),基质效应为101.4%¹05.8%(n=6);格拉司琼在巴马小型猪血浆中主要药物动力学参数:t1/2为(18.0±1.4)h,ρmax为(15.3±4.0)μg·L-1,MRT为(91.9±4.9)h,Ke为(0.04±0.00)h-1,AUC0-216为(1.22±0.35)mg·h·L-1,AUC0-∞为(1.23±0.35)mg·h·L-1。结论该方法适用于格拉司琼贴剂在巴马小型猪体内药物动力学行为的研究,贴剂可延长格拉司琼作用时间。     

高效液相色谱法测定依维菌素血药浓度

目的 :建立依维菌素血药浓度的HPLC测定法。方法 :依维菌素与N 甲基咪唑、三氟醋酸酐经脱水反应生成荧光产物 ,该产物以HPLC进行分离。色谱柱为SuplecosilLC 18(15 0mm×4.6mm ,5 μm) ,乙腈 水 (96∶4)为流动相 ,柱温 5 0℃ ,流速1mL·min-1,检测波长为 :λex =36 5nm ,λem =475nm。结果 :依维菌素血药浓度在 1～ 40 μg·L-1范围内 ,浓度与峰面积比有良好的线性关系 ,最低检测浓度为 0 .5 μg·L-1。平均回收率为 (99.6± 7.3) %。日内RSD≤ 8.7% ,日间RSD≤ 11.2 %。结论 :本方法简单、快速、准确 ,可用于依维菌素的临床药动学研究     

紫外分光光度法测定苯妥英钠血药浓度

目的 :建立一种简单、准确的紫外分光光度法 ,用于苯妥英钠血药浓度监测。方法 :采用紫外分光光度法测定苯妥英钠血药浓度 ,检测波长 2 5 0nm ,以环己烷为提取剂。结果 :苯妥英钠 10 ,4 0 ,80mg·L-13个浓度的平均回收率为 93 5 0 %。日内RSD <8% (n =4 ) ,日间RSD <10 % (n =5 )。分析方法的最低定量限为 1 1mg·L-1。线性范围为 5～ 80mg·L-1,线性回归方程为A =1 5 81× 10 -3 c+7 917× 10 -4,r=0 9992 (n =5 )。该方法监测口服苯妥英钠患者 6例 ,血药浓度为 8 4 8～ 37 4 5mg·L-1。结论 :该方法简单、快速 ,适用于基层单位临床血药浓度监测     

高效液相色谱法测定人血浆中麦考酚酸的血药浓度

目的 :建立测定麦考酚酸 (MPA)血药浓度的方法并对肾移植病人给药后的血药浓度进行测定。方法 :采用高效液相色谱 (HPLC)法测定血药浓度 ,检测波长 30 3nm。乙腈 (含有 0 .1mol·L- 1磷酸 )作为血样的蛋白沉淀剂。色谱柱 :AgilentXDBC18(15 0mm× 4 .6mm ,5 μm) ;流动相 :乙酸钠缓冲液 (pH =3.0 ,30mmol·L- 1)∶乙腈 =5 7∶4 3(V/V) ;流速 :1mL·min- 1。结果 :MPA血药浓度线性范围为 0 .6～ 30mg·L- 1(r =0 .9995 ,n =6 ) ,其血浆最低检测浓度为 0 .2mg·L- 1;低、中、高 3种浓度MPA的方法回收率为 (98.9± 1.5 ) % ,提取回收率为 (10 6 .73± 0 .2 7) % ;相应 3种浓度MPA的精密度RSD均小于 5 %。结论 :HPLC法能快速、准确对MPA进行血药浓度测定 ,可以用于MPA的临床血药浓度监测和药动学研究。     

反相高效液相色谱法测定血浆中文拉法辛浓度

目的 :建立高效液相色谱法检测人血浆中文拉法辛浓度。方法 :血浆样品经石油醚 乙醚 (2∶1 )提取后 ,有机相再用50mmol·L- 1盐酸反萃取并浓缩进样。色谱柱为氰基柱 (2 50× 4.6mm ,5μm) ,乙腈 -0 .1mol·L- 1NH4 H2 PO4 (2 5∶75)为流动相 ,UV检测波长 2 2 9nm。结果 :文拉法辛血浆最低检测浓度 1 0 μg·L- 1,线性范围 2 5～ 80 0 μg·L- 1,萃取回收率 75.5%～79.3%,加样回收率 97.4%～ 1 0 1 .2 %,日内RSD 4.87%～ 6 .39%,日间RSD 7.55%～ 1 0 .80 %。结论 :该法准确可靠 ,已用于临床患者文拉法辛血药浓度测定。     

阿洛司琼治疗过敏性肠综合征

阿洛司琼是一种高选择性 5- HT3受体拮抗剂 ,现正试用于治疗过敏性肠综合征 (IBS)。药效学特征　阿洛司琼 (0 .0 1～ 1 .0μmol·L-1)阻滞游离豚鼠肠肌层和粘膜下层由 5- HT3介导的神经元快速去极化 ;该效应呈剂量依赖性 (IC50约为 55nmol· L-1)。高浓度阿洛司琼 (1μmol·L-1)抑制上述两种神经元由 5- HT1p介导的慢性去极化 ,此外 ,在次级粘膜下神经元还可抑制由粘膜刺激诱发的快速和慢速兴奋性突触后电位 ,而昂丹司琼 (ondansetron)或格拉司琼 (granisetron)无此作用。药代动力学　 2 4名男性志愿者连服 2 8d阿洛司琼 (2 mg,bid) ,…     

HPLC法测定阿奇霉素的血药浓度

目的 :建立阿奇霉素血药浓度的测定方法。方法 :采用HPLC紫外检测法 ,岛津CLC CN分析柱 ,流动相为 0 1mol·L-1磷酸二氢钠 甲醇 乙腈 ( 85∶7∶8,,V/V/V) ,pH 3 0～ 3 5 ,流速 1mL·min-1,柱温 4 0℃ ,检测波长 2 10nm ,灵敏度 0 0 0 3AUFS ,提取液为氯仿 正己烷 ( 3∶2 ,V/V) ,以峰面积外标法定量。结果 :阿奇霉素血药浓度线性范围 5 0～ 5 0 0 0 μg·L-1,平均回收率( 10 0 9± 2 7) % ,日内RSD 1 2 %～ 4 3% ,日间RSD 2 8%～ 6 8%。结论 :本法简便 ,分析速度快 ,灵敏度较高 ,重复性好 ,基本能适用于临床血药浓度测定及药动学研究。     

反相高效液相色谱法测定氨氯地平血药浓度

目的 　建立反相高效液相色谱法 ( HPLC)测定人血浆中氨氯地平浓度。 方法 　血浆样品用重蒸馏乙醚提取 ,以达克罗宁为内标 ;甲醇 -0 .0 3 mol· L- 1磷酸二氢钾缓冲液 ( 72∶ 2 8)为流动相 ,流速 1.0 ml·min- 1 ;检测波长 2 3 8nm;柱温 :室温。 结果 　本法在 1.0～ 12 .0 ng·m L- 1范围内线性关系良好 ,r=0 .9980。日内 RSD为 3 .7%～ 6.7% ( n=5 ) ,日间 RSD为 6.0 %～ 7.1% ( n=15 ) ;回收率 89.0 %～ 10 1.7% ;血清最低检测浓度为 0 .15 ng·m L- 1 ( S/N=2 )。 结论 　本法灵敏、准确、快速 ,为该药物的临床血药浓度监测和药代动力学研究提供依据。     

高效液相色谱法测定异丁司特的血药浓度

目的 :建立高效液相色谱法测定人血浆中异丁司特浓度的方法。方法 :采用YWG C18色谱柱 ,以甲醇 0 .0 5mol·L-1磷酸二氢钾 (6 5∶35 ,用磷酸调pH值 3.5 )为流动相 ,检测波长 2 2 5nm ,流速 1.0mL·min-1,进样量 5 0 μL ,内标物为桂利嗪。 结果 :异丁司特标准曲线在 2～ 12 0 μg·L-1范围内线性关系良好 (r =0 .995 6 ) ,最低检测浓度为 2 μg·L-1,平均回收率为10 0 .2 % ,RSD为 4 .7% (n =5 )。结论 :该法操作简便 ,灵敏 ,准确度高 ,适用于异丁司特血药浓度的测定和药动学的研究。     

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.     

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.