黄芩苷灌胃给药经兔眼血-房水屏障的通透性

目的:研究黄芩苷灌胃给药经兔眼血.房水屏障的通透性.方法:建立测定黄芩苷兔眼房水和血浆药物浓度的HPLC方法,色谱条件:Diamonsil C18色谱柱(200 mm×4.6 mm,5 μm);流动相为甲醇-0.2%磷酸溶液(47:53);流速为1.0 mL·min-1;检测波长为279 nm;柱温为35 ℃;以对二甲氨基苯甲醛为内标物.健康纯种日本长耳白兔单剂量灌胃黄芩苷80 mg·kg-1后,比较不同时间兔眼房水和血浆药物浓度,绘制药物浓度-时间曲线,用3p87药动学软件计算黄芩苷在房水和血浆中的药动学参数.结果:在本色谱条件下,黄芩苷在房水和血浆中的线性范围分别为0.02～0.25和0.012 5～24.0 mg·L-1,相关系数(r)分别为0.996 8和0.998 2.黄芩苷在房水中的AUC0～12h显著低于血浆[(0.639±0.067) vs (80.1±2.1)h·mg·L-1,P<0.01],各个时间点比较,黄芩苷在房水中的质量浓度均显著低于其血浆中的质量浓度(P<0.01).结论:黄芩苷经灌胃给药较难通过血-房水屏障进入眼内.     

HPLC法测定不同厂家丹参注射液中丹参素和原儿茶醛的含量

目的 测定不同厂家丹参注射液中丹参素和原儿茶醛的含量,以考察其质量差异.方法 RP-HPLC法.Kromasil ODSC18色谱柱(250 nm ×4.6 mm,5 μm);流动相:甲醇:0.3%冰醋酸(22:78);流速1.0 ml·min-1;检测波长281 nm.结果 不同厂家丹参注射液中丹参素和原儿茶醛的含量分别为:0.497 9～7.588 5 g·L-1,0.193 4～0.635 8 g·L-1.结论 不同厂家丹参注射液中丹参素和原儿茶醛的含量存在较大差异.     

HPLC法同时测定肿瘤Ⅰ号胶囊中丹参素与淫羊藿苷的含量

目的 建立肿瘤Ⅰ号胶囊中丹参素与淫羊藿苷的含量测定方法.方法 采用HPLC法,以乙腈-体积分数为1%的冰醋酸溶液梯度洗脱,色谱柱为Kromasil C18(4.6mm×200mm,5μm),流速为1.0mL·min-1,柱温为35℃,检测波长为275nm.结果 丹参素在11.38～227.50mg·L-1内,淫羊藿苷在2.0～40.0mg·L-1内,与峰面积呈良好的线性关系,相关系数分别为0.9995和0.9996.方法平均回收率分别为98.6%(RSD=1.9%)、96.0%(RSD=0.84%).结论 可作为肿瘤Ⅰ号胶囊质量控制方法之一.     

RP-HPLC法同时测定乙肝舒康胶囊中没食子酸和丹参素含量

目的建立同时测定乙肝舒康胶囊中没食子酸和丹参素的高效液相色谱法。方法采用Hy-persil C18色谱柱(200.0 mm×4.6 mm,5μm),以甲醇-体积分数为0.5%的冰醋酸溶液(体积比为4∶96)为流动相,流速:1.0 mL.min-1,检测波长:280 nm。结果没食子酸和丹参素的线性分别为4.5~90.0 mg.L-1(r=0.999 9)和7.5~150.0 mg.L-1(r=0.9994),平均回收率分别为99.1%和100.2%,RSD分别为2.2%和2.4%。     

高效液相色谱法测定人尿中盐酸多西环素

目的:建立测定人尿中多西环素含量的反相高效液相色谱方法。方法:以盐酸土霉素为内标,色谱分离采用Hyper-sil-ODS分析柱(4.6mm×250mm10μm),柱温30℃,以N,N-二甲基甲酰胺-0.05mol·L-1草酸铵缓冲液(40∶60,pH7.5)为流动相;流速:1.0mL·min-1,紫外检测波长:269nm。结果:尿中多西环素测定方法的线性范围为5~310mg·L-1,方法回收率平均为99.63%;日内精密度RSD小于0.49%、日间精密度RSD小于0.63%,最低检测限为0.03mg·L-1。多西环素尿样在检测过程中保持稳定。结论:本方法操作简便,灵敏度高,专一性强,可用于多西环素临床药动学研究。     

HPLC法测定养心活血片中丹参素的含量

目的建立HPLC法测定养心活血片中丹参素的含量。方法采用HPLC法,色谱柱为Phenomenex ODS柱(150mm×4.6mm,5μm);流动相为甲醇-5mL.L-1醋酸(10∶90);流速:1.0mL.min-1;检测波长:281nm;柱温:室温。结果对照品进样量在0.010 4～0.104 0μg范围内线性关系良好,平均回收率为99.4%,RSD为1.6%(n=5)。结论建立的方法适用于养心活血片的质量控制。     

高效液相色谱法测定西罗莫司血药浓度

目的:建立快速测定人全血中西罗莫司浓度的高效液相色谱方法.方法:色谱柱为Zorbax Eclipse XDB C18(4.6mm×150mm,5μm);流动相为甲醇-乙腈-去离子水(50∶22∶28,v/v);流速1.2mL·min-1;紫外检测波长278nm;柱温50℃.结果:西罗莫司浓度测定的线性范围为2.5～50.0μg·L-1,最低检测浓度为2.0μg·L-1,平均回收率为103.2%,日内RSD小于5%,日间RSD小于4%.结论:本方法简便、快速,定量准确,可用于西罗莫司临床药动学研究,也可用于西罗莫司常规血药浓度监测.     

HPLC测定丹参素冰片酯脂肪乳注射液含量及有关物质

目的:建立丹参素冰片酯脂肪乳注射液含量测定及有关物质检查方法。方法:采用高效液相色谱法。色谱柱:KromasilC18(150 mm×4.6 mm,5μm)色谱柱,流动相:乙腈-0.2%甲酸水(42︰58),流速为1.0 mL·min-1,检测波长280 nm,进样体积20μL。结果:试验结果表明,HPLC法检测主峰与杂质峰有较好的分离度,且重复性较好;丹参素冰片酯的浓度在5～60μg·mL-1范围内与峰面积呈良好线性关系(r=1.000),平均回收率为98.2%(n=9)。结论:该法操作简便,结果可靠,适用于丹参素冰片酯脂肪乳注射液含量测定及有关物质检查。     

RP-HPLC法测定心宁片中丹参素和原儿茶醛的含量

目的 建立同时测定心宁片中丹参素和原儿茶醛含量的方法.方法 采用高效液相色谱法,色谱柱为LinkSil ODS C18;柱温:35℃;流动相:甲醇-1％冰醋酸溶液(8∶92);流速:1.0 mL· min-1;检测波长:280 nm.结果 丹参素在23.4～187.2 mg·L-1(r=0.999 8)、原儿茶醛在1.92～38.40 mg· L1(r=0.999 9)浓度范围内线性关系均良好;平均回收率分别为100.29％和98.96％.结论 该方法简单、准确、快速,可用于心宁片中丹参素和原儿茶醛的质量控制.     

反相高效液相色谱法测定人血浆中米氮平的浓度

目的:建立测定人血浆中米氮平浓度的高效液相色谱法.方法:以美国迪马公司钻石C18反相柱(250 mm×4.6 mm,5 μm)为色谱柱,流动相为甲醇-水(90∶10),流速为0.8 mL·min-1,检测波长294 nm,以乙酸乙酯为提取剂.结果:米氮平高、中、低(500.0,250.0,50.0 μg·L-1)3个浓度的平均回收率分别为100.21%,98.47%,97.00%,日内、日间差RSD均低于6%;分析方法的定量测定下限为15.0 μg·L-1.线性范围为25.0～1000.0 μg·L-1.结论:该方法灵敏、准确、简单、快速,可用于临床血浓监测和药动学研究.     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.