高效液相色谱法测定洛美沙星局部应用的兔眼通透性研究

采用高效液相色谱法（ＨＰＬＣ）测定了洛美沙星在兔眼组织中的通透性。以０．３％滴眼液单次点眼３０ｍｉｎ后，角膜、房水和虹膜睫状体组织的药物浓度分别是８．７５±０．３９μｇ·ｇ－１，０．２１±０．１ｍｇ·Ｌ－１和１．４９±０．３９μｇ·ｇ－１。去除角膜上皮后，多次点眼（１滴／５ｍｉｎ×６）和结膜下注射（０．５ｍｇ，０．５ｍｌ），眼组织达较高药浓度，超出多数病菌的ＭＩＣ９０。实验结果证实，洛美沙星可做为内眼术前的预防用药和治疗由敏感菌引起的眼内炎。     

环丙沙星滴眼剂在家兔眼内组织分布及其药物动力学

环丙沙星（ｃｉｐｒｏｆｌｏｘａｃｉｎ，ＣＰＦＸ）滴眼液点入兔眼后，用ＨＰＬＣ法测定眼内各组织中药物浓度。结果在角膜、房水、虹膜－睫状体、晶体、玻璃体内峰浓度值分别为１９．４３μｇ／ｇ，１．５８μｇ／ｍｌ，１６．６８μｇ／ｇ，１．４２μｇ／ｇ和０．９６μｇ／ｍｌ；其半衰期分别为０．７６，０．６９，０．９２，０．６１和１．４０ｈ。结果表明ＣＰＦＸ能在眼内达到较高的抗菌浓度。     

阿莫西林克拉维酸钾口服干混悬剂含量测定方法研究

目的：对阿莫西林克拉维酸钾口服干混悬剂含量测定方法研究。方法：采用高效液相色谱法，在３×３ＣＲＣ１８柱（４ｍｍ×３．５ｃｍ）上，以ｐＨ４．４磷酸二氢钠溶液－甲醇（９５∶５）为流动相，流速１．０ｍｌ·ｍｉｎ－１，检测波长为２２０ｎｍ。结果：阿莫西林和克拉维酸浓度分别在２５～５００μｇ·ｍｌ－１及１０～２００μｇ·ｍｌ－１范围内有良好的线性关系，平均方法回收率分别为９９．４％±１．９％和９９．５％±２．０％，日内精密度分别在１．１％～２．３％和１．７％～２．６％之间，日间精密度分别＜３．１％和＜２．５％。结论：本法实用简便，结果可靠。     

柱切换高效液相色谱法测定头孢拉定血清浓度

建立一种ＨＬＣ法快速测定头孢拉定血清浓度。取全血１ｍＬ，离心，２０μＬ直接进样。色谱柱：Ｈｉ－ＰｏｒｅＲｅｖｅｒｓｅｄＰｈａｓｅＣｏｌｕｍｎ（４．６ｍｍ＊２５０ｍｍ），预柱：Ｂｉｏ－ｓｉｌＯＤＳ－５ｓＣａｒｔｉｄｇｅｓ，分析流动相１０％乙腈，预流动相０．９％氯化钠，切换时间２ｍｉｎ，检测波长２５４ｎｍ。药物保留时间７．０５ｍｉｎ，分离良好；血清浓度２－１００μｇ／ｍＬ范围内线性良好，ｒ＝０．９９９     

诺氟沙星滴入兔眼与注入球结膜下其组织分布及药动学比较

用高效液相色谱法对诺氟沙星点眼与球结膜下注射后眼各组织药物浓度进行测定，比较两种给药途径的眼各组织浓度及其药物动力学参数。结果表明，诺氟沙星点眼与球结膜下注射后４ｈ，泪液诺氟沙星浓度分别为２．０８±０．１９与１６．０７±３．１４μｇ／ｍｌ（Ｐ＜０．０１）；角膜分别为０．７１±０．０７与１．６５±０．２４μｇ／ｇ（Ｐ＜０．０１）。泪液ＡＵＣ分别为９８．３３±７．３１与２７９．８２±３１．７ｈ·μｇ／ｍｌ；角膜ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２Ｋｃ分别为１７．４２±１．２１ｈ·μｇ／ｇ、８．９４±０．８μｇ／ｇ、０．５７±０．０６ｈ、０．９１７±０．１６ｈ与２０．０１±１．０１ｈ·μｇ／ｇ、１０．０５±０．０７μｇ／ｇ、０．４５±０．０５ｈ、１．１５±０．２０ｈ；房水ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ分别为１．１３±０．２１ｈ·μｇ／ｍｌ、０．３９±０．０５μｇ／ｍｌ、０．６２±０．０９ｈ与１．７９±０．０７ｈ·μｇ／ｍｌ、１．００±０．１５μｇ／ｍｌ、０．４７±０．１０ｈ。诺氟沙星点眼与球结膜下注射两种给药途径的上述药动学参数有明显差异（Ｐ＜０．０５或０．０１）。     

HPLC测定血浆中奥美拉唑的浓度

本文采用ＨＰＬＣ测定人血浆中奥美拉唑的浓度、色谱柱为ＵｌｔｒａｓｐｈｅｒｅＯＤＳ４．６×２５０ｍｍ，流动相为甲醇－磷酸盐缓冲液（６０／４０），检测波长为３０２ｎｍ，流速为１ｍｌ／ｍｉｎ，血浆浓度在０．０２５～１．０μｇ／ｍｌ范围内线性关系良好（γ＝０．９９９８），最低检测浓度０．０２５μｇ／ｍｌ，平均回收率１００．５±１．９％。日间、日内ＲＳＤ％均＜４．１％。     

肉苁蓉类生药中苯乙醇甙类成分的 RP-HPLC 分析

采用反相高效液相色谱法，对４种及１变种肉苁蓉类生药和２５份商品药材所含的苯乙醇甙类成分进行了定性和定量分析，结果表明，荒漠肉苁蓉ＣｉｓｔａｎｃｈｅｄｅｓｅｒｔｉｃｏｌａＭａ，盐生肉苁蓉Ｃ．ｓａｌｓａ（Ｃ．Ａ．Ｍｅｙ）Ｇ．Ｂｅｃｋ，白花盐苁蓉Ｃ．ｓａｌｓａｖａｒ．ａｌｂｉｆｌｏｒａＰ．Ｆ．ＴｕｅｔＺ．Ｃ．Ｌｏｕ和管花肉苁蓉Ｃ．ｔｕｂｕｌｏｓａ（Ｓｃｈｅｎｋ）Ｗｉｇｈｔ所含成分相似，沙苁蓉Ｃ．ｓｉｎｅｎｓｉｓＧ．Ｂｅｃｋ区别较大；松果菊甙（ｅｃｈｉｎａｃｏｓｉｄｅ）和类叶升麻甙（ａｃｔｅｏｓｉｄｅ）的含量以盐生肉苁蓉最高，分别为２１３％和１５１％。采用ＡｌｔｉｍａＣ１８，５μｍ，２５０×４６ｍｍ色谱柱；乙腈─１５％乙酸水溶液，其中乙腈浓度从８％→２０％，０～６０ｍｉｎ线性梯度洗脱，作为定性分析流动相，乙腈浓度从１１５％→２０％，０～３５ｍｉｎ线性梯度洗脱，作为定量分析流动相；流速１２ｍｌ·ｍｉｎ－１，ＵＶ３３５ｎｍ检测。     

反相高效液相色谱法测定萘普生钠血浆浓度

目的：建立用高效液相色谱法测定萘普生钠血浆浓度的方法。方法：血浆样品在酸性条件下,以１,２二氯乙烷提取,吲哚美辛为内标,采用ＬｉｃｈｒｏｓｏｒｂＣ１８（５μｍ）柱,流动相为甲醇∶醋酸醋酸铵缓冲液（ｐＨ４．５）＝７４∶２６,流速为１．０ｍｌ·ｍｉｎ－１,检测波长３１８ｎｍ,萘普生和内标的保留时间分别为３．３５和４．７１ｍｉｎ。结果：线性范围在１～９０μｇ·ｍｌ－１（ｒ＝０．９９９９,最低检测浓度为０．４μｇ·ｍｌ－１血浆,ＲＳＤ％＜３．５。结论：本方法可用于萘普生钠的药物动力学研究     

高效液相色谱法测定外用培氟沙星软膏后兔皮肤中药物浓度

采用高效液相色谱法（ＨＰＬＣ）测定了外用培氟沙星软膏后兔用药部位皮肤中药物浓度,薄涂０．７５％软膏后兔皮肤中药物浓度经时过程表明,药物能迅速渗入皮肤,涂药后即刻检出的浓度为８．０４±２．４０μｇ／ｇ,１ｈ浓度达峰值（２４．６４±３．２９μｇ／ｇ）,１２ｈ时仍保持较高浓度（８．２８±２．４３μｇ／ｇ）;不同浓度软膏涂药后１ｈ和１２ｈ的测定结果显示,皮肤中药物浓度与软膏浓度具良好相关性,０．３７５％软膏的皮肤药浓分别为１６．１１±５．１９μｇ／ｇ和５．５５±１．４０μｇ／ｇ,１．５％软膏分别为３３．２０±５．９７μｇ／ｇ和１７．６７±３．８０μｇ／ｇ。根据试验结果结合培氟沙星对皮肤主要致病菌的ＭＩＣ９０,建议临床用培氟沙星软膏浓度以０．７５％为宜。     

高效液相色谱法测定生物样品中两性霉素B

两性霉素Ｂ（ＡＭＢ）常用于内脏或全身真菌感染的治疗。由于ＡＭＢ对肝、肾等有较大毒性，应监测血浆中ＡＭＢ的浓度，以便调整其用量。我们采用高效液相色谱法（ＨＰＬＣ），在μ－ＢｏｎｄａｐａｋＣ１８柱（３．９ｍｍ×３００ｍｍ，１０μｍ）上，以０．０５ｍｏｌ／ＬＥＤＴＡ－２Ｎａ溶液－乙腈（１∶１）为流动相；流速为１．４ｍｌ／ｍｉｎ；检测波长为４０５ｎｍ，测定了血浆、脑脊液中ＡＭＢ浓度。ＡＭＢ血浆中最小检出量为０．０２μｇ／ｍｌ。血浆中ＡＭＢ提取率＞８７％。日内精密度在５．０１％～６．２８％之间，日间精密度血样＜７．８６％，ＣＳＦ＜５．９８％。血浆中ＡＭＢ浓度在０．０５～２．０μｇ／ｍｌ范围内有良好线性关系。方法回收率为９９．０４％±３．９０％。该法用于１例曲霉菌全身感染者ＡＭＢ血药浓度测定，为制定给药方案提供了依据。     

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.