赖氨匹林与妥布霉素注射液在生理盐水中配伍观察

在２５℃，３７℃下对赖氨匹林与硫酸妥布霉素注射液在０．９％氯化钠注射液中的配伍进行了观察。用紫外分光光度法和旋光度法分别测定赖氨匹林，妥布霉素的含量变化。结果表明，两者在２５℃，３７℃与配伍后６ｈ内含量药液的外观，ｐＨ值等无改变。     

异环磷酰胺与头孢噻肟的配伍稳定性

目的：考察不同温度下,注射用异环磷酰胺与头孢噻肟在０．９％氯化钠注射液中配伍的稳定性。方法：采用反相高效液相色谱法测定异环磷酰胺与头孢内配伍后２４ｈ内各时间的含量,同时观察外观变化并测定ｐＨ值。结果：两药在０．９％氯化钠注射液中配伍后,异环磷酰胺在不同温度下２４ｈ内的含量在９７．４８％以上。头孢噻肟钠随着时间的推移有水解,呈一级反应规律０℃￣４℃,Ｔ０．９＝７６．８５ｈ,２５℃Ｔ０．９＝２１．９６     

注射用阿莫维酸钾的HPLC分析及稳定性研究

本文以硼砂缓冲液（０．０８ｍｏｌ／Ｌ，ｐＨ４．０）—甲醇（９５５）为流动相，在ＯＤＳ柱上分析注射用阿莫维酸钾，２２０ｎｍ检测。各成分线性关系良好，阿莫西林（ＡＭＯ）及克拉维酸（ＣＬＶ）回收率分别为（９９．９０±０．１８）％和（９９．７６±０．２１）％。运用线性升温法考察了本品稳定性，ＡＭＯ的室温降解速率常数Ｋ２５℃＝２．２６×１０－６／ｈ，ｔ０．９＝３．４年；ＣＬＶ为Ｋ２５℃＝３．６０×１０－８／ｈ，ｔ０．９＝５．４年。并证实本品的水溶液浓度越大，越易降解。考察了本品在不同ｐＨ水溶液及几种常用输液中的稳定性。     

枢复宁在肺癌患者体内的药物动力学和生物利用度

９名接受顺铂化疗的原发性肺癌患者单次口服和静脉注射枢复宁８ｍｇ后，用反相高效液相色谱法测定血浆药物浓度。经用ＰＫＢＰ－Ｎ１程序在计算机上拟合计算表明，枢复宁在人体内表现为二房室模型。口服后主要药动学参数：Ｔ１／２Ｋａ＝０．４１±０．３０ｈ，Ｔ１／２α＝０．９±０．４３ｈ，Ｔ１／２β＝３．３±１．２ｈ，Ｃｍａｘ＝２８．６±９．５ｎｇ／ｍｌ，Ｔｍａｘ＝１．７±０．９ｈ，ＡＵＣ＝１５８±７３ｎｇ·ｈ／ｍｌ，绝对生物利用度为５５％。     

国产硫酸奈替米星注射液的药动学研究

采用微生物法对８名健康受试者单剂静脉滴注和肌注１００ｍｇ硫酸奈替米星注射液进行药动学研究，测定了给药后不同时间的血、尿药浓度，并经计算机程序计算药动学参数。结果显示：单剂静滴和肌注后的药动学符合二室开放模型，静滴药动学方程式为：Ｃ＝１０．８１２２ｅ－３．６７１４ｔ＋４．８８３１ｅ－０．２２０５ｔ；肌注药动学方程式为：Ｃ＝９．６８６８ｅ－１．４９１８ｔ＋５．４７５４ｅ－０．２０８６ｔ－１０．９７７０ｅ－３．７２５９ｔ。Ｔ１／２α分别为０．７４７８和０．４１２１ｈ，Ｔ１／２β分别为３．２３０８和２．８７４０ｈ，峰浓度分别为１３．１１和７．６０μｇ／ｍｌ，肌注后达峰时间为０．４８ｈ，总清除率分别为３．２２和３．２６（Ｌ／ｈ），２４ｈ肾排出率分别为５９．０６％和６８．５７％。给药后６ｈ内血药浓度及２４ｈ内尿药浓度＞１μｇ／ｍｌ，尿药浓度明显高于血药浓度。本研究结果与进口硫酸奈替米星注射液药动学过程基本一致。根据其药动学特征，建议一般给药方案为１００ｍｇ每日２次，可达到和维持有效血药浓度。     

头孢噻肟钠在3种常用输液中的配伍实验

用紫外分光光度法对头孢噻肟钠与０．９％氯化钠注射液，５％葡萄糖氯化钠注射液等分别进行配伍实验，结果在胝于３７℃时５ｈ内可与１０％葡萄糖注射，５％葡萄糖氯化钠注射液配伍，与０．９％氯化钠注射液配伍不稳定。     

先锋必素在10％葡萄糖注射液中配伍维生素C注射液的稳定性研究

本文用紫外分光光度法对先锋必素在１０％葡萄糖注射液中配伍Ｖｉｔｃ注射液的稳定性，按经典恒温加速实验进行动力学实验研究。结果表明：先锋必素配伍ＶｉｔＣ后的降解反应为一级反应。２５℃，３５℃时配伍液的有效期Ｔ０．９分别为３１．１８ｈ，２３．１６ｈ，为临床合理用药提供了实验依据。     

头孢噻肟钠在3种常用输液中的配伍实验

用紫外分光光度法对头孢噻肟钠与０．９％氯化钠注射液，１０％葡萄糖注射液，５％葡萄糖氯化钠注射液等分别进行配伍实验，结果表明在低于３７℃时５ｈ内可与１０％葡萄糖注射液，５％葡萄糖氯化钠注射液配伍，与０．９％氯化钠注射液配伍不稳定．     

可乐必妥在肾衰尿毒症患者中血液透析的药物动力学

８名尿毒症患者单次口服可乐必妥（ＬＶＦＸ）１００ｍｇ，３．５ｈ后开始血液透析，血清及透析液标本用ＨＰＬＣ法测定，经３ｐ８７程序自动拟合。结果表明：透析过程中ＬＶＦＸ的消除半衰期、曲线下面积、血浆清除率分别是４．０±０．７ｈ，８．１±０．９ｍｇ·ｈ·Ｌ－１，１２．６±１．９Ｌ·ｈ－１；透析间期消除半衰期、曲线下面积、血浆清除率分别是４０．７±４．０ｈ，３４．８±５．６ｍｇ·ｈ·Ｌ－１和２．９±０．４Ｌ·ｈ－１。透析过程中透析器的药物消除率为６０％，提示血透患者服用ＬＶＦＸ时，透析结束后应补充ＬＶＦＸ，以维持有效血药浓度。     

头孢他啶与5种常用输液配伍的稳定性

目的：探讨头孢他啶在５％葡萄糖,１０％葡萄糖,０．９％氯化钠,葡萄糖氯化钠,复方氯化钠５种输液中的稳定性。方法：用紫外分光光度法测定头孢他啶的含量。并观察输液的外观、ｐＨ的变化,结果：头孢他啶在５种输液中的含量与温度有关,温度越高,其含量下降越快。在５％葡萄糖中２ｈ内含量为１０１％（２５℃）,９１．６％（３７℃）,在１０％葡萄糖中４ｈ内含量为９１．８％（２５℃）,９６．９％（３７℃）,在０．９％氯     

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.