水合氯醛溶液稳定性考察

目的考察贮存时间、光照、温度对水合氯醛溶液稳定性的影响,确定水合氯醛溶液的有效期。方法采用酸碱滴定的方法,观察水合氯醛溶液含量随贮存时间、光照、温度的变化情况;分别在2⁶℃冰箱中见光和避光保存50 d,并且在避光的条件下冷藏和常温保存50 d,观察水合氯醛溶液的性状、含量的变化情况;在25℃加速试验条件下放置40 d,考察水合氯醛溶液的稳定性。结果随着贮存时间的增加和贮存条件的改变,水合氯醛溶液的含量有较明显的改变。结论水合氯醛溶液的稳定性受贮存时间、贮存条件及温度的影响,本品应避免光照及长期贮存,宜低温贮存,现用现配。     

维生素K_1注射液在临床贮存时的稳定性考察

目的:研究维生素K1注射液在临床常规条件下贮存的稳定性。方法:采用高效液相色谱法测定维生素K1注射液在常温且不避光条件下贮存不同时间(24h)后的含量变化,并观察溶液的颜色变化。结果:维生素K1注射液在24h内含量由98.7%下降至81.7%,溶液颜色由黄绿色变为黄棕色。结论:维生素K1注射液在未避光条件下贮存溶液稳定性较差,临床使用时应注意避光贮存。     

依沙吖啶溶液变色原因的探讨

目的：探讨引起依沙吖啶溶液在贮存期变色与含量变化的关系。方法：以依沙吖啶溶液的外观性状、透光率、含量为指标,考察贮存条件、光强度、附加剂对其稳定性的影响。结果：不同的贮存条件及附加剂对依沙吖啶溶液的稳定性有不同的影响,光线对依沙吖啶的分解影响较大,光作用的结果导致溶液透光率下降、颜色加深,含量下降。结论：依沙吖啶溶液在贮存期变色受光线的影响很大,应注意避光贮存     

盐酸丁卡因注射液的贮存期探讨

目的研究盐酸丁卡因的稳定性和贮存期。方法用HPLC测定盐酸丁卡因及分解产物对丁氨基基苯甲酸的含量,将产品用加速实验法,经典恒温法和室温留样观察法进行实验。结果盐酸丁卡因的含量随温度升高和时间延长逐渐下降,产品加速实验得出:温度40℃,湿度75%条件下,盐酸丁卡因放置1个月含量为98.68%,2个月为96.33%,3个月为94.37%。经典恒温法测定得25℃的储存期为15个月。室温留样观察实验证实:盐酸丁卡因注射液放置1年含量为96.67%,放置2年为89.34%。结论3种实验方法测得的数据基本一致。盐酸丁卡因注射液的贮存期可暂定1年。     

0．02％呋喃西林溶液的贮存期预测

目的预测0．02％呋喃西林溶液的贮存期。方法用分光光度法于波长376nm处测定0．02％呋喃西林溶液的含量,采用经典恒温实验法预测其在25℃时的贮存期。结果测得0．02％呋喃西林溶液25℃预测贮存期为130d,与留样观察结果相符。结论0．02％呋喃西林溶液的贮存期可定为4个月,以10～25℃、避光条件下贮存为宜。     

温度对环磷酰胺注射液配制及配伍后稳定性的影响

目的考察温度对环磷酰胺(cyclophosphamide,CTX)注射液配制的影响及配伍后CTX在5种溶液中的稳定性。方法按临床常规给药剂量配制CTX注射液,放置于不同温度水浴(20,40,60℃),记录完全溶解所耗时间并测定溶解后的含量有否变化。将配伍后的溶液,于不同条件下(8和20℃避光,20,30℃)放置24 h,用高效液相色谱(HPLC)法测定配伍后不同时间点溶液中CTX的含量,同时观察外观性状、紫外吸收光谱和HPLC色谱图的变化。结果在40℃水浴温度条件下CTX溶解较快(≤15 min),且稳定性较好,而在20℃条件下完全溶解耗时太长(40~50min),在60℃条件下CTX溶解后含量下降明显(幅度约为15%);于8和20℃避光及20,30℃条件下放置,CTX与5种常用输液的配伍溶液在24 h内含量较稳定(RSD≤6%),其外观性状、紫外吸收光谱图在观察其间无明显变化,色谱图中除峰面积有变化外未见其他变化。结论CTX溶液配制以水浴温度40℃助溶为宜,配伍后CTX溶液在8和20℃避光及20,30℃条件下在观察的24 h内较稳定,以8和20℃避光保存最佳。     

温度对环磷酰胺注射液配制的影响及配伍后的稳定性

目的 考察温度对环磷酰胺(cyclophosphamide, CTX)注射液配制的影响及配伍后CTX在5种溶液中的稳定性。方法 按临床常规给药剂量配制CTX注射液，放置于不同温度水浴（20，40，60 ℃），记录完全溶解所耗时间并测定溶解后的含量有否变化。将配伍后的溶液，于不同条件下（8 和20 ℃避光，20，30 ℃）放置24 h，用高效液相色谱（HPLC）法测定配伍后不同时间点溶液中CTX的含量，同时观察外观性状、紫外吸收光谱和HPLC色谱图的变化。结果在40 ℃水浴温度条件下CTX溶解较快（≤15 min），且稳定性较好，而在20 ℃条件下完全溶解耗时太长（40～50 min），在60 ℃条件下CTX溶解后含量下降明显（幅度约为15%）；于8和20 ℃避光及20，30 ℃条件下放置，CTX与5种常用输液的配伍溶液在24 h内含量较稳定(RSD≤6%)，其外观性状、紫外吸收光谱图在观察其间无明显变化，色谱图中除峰面积有变化外未见其他变化。结论CTX溶液配制以水浴温度40 ℃助溶为宜，配伍后CTX溶液在8和20 ℃避光及20，30℃条件下在观察的24 h内较稳定，以8和20 ℃避光保存最佳.     

盐酸阿扎司琼注射液与输液配伍的稳定性研究

目的考察盐酸阿扎司琼注射液在不同条件下与输液配伍的稳定性,为临床合理给药方法提供理论依据。方法盐酸阿扎司琼注射液与0.9%氯化钠注射液、5%葡萄糖注射液配伍,分别在室温（25℃）光照（自然光）、室温避光、水浴（35℃）避光、冷藏（4℃）避光条件下,于0,0.5,1.0,2.0,4.0,8.0,24.0 h时考察配伍液外观、pH及含量变化。结果盐酸阿扎司琼注射液与0.9%氯化钠注射液、5%葡萄糖注射液配伍,避光条件下较稳定;室温光照下,配伍液的外观、pH、含量均有变化,在0.9%氯化钠注射液、5%葡萄糖注射液中4h内含量分别下降为30.5%和34.0%,pH分别由4.93和4.40降至4.11和3.95,颜色由无色变成粉红色。结论盐酸阿扎司琼注射液与两种输液可以配伍使用,单从稳定性角度考虑,可以采用静脉滴注方式给药,但必须严格避光。     

盐酸恩丹西酮葡萄糖注射液稳定性研究

目的 :研究盐酸恩丹西酮葡萄糖注射液的稳定性。方法 :以高效液相色谱法测定盐酸恩丹西酮及其有关物质的含量 ,分别用强光照射法、加速试验法和室温留样观察法对盐酸恩丹西酮葡萄糖注射液进行稳定性试验。结果 :除强光照射条件下本品含量略有下降外 ,加速试验和室温留样观察各项指标均符合质量标准的规定。结论 :本品在避光、密闭的贮存条件下性质稳定 ,室温下贮存期可定为2年。     

金丝桃素提取物稳定性考察

目的考察金丝桃素提取物的稳定性。方法以金丝桃素和伪金丝桃素含量变化为指标,考察光照、温度、抗坏血酸等因素对金丝桃素提取物短、长期稳定性的影响。结果短期内,金丝桃素提取物在常温避光及加抗坏血酸条件下较稳定;光照能使提取物中金丝桃素、伪金丝桃素含量短时间内升高,然后开始下降;在高温条件下,提取物稳定性差。8周内,提取物在常温光照、常温避光及加抗坏血酸条件下金丝桃素、伪金丝桃素含量均有不同程度地下降,在低温避光条件下比较稳定。结论金丝桃素提取物应低温、避光保存。     

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.