恩丹西酮注射液与异环磷酰胺在生理盐水中配伍的稳定性

目的：考察０℃～４℃,２５℃和３５℃下,恩丹西酮注射液与注射用异环磷酰胺在生理盐水中的配伍稳定性。方法：采用反相高效液相色谱法测定配伍后不同时间恩丹西酮与异环磷酰胺的含量,同时观察外观并测定ｐＨ值。结果：０℃～４℃,２５℃和３５℃下,两种药物在生理盐水中配伍后,２４ｈ内配伍液的外观澄明,未见气泡及颜色变化,ｐＨ值及含量均无明显变化。结论：两种药物在生理盐水中２４ｈ可以配伍使用。     

室温放置后氟脲脱氧核苷在3种输液中的稳定性

目的 考察注射用氟脲脱氧核苷在１０％葡萄糖等３种输液中的稳定性。方法 采用紫外分光光度法测定配伍后２４ｈ不同时间氟脲脱氧核苷的含量,同时测定ｐＨ值。结果 ４℃,２５、３７℃２４ｈ内配伍溶液的ｐＨ和氟脲脱氧核苷的含量无明显变化。结论：４℃,２５℃,３７℃,２４ｈ内注射用氟脲脱氧核苷与３种输液可配伍使用。     

替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍稳定性

目的：考察４℃、２５℃、３７℃下２４ｈ内替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍稳定性。方法：采用反相高效液相色谱法测定配伍后４℃、２５℃、３７℃下２４ｈ内不同时间替硝唑与头孢噻肟钠的含量,同时观察外观并测定ｐＨ值。结果：在３种温度下２４ｈ内,配伍液的 ｐＨ值无明显变化;配伍液的外观、替硝唑和头孢噻肟钠的含量随时间有明显变化;在 ４℃ ６ｈ时、２５℃２ｈ时、３７℃１ｈ时,配伍液的吸收曲线发生微小变化,产生了新的最大吸收峰位。结论：在４℃ ６ｈ内、２５℃２ｈ内、３７℃１ｈ内,替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍液稳定。     

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     

5-氟尿嘧啶与3种输液配伍的稳定性考察

目的：考察室温,３７℃下,５－Ｆｕ与３种输液配伍的稳定性。方法：用ＨＰＬＣ法测定配伍后２４ｈ内５－Ｆｕ的含量、ｐＨ,同时观察外观。结果;室温,３７℃下２４ｈ内配伍液的外观澄明,无色变及沉淀,ｐＨ及含量无明显变化。结论;室温,３７℃下２４ｈ内,５－Ｆｕ与３种输液可以配伍使用。     

优普林在四种输液中的稳定性考察

目的：考虑优普林在输液过程中与５％、１０％的葡萄糖溶液、葡萄糖氯化钠溶液和氯化钠溶液中的配伍稳定性。方法：采用紫外分光光度法测定优普林与四种输液配伍后６ｈ内优普林的含量,同时观察外观及ｐＨ值。结果：在温度２５℃、３７℃时,混合液６ｈ内外观ｐＨ值无明显变化,含量有所下降,尤其是和葡萄糖输液配伍后含量下降明显。结论：优普林与四种输液配伍静滴应限制时间。     

β-七叶皂苷钠与诺氟沙星葡萄糖注射液配伍的稳定性考察

目的：考察注射用β－七叶皂苷钠与诺氟沙星葡萄粮注射液在２５℃条件下的配伍稳定性。方法：采用分光光度法测定诺氟沙星和β－七叶皂苷钠配伍后６ｈ内的含量,同时考察两药配伍后ｐＨ、外观及吸收曲线的变化情况。结果：在２５℃条件下,６ｈ内配伍液外观澄明无变色,未见气泡或沉淀、ｐＨ值及吸收曲线无明显变化。结论：在２５℃６ｈ内注射用β－七叶皂苷钠在诺氟沙星葡萄糖注射液中稳定,可以配伍使用。     

氨茶碱注射液在4种输液中的稳定性考察

本实验选择４种输液与氨茶碱注射液进行配伍。模拟临床使用浓度，分别在２５℃、３７℃时观察配伍药液从０～２４ｈ的外观性状、ｐＨ值、紫外光谱的改变及经时含量变化情况，经果表明：氨茶碱与０．９％氯化钠注射液配伍稳定，２４ｈ内外观、ｐＨ值、紫外光谱及含量基本不变，配伍静滴可行；与葡萄糖氯化钠、５％葡萄糖、１０％葡萄糖注射液配伍药液ｐＨ值略有下降、１２ｈ以后色泽有所加深，但２４ｈ内紫外光谱及含量基本未变，配伍静滴宜掌握在１２ｈ内用完，以上两种温度下结果基本一致。     

利巴韦林与6种药物的配伍变化考察

目的：考察２０ ℃下６ ｈ 内,注射用三氮唑核苷与６ 种药物的配伍稳定性。方法：采用分光光度法测定配伍后６ ｈ 内三氮唑核苷的含量,同时观察外观并测定ｐ Ｈ 值。结果：２０ ℃下６ ｈ 内配伍液外观澄明无变色,未见气泡或沉淀,ｐ Ｈ 值及三氮唑核苷等含量均无明显变化。结论：２０ ℃下６ ｈ 内注射用三氮唑核苷与６ 种药物在５ ％ 葡萄糖氯化钠注射液中配伍可以使用。     

5种抗生素在替硝唑葡萄糖注射液中的配伍稳定性

目的：研究头孢噻肟钠等５种抗生素在替硝唑葡萄糖注射液中的配伍稳定性。方法：将５种抗生素分别加入替硝唑葡萄糖注射液中混合,在２５℃下观察２４ｈ。结果：各配伍液外观及ｐＨ值均无变化,５种抗生素及替硝唑的相对百分含量均在９７％以上。结论：头孢噻肟钠等５种抗生素可以与替硝唑葡萄糖注射液配伍使用。     

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.