二磷酸果糖抗心肌缺血

综述二磷酸果糖（FDP）在抗心肌缺血方面的研究进展情况。FDP在实验研究及临床上均显示出抗心肌缺血作用，机制涉及改善心肌能量代谢，纠正缺血性代谢紊乱，减少组织过氧化，抑制心律失常抗因小板凝聚等作用，FDP的抗心肌缺血作用受到广泛重视，显示出良好的研究前景。     

预防性口服氯化镁抗实验性心肌缺血作用的研究

目的观察预防性口服氯化镁对实验性心肌缺血的保护作用。方法用结扎清醒大鼠左冠状动脉（ＬＡＤ）前降支致急性心肌梗塞（ＡＭＩ）模型。结果预防性口服氯化镁能显著缩小心肌梗塞范围，降低血清磷酸肌酸激酶（ＣＰＫ）、天门冬氨酸氨基转移酶（ＡＳＴ）活性，提高血清钾、镁浓度，减轻清醒大鼠缺血早期心律失常。结论预防性口服氯化镁对心肌缺血损伤具有保护作用     

水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤的保护作用研究

目的:研究水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤的保护作用。方法:使用线栓法复制急性心肌缺血和缺血再灌注损伤模型。缺血前5min静脉注射水芹乙酸乙酯提取物,动态观察模型大鼠心电图的变化,测定心肌缺血引起的心律失常和心肌梗死面积、心肌缺血再灌注引起心律失常情况、血浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:水芹乙酸乙酯提取物可显著对抗心肌缺血引起的心律失常和缩小心肌梗死面积;可显著对抗心肌缺血再灌注损伤引起的心律失常,提高血浆中SOD活性和降低MDA含量。结论:水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤具有保护作用,其机制可能与抗过氧化作用有关。     

西洋人参皂甙的抗心律失常作用

本文研究了西洋人参皂甙(GQS)的抗心律失常作用。GQS 60mg/kg i.v.对氯仿诱发小鼠室颤具有保护作用,与对照组相比可使室颤发生率降低73.4%。GQS 80mg/kg i.v,对氯化钡诱发大鼠心律失常具有明显的预防和治疗作用。GQS 80mg/kg i.v,能明显提高哇巴因诱发豚鼠室早、室速、室扑颤以及停搏的阈剂量。GQS 60mg/kg、80mg/kg i.v,对垂体后叶制剂所致大鼠心肌缺血和心律失常均有明显拮抗作用。GQS 对乌头碱诱发大鼠心律失常则无效。     

邻卤代苄基异喹啉碘盐抗心律失常作用的研究

目的：比较1-(邻-碘苄基)-6，7-甲二氧基-2-甲基-3，4-二氢异喹啉碘盐(O-BIMMDI)与1-(邻-溴苄基)-6，7-甲二氧基-2-甲基-3，4-二氢异喹啉碘盐(O-BBMMDI)，对实验性心律失常模型的影响。方法：采用乌头碱、氯化钡和结扎左冠状动脉前降支方法制备大鼠心律失常模型，观察并比较O-BIMMDI与O-BBMMDI的保护作用。结果：O-BIMMDI和O-BBMMDI可对抗乌头碱、氯化钡所致的大鼠心律失常，延长心律失常诱发时间，缩短心律失常持续时间；对结扎左冠状动脉前降支所诱发的大鼠心律失常也有一定的对抗作用，并可减轻结扎造成的心肌缺血。O-BBMMDI抗心律失常作用优于O-BBMMDI。结论：O-BBMMDI和O-BBMMDI均可对抗大鼠心律失常模型，而O-BBMMDI抗心律失常作用优于O-BBMMDI．     

二磷酸果糖抗心肌缺血作用

综述二磷酸果糖(FDP)在抗心肌缺血方面的研究进展情况.FDP在实验研究及临床上均显示出抗心肌缺血作用,机制涉及改善心肌能量代谢、纠正缺血性代谢紊乱、减少组织过氧化、抑制心律失常和抗血小板凝聚等作用.FDP的抗心肌缺血作用受到广泛重视,显示出良好的研究前景.     

安心颗粒抗心律失常及心肌缺血的作用研究

目的研究安心颗粒对心律失常和心肌缺血的改善作用。方法制备氯化钙、氯仿和乌头碱所致的小鼠心律失常模型及异丙肾上腺素（ISO）引起的小鼠心肌缺血模型,经安心颗粒治疗后,通过观察室颤发生率和心动过速的发生时间等指标评价其抗心律失常作用;通过检测血清超氧化物歧化酶（SOD）、脂质过氧化产物丙二醛（MDA）、乳酸脱氢酶（LDH）和磷酸肌酸激酶（CK）等指标评价其改善心肌缺血的作用。结果安心颗粒可降低氯仿诱发小鼠的室颤发生率;延迟氯化钙引起大鼠室性心动过速的发生时间;提高大鼠对乌头碱的耐受剂量。在ISO所致心肌缺血模型中,安心颗粒可增加SOD的活性,减少MDA的含量,降低血清LDH、CK的水平。结论安心对氯仿、氯化钙和乌头碱引起的心率失常及ISO引起的心肌缺血均有较好的改善作用。     

参葛胶囊对缺血及再灌性心律失常大鼠的影响

摘要参葛胶囊对大鼠冠状动脉结扎诱发的缺血性心律失常有明显保护作用，表现在降低病理性Q波、VP、VT的发生率、延长出现心律失常的潜伏期、缩短VT持续时间。参葛胶囊对大鼠心肌缺血再灌注诱发的心律失常也有明显的保护作用。     

平律复方抗实验性心律失常的作用及其机理研究

目的:研究平律复方(PL)抗实验性心律失常的作用,并初步探讨其作用机理。方法:采用氯仿、氯化钙以及心肌缺血再灌注三种心律失常动物模型,监测标准Ⅱ导联心电图;测定缺血再灌注大鼠血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;放射配基受体结合法分析心肌组织血小板激活因子(plate-let activating factor,PAF)受体蛋白表达水平;RT-PCR法检测PAF受体mRNA表达水平;测定心肌脂质过氧化产物丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:PL(ig,0.04、0.20、1.00 g.kg-1)对氯仿引起的小鼠心室纤颤有一定的保护作用;能减少氯化钙致大鼠室颤的发生率,降低死亡率;可显著降低心肌缺血再灌注大鼠心律失常的发生率,缩短持续时间,与模型对照组比较,PL小、中、大剂量组心肌CK和LDH分别降低了35.4%、51.8%、57.5%和22.4%、34.4%、38.4%;剂量依赖性下调心肌细胞PAF受体蛋白及mRNA表达水平,升高心肌SOD活性、降低MDA含量。结论:PL对氯仿、氯化钙以及心肌缺血再灌注诱发的心律失常均有较好的保护作用,其作用机制可能与下调心肌细胞PAF受体水平,抑制脂质过氧化有关。     

心肌缺血预处理研究新进展

心肌缺血预处理（ischemic preconditioning，IPC）是指心肌经过一次或多次反复的短暂缺血／再灌注后，通过激活心肌内源性保护机制来对抗心肌缺血／再灌注损伤，具有限制心肌梗死面积、减少再灌注心律失常发生和改善心室收缩功能的作用。目前人们对缺血预处理的作用机制及临床应用进行了大量研究，本文就其研究进展综述如下。     

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.