君子兰水提液抗实验性心律失常的作用

目的：观察君子兰水提液(WELC)的抗心律失常作用.方法：制备大鼠心律失常模型.结果：君子兰水提液6,12 g•kg 1能明显对抗乌头碱20 μg•kg 1,BaCl2 2 mg•kg 1和结扎左冠状动脉前降支诱发的大鼠室性心律失常.WELC也能明显对抗CaCl2 Ach(CaCl2 0.6%＋Ach 0.002 5%)混合液10 mL•kg 1诱发小鼠心房纤颤或扑动.WELC 对大鼠心电图的影响试验证明有负性频率作用及负性传导作用.这些作用可能是WELC抗心律失常作用的药理基础.结论：君子兰水提液对大鼠有明显的抗心律失常作用.     

三磷酸腺苷及双异丙吡胺防治家兔心房纤颤

实验结果表明：静脉注射三磷酸腺苷（１ｍｇ·ｋｇ－１）和双异丙吡胺（２．５，５ｍｇ·ｋｇ－１）均能有效地防治在体家兔右心房肌层注射乙酰胆碱诱发的心房纤颤。小剂量双异丙吡胺与三磷酸腺苷合用后，抗心房纤颤作用明显加强，除使ＡＦ持续时间明显缩短外，还显著降低了心房纤颤及心室纤颤发生率，动物死亡率亦明显低于单独用药组。两药单用均有抗心律失常作用及抗胆碱作用，合用后因抗胆碱作用加强而使抗心律失常效果更佳。此外，两药合用后对房室传导系统无明显不良影响。     

磷酸喹哌抗实验性心律失常作用

磷酸喹哌(PQP)9mg·kg~(-1)iv明显降低小鼠室颤的死亡率;PQP 18mg·kg~(-1)ip对氯仿诱发小鼠室颤具有保护作用;PQP 6.3mg·kg~(-1)ip显著增加恒速(10mg·L~(-1)·min~(-1)滴注乌头碱引起麻醉大鼠室性早搏(VE)、室性心动过速(VT)、室性纤颤(VF)所需的乌头碱用量;PQP5.4 mg·kg~(-1)iv显著增加恒速(50mg·L~(-1)·min~(-1))滴注哇巴因引起麻醉豚鼠VE、VT和VF所需哇巴因用量;PQP3.36mg·kg~(-1)iv明显缩短肾上腺素诱发家兔室性心律失常的持续时间.结果表明PQP具有抗心律失常作用。小鼠PQPLD_(50)iv为93.33 mg·kg~(-1)。     

甘露醇对动物血清胆碱酯酶的影响

目的：研究甘露醇对小鼠和家兔外周血清胆碱酯酶的影响。方法：取小鼠36只、家兔32只均随机平分为4组。A组给予2.5%敌百虫500 mg·kg 1，小鼠用腹腔注射，家兔用耳缘静脉注射；B组给予20%甘露醇200 mg·kg 1，iv，C组给予10%甘露醇100 mg·kg 1；D组给予等容量0.9%氯化钠注射液，iv。A组于给药10 min，其他组静脉注射30 min后，采血测定血清胆碱酯酶活性。结果：B、C组的小鼠、家兔胆碱酯酶活性明显低于D组，但高于A组。结论：甘露醇可抑制血清胆碱酯酶活性，抑制作用具有剂量依赖性，但抑制作用低于敌百虫。     

静注索他洛尔终止室上速、心房纤颤和心房扑动的效果与安全性

索他洛尔是一种具有Ⅲ类抗心律失常特性的p阻滞剂，本研究的目的在于评价静注（汀）索他洛尔终止室上速（SVT）、心房纤颤（AFib）和心房扑动（AFI）的效果与安全性。选择93例病人作为观察对象，其中SVT45例，AFib34例，AFI14例，发作持续时间＞5min，但rt7d，心室率均＞120次·min－‘。其中自发性56例，在电生理实验室中诱发的37例。研究过程分为两期，即双盲期和开放期，每期包括10min静注，接着观察20min，在双盲期内，SVT及AFib和AFI病人被随机分到3个组：安慰剂组，tv索他洛尔1．0mg·kg－‘组，计索地洛尔1．5mg·kg‘组。…     

莫昔沙星对家兔茶碱药动学的影响

目的：探讨莫昔沙星对茶碱药动学的影响，为临床合理用药提供参考。方法：采用自身对照法，给家兔静脉注射茶碱10 mg·kg 1后测定血浆中茶碱浓度，停药7 d后，灌胃给予莫昔沙星20 mg·kg 1，qd，连续6 d，再静脉注射茶碱10 mg·kg 1后测定血浆中茶碱浓度，计算药动学参数。结果：合用莫昔沙星前后茶碱呈一室模型，K值分别为(0.162±0.057)，(0.158±0.059 )h 1；t1/2分别为(4.79±1.85)，(5.16±2.26) h；V分别为(0.524±0.109)，(0.516±0.114) L·kg 1；AUC0～10分别为(97.39±12.40)，(101.27±16.49) mg·h 1·L 1；CL分别为(0.081±0.018)，(0.077±0.021) L·kg 1·h 1；Cmax分别为(20.09±3.77)，(20.53±4.21) mg·L 1，合用莫昔沙星前后茶碱的药动学参数差异无显著性(P＞0.05)。结论：莫昔沙星对茶碱的血药浓度及药动学参数没有明显影响。     

杭白芷香豆素在戊巴比妥钠及巴比妥钠对小鼠催眠作用中的影响

目的：观察杭白芷香豆素(CAD)对戊巴比妥钠及巴比妥钠催眠作用的影响。方法：将小鼠随机分为溶媒(5%吐温 80，20 mL·kg 1)组、氯霉素(25 mg·kg 1)组及CAD(25，50，100 mg·kg 1)组，等容灌胃给药1 h后，再腹腔注射戊巴比妥钠40 mg·kg 1或巴比妥钠200 mg·kg 1，观察催眠潜伏期和催眠时间。结果：氯霉素组和3个剂量的CAD组使戊巴比妥钠的催眠时间分别延长280.9%，185.1%，252.2%和266.9%，均P＜0.01；100 mg·kg 1 CAD组则显著延长巴比妥钠催眠潜伏期(P＜0.01)，并缩短催眠时间(P＜0.01)。结论：CAD能抑制肝微粒体细胞色素P450，大剂量时有中枢兴奋作用。     

阿奇霉素治疗儿童支原体肺炎38例

目的：比较静脉注射阿奇霉素与红霉素治疗儿童支原体肺炎的疗效及安全性。方法：儿童支原体肺炎72例，随机分为2组，治疗组38例，静脉滴注阿奇霉素10 mg·kg 1·d 1，qd，连用5 d；对照组34例，静脉滴注红霉素20～30 mg·kg 1·d 1，分3或4次滴注，连用14 d。结果：治疗组和对照组的有效率分别为97.4%和94.1%(P＞0.05)，复发率分别为5.3%和5.8%(P＞0.05)。结论：静脉注射阿奇霉素与红霉素治疗儿童支原体肺炎的疗效相当，但阿奇霉素疗程短，不良反应小。     

胺碘酮治疗阵发性房颤34例

我院自1994～2004年收治34例阵发性心房纤颤患者 ,在其它抗心律失常药物治疗无效的情况下 ,以胺碘酮负荷量治疗后改用小剂量维持窦性心律 ,现介绍如下。1临床资料经心电图、心电监护和 (或 )动态心电图证实为阵发性心房纤颤34例 ,其中男20例、女14例 ,平均年龄 (58 4 10 2)岁。     

牛磺酸、艾司洛尔单用及合用对麻醉大鼠缺血性心律失常的作用

本实验用麻醉大鼠冠状动脉左前降支结扎方法,研究了牛磺酸、艾司洛尔两药单用及合用的抗缺血性心律失常作用。结果表明,牛磺酸70mg·kg~(-1),140mg·kg~(-1)可使心律失常发生时间推迟,减少重性早博(PVCs)次数,缩短室性心动过速(VT)、心室纤颤(VF)累计持续时间并降低其发生率,恢复窦律时间提前。艾司洛尔25mg·kg~(-1)推迟心律失常发生时间,缩短VT累计持续时间,降低VF发生率.牛磺酸70mg·kg~(-1)与艾司洛尔25mg·kg~(-1)合用,其抗心律失常效果较单用增强。血流动力学实验结果表明.两药合用较艾司洛尔单用对心缩力的抑制减弱。离体大鼠心脏用牛磺酸40mmol·L~(-1)灌流后,抑制苯肾上腺素对心脏的正性肌力和正性频率作用。     

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.