头风饮改善实验性大鼠微循环障碍的研究

目的观察头风饮对实验性大鼠肠系膜微循环障碍的改善作用。方法大鼠ip戊巴比妥钠 5 0mg·kg-1麻醉 ,十二指肠内给予头风饮 (生药 3. 0、6 .0、12 .0g·kg-1) ,2 0min后 ,在肠袢肠系膜观测区滴加 1∶1× 10.5盐酸肾上腺素 10 μl,滴加前、后的不同时间用微循环显微镜观察肠系膜微血管管径、血液流态及毛细血管网交点计数的变化情况 ,观察记录直至肠系膜观测区微循环恢复至滴加盐酸肾上腺素前的情况为止。结果生药 6 .0、12 .0g·kg-1能非常显著地缩短盐酸肾上腺素所致肠系膜血管血流减慢或停滞的恢复时间 ;具有显著地拮抗盐酸肾上腺素收缩肠系膜微动脉、静脉血管的作用 ;相同剂量可显著改善盐酸肾上腺素所致肠系膜微动脉、静脉血液血流减慢或停滞的作用 ,并且显著地增加肠系膜毛细血管网交点的开放数。结论头风饮在大鼠十二指肠内给药具有显著地改善肠系膜微循环的作用。     

松针提取物对小鼠肠系膜微循环障碍的影响

目的:研究松针提取物对小鼠肠系膜微循环障碍的影响。方法:采用小鼠肠系膜微循环实验,空肠袢滴加肾上腺素0.2mL(1∶10000),分别于滴加前及滴加2、5min时观察微血管管径大小、微血流速度、毛细血管网交点开放数的变化情况。结果:松针提取物能明显改善肾上腺素引起的微静脉、微动脉管径的收缩;提高血管内微血流的速度,但作用时间不长;同时还能改善毛细血管网交点开放数的减少。结论:松针提取物能改善肾上腺素引起的小鼠肠系膜微循环障碍,有一定的活血作用。     

复荣通脉胶囊主要药效学考察

目的:研究复荣通脉胶囊的药效学作用,为临床应用提供理论依据。方法:采用肾上腺素致小鼠耳廓微循环障碍、实验性大鼠动-静脉旁路血栓形成、大鼠体内血栓形成,观察复荣通脉胶囊的药理作用。结果:复荣通脉胶囊可明显增加肾上腺素致微循环障碍小鼠耳廓微动脉及微静脉管径,加快微血管内RBC流速,改善小鼠耳廓微循环;可明显减轻实验性大鼠动-静脉旁路血栓形成;可明显延长大鼠体内血栓形成时间。结论:复荣通脉胶囊可改善微循环;预防血栓形成。     

皮肤辐射防护软膏对小鼠耳廓微循环障碍的作用

目的:探讨皮肤辐射防护(RPA软膏)对小鼠耳廓微循环障碍的作用。方法:采用皮下注射盐酸肾上腺素与冷水浸泡方法造成小鼠耳廓微循环障碍动物模型,然后给小鼠耳廓涂RPA软膏,并评价RPA软膏对小鼠耳廓微循环障碍改善的情况。结果:RPA软膏三个剂量组给药10、20、30 min后均能增加血液输入管径、输出管径与血液微动脉流速。结论:RPA软膏具有明显的改善微循环作用。     

家兔肾缺血再灌注损伤时肠微循环的变化及其意义

目的研究家兔肾脏缺血再灌注损伤时肠系膜微循环的变化,并探讨其意义。方法用BI医学图像分析系统对8只家兔的肠系膜微循环进行观察,在肾缺血前,缺血30min,再灌注30min、60min时分别记录肠系膜微动脉和微静脉管径、微动脉和微静脉血流速度、管袢数,并进行分析。结果与兔肾脏缺血前比较,缺血30min、再灌注30min、再灌注60min时,兔肠系膜微动脉和微静脉管径缩小(P<0.01),膜微动脉和微静脉血流速度减慢(P<0.01),管袢数减少(P<0.01);再灌注30min、60min分别与缺血30min比较微循环情况恶化,表现为肠系膜微动脉和微静脉口径进一步缩小(P<0.01),膜微动脉和微静脉血流速度明显减慢(P<0.01),管袢数显著减少(P<0.01)。结论兔肾脏缺血再灌注时存在肠微循环障碍。     

阿加曲班对大鼠肢体缺血再灌注损伤肠系膜微循环影响的实验研究

目的探讨阿加曲班对大鼠肢体缺血再灌注损伤肠系膜微循环的影响,为缺血再灌注损伤的防治提供新的思路。方法采用大鼠肢体缺血再灌注模型,将14只Wistar大鼠随机分为每组7只：对照组和阿加曲班组,每组7只。2组大鼠均于再灌注2h后,酶联免疫吸附（ELISA）法测定血浆P-选择素、细胞间粘附分子-1（ICAM-1）浓度;应用BI-2000医学图像分析系统观察和记录肠系膜微循环改变,指标包括肠系膜微动脉管径（AD）和微静脉管径（VD）、肠系膜微动脉血流速度（AFV）和微静脉血流速度（VFV）以及白细胞粘附情况。结果大鼠肢体缺血再灌注2h后,阿加曲班组血浆P-选择素浓度、血浆ICAM—1浓度显著低于对照组（P〉0．05）。与对照组相比,阿加曲班组肠系膜微循环障碍较轻,AD和VD与对照组之间差异无统计学意义（P〉0．05）,AFV和VFV明显高于对照组（P〈0．05）,白细胞粘附较对照组轻（P〈0．05）。结论阿加曲班能够降低血浆P-选择素和ICAM-1浓度,进而改善大鼠肢体缺血再灌注损伤时的肠系膜微循环障碍．     

葛根素对小鼠实验性微循环障碍的改善作用

本文报告了葛根素对肾上腺素(Adr)引起的小鼠肠系膜微循环障碍的影响,并与罂粟碱作比较。结果表明,预先局部滴注0.5%葛根素能够拮抗Adr所致微动脉收缩、流速减慢和流量减少;而局部先滴注Adr造成微循环障碍后,再局部滴注1%葛根素,获得与上类似结果。给小鼠ⅳ葛根素(52 mg/kg)后再局部滴注Adr,可减轻Adr引起的微动脉收缩、流速减慢和流量减少,其作用优于罂粟碱。因此葛根素可改善实验性微循环障碍。     

银杏叶提取物促进微循环作用研究

目的探讨银杏叶提取物（YXY）对小鼠耳廓微循环的影响,为临床治疗微循环障碍性疾病提供实验依据.方法将52只ICR小鼠随机分为5组（对照组,阳性对照组,YXY 60 mg/kg组、30 mg/kg组、15 mg/kg组）,均静脉注射给药.在WX-6微循环显微测试仪上测定给药前及给药后5,15,30 min时小鼠耳廓毛细血管数、细静脉及细动脉管径、细动脉血流速度.结果与结论YXY在15～60 mg/kg剂量范围内静脉给药,能剂量依赖性地增加毛细血管数,扩张细静脉、细动脉管径,加快细动脉血流速度,显示有明显改善微循环的作用.     

至宝三鞭酒新、旧配方对大鼠肠系膜微循环的影响

目的观察新、旧两种配方的至宝三鞭酒对正常青年和老年大鼠肠系膜微循环的影响。方法1.观察至宝三鞭酒对正常青年大鼠肠系膜肾上腺素滴注前后微循环的影响;2.观察至宝三鞭酒对正常老年大鼠肠系膜微循环的影响。结果1.至宝三鞭酒新方能改善肾上腺素滴注后红细胞流态、流速、血管管径、血管痉挛恢复时间的异常;2.至宝三鞭酒新、旧配方均能改善正常老年大鼠肠系膜微血管管径,且能显著增加毛细血管的流速。结论至宝三鞭酒新、旧配方均能改善正常青年及老年大鼠肠系膜微循环。     

透骨化毒酊对小鼠耳廓微循环障碍的作用

目的 探讨透骨化毒酊对小鼠耳廓微循环障碍的作用.方法 采用小鼠耳廓微循环障碍法,进行透骨化毒酊改善微循环的研究.结果 透骨化毒酊三个剂量组给药10、60 min后均能增加微动脉流速、血液输出管径和血液输入管径.结论 透骨化毒酊具有明显的改善微循环作用.     

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.