原发性高血压患者心率变异性的临床分析

目的：探讨原发性高血压（EH）患者自主神经功能变化。方法：对43例原发性高血压患者和20例正常人进行Holter记录，分析对比心率变异性（heart rate variability,HRV)指标。结果：EH患者HRV的时域指标（SDNN、SDNNi、RMSSD）及频域指标（TP、LF、HF）较正常对照均明显降低（P＜0．001－0．05），以RMSSD、HF降低最为显著。EH患者LF／HF较正常对照明显升高（P＜0．05），SDANN与对照组比较差异无显著性（P＞0．05）。EH患者中，重度高血压组的时域、频域的多项指标较轻、中度高血压组降低（P＜0．01－0．05）。极高危组的HRV多项指标亦较非极高危组减低（P＜0．01－0．05）。结论：原发性高血压患者存在迷走神经活性明显降低，同时伴有交感神经活性的相对增强。HRV的减低可能为预后不良的一个重要指标。     

辛伐他汀对陈旧性心肌梗死患者心率变异性的影响

目的 观察辛伐他汀对陈旧性心肌梗死（OMI）患者心率变异性（HRV）的影响，探讨其治疗价值。方法42例OMI患者随机分为辛伐他汀组和安慰剂组，每组各21例，治疗前后用数字化24hHoher记录测定心率变异性时域参数和频域参数。结果OMI患者用辛伐他汀治疗4周后，HRV各项指标均明显好转，SDNN、LF和HF均明显增加，LF／HF明显降低，差异有统计学意义（P〈0．05）。结论辛伐他汀具有降低陈旧性心肌梗死患者交感神经活性，提高迷走神经张力的作用，使交感神经和迷走神经平衡性趋向于正常，提示该药具有稳定OMI患者自主神经功能的作用。     

心肌梗死患者依那普利对心脏自主神经活性的影响

目的观察口服依那普利对急性心肌梗死（AMT）患者和陈旧性心肌梗死（OMT）患者自主神经力的影响，探讨其治疗价值。方法48例AMT和48例OMT患者均随机分为依那普利组和安慰剂组，以24小时R—R间期的标准差（SDNN）代表HRV时域指标，以高频段面积（HF）代表迷走神经活性，低频段面积（LF）代表交感神经活性，并计算LF／HF值。结果提示依那普利可显著改善AMT病人HRV指标，SDNN、LF和HF均明显增加，LF／HF明显降低，差异有显著性（P〈0.05）：结论依那普利具有降低心肌梗死患者交感神经活动性，提高迷走神经张力，使LF／HF之比趋向于正常，提示该药具有稳定心肌梗死患者自主神经功能的作用。     

高血压与体质量超重、血脂异常、糖耐量降低及糖尿病发病关系的分析

目的了解高血压病与体质量超重、血脂异常、糖耐量降低及糖尿病发病关系。方法对高血压组（观察组）1021例与非高血压组（对照组）522例体质量、血脂、血糖的测定结果进行比较。结果高血压组超重肥胖、血脂和血糖水平均高于非高血压组，两组比较差异有统计学意义（P〈0．001）。结论高血压病常与超重、血脂异常、糖耐量减低、糖尿病同时存在并相互作用，应采取适当的防治措施矫正上述心脑血管病的危险因素，降低心脑血管病的患病率。     

重症手足口病患儿心率变异性分析

目的：探讨对重症手足口病（HFMD）患儿进行心率变异性（HRV）分析的临床意义。方法选择55例重症 HFMD 患儿为研究对象,其中危重型病例25例为 B 组,其余30例重症 HFMD 患儿 A 组;另外选择同期门诊体检30例健康儿童作为对照组,分析及比较三组心率变异频域及时域指标。结果与对照组相比较,A 组患儿低频成分（LF）、RR 间期总体标准差（SDNN）、RR 间期平均值的标准差（SDANN）、RR 间期标准差的平均值（SDNNindex）降低,差异均有统计学意义（P ＜0．05）;而高频成分（HF）、相邻 RR 间期差值的均方根（RMSSD）、相邻 RR 间期差值＞50 ms 的个数占 RR 间期总数的百分比（PNN50）差异均无统计学意义（P ＞0．05）。B 组患儿 LF、HF、SDNN、SDANN、SDNNindex、RMSSD、PNN50均低于 A 组患儿,差异均有统计学意义（P ＜0．05）。结论HFMD 患儿存在自主神经系统功能紊乱,重症病例以交感神经张力增高为主,危重型HFMD 患儿伴有迷走神经活性显著降低,监测 HFMD 患儿自主神经系统活性变化有重要的临床意义。     

慢性充血性心力衰竭患者的心率变异性分析

目的：探讨慢性充血性心力衰竭（CHF）患者的心率变异性（HRV）的变化。方法：用24d,时动态心电图分析51例心力衰竭患者、27例心功能代偿的心血管病患者、25例健康人的HRV指标。比较3组HRV指标与心功能NYHA分级和关系。结果：心功能代偿组SDNN、SDANN较对照组显著下降（P〈0.01,P〈0．05）SDNNi、rMSSD和pNN50与对照组差异无显著性（P〉0．05）;CHF组的HRV各指标均显著低于对照组（P〈0．01）。心功能≥Ⅲ级者较Ⅱ级HRV各项指标显著降低（P〈0．01）,各种病因SDNN、SDANN较对照组显著下降（P〈0．01）,但各种病因间差异无显著性（P〉0．05）。结论：CHF患者HRV指标下降的变化与心功能损害程度相关,但原发病之间HRV指标下降无差异。     

哮喘儿童血浆神经肽Y与心率变异性相关性分析

目的 探讨哮喘儿童血浆神经肽Y（NPY）含量与其心率变异性（HRV）的关系。方法 随机选择哮喘儿童35例与健康儿童40例测定其空腹血浆NPY浓度，同时做24h动态心电图并进行HRV时域分析。结果 HRV中反映迷走神经张力指标的高频（HF）、rMSSD和pNN50在哮喘儿童组数值明显高于正常对照组（P〈0．01），而反映交感神经张力的主要指标低频（LF）、SDNN和SDANN则明显低于对照组。哮喘儿童血浆NPY明显升高（P〈0．01），NPY与rMSSD（r=0．76）、pNN50（r=0．71）呈正相关。结论 哮喘儿童血浆NPY与其HRV密切相关。     

2型糖尿病合并高血压患者的心率变异性特点

目的：探讨2型糖尿病（DM）合并原发性高血压患者（EH）自主神经功能变化和心率变异（HRV）特点.方法：随机选取本中心就诊的30例DM病人为DM组,30例EH病人为EH组,30例DM＋EH病人为DM＋EH组,30例健康人为对照组,分别行24 h动态心电图记录,分析HRV时域和频域指标,对各组HRV指标进行比较研究.结果：EH组中反映交感神经张力的HRV指标数值升高,反映迷走神经张力的HRV指标数值降低,与对照组之间有明显变化（P＜0.05）;DM组、DM＋EH组中反映交感神经和迷走神经张力的HRV指标数值均明显降低,其中DM＋EH组的HRV指标数值降低最为明显,与对照组比较差异有统计学意义（P＜0.05）.结论：EH组、DM组较对照组存在自主神经功能受损害.DM＋EH组较对照组自主神经功能受损害程度更加明显,发生心源性猝死的危险性增加,应定期检查,密切随访.     

急性心肌梗死溶栓后心率变异性近日节律的变化研究

目的探讨急性心肌梗死（AMI）溶栓后心率变异性（HRV）的近日节律变化。方法将我院AMI患者按照是否溶栓及溶栓再通与否分为再通组、溶栓未通组、未溶栓组各40例,采用动态心电图评估HRV的变化规律。结果再通组患者TF、LF、HF明显高于未通组及未溶栓组,差异有显著性（P〈0．05）。再通组患者LF／HF明显低于未通组及未溶栓组,差异有显著性（P〈0．05）。未通组患者TF、LF、HF及LF／HF与未溶栓组比较差异无显著性（P〉0．05）。结论心肌梗死溶栓再通能明显改善HRV的近日节律。     

高血压患者胆红素与血脂综合指数的变化

目的：探讨胆红素与血脂综合指数的变化状况对高血压病的诊断价值。方法：对67例高血压组和72例正常组血清总胆红素（TB）、直接胆红素（DB）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL—C）指标进行测试，分析组间胆红素、血脂、血脂综合指数和肌红素与血脂综合指数的差异。结果：高血压组血清总肌红素明显低于正常组（P〈0．05）；高血压组血脂综合指数明显高于正常组（P〈0．05）；高血压组胆红素与血脂综合指数结合指标与正常组存在显著差异（P〈0．01）。结论：胆红素与血脂综合指数是具有临床使用价值的高血压病诊断预测指标。     

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.