氨氯地平对原发性高血压患者血管内皮功能及胰岛素抵抗的影响

目的探讨氨氯地平对原发性高血压患者内皮功能及胰岛素抵抗的影响。方法选择42例原发性高血压患者为治疗组,血压正常的健康人30例为对照组。治疗组口服氨氯地平8周,并在治疗前后采取静脉血测定空腹血糖及胰岛素,计算胰岛素敏感性指数（ISI）;采用血管外超声法检测治疗前后肱动脉内皮依赖性血管舒张功能（FDM）,并观察肱动脉内径基础值（D0）变化。结果治疗组治疗前收缩压、舒张压、空腹血糖、空腹胰岛素均明显高于对照组,且D0、ISI、FMD均低于对照组,差异均有统计学意义（P〈0.01）;治疗8周后患者收缩压、舒张压、空腹胰岛素水平降低,ISI升高,D0及血流介导的FDM明显改善,与治疗前比较差异均有统计学意义（P〈0.01）。结论氨氯地平在有效降压的同时,能改善原发性高血压患者胰岛素抵抗及肱动脉内皮依赖性血管舒张功能。     

糖耐量减低合并原发性高血压患者血管内皮功能的变化

目的观察糖耐量减低（IGT）合并原发性高血压（EH）对血管内皮功能的影响。方法选择38例IGT合并EH患者,分别测定血浆内皮素（ET）、一氧化氮（NO）水平,并应用高分辨率超声测量不同情况下右侧肱动脉舒张末期内径,包括静息时肱动脉的基础内径（D0）、流量介导血管舒张时肱动脉内径（D1）和含服硝酸甘油介导血管舒张时肱动脉内径（D2）,并分别计算流量介导血管舒张时肱动脉内径较基础内径的变化率（即内皮依赖性舒张功能,△D1）和含服硝酸甘油介导血管舒张时肱动脉内径较基础内径的变化率（即非内皮依赖性舒张功能,△D2）。选择32例单纯原发性高血压患者作为EH对照组和38例查体健康者作为健康对照组。结果三组ET值比较,IGT合并EH组〉EH对照组〉健康对照组,两两比较差异有统计学意义（P〈0．05）。三组NO值比较,IGT合并EH组〈EH对照组〈健康对照组,两两比较差异有统计学意义（P〈0．05）。三组内皮依赖性舒张功能（△D1）比较,IGT合并EH组〈EH对照组〈健康对照组,两两比较差异有统计学意义（P〈0．05）。三组非内皮依赖性舒张功能（△D2）无明显差异。结论IGT和EH均为血管内皮损伤的独立危险因子,而且两者有明显的协同破坏作用,IGT合并EH时血管内皮功能损伤更加明显,此时更应该提早干预,以更好地预防心脑血管疾病的发生和发作。     

卡维地洛对高血压病并发2型糖尿病患者血管内皮功能及胰岛素抵抗的影响

目的:探讨卡维地洛对高血压合并糖尿病患者血管内皮功能及胰岛素抵抗的影响。方法:经2周导入期后熏将41例高血压合并2型糖尿病患者熏随机分为卡维地洛组(21例)和美托洛尔组(20例)。治疗前及治疗6月后熏采静脉血测定空腹胰岛素、空腹血糖熏计算胰岛素敏感性指数;采用高分辨率超声检测反应性充血和硝酸甘油介导的肱动脉舒张功能。结果:卡维地洛治疗6月后,患者收缩压和舒张压均有效下降熏空腹胰岛素降低,胰岛素敏感指数显著升高熏反应性充血和硝酸甘油介导的血管舒张功能均明显改善。美托洛尔治疗后,空腹血糖和空腹胰岛素均轻度升高,胰岛素敏感指数降低,但差异均不具有统计学意义;反应性充血和硝酸甘油介导的血管舒张功能均无明显变化。结论:卡维地洛可有效降低高血压合并2型糖尿病患者的血压,改善胰岛素抵抗及肱动脉内皮依赖性及非内皮依赖性的血管舒张功能。     

胰岛素抵抗、血管内皮功能变化与急性冠脉综合征

目的探讨胰岛素抵抗（IR）和血管内皮功能的相互关系，评价IR和血管内皮功能紊乱在急性冠状动脉综合征（ACS）中的作用。方法选择35例ACS、33例稳定型心绞痛（SA）和30例正常人作为对照组，采用放射免疫分析法和生化法分别测定空腹血清胰岛素和血糖水平，用稳态模型2计算机软件（HOMA2 Caculater）计算胰岛素抵抗指数（HOMA2-IR），应用超声诊断仪，测量肱动脉血管舒张功能，用SPSS11．5软件包进行统计分析。结果ACS组和SA组HOMA2-IR显著高于对照组（P〈0．001），内皮依赖性血管舒张功能显著低于对照组，ACS组HOMA2-IR显著高于SA患组（P〈0．001），内皮依赖性血管舒张功能显著低于SA患者，ACS患者内皮依赖性血管舒张功能与胰岛素水平和HOMA2-IR呈显著负相关（P〈0．001）。结论血管内皮功能失调与高胰岛素血症和IR密切相关，三者与ACS的发生发展密切相关。     

阿托伐他汀对冠心病合并2型糖尿病血管内皮功能影响

目的研究阿托伐他汀对冠心病合并2型糖尿病患者血管内皮功能的影响。方法分别检测70例冠心病合并2型糖尿病患者给予阿托伐他汀治疗前后血糖、血脂及一氧化氮（NO）、6-酮-前列腺素（6-Ke-to-PGF1a）及内皮素（ET）水平;同时用高分辨血管外超声多普勒测定肱动脉内皮依赖性舒张功能。结果治疗前后比较血脂和肱动脉内皮依赖性舒张功能均有显著性改善（P〈0．05及P〈0．01）。治疗后NO、PGFla水平明显升高（P〈0．01）,ET水平明显降低（P〈0．01）。肱动脉内皮依赖性舒张功能的改善程度与NO、PGF1a水平升高及ET水平降低呈正相关,与患者血TC和LDL降低的程度呈负相关。结论阿托伐他汀保护内皮功能,对冠心病合并2型糖尿病有治疗作用。     

肥胖人群血管内皮功能与高血压发生的相关因素分析

目的探讨肥胖人群血管内皮功能与高血压发生的相关因素。方法368例单纯肥胖者（体质指数≥25kg／m^2），根据血管内皮功能进行分组，测定体重、腰臀比、血压、空腹血糖、空腹胰岛素、胰岛素抵抗指数等，7年后对此人群进行随访调查，并复查上述指标。结果共随访到334例。单纯肥胖者合并血管功能异常，基线时空腹血糖、空腹胰岛素、胰岛素抵抗指数显著升高（均P〈0．05），7年随访高血压累积发生率60．2％。显著高于血管内皮功能正常者，Logistic回归分析显示，收缩压与腰臀比、体质指数和内皮依赖性血管舒张显著相关，舒张压与腰臀比、内皮依赖性血管舒张、胰岛素抵抗指数显著相关。结论血管内皮功能不全可能是肥胖人群高血压发生早期原发表现，在高血压发生、发展过程中起重要作用。     

原发性高血压患者血清瘦素与血管内皮舒张功能的关系探讨

目的通过检测原发性高血压患者血清瘦素与血管内皮功能,探讨原发性高血压患者血清瘦素与血管内皮功能之间的可能关系。方法原发性高血压者33例和非高血压患者18例,分别测定血清瘦素,血糖和血脂;采用高分辨率彩超检测肱动脉血流介导的内皮依赖性和非内皮依赖性血管舒张功能。结果与对照组相比,原发性高血压患者血清瘦素水平高（3．553±0．107 vs 3．436±0．095ng／ml,P〈0．01）。与对照组比较,原发性高血压患者肱动脉内径无明显差别（0．387±0．601 vs 0．354±0．607mm,P〉0．05）;肱动脉血流介导的内皮依赖性血管舒张功能（EDF）差异有统计学意义（15．58±4．701％ vs 19．38±6．452％,P〈0．05）;肱动脉血流介导的非内皮依赖性血管舒张功能（NEDF）差异无统计学意义（17．095±4．412％ vs 19．648±4．635％,P〉0．05）。瘦素与血管舒张功能之间的Pearson相关分析,未发现有明显的相关关系。结论原发性高血压患者血清瘦素增高与肱动脉血流介导的内皮依赖性血管舒张功能减退可能无关。     

奥利司他对肥胖高血压患者非内皮依赖性血管舒张功能的影响

目的：观察肥胖高血压患者服用奥利司他治疗前后血压和硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能的变化。方法：30例肥胖合并轻度高血压患者（肥胖高血压组）奥利司他120 mg,3次/d,共12周,服药前后诊所测量身高、体重、腰围及血压,计算BMI。并行肱动脉高解像度超声检查,舌下含服硝酸甘油0.3 mg,测定硝酸甘油介导的血管舒张（NMD）程度的变化。15例非肥胖的高血压患者作为对照组。结果：两组基线的特征具有可比性。肥胖高血压组患者治疗前与非肥胖高血压患者的NMD无差别,但BMI及腰围明显增加（P均〈0.01）。奥利司他治疗12周后BMI、腰围、血压均有显著下降（P〈0.05或P〈0.01）;NMD较治疗前无明显改善（16.2%vs15.5%,P〉0.05）。结论：奥利司他短期治疗能降低肥胖高血压患者的体重及血压,但对硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能无作用。     

左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度及血管内皮依赖性舒张功能的影响

目的观察左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度（CIMT）及血管内皮依赖性舒张功能的影响。方法采用高分辨率超声技术，检测93例原发性高血压患者左旋氨氯地平（2．5～5mg／d）治疗前后CIMT的变化，并观察休息状态、反应性充血后肱动脉内径变化。结果左旋氨氯地平治疗12个月后，降压疗效明显，CIMT明显降低，肱动脉内皮依赖性舒张功能明显改善（P〈0．05）。结论左旋氨氯地平降压疗效显著，能延缓CIMT进展，改善血管内皮依赖性舒张功能。     

左旋氨氯地平对颈动脉内膜-中膜厚度及血管内皮依赖性舒张功能的影响

目的观察左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度（CIMT）及血管内皮依赖性舒张功能的影响。方法采用高分辨率超声技术,检测原发性高血压患者93例左旋氨氯地平（2．5—5mg／d）治疗前后CIMT的变化,并观察休息状态、反应性充血后肱动脉内径变化。结果左旋氨氯地平治疗12个月后,降压疗效明显,CIMT明显降低,肱动脉内皮依赖性舒张功能明显改善（P〈0．05）。结论左旋氨氯地平降压疗效显著,能延缓CIMT进展,改善血管内皮依赖性舒张功能。     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.