老年心力衰竭患者心室重构与血管紧张素转换酶基因多态性的相关性及药物干预效果的研究

目的探讨老年充血性心力衰竭(CHF)患者心室重构与血管紧张素转换酶(ACE)基因多态性的相关性,并观察美托洛尔缓释片、依那普利的干预效果。方法选择50例正常对照组和104例老年CHF患者,并将104例老年CHF患者随机分为A组(常规治疗)26例;B组(常规治疗+美托洛尔缓释片)26例;C组(常规治疗+依那普利)26例;D组(常规治疗+美托洛尔缓释片+依那普利)26例,均连续治疗3个月。所有受试着进行ACE基因分型,用放射免疫法测定AngⅡ、ALD;紫外吸收法测定ACE;PCR测定基因多态性;超声心动图测量LVEDD、LVEDV和LVEF。结果老年CHF组DD基因型频率和D等位基因频率较正常对照组明显增高,P<0.01;DD基因型患者血清ACE、AngⅡ、ALD水平明显高于ID型、II型和正常对照组,P<0.01;DD基因型较ID型、II型患者LVEDD、LVEDV明显高,而LVEF明显低,P<0.01;ACEI/D多态性与血清中ACE水平明显相关,DD型水平最高,II型最低;老年CHF伴左心室肥厚组DD基因型频率及D等位基因频率较不伴左室肥厚组明显增高,P<0.01;治疗3个月后,B组及C组中ACEDD基因型患者LVEDD、LVEDV明显低于ID型、II型及A组,而LVEF明显增高;且DD基因型患者的血清ACE、AngⅡ、ALD水平明显低于ID型、II型及A组;联合用药组DD基因型患者的LVEDD、LVEDV明显低于B组及C组,而LVEF明显增高。结论老年CHF患者血清ACE、AngⅡ、ALD水平与ACE基因多态性中DD基因型及D等位基因密切相关;老年CHF患者LVEDD、LVEDV、LVEF与ACE基因多态性中DD型及D等位基因关系密切;ACE基因多态性中DD基因型及D等位基因是老年CHF患者预后的重要预测因素,可作为判定老年CHF患者心室重构、估计病情、判断预后的重要指标之一;美托洛尔缓释片与依那普利均能改善老年CHF的心室重构及预后,但两药联合治疗效果更好,使其病死率进一步降低。     

ACE 2350 G/A基因多态性与高血压左心室肥厚的关系

目的:探讨血管紧张素转换酶(ACE)2350G/A基因多态性与原发性高血压及合并左心室肥厚(LVH)的关系。方法:利用聚合酶链反应(PCR)及限制性酶切技术对194例健康人(对照组)与246例原发性高血压病患者(高血压组)ACE2350G/A基因多态性进行检测;利用二维超声心动图对178例未治疗原发性高血压患者检测左心室质量(LVM),计算左心室质量指数(LVMI)。结果:高血压组与对照组的ACE2350G/A基因分型及等位基因的频率差别无统计学意义;但原发性高血压伴LVH组基因分型及等位基因的频率与非LVH组差别有统计学意义;左心室肥厚A等位基因的频率(58.09%)高于非左心室肥厚的频率(42.27%,P=0.0037)。结论:原发性高血压患者ACE2350A等位基因与左心室肥厚密切相关。     

食管癌肿瘤组织血管紧张素转换酶基因多态性

目的研究食管癌患者肿瘤组织中血管紧张素转换酶(ACE)基因多态性,探讨该基因与食管癌之间的关系。方法共检测50例食管癌患者组织标本,利用聚合酶链反应(PCR)检测ACE基因,观察插入型(ID型)、缺失型(DD型)和Ⅱ型3种基因型多态性分布,并计算I/D等位基因的比例,以10例癌旁正常组织为对照。结果食管癌患者肿瘤组织中ACE基因插入/缺失(I/D)多态性分布特点:ID型、DD型和Ⅱ型基因比例分别为16%,64%,20%,而I/D等位基因分布频率分别为20%和80%,对照组ID型、DD型和Ⅱ型3种基因型的比例分别为40%、30%、30%,其I/D等位基因分布频率分别为30%和70%,两组间DD型基因分布频率有统计学显著性差异(P<0.05)、I/D等位基因分布频率无显著性差异(P>0.05)。结论食管癌患者肿瘤组织中存在ACE基因I/D多态性,DD型基因分布较癌旁正常组织显著升高,结果表明DD基因型高表达可能与食管癌发病相关。     

ACE基因多态性在佳木斯正常人及高血压患者中的分布频率

目的:分析ACE基因在佳木斯区域内正常人和高血压患者的基因型与等位基因的分布频率.方法:应用荧光原位杂交技术对正常对照组和高血压组进行ACE基因型检测.结果:正常对照组Ⅱ型39.8％、ID型44.1％、DD型16.1％,Ⅰ等位基61.8％、D等位基因38.2％;高血压组Ⅱ型36.4％、ID型42.4％、DD型21.2％,Ⅰ等位基57.6％、D等位基因42.4％.两组数据经x2检验P＞0.05.结论:黑龙江佳木斯区域内正常人和高血压患者的ACE基因型与等位基因的分布频率无显著差别.     

ACE基因多态性与ACE、血管紧张素Ⅱ及醛固酮的关系

目的:探讨原发性高血压患者血管紧张素转化酶(ACE)基因插入/缺失(I/d)多态性与血清ACE、血管紧张素Ⅱ及醛固酮的关系。方法:应用PCR技术测定146例高血压患者的ACE基因型,并测定其血清ACE、血管紧张素Ⅱ及醛固酮浓度。结果:ACE在DD、ID、Ⅱ三种ACE基因型之间的差异有显著性,ACE活性DD>IDⅡ,而血管紧张素Ⅱ及醛固酮在三种基因型之间的差异无显著性。结论:ACE基因多态性与ACE密切相关,而与血清血管紧张素Ⅱ及醛固酮没有关系。     

血管紧张素转化酶基因多态性与依那普利降压疗效的相关性研究

目的：研究血管紧张素转化酶（angiotensinconverting enzyme,ACE）基因多态性与依那普利降压疗效的相关性。方法：采用聚合酶链式反应一限制性片断长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR—RFLP）对68例原发性高血压患者进行ACE基因型分析,根据ACE三种基因型DD型、ID型和Ⅱ型将受试者分为三纽,所有受试者每天服用依那普利20mg进行2周的降压治疗,观察依那普利在三种不同ACE基因型中的降压疗效及差异。结果：在所有68例原发性高血压患者中,依那普利治疗前与治疗后每组SBP和DBP的降低均有统计学意义（P〈0．05）,其中DD型与Ⅱ型两组之间的SBP和DBP降压幅度（即治疗前与治疗后血压的差值）有统计学意义（P〈0．05）。DD型组依那普利的总有效率为91．30％,ID型组为85．71％,Ⅱ型组是79．16％。结论：原发性高血压患者中ACE基因多态性与依那普利降压疗效相关。     

ACE基因多态性与原发性高血压患者血清ACE和血浆AngⅡ水平的相关性

目的研究血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与原发性高血压(EH)患者血清ACE、血浆血管紧张素Ⅱ(AngⅡ)水平的相关性。方法选择青岛地区EH患者246例和130例正常对照,测定两组血压、血脂、血糖等临床及生化指标,并对高血压进行分级,同时检测血清ACE、血浆AngⅡ水平,采用聚合酶链反应(PCR),检测ACE基因型,比较不同基因型、不同血压分级患者其血清ACE、血浆AngⅡ水平有无差别。结果EH组中,II、ID、DD基因型患者血清ACE水平分别为(36.69±14.05)U/L,(42.98±16.61)U/L,(49.37±17.43)U/L,组间差异有统计学差异(P<0.05);三组基因型患者血浆AngⅡ水平比较,组间差异无统计学差异(P>0.05);随着高血压分级的升高,血清ACE及血浆AngⅡ水平逐渐增加,差异均有统计学意义(P<0.05);EH患者血清ACE水平与ACE基因多态性之间有相关性(r=0.324,P<0.05)。结论 DD基因型EH患者血清ACE水平明显高于ID型和II型患者,血浆AngⅡ水平在不同基因型间无统计学差异。     

妊高征与血管紧张素转换酶基因多态性的相关性研究

目的探讨妊娠期高血压综合征（pregnancy-induced hypertension,PIH）与血管紧张素转换酶（ACE）基因多态性的关系。方法运用多聚酶链反应技术检测61例PIH患者及胎儿和70例正常妊娠妇女及胎儿血管紧张素转换酶基因多态。结果妊娠妇女两组中DD型、ID型Ⅱ型基因频率分别比较,D型等位基因分别比较差异有统计学意义;胎儿两组中DD型、ID型Ⅱ型基因频率分别比较,D型等位基因分别比较均无统计学差异。结论PIH患者ACE基因多态性与PIH的发病有关;PIH胎儿ACE基因多态性与PIH的发病无关。     

血管紧张素转换酶基因多态性与血管紧张素转换酶抑制剂的降压作用

目的:从基因多态性研究药效的差异。方法:选择健康志愿者99 例,未治疗的原发性高血压病人40 例,用PCR 方法检测血管紧张素转换酶(ACE) 基因的插入与缺失(I/D) 多态性, 用血管紧张素转换酶抑制剂(ACEI) 卡托普利治疗高血压病人。结果:正常人与原发性高血压患者的ACE等位基因频率及基因型频率无显著差异(P>0.05) 。卡托普利降压有效病人与无效病人ACE 基因的I/D等位基因频率及基因型频率,基因缺失型纯合子(DD)或/ 和杂合子(ID) 与非缺失型(II) 也均无显著差异(P>0.05) 。结论: ACE基因的I/ D多态性与原发性高血压的发病无关, ACEI降压作用的个体差异与ACE基因的I/D多态性无关。     

血管紧张素转换酶基因多态性在北方汉族、达斡尔族、鄂温克族中的分布

目的：观察血管紧张素转换酶（ACE）基因多态性在北方汉族、达斡尔族和鄂温克族中的分布。方法：采用聚合酶链反应（PCR）检测90例北方汉族,84例达斡尔族和64例鄂温克族ACE基因内含子16的插入/缺失多态标记,得到三种基因型：插入/缺失杂合子（ID）、缺失纯合子（DD）、插入纯合子（Ⅱ）。结果：北方汉族ACE基因频率ID27.8%、DD17.8、Ⅱ54.4%,达斡尔族ID60.7%、DD26.2%、Ⅱ13.1%;鄂温克族ID70.3%、DD21.9%、Ⅱ7.8%。结论：中国北方汉族与达斡尔族和鄂温克族间ACE基因多态性存在差异。     

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.     

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.     

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.