重组人脑利钠肽和米力农治疗慢性心力衰竭急性发作期的对比研究

目的比较重组人脑利钠肽(rhBNP)和米力农治疗慢性充血性心力衰竭(CHF)急性发作期的临床疗效,观察rhBNP对心功能及血清脑利钠肽(BNP)和去甲肾上腺素(NE)水平的影响。方法入选CHF急性加重期患者100例,随机分为rhBNP组、米力农组各50例,观察2组治疗前后的临床疗效、心功能、血清BNP及NE水平变化。结果治疗后48h比较rhBNP组显效率及总有效率均高于米力农组(P<0.05),rhBNP组血清BNP、NE水平较米力农组下降(P<0.05),2组治疗后48h血清BNP、NE均较基线值下降(P<0.01);rhBNP组治疗后2周左室耐酚玫(LVEF)值较治疗前升高(P<0.05),米力农组治疗后2周EF值与治疗前比较差异无统计学意义(P>0.05)。结论 rhBNP能改善心室的收缩功能,延缓心室重构,可用于CHF急性加重期的治疗。     

米力农对充血性心力衰竭患者BNP的影响

目的 观察米力农治疗重症充血性心力衰竭（CHF）的临床疗效及其对脑钠素（BNP）的影响。方法 82例重症充血性心力衰竭患者,随机分为米力农组（42例）和对照组（40例）,对照组予以常规治疗,米力农组在常规治疗基础上静脉应用米力农7d,用放射免疫法测定血浆BNP在治疗前后的改变。结果 治疗后米力农组BNP水平明显降低,并明显低于对照组（P〈0．01）。心功能改善1～2级,药物副反应少,患者耐受性好。结论 米力农治疗CHF疗效较好,并能在一定程度上改善心衰患者的神经内分泌失调。     

米力农联合曲美他嗪对充血性心力衰竭患者血清TNF-α和hs-CRP水平的影响

目的观察米力农联合曲美他嗪对充血性心力衰竭患者心功能及血清肿瘤坏死因子(TNF-α)、超敏C-反应蛋白(hs-CRP)水平的影响。方法 CHF患者125例,随机分为3组,对照组(A组)40例,米力农组(B组)42例,米力农加曲美他嗪组(C组)43例,A组采用常规抗心力衰竭治疗,B组在对照组基础上加用米力农,C组在对照组基础上加用米力农联合口服曲美他嗪,10d为1个疗程。治疗前后测定心功能及血清TNF-α、hs-CRP水平的变化。结果 C组临床疗效高于A、B组,治疗后血清TNF-α、hs-CRP水平明显下降(P<0.05或<0.01)。结论米力农联合曲美他嗪治疗CHF可明显改善心功能,降低血清TNF-α、hs-CRP水平。     

左西孟旦和米力农治疗慢性心衰急性发作的对比研究

目的:观察对比左西孟旦和米力农治疗慢性心衰急性发作的临床疗效。方法:入选CHF急性发作的患者80例,随机分为左西孟旦组43例、米力农组37例,观察两组治疗前后每搏心输出量(SV)、左室射血分数(LVEF)、血清NT-proBNP及NE的水平变化。结果:左西孟旦组治疗后血清NT-proBNP、NE水平均较米力农组下降(P0.05),EF、SV水平均较米力农组升高(P0.05)。结论:左西孟旦相对于米力农更能改善心室的收缩功能,延缓心室重构。     

米力农短期治疗难治性心力衰竭的疗效与安全性

目的观察米力农短期治疗难治性心力衰竭的疗效与安全性。方法采用随机数字表法将108例难治性心力衰竭患者随机分为常规治疗组（n＝40）和米力农负荷量治疗组（n＝32）及米力农无负荷量治疗组（n＝36），后两组在常规治疗（强心、利尿、血管紧张肽转换酶抑制药等）基础上加用米力农，7 d为1个疗程。观察治疗前后患者的心功能分级、6 min步行距离、血浆脑钠肽（BNP）浓度、左室射血分数（LVEF）、左室舒张末径（LVEDD），并记录可能与药物有关的不良反应。结果米力农治疗组总有效率85.29%，常规治疗组62.50%，米力农负荷量治疗组84.38%，米力农无负荷量组86.11%。米力农有无负荷量治疗组均优于常规治疗组。治疗后3组患者心功能分级均不同程度改善，6 min步行距离明显延长，LVEF及LVEDD均较治疗前有所改善。米力农治疗组治疗后心功能分级、6 min步行距离、LVEF及LVEDD优于常规治疗组，米力农治疗组治疗后血浆BNP优于常规治疗组。米力农有无负荷量治疗组比较差异无统计学意义，但负荷量治疗组出现低血压3例和室性心律失常2例。结论米力农短期治疗难治性心力衰竭能够显著改善患者心功能，减轻症状，不良反应少。     

BiPAP在充血性心力衰竭治疗中的应用

目的 探讨无创双水平气道正压通气(BiPAP)对重度充血性心力衰竭(CHF)的作用.方法 60例CHF患者随机均分为常规药物治疗(B)组和BiPAP治疗(A)组.A组在常规药物治疗的基础上,应用BiPAP呼吸机无创通气.两组疗程均为3 d.观察治疗前后左心室射血分数(EF)、血气分析及脑型利钠肽(BNP)的变化.结果 A组治疗显效率63.3%,明显高于B组的36.7%(P<0.05).与B组相比,治疗后A组PaO_2、SaO_2和EF改善更明显,A组BNP水平下降更明显(P<0.05).结论 BiPAP不仪能改善CHF患者的通气功能,也能改善CHF患者的心功能及降低BNP水平.     

米力农治疗慢性心衰急性加重期的疗效观察

目的观察米力农治疗慢性心衰急性加重期的疗效。方法选择慢性心衰急性加重期病例47例,随机分成治疗组24例,对照组23例,治疗组在常规抗心衰治疗基础上加用米力农,5～7 d为1个疗程,对照组采用常规抗心衰治疗,观察治疗前后患者的心功能分级、6 min步行实验、超声心动图测定左心功能指标及BNP指标。结果治疗组总有效率100%,对照组78%,2组6 min步行实验、EF值、BNP结果均有改善,治疗组改善更明显。结论短期使用米力农治疗慢性心衰急性加重期疗效确切,无明显副反应。     

米力农间歇使用治疗顽固性心力衰竭临床疗效分析

目的：分析顽固性心力衰竭患者应用米力农治疗后的临床疗效。方法回顾性分析82例在本院住院心功能Ⅲ-Ⅳ级（NYHA分级）的患者，临床已合理用药且积极纠正心衰诱因的难治性心衰患者，按治疗方案不同分为两组：对照组，予以常规纠正心衰治疗，共37例；研究组，在常规治疗基础上间歇加用米力农治疗，共45例。前后两组患者分别进行6 min步行试验、心脏超声检查和BNP检验，对比两组患者心功能改变。结果与对照组相比，研究组在6 min步行试验距离、LVEF及BNP上有明显改善（P〈0.05）。结论米力农间歇使用，并与常规治疗心衰药物联共同使用，对短期内纠正心功能效果较好。     

磷酸肌酸钠对心瓣膜病慢性心功能不全患者心功能和BNP的疗效观察

目的观察磷酸肌酸钠对心瓣膜病慢性心力衰竭(CHF)患者心功能和BNP的影响。方法心瓣膜病慢性心力衰竭患者90例,治疗组45例,对照组45例。对照组给予常规抗心力衰竭治疗,治疗组在常规治疗基础上加用磷酸肌酸钠,疗程2周。根据纽约心脏协会心功能(NYHA)分级法评价两组患者治疗前后的临床心功能分级情况、左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)和左室射血分数(LVEF)的改善情况及血浆BNP水平的变化。结果治疗2周后,治疗组总有效率、心功能改善情况及血浆BNP下降水平显着高于对照组(P<0.05)。结论磷酸肌酸钠联合常规治疗心力衰竭药物能显着改善心瓣膜病CHF患者心功能、降低血浆BNP水平。     

米力农联合利尿剂治疗慢性肺源性心脏病严重心力衰竭疗效观察

目的观察米力农联合利尿剂治疗慢性肺源性心脏病严重心力衰竭的疗效和安全性。方法 50例慢性肺源性心脏病合并重症心力衰竭患者,采用自身前后对照法,在常规治疗无效后,给予米力农联合呋塞米等利尿剂。观察治疗前后症状、体征、血压、心率、超声心动参数、B型脑钠肽(BNP)及心功能指标。结果应用米力农联合利尿剂治疗后显效11例,有效35例,无效4例,总有效率92%。米力农同时明显改善左室收缩功能,对血压、心率无不良影响。结论米力农联合利尿剂能有效改善慢性肺源性心脏病严重心力衰竭的心功能。     

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.

---

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.