沙库巴曲缬沙坦应用于心血管疾病研究进展

心力衰竭是各种心血管疾病的严重和终末阶段,致残致死性高,严重威胁人类的健康。据估计,中国目前拥有超过 1 000万的心衰病人。尽管近 20年来慢性收缩性心力衰竭一直使用血管紧张素转换酶抑制剂( ACEI)、血管紧张素 II受体拮抗剂(ARB)、β受体阻断剂和醛固酮受体拮抗剂为主药物治疗,但心力衰竭在全球范围内发病率、死亡率和医疗保健支出均呈升高趋势。对更高效医疗的要求以及生物医学创新的发展,血管紧张素受体脑啡肽酶抑制剂(ARNI)——沙库巴曲缬沙坦(诺欣妥)应运而生。 PARADIGM?HF研究是在射血分数降低的心力衰竭病人中与依那普利对比,提供了沙库巴曲缬沙坦在心血管和全因死亡中获益的有力证据。而对射血分数保留的心力衰竭、高血压及其亚组、肺动脉高压、心肌梗死、糖尿病和肾脏疾病的临床研究表明,沙库巴曲缬沙坦对各种心血管疾病均能获益。沙库巴曲缬沙坦在心血管疾病治疗中显现出巨大的前景。     

射血分数保留心力衰竭合并高血压和心房颤动使用沙库巴曲缬沙坦1例并文献复习

沙库巴曲缬沙坦说明书推荐用于射血分数降低的慢性心力衰竭成人患者,可降低心血管死亡和心力衰竭住院的风险,还可用于治疗原发性高血压。指南推荐沙库巴曲缬沙坦用于射血分数保留心力衰竭的治疗,2023年的高血压指南也将其纳入新的一线治疗药物,但是对于射血分数保留心力衰竭合并高血压和心房颤动的患者的药物治疗并无明确的推荐,通过文献复习发现沙库巴曲缬沙坦对这类患者的预后有潜在的作用。     

沙库巴曲缬沙坦在心肾功能不全患者中的应用进展

心力衰竭(HF)是成年人最常见的住院和死亡的原因,其发病率和死亡率较高。目前,血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体阻滞剂(ARB)、β受体阻滞剂、醛固酮受体拮抗剂(MRA),已成为治疗射血分数减低心力衰竭(HFrEF)的药物基础。但超过一半的心力衰竭患者近五年内死亡率仍较高。心力衰竭造成射血功能减低,进而导致肾脏血流量不足引起严重的肾功能不全。沙库巴曲缬沙坦已被证实在降低心力衰竭死亡率和住院率方面优于依那普利,且对心力衰竭造成的肾功能不全有显著的临床意义,作用于多种机制。本文就沙库巴曲缬沙坦在心肾功能不全患者中的临床应用等方面作一综述。     

沙库巴曲缬沙坦治疗心力衰竭的快速卫生技术评估

目的 快速评估沙库巴曲缬沙坦治疗心力衰竭的有效性、安全性和经济性，为药物遴选和准入决策提供循证证据。方法 系统检索2021年5月前发表的PubMed、Cochrane Library、中国国家知识基础设施(CNKI)、维普中文科技期刊数据库(VIP)和万方数据库等数据库，收集沙库巴曲缬沙坦与对照药物治疗(包括射血分数降低、射血分数保留及射血分数中间值的心力衰竭)的系统评价/Meta分析、卫生技术评估(HTA)报告和药物经济学研究等文献。由2名评价者根据纳入和排除标准独立筛选文献、提取资料和评价质量后，综合比较研究结果，对有效性、安全性、经济学结果进行定性描述。结果 共纳入文献25篇，其中HTA报告1篇、系统评价/Meta分析13篇，药物经济学研究11篇。有效性方面，与血管紧张素转化酶抑制药(ACEI)/血管紧张素受体阻断药(ARB)比较，沙库巴曲缬沙坦可显著降低所有心力衰竭患者再住院率、纽约心脏病学会(NYHA)心功能分级，提高心衰患者生活质量，可显著降低射血分数降低的心力衰竭患者心血管死亡风险、全因病死率、N末端B型利钠肽原(NT-proBNP),对超声心动图相关参数也有显著改善。安...     

沙库巴曲缬沙坦减少严重心力衰竭患者利尿剂维持用量的疗效观察

目的 探讨应用沙库巴曲缬沙坦对重度心力衰竭患者的临床改善及对襻利尿剂维持剂量的影响.方法 2018年2月至2020年2月我院收治的重度心力衰竭住院患者74例,随机分为两组,对照组采用常规药物治疗,观察组口服沙库巴曲缬沙坦,并根据血压、心率及尿量调整β受体抑制剂及利尿剂用药剂量.结果 治疗6个月后,观察组临床症状改善及心功能指标改善优于对照组,且观察组襻利尿剂维持量少于对照组,差异有统计学意义(p＜0.05).结论 沙库巴曲缬沙坦治疗射血分数降低的心力衰竭患者安全有效,改善射血分数降低的心力衰竭患者的心室重构,并降低襻利尿剂维持剂量.     

沙库巴曲缬沙坦治疗不同射血分数慢性心力衰竭的临床研究

目的:观察沙库巴曲缬沙坦治疗不同射血分数慢性心力衰竭(CHF)的临床疗效。方法:选取某院急诊住院部收治的慢性心力衰竭患者133例,依据左心室射血分数分成射血分数降低心力衰竭(HFr EF) 68例和射血分数保留心力衰竭(HFp EF)65例,2组内分别设置观察组与对照组,对照组患者给予指南推荐的抗心力衰竭药物血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻滞剂(ARB)治疗,观察组予以沙库巴曲缬沙坦治疗。随访6月,比较在2种不同射血分数心力衰竭患者中,2种治疗方法的临床疗效、纽约心功能分级(NYHA)、心功能指标[氨基末端脑钠肽前体(NT-proBNP)水平、左室射血分数(LVEF)、左心室舒张末期内径(LVEDD)、6分钟步行试验距离(6MWT)]变化情况,同时评估2组间主要不良反应和主要心脏不良事件发生情况。结果:治疗6个月后,在HFr EF和HFp EF2组患者内,观察组LVEF值增加、NT-proBNP水平下降、6MWT增加均显著优于对照组(P <0.05); 2组患者内观察组与对照组间纽约心功能分级改善、主要不良反应差异均无统计学意义(P>0.05);观察组...     

沙库巴曲缬沙坦抑制心脏重构的研究进展

心脏重构是心血管疾病发生、发展的重要病理生理基础，与患者预后关系密切。沙库巴曲缬沙坦（LCZ696）是一种血管紧张素受体脑啡肽酶抑制剂，可同时作用于肾素-血管紧张素-醛固酮系统（RAAS）和利钠肽系统，主要用于治疗射血分数降低的心力衰竭。在不同类型的心血管疾病中，与肾素-血管紧张素系统抑制剂（RASI）比较，LCZ696能够显著抑制心脏重构，改善心功能及心血管病预后。本文就LCZ696对心脏重构抑制作用的机制及研究现状作一综述。     

第63讲血管紧张素受体-脑啡肽酶抑制药有望成为抗全射血分数心力衰竭的新星

血管紧张素受体-脑啡肽酶抑制药(ARNI)的代表药物是沙库巴曲缬沙坦,要想搞清关于ARNI的问题,首先要回顾一下心力衰竭(心衰)的分类和病理生理学进展. 一、心衰按左室射血分数如何分型 心衰的分型繁多,如充血性心衰与淤血性心衰、左侧心衰与右侧心衰、收缩性心衰与舒张性心衰等,近年沿用按左室射血分数(LVEF)进行心衰分型...     

沙库巴曲缬沙坦联合美托洛尔对冠状动脉粥样硬化性心脏病伴慢性心力衰竭的心功能保护作用研究

目的 探究沙库巴曲缬沙坦联合美托洛尔治疗冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease,CHD)伴慢性心力衰竭(chronic heart failure,CHF)的疗效及心功能保护作用。方法 将180例CHD合并CHF患者随机分为两组,每组90例。对照组应用血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂联合美托洛尔治疗,干预组应用沙库巴曲缬沙坦联合美托洛尔治疗,疗程6个月。对比两组临床疗效及主要不良心血管事件,测量治疗前后心功能指标左心室射血分数(left ventricular ejection fraction,LVEF)、左心室舒张早期最大血流速度与舒张末期最大血流速度比(E/A)、左心室收缩末期内径(left ventricular end systolic diameter,LVESD)、左心室舒张末期内径(left ventricular end diastolic diameter,LVEDD)和左心室质量指数(left ventricular mass index,LVMI),检测血浆N-末端脑钠肽(N-termi...     

沙库巴曲缬沙坦治疗慢性心力衰竭患者的疗效分析

目的 分析沙库巴曲缬沙坦治疗慢性心力衰竭患者的疗效.方法 70例慢性心力衰竭患者,随机分为对照组和观察组,每组35例.对照组在常规治疗基础上联合缬沙坦治疗,观察组在常规治疗基础上联合沙库巴曲缬沙坦治疗.比较两组患者慢性心力衰竭纠正时间.治疗前后血浆N末端脑钠肽前体、醛固酮、去甲肾上腺素、血管紧张素Ⅱ,左心室收缩末期内径...     

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.     

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.