肺动脉高压的药物治疗及药物递送策略

肺动脉高压(pulmonary arterial hypertension,PAH)属于罕见性疾病,被称为"心血管疾病中的癌症",其发病机制复杂.近年来,PAH发病机制的研究取得了一定的进展.针对病理机制与作用途径,目前临床治疗药物主要包括前列环素类似物和前列环素受体激动剂、内皮素受体拮抗剂、磷酸二酯酶-5抑制剂和可溶...     

治疗肺动脉高压方法的研究进展

肺动脉高压(pulmonary artery hypertension,PAH)是威胁生命的难治性疾病,主要表现为肺动脉压力的上升和肺血管阻力的增加,导致右心室肥厚,逐渐出现右心衰竭,甚至死亡。目前的治疗主要是改善症状,减轻血流动力学紊乱,但如果进一步恶化,需要进行肺移植。     

小儿肺动脉高压治疗进展

肺动脉高压(pulmonary artery hypertension,PAH)是肺血管和肺实质发生病变的主要表现,是由于肺大小动脉、肺微血管和肺静脉受损害而引起的临床常见病征。正常肺动脉压力为15～30mmHg/5-10mmHg,平均压(MPA)为10～20mmHg,肺血管阻     

活血化瘀中药治疗肺动脉高压的实验及临床研究进展北大核心CSCD

肺动脉高压(pulmonary hypertension,PH)是一类进行性发展的心血管疾病或临床综合征。其病理机制复杂,现有临床药物治疗不能很好地抑制病程进展,传统中药因其多成分、多靶点协同发挥作用的特点,在肺动脉高压的治疗中具有独特优势。近年的研究发现,活血化瘀类中药在治疗PH中可发挥扩张肺血管、改善内皮功能、缓解右心衰竭等作用,疗效显著。该文就活血化瘀中药对肺动脉高压的治疗效果、作用机制等进行简要总结讨论。     

肺源性肺动脉高压研究进展

肺动脉高压(pulmonary hypertension)是晚期肺疾病的常见并发症,预后差。肺源性肺动脉高压是“继发性”肺动脉高压分类中的一个子类,其病理生理、治疗与原发性肺动脉高压症有差异。     

肺动脉高压的药物治疗

肺动脉高压(pulmonary hypertension,PH)是临床上常见的一种致残率和致死率较高的疾病,WHO根据病因将PH分为5类。PH治疗从病情严重程度的基线评估开始,进行基础治疗。基础治疗针对PH的基础病因。部分PH患者会进展至需要针对PH本身而并非基础病因的高等级治疗。对于治疗PH的基础病因后仍持续存在PH且WHO分级为Ⅱ、Ⅲ或Ⅳ级的患者,应转诊至专科医学中心进行高等级治疗的评估。高等治疗包括类前列腺素(prostaglandin,PG)、内皮素受体拮抗剂(endothelin receptor antagonist,ERA)、5型磷酸二酯酶(phosphodiesterase 5,PDE5)抑制剂、可溶性鸟苷酸环化酶(soluble guanylate cyclase,sGC)激动剂和钙通道阻滞剂(calcium channel blocker,CCB)。     

先天性心脏病伴肺动脉高压的治疗进展

肺动脉高压(pulmonary arterial hypertension,PAH)是由多种病因引起的复杂疾病,发病机制尚未完全明了,其中先天性心脏病合并肺动脉高压的病人在临床上占相当大的比例,最终会导致心功能衰竭甚至死亡。随着医学的进步,肺动脉高压的治疗也在不断完善。本文通过复习文献,对目前肺动脉高压的诊断及治疗进行综述。     

改善肺动脉高压中肺血管重构治疗策略的研究进展

肺动脉高压(pulmonary hypertension, PH)是一种慢性、进行性、高死亡率的疾病。各类PH具有相同特征：肺动脉内皮细胞和平滑肌细胞的过度增殖、抗凋亡和炎症导致的肺小血管的渐进性增厚,引发肺血管的重构和肺血管阻力增加,最终导致右心室肥厚、心衰、死亡。目前治疗PH的药物(L型钙通道阻滞剂、磷酸二酯酶5抑制剂、鸟苷酸环化酶激活剂、内皮素受体拮抗剂、合成前列环素及其类似物)主要通过松弛肺血管降低肺动脉压,不能根本治愈患者。因此,研发有效改善甚至逆转肺血管重构的药物,是治疗PH的关键。近年来,围绕肺血管重构开展的研究主要有：新的小分子化合物的合成;成熟药物的改造;联合用药及剂型改造等;基于中医“肺胀”等理论,对中药制剂以及中药复方的药效评价;中药单体的研究;新靶点的研究。     

西地那非治疗小儿先天性心脏病合并肺动脉高压的临床疗效分析

<正>先天性心脏病(congenital heart disease,CHD)是心脏病患儿在儿童期发病最主要的一种疾病类型,目前在全球范围内每年都有150万左右的新发CHD患儿,该疾病已成为婴幼儿最主要的死亡原因[1]。而肺动脉高压(pulmonary arterial hypertension,PAH)是CHD的一种严重的并发症,其发病率逐年升高。传统治疗PAH的药物虽然较多,但大     

基于肺血管细胞增殖抑制的肺动脉高压治疗药物

肺动脉高压(pulmonary hypertension, PH)是一种进展迅速的肺血管疾病,预后不良,最终导致右心衰竭和死亡。肺小动脉的重塑是PH的重要病理特征。位于肺动脉中层的肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells, PASMCs)表现出类似于肿瘤细胞的异常增殖和抗凋亡特征,是肺血管重塑的主要启动因素。本文主要讨论在PASMCs增殖中起关键作用的信号通路以及对细胞增殖通路为靶点的抑制剂的最新研究进展做一综述,以期为PH的靶向治疗提供新的视角。     

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.     

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.