小剂量利妥昔单抗治疗难治性免疫性血小板减少症的疗效

目的探讨小剂量利妥昔单抗治疗难治性免疫性血小板减少症(ITP)的临床疗效及安全性。方法 6例小剂量利妥昔单抗(RTX 100 mg/次,每周1次,连续4周)治疗的难治性ITP患者,监测治疗前后血小板计数、血清免疫球蛋白等指标变化。结果完全反应1例,有效3例,无效1例,复发1例,总有效率为66.7%,持续反应率达33.3%,未发现严重不良反应。结论小剂量RTX治疗难治性ITP有效,其作为脾切除前可供选择的替代治疗方案,值得推荐。     

利妥昔单抗治疗难治性免疫性血小板减少症的临床疗效观察

目的观察利妥昔单抗治疗难治性免疫性血小板减少症(ITP)的临床疗效。方法 10例难治性免疫性血小板减少症患者,静脉注射利妥昔单抗,检测血小板数及淋巴细胞亚群等,观察临床疗效。结果完全反应(CR)30%,有效(R)40%,无效(NR)30%,中位起效时间3周。治疗后所有患者CD19(+)/CD20(+)B细胞数均明显下降。治疗过程中及治疗后12个月内均无严重不良反应。结论利妥昔单抗在治疗难治性免疫性血小板减少症中显示了良好的疗效,是一种安全有效的方法。     

小剂量利妥昔单抗注射液联合环孢素A治疗难治性ITP的临床观察

目的:探讨小剂量利妥昔单抗注射液(通用名为利妥昔单抗注射液)联合环孢素A治疗难治性特发性血小板减少性紫癜(简称难治性ITP)的疗效。方法:38例诊断为难治性ITP患者随机分为观察组和对照组,观察组采用小剂量利妥昔单抗注射液联合环孢素A治疗,对照组采用大剂量地塞米松冲击联合硫唑嘌呤治疗,并评估两组患者的近期及远期疗效和副作用。结果:观察组的近期及远期疗效优于对照组,2组间差异有显著性(P<0.05),除肝功能方面,不良反应的其他指标的比较,2组间差异无显著性(P>0.05)。结论:小剂量利妥昔单抗注射液联合环孢素A可作为难治性ITP的有效治疗手段之一。     

小剂量利妥昔单抗联合大剂量地塞米松治疗难治性特发性血小板减少性紫癜的临床研究

目的 研究分析小剂量利妥昔单抗联合大剂量地塞米松在治疗难治性特发性血小板减少性紫癜中的临床价值.方法 选择64例我院2008年3月至2012年3月间难治性特发性血小板减少性紫癜患者,根据治疗方法的不同分为试验组和对照组,每组32例.对照组患者予大剂量地塞米松治疗,试验组患者予小剂量利妥昔单抗联合大剂量地塞米松治疗,比较分析两组患者不同治疗方法的临床疗效.结果 试验组的临床有效率93.75%显著高于对照组的总有效率81.25%,两组比较后差异显著,具有统计学意义（P＜0.05）.结论 小剂量利妥昔单抗联合大剂量地塞米松在治疗难治性特发性血小板减少性紫癜中疗效优异,止血效果良好,值得临床推广与应用.     

小剂量利妥昔单抗治疗系统性红斑狼疮合并血小板减少症临床报道

目的：评价小剂量利妥昔单抗（Rituximab,RTX）治疗系统性红斑狼疮（SLE）合并血小板减少症的疗效及安全性。方法9例继发于SLE的血小板减少症患者,给予静脉滴注利妥昔单抗100mg,每周1次,连用2～4次,同时根据病情联合使用激素等免疫抑制剂。观察患者临床表现和不良反应,比较患者治疗前后各项临床指标的变化。结果第一次使用利妥昔单抗后,6例（66.7％）患者在2～4周内血小板计数上升至正常,随访6～12个月后,其中3例患者维持完全缓解,3例患者复发,但在加用环孢 A和／或达那唑后,血小板又上升至正常且维持良好。1例达部分缓解,2例无效（其中1例死亡）。在随访期间,患者的激素用量均逐步减少。研究期间1例患者发生隐球菌脑膜炎。结论小剂量利妥昔单抗对部分SLE合并血小板减少症有效,安全性较好,但需谨慎除外感染。该生物试剂可能成为免疫相关的血小板减少症的诱导缓解手段之一。     

慢性原发性免疫性血小板减少症的临床治疗分析

原发免疫性血小板减少症（idiopathic throm—bopoenic parpara,ITP）,既往亦称特发性血小板减少性紫癜,由机体免疫功能紊乱引起血小板破坏增加而致的血液系统疾病,在临床上为最常见的出血性疾病。平顶山市新华区人民医院应用小剂量利妥昔单抗100mg,每周一次,     

难治性免疫性血小板减少性紫癜患者应用小剂量利妥昔单抗联合IL-11治疗的临床效果探讨

目的探讨应用小剂量利妥昔单抗联合IL-11治疗难治性免疫性血小板减少性紫癜患者的临床效果。方法将2013年1月～2018年1月我院36例难治性免疫性血小板减少性紫癜患者,采用随机数字表法将其分为两组,其中对照组患者应用常规方法进行治疗,实验组在常规用药基础上,应用小剂量利妥昔单抗联合IL-11治疗,观察并比较两组患者术后临床疗效。结果经过不同药物治疗后,实验组难治性免疫性血小板减少性紫癜患者治疗总有效率(94.44%)明显高于对照组总有效率(61.11%),差异有统计学意义(P <0.05);实验组患者乏力、心房颤动、皮疹、感染不良反应发生率(11.11%)明显低于对照组不良反应发生率(50.00%),差异有统计学意义(P <0.05);随访一年,实验组患者该疾病复发率(5.56%)明显低于对照组该疾病复发率(38.89%),差异有统计学意义(P <0.05)。结论对难治性免疫性血小板减少性紫癜患者,应用小剂量利妥昔单抗,联合IL-11治疗,可有效提升血小板计数,缓解患者出现倾向,避免耐药性的产生,有助于患者疾病的恢复,提高患者生活质量。     

小剂量与标准剂量利妥昔单抗对老年慢性难治性原发性免疫性血小板减少症患者的临床疗效分析

<正>原发性免疫性血小板减少症(ITP)是免疫系统障碍疾病,临床症状主要表现为皮肤黏膜出血,病情不断进展可能导致继发性内脏出血或颅内出血,严重威胁患者生命健康,影响患者生活质量,严重的会导致死亡[1-3]。本文就小剂量与标准剂量利妥昔单抗对老年慢性难治性ITP患者的临床疗效分析展开探讨,选取2016年12月至2019年12月宝鸡市中心医院就诊的老年慢性难治性ITP患者100例作为研究对象进行分析,结果报告如下。     

地塞米松、环孢霉素和利妥昔单抗联合治疗血小板减少有疗效

研究表明,经地塞米松、环孢霉素和利妥昔单抗联合疗法治疗原发性免疫血小板减少症（ ITP）显示疗效良好。原发性免疫血小板减少症患者可能达到持久缓解。表明这是一种进一步优化疗效的疗法。     

利妥昔单抗治疗难治性重症系统性红斑狼疮的临床初步观察

目的初步观察利妥昔单抗治疗难治性重症系统性红斑狼疮(SLE)的疗效及不良反应。方法难治性重症SLE 15例(神经精神狼疮6例,狼疮肾炎4例,免疫性血小板减少5例),予静脉滴注利妥昔单抗500mg,使用1～4次,同时依据病情联合使用激素等免疫抑制剂。采用BILAG和系统性红斑狼疮疾病活动指数(SLEDAI)积分对病情进行评价,监测不良反应及外周血B细胞清除情况和血清学指标变化。结果利妥昔单抗治疗难治性重症SLE,至随访终点BILAG临床完全缓解、部分缓解和无缓解分别占总例数的33%,40%和27%。其中神经精神狼疮和免疫性血小板减少临床改善显著,起效时间≤1个月,部分患者可获得长期缓解(>12个月);入组狼疮肾炎患者效果不佳。研究期间共发生4例严重感染,并导致2例死亡。结论初步提示利妥昔单抗对部分难治性重症SLE有效,该生物制剂可能成为SLE新的诱导缓解手段之一。由于尚缺乏有力的循证医学指导,临床应用需谨慎从事。尤需警惕免疫抑制状态继发感染问题。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.