小剂量利妥昔单抗治疗难治性免疫性血小板减少症临床观察

目的：探讨应用利妥昔单抗治疗难治性免疫性血小板减少症（ ITP）的疗效。方法选择诊断为难治性ITP16例,应用小剂量利妥昔单抗,每周1次（100 mg）静脉滴注,连用4周。动态检测血常规。结果完全反应4例有效,7例,无效5例,总有效率68．75％。有效患者疗效持续时间5～28个月,2例复发,其余患者疗效维持较好。结论小剂量利妥昔单抗治疗难治性免疫性血小板减少症疗效确切,毒副作用较小。     

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。     

小剂量利妥昔单抗治疗原发性干燥综合征(pSS)继发血小板减少的疗效探究

目的探讨小剂量利妥昔单抗治疗原发性干燥综合征(pSS)继发血小板减少的临床效果。方法收集我院自2010年5月至2013年5月收治的13例原发性干燥综合征继发血小板减少患者作为研究对象,患者均接受小剂量利妥昔单抗治疗,观察患者外周血B细胞及血小板变化情况。结果 13例患者中12例患者治疗后血小板在治疗后1²周内出现上升,治疗32周内出现上升,治疗3⁸周后升至正常,维持缓解288周后升至正常,维持缓解28⁵3周,患者48周时血小板计数均恢复正常。经积极治疗,13例患者外周血B细胞降至正常值,然而尚未达到清除状态;患者治疗总有效率为92.3%,患者在治疗中均未出现严重不良反应。结论小剂量利妥昔单抗治疗原发性干燥综合征继发血小板减少能够对部分B细胞进行清除,阻滞血小板减少,促进患者康复。     

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。     

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。     

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.     

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,     

血浆置换联合利妥昔单抗治疗初诊特发性血栓性血小板减少性紫癜的临床分析

目的分析血浆置换联合利妥昔单抗治疗初诊特发性血栓性血小板减少性紫癜(TTP)临床特征、治疗效果及生存情况。方法回顾性分析4例采用血浆置换联合利妥昔单抗方案治疗的初诊特发性TTP患者的临床资料。结果 3例患者有典型的"五联征",1例患者表现为微血管病性溶血性贫血、血小板减少和中枢神经系统症状。4例患者初诊时ADAMTS13无活性,ADAMTS13抗体阳性。4例患者治疗后获得临床缓解,治疗过程中无利妥昔单抗输注反应,无严重感染事件发生。中位随访29个月,患者均未复发,长期存活。结论 4例初诊特发性TTP患者在血浆置换基础上联用利妥昔单抗安全、有效、耐受性良好。     

利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血2例并文献复习

目的:探讨利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血(AIHA)的疗效、毒副作用。方法:(1)总结2例难治性AIHA患儿的临床表现、实验室检查结果及使用利妥昔单抗治疗前后的情况。(2)对2例患儿选用利妥昔单抗治疗(每次375 mg/m2,每周1次,共4次),随访利妥昔单抗使用后CD20+细胞、血红蛋白等的变化情况,探讨利妥昔单抗治疗儿童AIHA的疗效;同时观察发热、皮疹、感染等毒副作用。结果:2例患儿诊断AIHA后均首先选用糖皮质激素治疗,初期都能显效,但不能长期维持,需长期依赖激素及输血。使用利妥昔单抗治疗后,2例患儿均能显效,其中1例治愈,1例病情反复,最终死于严重贫血。结论:尽管糖皮质激素是治疗AIHA的一线药物,但激素依赖或难治性病例较常见,因此利妥昔单抗已逐渐成为儿童难治性AIHA安全有效的二线治疗药物。     

多次使用利妥昔单抗致3级过敏反应一例

3级过敏反应是利妥昔单抗少见却严重的不良反应,本文报道1例66岁抗中性粒细胞胞质抗体相关性肾小球肾炎患者,使用激素加利妥昔单抗治疗,前6次输注利妥昔单抗后未出现严重不良反应,第7次接受利妥昔单抗后出现3级过敏反应,抢救成功后未再给予该药,提示多次利妥昔单抗治疗仍然需注意过敏反应。     

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.