霉酚酸酯和环孢素A合用预防和治疗肾移植早期急性排斥反应

目的 :考察霉酚酸酯 (MMF)预防移植肾急性排斥反应的疗效及安全性。方法 :对MMF 1.5 g·d-1联合应用环孢素A(CsA)和皮质类固醇与硫唑嘌呤 (Aza)联合应用环孢素A和皮质类固醇预防和治疗急性排斥反应进行随机比较研究。结果 :MMF组的CsA平均给药量、血药浓度与Aza组统计学检验差异有非常显著性 (P <0 .0 1)。急性排斥反应MMF组发生率为12 % (3/ 2 5 ) ,Aza组为 33% (12 / 36 ) ,急排发生时两组CsA浓度差异有显著性 (P <0 .0 1) ,但平均给药差异无显著性 (P >0 .0 5 )。结论 :MMF可有效地减少急性排斥反应的发生。     

霉酚酸酯替代硫唑嘌呤在肾移植中的应用

目的 观察霉酚酸酯(MMF)替代硫唑嘌呤(Aza)在预防肾移植术后急性排斥中的作用。方法 回顾性分析我院95例肾移植后应用皮质激素(Perd)，环孢素(CsA)，MMF(或)硫唑嘌呤(Aza)三联免疫抑制剂治疗，其中分成MMF组57例，Aza组38例，MMF组适当减少环孢素用量。结果 MMF组发生急性排斥率为8．89%(5／57)，Aza组为23．7%(9／38)。结论 以MMF代替Aza应用于肾移植术后，可以减少术后急性排斥及CsA的用量，减少药物的肝肾毒性。     

肾移植患者应用咪唑立宾与麦考酚酸酯2种三联免疫抑制方案的疗效比较

目的:观察咪唑立宾(MZR)的免疫抑制效果及安全性,采用MZR替代麦考酚酸酯(MMF),比较环孢素A(CsA)+MZR/MMF+泼尼松龙(Pre)两种三联免疫抑制治疗的疗效。方法:尸体肾移植患者70例,按手术顺序交替登记MZR组和MMF组。移植后采用CsA+MZR/MMF+Pre三联免疫抑制疗法,MZR组剂量为200mg.d-1(体重>60kg)或150mg.d-1(体重<60kg);MMF组剂量为1500mg.d-1(体重>60kg)或1000mg.d-1(体重<60kg)。观察肾移植术后1年的人/肾存活率、急性排斥反应发生率及治疗逆转率、感染发生情况及药物毒副作用。结果:全部病例术后随访至少1年,MZR组和MMF组的急性排斥反应发生率分别为17.1%和11.4%,两组之间无显著性差异。MZR组和MMF组肺部感染的发生率分别为8.6%和48.6%,MMF组的发生率显著升高。血尿酸升高的发生率两组之间比较未见显著性差异,MZR组在术后24,36,48周时血尿酸的水平要高于MMF组。MZR组的持续用药率显著高于MMF组。结论:MZR可以与钙调神经素阻滞剂、激素联合应用于肾移植患者,具有一定的安全性和有效性,不良...     

肾移植后应用霉酚酸酯与硫唑嘌呤的疗效比较

目的:比较肾移植受者应用霉酚酸酯(MMF)与硫唑嘌呤(Aza)的临床疗效.方法:肾移植术后患者86例随机分为MMF组,即用环孢素(CsA)加MMF、泼尼松(Pred)三联用药方案者40例;Aza组为CsA加Aza、Pred三联用药方案者46例;定期监测其肝肾功能、CsA全血浓度等,观察时间为1 a.结果:两组患者术后肾功能恢复情况基本相同,但MMF组患者血肌酐(Cr)值显著低于Aza组,差异有显著性,;MMF组的CsA用量及其血药浓度也显著低于Aza组;MMF对急慢性排斥反应效果较Aza好;两组患者消化道反应、白细胞减少、感染等并发症的发生率差异无显著性,Aza组药物性肝损害发生率高于MMF组.结论:含MMF的三联用药更有利于移植肾功能的恢复和降低肝肾毒性发生率.     

霉酚酸酯在肾移植患者中的应用

目的：将免疫抑制剂霉酚酸酯（MMF）在预防肾移植术后的排斥反应及肝毒性发生率等指标与硫唑嘌呤（Aza）进行临床对照观察。方法：MMF组（环孢素A＋泼尼松＋MMF）35例,对照组（环孢素A＋泼尼松＋Aza)25例。试验观察期24mo。结果：MMF组移植术后排斥反应及肝毒性发生率明显低于对照组,2组差异有高度统计学意义（P肝＜0．01,P肾＜0．01）;且MMF组肾功能较对照组平稳。结论：MMF与环孢素A及泼尼松三药联用,可降低急慢性排斥反应及肝肾毒性发生率,从而提高了免疫抑制剂应用的安全性和耐受性。     

他可莫司与环孢素A用于肾移植的对比观察

为了观察他可莫司(FK506)对肾移植患者免疫抑制作用的疗效和安全性，将79例首次肾移植患者分为FK506与环孢素A(CsA)两组，进行对比观察。FK506组(n=23)：FK506+霉酚酸酯(MMF)+泼尼松(Pred)；CsA组(n=56)：CsA+MMF+Pred。结果表明，FK506组和CsA组急性排斥反应的发生率分别为4．4％和14．3％，差异有显著意义(P&;lt;0．05)。1年人、肾存活率分别为100％／100％和100％／96．4％。FK506组高血压、高血脂及肝功能异常的发生率低于CsA组，而糖尿病发生率高于CsA组。结论：FK506能有效地预防肾移植术后急性排斥反应，且不良反应较少。     

普乐可复在肾移植中的疗效分析

目的:观察普乐可复(FK506)预防移植肾急性排斥的安全性及有效性,进行疗效分析.方法 :将68例肾移植受者分成2组.(1) 普乐可复组(n=30):主要用药为普乐可复+硫唑嘌呤(Aza) +泼尼松 (Pred);(2)环孢素A(CsA)组(n=38):主要用药为CsA+Aza+Pred.结果:观察6个月.普乐可复组急性排斥发生率为0.CsA组有9例(23.7%)发生急性排斥反应(P<0.05).普乐可复组的肝毒性反应及感染发生率均比CsA组低(P>0.05).普乐可复组有3例(10%)发生高血糖反应(P> 0.05) .结论:普乐可复是一种安全高效的免疫抑制剂,排斥发生率低,毒副作用小,可媲美CsA .     

高龄患者肾移植126例临床分析

目的 :探讨高龄患者肾移植的临床特点及四联免疫抑制疗法对临床治疗效果的影响。方法 :分析 1990年 1月至 2 0 0 0年 12月 12 5 1例肾移植中 12 6例高龄患者临床资料 ,将术后使用免疫抑制剂为三联疗法 (CsA +Aza +激素 )的 5 5例作组Ⅰ ;而使用四联疗法 (CsA +MMF +激素 +抗T细胞单抗 )的 71例作为组Ⅱ ,组Ⅱ中 4 7例患者术后使用 2周Wu -T3抗排斥治疗 ,另 2 4例应用抗IL- 2R抗体预防急性排斥反应。将两组的术后并发症、急性排斥率及 1年人 /肾存活率相比较 ,并与本院同期非高龄患者相同指标比较。结果 :高龄患者肾移植后心脑血管并发症以及感染发生率均明显高于非高龄患者。组Ⅰ和组Ⅱ患者的术后并发症发生率分别为 74 5 5 %和 38 0 3% ;急性排斥发生率分别为 12 73%和 4 2 3% ;1年人 /肾存活率分别为 81 82 % /78 18%和 97 18% /95 77%。结论 :高龄患者肾移植术后较容易发生心脑血管并发症及感染 ,使用新的四联免疫抑制疗法能有效地降低心脑血管并发症、感染和急性排斥反应的发生率 ,1年人 /肾存活率亦明显提高。     

肾移植病人应用霉酚酸酯与硫唑嘌呤的临床疗效比较

目的：比较霉酚酸酯（MMF）、硫唑嘌呤（Aza）在肾移植病人中的临床效果。方法：肾移植术后服用霉酚酸酯、硫唑嘌呤患者各28例，均采用同服环孢菌素和泼尼松三联用药方案，每月常规监测环孢菌素A（CsA）全血浓度、血常规、肾功能、肝功能、尿常规。结果：MMF组的CsA用量及其血药浓度显著低于Aza组（P〈0．05），MMF组患者血肌酐（Cr）值也显著低于Aza组（P〈0．05），同时MMF组对急慢性排斥反应效果较Aza组好，药物性肝损害发生率低于Aza组。结论：MMF较Aza不良反应小，减少或避免肝、肾功肾功能损害的发生机会，使肾移植的成功率明显提高。     

雷帕霉素联合环孢素预防肾移植急性排斥反应的随机对照前瞻性研究

目的:评价雷帕霉素(RPM)口服液联合环孢素(CsA)预防肾移植术后早期急性排斥反应的疗效。方法:首次肾移植患者20例,随机分成RPM试验组和硫唑嘌呤(Aza)对照组,每组各10例,分别接受以CsA和类固醇激素为基础的免疫抑制治疗方案6mo,比较2组人/肾存活率、急性排斥反应发生、不良事件发生等指标的差异。结果:17例完成治疗者人/肾均存活;仅Aza组1例发生2次急性排斥反应;2组各发生2例严重不良事件。结论:RPM联合CsA可有效预防移植肾急性排斥反应,并维持肾功能于良好水平,但是也可能增强CsA的肝毒性。     

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.